Method for manufacturing micro-implement and micro-implement

Abstract

Provided are: a micro-implement manufacturing method which is capable of forming microneedles accurately from maltose in a desired shape and freely in a desired arrangement on a substrate, and is also highly productive; and a micro-implement. This method includes a microneedle formation step in which a material to which maltose is adherable is used as a substrate (1) and a micro-processing head (120) capable of forming microneedles from pure maltose or a maltose composite material with freedom of arrangement is used to form a plurality of microneedles individually and sequentially. In the microneedle formation step, the temperature of the micro-processing head (120) is varied so as to increase and decrease on the basis of temperature profile control expressed by the following formula: {F (Ln, Tn, tn) = Σn (Ln, Tn, tn)}, while pure maltose or a maltose composite material is supplied sequentially from the micro-processing head (120) toward the surface (1a) side of the substrate (1), thereby forming microneedles so as to grow sequentially from the base end.

Description

Method for manufacturing a microimplement and microimplement

[0001] The present invention relates, in particular, to a method for producing a microimplement, which is a microneedle in a medical dosage form for administering functional ingredients such as drugs, biomaterials, cosmetics, nutrients, or various powders to the superficial and / or deep layers of the skin, and to the microimplement itself.

[0002] In recent years, transdermal administration devices utilizing microdevice technology have gained increasing recognition in the medical industry due to the demand for ease of treatment, gentleness (friendly), and high-precision administration. A typical example of such a transdermal administration device is the microneedle. Conventional microneedles were mostly made of metal or plastic, due to the need for materials that were easy to process with high precision. However, these materials are foreign objects in the human body and, in some cases, may remain in the body.

[0003] To avoid the problem of foreign substances remaining in the body, as described above, there has been a long-standing demand for biodegradable materials with excellent biocompatibility (degradable) that are easily absorbed by the human body as materials for transdermal administration devices. Polylactic acid is a prime example of such a material. However, since polylactic acid takes weeks or more to dissolve in the body, it has not truly solved the aforementioned problem.

[0004] Meanwhile, recent advancements in material exploration have led to the development of even safer microneedles made from endogenous substances, and among these materials, maltose is establishing itself as a central player. Due to these circumstances, maltose is increasingly being used as a material for microneedles. However, unlike conventional microneedles, maltose microneedles dissolve and disappear immediately in the body's water during use (water-soluble), and are therefore classified as a medical dosage form rather than a medical device. In other words, maltose microneedles differ significantly from conventional microneedles in terms of characteristics and technical attributes, and thus belong to a different technological field; they are called microimplements.

[0005] One of the new functions of the microimplements described above, which are not found in conventional microneedles, is that functional components or pharmaceutical components can be mixed into maltose, and when administered into the body, these components can be penetrated simultaneously with the dissolution of the microneedles. As mentioned above, this form of microimplementation is classified as a medical dosage form rather than a medical device, and the realization of its function is of great importance. In fact, microimplements in which microneedles containing various functional components are provided on the surface of a substrate can introduce various functional components into the superficial and / or deep layers of the skin without causing the user pain, and are attracting great attention in fields such as medicine and cosmetics. Examples of functional components introduced through the skin by microimplements include drugs, biomaterials, cosmetics, nutrients, or various powders, and their applications are not limited to skin treatment, cosmetic and reconstructive procedures, but can also be applied to advanced treatment of immune system diseases affecting deep subcutaneous tissue and the entire body, and are therefore particularly expected to be a painless and minimally invasive medical dosage form.

[0006] As for the microneedles described above, in addition to maltose, other materials that are easily soluble in the human body and highly safe, such as hyaluronic acid, collagen, elastin, and starch, can be used as materials, and various functional components can be used in the form of mixtures, encapsulation, or attachment. On the other hand, in recent years, maltose has been increasingly adopted as a material for microneedles from the standpoint of its excellent solubility and safety. Maltose, which is originally a substance in the body, has a lower melting point than other materials and has excellent water solubility, and as mentioned above, it has the advantage of being easily soluble in the water in the human body and not remaining as a foreign substance.

[0007] Conventionally, microimplements have often been designed to ensure that various functions are performed effectively by functional components, for example, by regularly arranging multiple (numerous) microneedles in a roughly grid-like 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 concave cavities for 20 microneedles are arranged in a line.

[0008] Japanese Patent Publication No. 2015-205094

[0009] In the microimplement disclosed in Patent Document 1, as described above, multiple microneedles are arranged regularly on a substrate. However, when simple cone-shaped (cone-shaped with a basic geometric form) microneedles are arranged in this manner, it becomes difficult for the multiple microneedles to adhere to the skin surface, resulting in the problem of difficulty in uniformly and effectively administering functional components to the superficial and / or deep layers of the skin.

[0010] Furthermore, when forming numerous maltose microneedles on a substrate using conventional methods, using a multi-cavity mold as described above results in a larger overall mold size, leading to a larger heat capacity and a slower cooling rate of the mold during microneedle formation. Consequently, when forming multiple microneedles from a maltose mass while melting the maltose, it is difficult to accelerate the cooling of the mold, making it challenging to quickly fix and form the maltose mass attached to the substrate in the desired shape. This problem poses a significant challenge from a productivity standpoint.

[0011] Furthermore, when using conventional molds that produce multiple microneedles, for example, to manufacture a wide variety of microimplements with different microneedle arrangement patterns, it is necessary to create molds tailored to the specifications of each microneedle, as well as to change molds. Therefore, as the variety of microimplements to be manufactured increases, the frequency of mold changes increases, which may lead to a decrease in productivity.

[0012] Furthermore, conventional microimplements had the tip of the microneedle shaped into a cone (pyramidal) form. However, if the microneedle has a simple conical geometric shape, it is difficult for it to conform to the shape formed by multiple microneedles on complex surfaces such as the skin, and it becomes difficult to uniformly and effectively deliver functional ingredients to the superficial and / or deep layers of the skin. Moreover, even if one were to try to form the microneedle into a pyramidal shape other than a simple cone, conventional methods and equipment present a problem in that it is extremely difficult to form low-temperature melting maltose into the desired shape with high precision.

[0013] In recent years, the shape and arrangement specifications of micro-needles in microimplements have become diverse to meet the diversification of various applications and needs, resulting in a very large number of varieties, and a demand for higher quality for medical or cosmetic applications. For this reason, there is a need for microimplements that can deliver functional ingredients to the superficial and / or deep layers of the skin, and there has been a strong desire for a method that can easily accommodate changes in the shape and arrangement specifications of the micro-needles, and that can form micro-needles with high shape precision.

[0014] The present invention has been made in view of the above problems, and aims to provide a method for manufacturing microimplements that allows for the precise formation of fine needles of maltose, which is meltable at low temperatures, on a substrate, in a desired shape, and also allows for the free formation of fine needles in a desired arrangement, thereby providing a highly productive method for manufacturing microimplements. Furthermore, the present invention aims to provide a microimplement having fine needles with a high administration rate while incorporating functional components.

[0015] To solve the above problems, the inventors conducted extensive research. As a result, they found that by using maltose for the multiple microneedles provided on the substrate in the microimplement, and by optimizing the shape of the microneedles and providing them individually and freely arranging them on the surface of the substrate, the administration rate of functional components can be increased compared to when microneedles are formed and arranged in a simple shape as in the past. Furthermore, they found that when forming the microneedles, by repeatedly heating and cooling the micro-process head used in the microneedle forming means using temperature profile control that changes the temperature over time under specific conditions, multiple microneedles can be formed individually and sequentially, and even when forming microneedles using maltose, which melts at low temperatures, stretching distortion can be avoided and the needles can be formed with high precision. Moreover, they found that by forming multiple microneedles individually and sequentially using the above method, the microneedles can be freely formed in the desired shape and arrangement, and that it is possible to easily accommodate changes in specifications such as shape and arrangement, thus completing the present invention.

[0016] The present invention is a method for manufacturing a micro-imprint that forms a plurality of fine needles on a substrate using pure maltose or a maltose composite material in which one or more functional components are mixed on the surface of the substrate. The method uses a substrate made of a polymer material, biodegradable material, water-soluble material, or a mixture thereof to which the maltose can adhere, and forms the fine needles from the pure maltose or the maltose composite material by means of a fine process head, which is a fine jig for freely arranging the fine needles. The method includes a fine needle forming step of individually and sequentially forming the plurality of fine needles. The fine needle forming step forms the fine needles so as to sequentially grow from the base end portion on the substrate side by variably controlling the temperature of the fine process head while increasing and decreasing the temperature based on the temperature profile control represented by the following general formula (1), and sequentially supplying the pure maltose or the maltose composite material from the fine process head toward the surface side of the substrate. F(L ｎ , T ｎ , t ｎ ) = Σ ｎ (L ｎ , T ｎ , t ｎ ) ・・・・・(1) However, in the general formula (1), L ｎ : The direction from the base end portion to the tip portion of the fine needle or the needle length direction, which is an arbitrary growth height H when the growth height at which the fine needles sequentially grow, between the growth height H ｎ and the growth height H ｎ＋１ of the growth region, T ｎ : The temperature of the fine process head in the growth region L ｎ , t ｎ : The required time for the fine process head to move through the growth region L ｎ , where n is an integer of 1 or more that sequentially increases from the base end portion side as the fine needles grow.

[0017] In the above embodiment, the method for manufacturing a microimplement of the present invention includes: an adhesion process in which, when the microprocess head is in close proximity to the substrate, the heated microprocess head adheres the maltose or maltose composite material to the surface of the substrate in a molten state; and a growth solidification process in which, as the microprocess head gradually detaches from the substrate, and based on the temperature profile control represented by the general formula (1), the solid maltose or maltose composite material is sequentially supplied from the microprocess head toward the surface of the substrate, thereby solidifying the solid maltose or maltose composite material adhered to the surface of the substrate while sequentially growing from the base end; and by repeating the adhesion process and the growth solidification process, a method can be employed to continuously form a plurality of microneedles on the surface of the substrate.

[0018] In the present invention, the method for manufacturing a micro-implement is, in the above embodiment, a micro-process head having a concave cavity for forming the micro-needles, wherein the micro-molding head has a total volume of 10 mm² including the cavity. ３ A rectangular prism structure made of the following metal materials can be adopted.

[0019] In the above embodiment, the method for manufacturing a microimplement of the present invention allows the micro-mold head to have a structure consisting of a triangular pyramidal recess, where the cavity is arranged to expand toward the end face facing the surface of the substrate.

[0020] In the above embodiment, the method for manufacturing a microimplement of the present invention may also involve a micro-mold head having a structure consisting of a semi-conical recess in which the cavity is arranged to expand toward the end face facing the surface of the substrate.

[0021] In the above embodiment, the method for manufacturing a microimplement of the present invention may be configured such that the micro-mold head is made of a material capable of generating heat when an electric current is supplied, and has a current supply unit to which the electric current is supplied.

[0022] In the above embodiment of the method for manufacturing a microimplement of the present invention, the micro mold head may also be structured such that a concave notch is provided at least at one location on its outer surface.

[0023] In the above embodiment of the method for manufacturing a microimplement of the present invention, the micro mold head may also be provided with a structure in which a fin portion is provided at least at one location on the outer surface that protrudes outward from the outer surface.

[0024] In the above embodiment, the method for manufacturing a microimplement of the present invention may also be configured such that the micro-mold head has a structure having ventilation holes that penetrate at least a portion of the micro-mold head.

[0025] In the above embodiment, the method for manufacturing the microimplement of the present invention may also employ a configuration in which the microprocess head is a microheater head consisting of a heating coil in which a heating wire is wound so as to gradually decrease in diameter toward the substrate side, and a material supply space for forming the microneedles can be freely arranged is secured within the coil.

[0026] In the above embodiment, the method for manufacturing the microimplement of the present invention may include a component mixing step, prior to the microneedle formation step, in which a functional component is mixed with the maltose to prepare the maltose composite material.

[0027] In the above embodiment, the method for manufacturing the microimplement of the present invention may involve a component mixing step in which a plurality of maltose composite materials are prepared using two or more different functional components, each of which is mixed with the other functional components, and a microneedle formation step in which the plurality of microneedles are formed sequentially, each containing one of the two or more different functional components.

[0028] In the above embodiment, the method for manufacturing the microimplement of the present invention may further include a scattering step of attaching the functional component to the surface of the substrate before the microneedle formation step, and the microneedle formation step may employ a method in which the plurality of microneedles are formed by overlapping the functional component attached to the surface of the substrate.

[0029] In the above embodiment, the method for manufacturing the microimplement of the present invention may employ a method in which the spraying step involves attaching two or more different functional components to the surface of the substrate at different positions.

[0030] The present invention provides a microimplement comprising a substrate made of a polymer material, a biodegradable material, a water-soluble material, or a mixture thereof, which is a material to which maltose can adhere; and a plurality of microneedles arranged on the surface of the substrate, wherein the maltose is used in its pure form or in a maltose composite material mixed with one or more functional components, and the plurality of microneedles are provided on the surface of the substrate by being individually formed and arrangable, and one or more locations in the longitudinal direction from the base end to the tip on the substrate side are constricted (waisted) in shape, consisting of a thick needle region and a thin needle region.

[0031] In the above embodiment, the microimplement of the present invention may employ a configuration in which the plurality of fine needles are arranged alternately in a plurality of thick needle regions and thin needle regions, so that multiple locations in the longitudinal direction are constricted (narrowed), and the plurality of thick needle regions are made of a maltose composite material in which different functional components are mixed, and the thin needle regions are regions in which the different functional components change continuously.

[0032] In the above embodiment, the microimplement of the present invention may have a configuration in which each of the plurality of fine needles is a mixture of two or more different functional components.

[0033] In the above embodiment, the microimplementation of the present invention may 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, hyaluronic acid, collagen, proteins, DNA, peptides, vaccines, drugs, nutrients, nutritional supplements, cosmetic materials, antibody test agents, body-use color materials, body-use metals, body-use metal oxides, and body-use magnetic materials.

[0034] In the above embodiment, the microimplement of the present invention may employ a configuration in which the material used for the substrate is any of polyvinyl alcohol, pullulan, hyaluronic acid, collagen, ceramic, or paper.

[0035] The present invention's method for manufacturing microimplements involves forming multiple microneedles on the surface of a substrate from solid maltose or a maltose composite material. This method involves sequentially forming multiple microneedles individually while fluctuating the temperature of a micro-process head, which is a micro-jig, based on a specific temperature profile control, causing the temperature to rise and fall. This allows for accurate formation of various shapes even when forming microneedles from solid maltose or a maltose composite material, which is meltable at low temperatures. Furthermore, the microneedles can be freely formed in desired shapes and arrangements, and modifications to specifications can be easily accommodated. By forming microneedles in various shapes and arrangements, the rate of functional component delivery from the microneedles is increased, and the microneedles can be easily inserted into the superficial and / or deep layers of the skin. This enables the production of microimplements that provide a more noticeable user experience and therapeutic or cosmetic effects.

[0036] According to the microimplementation of the present invention, a plurality of microneedles provided on a substrate are made of pure maltose or a maltose composite material, and the plurality of microneedles are individually formed and freely arranged on the surface of the substrate, and a structure is adopted in which one or more locations in the direction from the base end (base portion) on the substrate side toward the tip portion or in the direction of the needle length are constricted, with thick needle regions and thin needle regions arranged alternately. As a result, compared to when the microneedles have a simple shape, the rate of administration of functional components from the microneedles is increased, and the microneedles are easier to insert into the superficial and / or deep layers of the skin, resulting in excellent biocompatibility, and for example, the effects of treatment and cosmetic procedures can be obtained more significantly.

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

[0038] Figure 1 is a schematic diagram illustrating an embodiment of the manufacturing method for a microimplement according to the present invention, and is a schematic diagram showing an example of a microneedle formation process in which a plurality of microneedles are individually and sequentially formed on the surface of a substrate while fluctuating the temperature of the microprocess head so that the temperature rises and falls based on a specific temperature profile control. Figure 2A is a schematic diagram illustrating an embodiment of the manufacturing method for a microimplement according to the present invention, and is a perspective view showing an example of a micromold head used as the microprocess head shown in Figure 1. Figure 2B is a schematic diagram illustrating an embodiment of the manufacturing method for a microimplement according to the present invention, and is a perspective view showing another example of a micromold head used as the microprocess head shown in Figure 1. Figure 2C is a schematic diagram illustrating an embodiment of the manufacturing method for a microimplement according to the present invention, and is a perspective view showing another example of a micromold head used as the microprocess head shown in Figure 1. Figure 2D is a schematic diagram illustrating an embodiment of the manufacturing method for a microimplement according to the present invention, and is a perspective view showing another example of a micromold head used as the microprocess head shown in Figure 1. Figure 2E is a schematic diagram illustrating an embodiment of the manufacturing method for a microimplement according to the present invention, and is a perspective view showing another example of a micromold head used as the microprocess head shown in Figure 1. Figure 2F is a schematic diagram illustrating an embodiment of the manufacturing method of a microimplement according to the present invention, and is a perspective view showing another example of a micro mold head used as a micro process head shown in Figure 1. Figure 3A is a schematic diagram illustrating an embodiment of the manufacturing method of a microimplement according to the present invention, and is a schematic diagram showing an example of a micro heater head used as a micro process head shown in Figure 1. However, in Figure 3A, the heating wires represented by reference numeral 128 (including all parts represented by reference numerals 128a, 128b, and 128c) are all connected, and the breaks in the figure that indicate overlapping heating wires are represented as hidden lines.Figure 3B is a schematic diagram illustrating an embodiment of the manufacturing method of the microimplement according to the present invention, and is a schematic diagram showing the procedure for melting solid maltose or maltose composite material using the microheater head shown in Figure 3A. Figure 4A is a schematic diagram illustrating an embodiment of the microimplement according to the present invention, and is a diagram showing an example of a microimplement that can be manufactured by the manufacturing method according to the present invention, and is a perspective view showing one of a plurality of fine needles provided on the surface of a substrate. Figure 4B is a schematic diagram illustrating an embodiment of the microimplement according to the present invention, and is a side view showing each growth height and growth region in the longitudinal direction of the fine needle of the microimplement shown in Figure 4A. Figure 5 is a schematic diagram illustrating an embodiment of the microimplement according to the present invention, and is a side view showing another example of a microimplement that can be manufactured by the manufacturing method according to the present invention. Figure 6 is a schematic diagram illustrating an embodiment of the microimplement according to the present invention, and is a diagram showing another example of a microimplement that can be manufactured by the manufacturing method according to the present invention, and is a perspective view showing one of a plurality of fine needles provided on the surface of a substrate. Figure 7 is a schematic diagram illustrating an embodiment of the microimplement according to the present invention, and shows another example of a microimplement that can be manufactured by the manufacturing method according to the present invention. It is an overall perspective view showing an example in which a plurality of fine needles are arranged irregularly on the surface of a substrate.

[0039] The following describes in detail the method for manufacturing a microimplement and embodiments of the microimplement according to the present invention, with appropriate reference to the drawings. Note that, for convenience, the drawings used in the following description may show slightly enlarged portions of characteristic parts to make the method for manufacturing a microimplement and the features of the microimplement easier to see, and the dimensional ratios of each component may differ from those in reality. Furthermore, the materials, dimensions, and arrangements exemplified in the following description are merely examples, and the present invention is not limited thereto; it can be implemented with appropriate modifications without altering its essence. For example, the present invention is applicable to cases where multiple microneedles are irregularly arranged on the surface of a substrate, and also to cases where they are regularly arranged.

[0040] The microimplement obtained by the manufacturing method according to the present invention consists of fine needles made of maltose, which is classified as a disaccharide of carbohydrates, provided on a substrate. As mentioned above, the fine needles dissolve and disappear in the body's water during use, and therefore it is classified as a medical dosage form. Accordingly, the microimplement according to the present invention is fundamentally different in its technological concept from conventional microneedles classified as medical devices, which use metals and plastics that are extremely difficult to dissolve in the body, or hyaluronic acid and polylactic acid, which take a considerable amount of time to dissolve.

[0041] The method for manufacturing the microimplement according to the present invention will be described in detail later, but is given by the following formula {F(L ｎ , T ｎ ,t ｎ ) = Σ ｎ (L ｎ , T ｎ ,t ｎ This method involves sequentially forming multiple microneedles individually while fluctuating the temperature of the microprocess head (see reference numeral 120 in Figure 1) so that the temperature rises and falls, based on temperature profile control represented by the formula (L in the above formula ｎ , T ｎ ,t ｎ(This will be described in detail later.) For this reason, in this embodiment, first, the configuration of the microimplement obtained by the manufacturing method of the present invention will be described, and then the configuration of the microimplement manufacturing apparatus that can be used in the manufacturing method of the present invention, and each manufacturing condition will be described in detail.

[0042] <Structure of Microimplement> The structure of a microimplement that can be manufactured by the manufacturing method of this embodiment will be described below, mainly with reference to Figures 4A, 4B, and 5, with the first and second examples being given.

[0043] [First Example] The first example of the microimplement 10 in this embodiment, shown in Figures 4A and 4B, will be described in detail below. Figure 4A is a perspective view showing one of the multiple microneedles 2 provided on the surface 1a of the substrate 1, and Figure 4B is a side view showing the growth regions L1 to L7 in the longitudinal direction of the microneedle 2 of the microimplement 10 shown in Figure 4A.

[0044] As shown in Figures 4A and 4B, the microimplement of this embodiment comprises a substrate 1 made of a polymer material, biodegradable material, water-soluble material, or a mixture thereof to which maltose can adhere, and multiple fine needles 2 arranged on the surface 1a of the substrate 1, where maltose is used as the solid material or a maltose composite material mixed with one or more functional components is used (only one fine needle 2 is shown in Figures 4A and 4B). The microimplement 10 of this embodiment is configured such that multiple fine needles 2 are individually formed and freely arranged on the surface 1a of the substrate 1, and in the longitudinal direction from the base end 21 on the substrate 1 side to the tip end 24, it has one or more constricted (waisted) areas consisting of thick needle areas (see reference numerals 23a, 23c, 23e) and thin needle areas (see reference numerals 23b, 23d). In the illustrated microimplementation 10, the fine needle 2 has two constricted (waisted) sections along its length, formed by alternating arrangements of thick needle sections 23a, 23c, 23e and thin needle sections 23b, 23d. Furthermore, the fine needle 2 in the illustrated example maintains an overall conical or cylindrical outline (roughly connected by dashed lines) from the base 21 to the tip 24, while the needle-shaped needle portion 23 has the aforementioned constricted (waisted) shape. In other words, the fine needle 2 in the illustrated example has a roughly circular cross-section.

[0045] As shown in the partial view of Figure 4A, the microimplement 10 is attached to the substrate 1 in an upright position by welding (adhering) the base end 21 of the microneedle 2 to the surface 1a side of the substrate 1. Although detailed illustrations are omitted, the microimplement 10 is provided on the surface 1a of the substrate 1 in a manner that allows for the arrangement of multiple microneedles 2 regularly or irregularly.

[0046] The substrate 1 functions as the base for the microimplement 10. As described above, a plurality of fine needles 2 are provided on the surface 1a side, while the back surface 1b side functions as a pressing surface when the user of the microimplement 10 presses the surface 1a side against their skin. The material of the substrate 1 is not particularly limited as long as it consists of a polymer material, biodegradable material, water-soluble material, or a mixture thereof to which the maltose composite material, which is the material of the fine needles 2, can be adhered. For example, polyvinyl alcohol, pullulan, hyaluronic acid, collagen, ceramic, or paper can be selected and used. Among these materials, using a cosmetic material made of polyvinyl alcohol for the substrate 1 is preferable from the viewpoint of safety for human skin, in addition to the adhesion of the maltose composite material.

[0047] The size of the substrate 1 is not particularly limited; for example, a plate made of a polyvinyl alcohol thin film with a thickness of 50 to 2000 μm can be used, with a planar size and shape appropriate to the application of the microimplement. The planar shape of the substrate 1 can be set as appropriate, taking into account the area where the microimplement will be used, such as a square, rectangle, circle, or ellipse. Similarly, the planar size of the substrate 1 is also flexible; if the substrate 1 is configured as a square in planar view, it can be, for example, about 0.3 to 50 x 0.3 to 50 mm, and if it is configured as a circle in planar view, it can be, for example, about 0.3 to 50 mm in diameter.

[0048] As described above, the micro-needle 2 is formed from solid maltose or a maltose composite material and has a sharp tip. The micro-needle 2 in the illustrated example has a base portion 21 which is a welding portion to the surface 1a of the substrate 1, a body portion 22 which grows from the base portion 21 toward the tip portion 24, a needle-shaped needle portion 23 which has a constricted shape in which the above-mentioned thick needle regions 23a, 23c, 23e and thin needle regions 23b, 23d are alternately arranged from the body portion 22 toward the tip portion 24, and has a tapered shape (needle-like) where the tip gradually decreases in diameter, and the above-mentioned tip portion 24.

[0049] When the microimplement 10 is used, the microneedle 2 is inserted into the skin from the surface by pressing it into the skin from the back surface 1b of the substrate 1, for example, in a stamping manner, and reaches the superficial and / or deep layers of the skin, and has the characteristic of dissolving in each layer in a short time of minutes. As a result, for example, if the microneedle 2 is made of pure maltose, it can be used to form pores on the surface of the skin. Furthermore, if the microneedle 2 is made of a maltose composite material mixed with functional components, which will be described in detail later, the functional components for which the desired effect is obtained can be effectively administered to the superficial and / or deep layers of the skin.

[0050] The number and density of microneedles 2 on the surface 1a of the substrate 1 are not particularly limited and can be set appropriately while considering the application of the microimplement 10. For example, if the purpose is to form pores or penetrate functional ingredients over a wide area of ​​the user's skin, many microneedles 2 can be placed on the surface 1a of the substrate 1. However, if the distance between the microneedles 2 is too close, that is, if the density of microneedles 2 on the surface 1a of the substrate 1 is too high, mutual interference will occur in the superficial and / or deep layers of the skin, which will increase the dissolution time of the microneedles 2 and the time required for the penetration of functional ingredients. Therefore, this point should be taken into consideration.

[0051] The maltose composite material that constitutes the microneedle 2 is made from maltose, a sugar material that has a low melting point and is easily dissolved in the skin. When maltose is used in microneedles, the time required for dissolution at human body temperature (internal body temperature) is about 2 to 3 minutes, which is very short compared to other materials, such as sodium hyaluronate (about 8 hours), and has the advantage of obtaining the desired function in a short time. In addition, because maltose is water-soluble, it has superior solubility in the skin layer compared to other materials such as sodium hyaluronate and starch, so there is no need to worry about undissolved residue, and since it is originally a substance that is part of the body, it is a very safe material.

[0052] The microneedle 2 is preferably constricted in shape, with thick needle regions 23a, 23c, 23e and thin needle regions 23b, 23d arranged alternately, as described above. This is preferable from the viewpoint of increasing the rate of administration of functional ingredients from the microneedle and facilitating insertion of the microneedle into the superficial and / or deep layers of the skin. On the other hand, the shape of the microneedle 2 can be any shape as long as at least one point in the length direction has the above-described constricted shape, while being designed and manufactured considering the above-described rate of administration of functional ingredients, ease of insertion into the superficial and / or deep layers of the skin, and reduction of discomfort for the user. That is, in the example microimplementation 10 shown in Figures 4A and 4B, the microneedle 2 has the above-described constricted shape while maintaining an overall conical outline, but it is not limited to such a shape. The overall shape (rough outline) of the needle-shaped needle portion 23 in the micro-needle 2 is not limited to the conical shape described above, but can also be any conical shape from among a triangular pyramid, a square pyramid, a bullet shape, or a polygonal pyramid with five or more sides. The cross-sectional shape can also be circular, triangular, square, or a polygon with five or more sides.

[0053] Furthermore, the microneedle 2 can be made into a constricted shape other than the constricted shape shown in the examples in Figures 4A and 4B, by adjusting the molding conditions using a microprocess head provided in the manufacturing apparatus, which will be described in detail later. That is, in the illustrated example of the microimplementation 10, there are two constricted shapes in the needle-shaped needle portion 23 of the microneedle 2, but for example, there may be only one constricted shape, or there may be three or more. Specifically, examples of such shapes include hourglass shapes, bowling pin shapes, and jewel shapes.

[0054] The size of the microneedle 2, that is, its axial length, and the maximum diameter and tip diameter when the overall outline of the microneedle 2 is conical and the cross-sectional shape is circular, are not particularly limited and can be set appropriately according to the application of the microimplementation 10. For example, the maximum diameter and tip diameter of the microneedle 2 can be determined while considering the ease of insertion from the skin surface as well as the strength of the microneedle 2. The length of the microneedle 2 can also be determined according to each application, such as whether the insertion position is only to the superficial and / or deep layers of the skin, or whether it is inserted even deeper. For applications where the microneedle 2 is inserted to the superficial and / or deep layers of the skin, for example, a length of about 0.3 to 0.7 mm is sufficient, and for applications where it is inserted even deeper than the superficial and / or deep layers of the skin, for example, a length of about 1.0 to 2.0 mm is sufficient.

[0055] Furthermore, when the micro-needle 2 is conical and its cross-sectional shape is circular, the maximum diameter is preferably about 50 to 200 μm from the above viewpoint, and the diameter of the tip portion 24 is preferably about 1 to 10 μm. The shape of the tip portion 24 is not particularly limited, and detailed illustrations are omitted, but for example it may be a flat surface. On the other hand, the shape of the tip portion 24 is more preferably spherical from the viewpoint of suppressing the user from feeling pain when inserting the micro-needle 2 into the skin.

[0056] Furthermore, if the approximate outline of the fine needle 2 is a triangular pyramid, a square pyramid, or a polygonal pyramid with five or more sides, and the cross-sectional shape is triangular, square, or a polygon with five or more sides, the diameter should be converted to the diameter equivalent to that of a circular cross-section, according to these cross-sectional shapes, and then set to the diameter within the above range.

[0057] As mentioned above, the microneedle 2 can be made of pure maltose, or it can be made of a maltose composite material mixed with functional components to add various functionalities to the microimplementation. The functional components are not particularly limited, but examples include one or more selected from the group consisting of vitamins, hyaluronic acid, collagen, proteins, DNA, peptides, vaccines, drugs, nutrients, nutritional supplements, cosmetics, antibody test agents, body-use color materials, body-use metals, body-use metal oxides, and body-use magnetic materials.

[0058] The form in which the functional component is mixed into the maltose composite material constituting the microneedle 2 is not particularly limited, but examples include mixing it into the maltose composite material, embedding it in the internal space, or coating (adhering) it to the surface of the molded microneedle 2. If multiple microneedles 2 are made of pure maltose, a structure in which the functional component is coated to the surface of the multiple molded microneedles 2 can be adopted as described above. Furthermore, if multiple microneedles 2 are composed of a maltose composite material in which the functional component is mixed, a maltose composite material in which the functional component is pre-mixed can be used.

[0059] When the microneedle 2 is made of a maltose composite material containing a functional component, the ratio of maltose to the functional component is not particularly limited and can be set appropriately while considering the expression of function by the functional component. On the other hand, in order to ensure that the microneedle 2 has a predetermined strength for insertion into the superficial and / or deep layers of the skin, it is preferable to maintain a maltose content ratio of 80% by mass or more relative to the total amount of the maltose composite material.

[0060] The surface morphology of the microneedle 2 is not particularly limited, but a structure that is water-repellent and prevents moisture from penetrating into the interior of the microneedle 2 is preferred. This prevents, for example, the microneedle 2 from softening due to humidity in the atmosphere.

[0061] According to the microimplementation 10 of this embodiment, the microneedle 2 has a constricted shape consisting of thick needle regions 23a, 23c, 23e and thin needle regions 23b, 23d. Compared to a simple shape without a constriction, this results in a higher administration rate that is more easily absorbed by living organisms or human skin. In other words, the constricted shape of the microneedle 2 makes it easier for the microneedle 2 to be inserted and dissolved in the superficial and / or deep layers of the skin, and further enhances the penetration of functional ingredients.

[0062] When using the microimplement 10, the user first takes out the microimplement 10, which is contained in a container (not shown) or temporarily attached to a sterilized cardboard backing, and presses the surface 1a side of the substrate 1, which is equipped with multiple microneedles 2, against the desired location on the skin surface. Then, by pressing the back surface 1b side of the substrate 1 with a finger or the like, the microneedles 2 are inserted into the superficial and / or deep layers of the skin, and this state is maintained for a predetermined time until the microneedles 2 completely dissolve.

[0063] In this case, the microimplement according to the present invention uses pure maltose or a maltose composite material for the material of the microneedle 2, so that the microneedle 2 dissolves completely beneath the skin surface in approximately 2 to 3 minutes. Therefore, the microneedle 2 does not remain as a solid foreign object, resulting in excellent safety and the ability to obtain the desired function in a short time.

[0064] Furthermore, in the microimplement 10 of this embodiment, in order to further improve the user's handling, a structure may be adopted in which, for example, a pressing assist mechanism (not shown) is provided on the back surface 1b side of the substrate 1. This makes it possible to more effectively apply pressing force with the user's fingers, etc., when pressing the microimplement 10 against the skin.

[0065] Furthermore, although detailed illustrations are omitted in this embodiment, for example, the fine needle 2 is provided so as to overlap with the position of a functional component (not shown) that is pre-dispersed on the surface 1a of the substrate 1, and the structure incorporates, mixes, and / or encapsulates this functional component.

[0066] Although detailed illustrations are omitted, the multiple microneedles 2 provided on the surface 1a of the substrate 1 may be of different sizes, and may also have different constriction shapes. When such a configuration is adopted, for example, larger microneedles can contain a large amount of functional components, making it possible to mix functional components in an appropriate and sufficient amount with the microimplement. Furthermore, by mixing functional components in different amounts with the multiple microneedles provided on the surface of the substrate, it is possible to create a gradation (graduality) in the amount of components in the planar direction of the microimplement, depending on the application.

[0067] Furthermore, in the microimplement of this embodiment, a configuration in which multiple microneedles 2 are mixed with two or more different functional components may be adopted. By adopting such a configuration, it becomes possible to impart multiple functions to the microimplement.

[0068] Here, when determining the placement positions of the micro-needles 2 on the surface 1a of the substrate 1, although not shown in the illustration, for example, a raster pattern consisting of grid-like imaginary lines is placed on the surface 1a of the substrate 1, and multiple planned mounting locations for the micro-needles 2 (see reference numeral 11 in Figure 7) are virtually assigned to the intersections of each imaginary line. Then, from among the multiple virtually assigned planned mounting locations, the positions where the micro-needles 2 will be placed, either regularly or irregularly, are determined. Such an arrangement of the micro-needles 2 can be obtained, for example, by vector drawing based on the grid-like pattern described above, which allows the micro-needles 2 to be placed at any position without any constraints.

[0069] In this embodiment, by adopting the arrangement of multiple microneedles 2 as described above and arranging the microneedles 2 in a unique pattern, it is possible to draw unique patterns or characters in the planar direction of the microimplement 10. For example, when the microimplement 10 is used in a hospital, it is possible to draw numbers, names, etc., which can prevent mix-ups between patients using the device. To determine the placement position of the microneedles 2, it is also possible to apply the traveling salesman model, commonly known as AI (Artificial Intelligence), to efficiently draw the patterns.

[0070] [Second Example] The microimplementation of the second example in this embodiment will be described below with reference to Figure 5. Figure 5 is a side view showing another example of microimplementation 10A in this embodiment.

[0071] The microimplement 10A of the second example of this embodiment, shown in Figure 5, has a shape similar to the microimplement 10 of the first example shown in Figures 4A and 4B, in that the needle-shaped needle portion 23A of the fine needle 2A has a constricted shape in which thick needle regions 23f, 23h, 23j and thin needle regions 23g, 23i are arranged alternately. On the other hand, the microimplement 10A of the second example differs from the microimplement 10 of the first example in that the three thick needle regions 23f, 23h, and 23j in the needle-shaped needle portion 23A are made of a maltose composite material mixed with different functional components, and the thin needle regions 23g and 23i are regions in which different functional components change continuously.

[0072] Furthermore, the positions of the fine needle regions 23g and 23i in the illustrated example microimplementation 10A are made of larger curved surfaces compared to the positions of the fine needle regions 23b and 23d in the example microimplementation 10 shown in Figures 4A and 4B, resulting in a gently constricted shape.

[0073] As described in this example, the microimplementation 10A allows for the imbuing of a single microneedle 2A with multiple functions, as each of the thick needle regions 23f, 23h, and 23j is a region where different functional components are mixed. Furthermore, the positions of the thin needle regions 23b and 23d are designated as boundaries between multiple different functional components, creating a continuous and indistinctly mixed fusion region. This results in a more continuous penetration of each functional component into the living organism compared to a case where the different functional components are clearly separated.

[0074] The constricted shape, consisting of a thick needle region and a thin needle region, as described above, can be achieved by optimizing the temperature profile control when forming the fine needles, as will be explained in detail in the manufacturing method section below.

[0075] [Other Examples] Although detailed illustrations are omitted below, the microimplement of this embodiment is not limited to the above configuration. For example, a configuration with fine needles as shown below can also be adopted (refer to the microimplements 10, 10B shown in Figures 4A and 4B, 6 and 7 as appropriate).

[0076] For example, in this embodiment, a structure can be adopted in which a plurality of micro-protrusions are arranged on the surface 1a of the substrate 1, and micro-needles are provided on these micro-protrusions. When such a configuration is adopted, a plurality of micro-protrusions, each containing one of two or more different functional components, can be arranged on the surface 1a of the substrate 1, and micro-needles made of pure maltose can be provided on these.

[0077] When a structure with multiple micro-protrusions as described above is adopted, micropores are formed on the user's skin surface by the multiple micro-needles, and then the functional components contained in the micro-protrusions gradually penetrate the superficial and / or deeper layers of the skin through these micropores.

[0078] Furthermore, in this embodiment, it is also possible to employ a structure in which, for example, functional component chips are placed on a plurality of micro-protrusions arranged on the surface 1a of the substrate 1, together with micro-needles. Even when such a structure is adopted, the micro-needles are easily dissolved, providing excellent biosafety, and the effect of increasing the administration rate of functional components from the micro-needles can be obtained, as described above.

[0079] <Method for Manufacturing Microimplements> The method for manufacturing microimplements according to this embodiment will be explained below using the microimplement manufacturing apparatus (hereinafter sometimes simply referred to as the manufacturing apparatus) 100 shown in Figure 1 as an example.

[0080] Figure 1 illustrates the manufacturing method of the microimplement of this embodiment (hereinafter sometimes simply referred to as the manufacturing method), and is a schematic diagram showing a microneedle formation process in which multiple microneedles are individually and sequentially formed while repeatedly heating and cooling the microprocess head 120. For the sake of explanation, the multiple microneedles on the surface 1a of the substrate 1 are not shown in Figure 1.

[0081] The manufacturing method of this embodiment involves forming a plurality of fine needles 2 on the surface 1a of the substrate 1 by using maltose alone or a maltose composite material which is a mixture of maltose and one or more functional components. Furthermore, the manufacturing method of this embodiment uses a polymer material to which maltose can adhere, a biodegradable material, a water-soluble material, or a mixture thereof as the substrate 1.

[0082] In the manufacturing method of this embodiment, a micro-needle formation step is provided in which a plurality of micro-needles 2 are individually and sequentially formed using a micro-process head 120, which is a micro-jig for forming micro-needles 2 from solid maltose or maltose composite material in a manner that allows for the arrangement of micro-needles 2. In the above micro-needle formation step, the temperature of the micro-process head 120 is fluctuated to cause an increase or decrease in temperature based on the temperature profile control represented by the following general formula (1), and solid maltose or maltose composite material is sequentially supplied from the micro-process head 120 toward the surface 1a side of the substrate 1, thereby forming the micro-needles 2 so that they grow sequentially from the base end 21 on the substrate 1 side. F(L ｎ , T ｎ ,t ｎ ) = Σ ｎ (L ｎ , T ｎ ,t ｎ ) ... (1) However, in the above general formula (1), L ｎ : When the direction from the base end 21 to the tip end 24 of the microneedle 2, or the direction along the length of the needle, is defined as the growth height at which the microneedle 2 grows sequentially, any growth height H along the length of the needle. ｎ and growth height H ｎ＋１ Growth area between T ｎ : Growth area L ｎ The temperature of the micro-process head 120, t ｎ : Growth area L ｎ n is the time required for the micro-process head 120 to move, and n is an integer of 1 or more that increases sequentially from the base end 21 side as the micro-needle 2 grows.

[0083] By employing a method that includes the microneedle formation process described above, the microimplement 10 of this embodiment, which has a constricted shape as shown in Figures 4A and 4B, or the microimplement 10A shown in Figure 5, can be manufactured with excellent shape accuracy and high productivity.

[0084] [Microimplementation Manufacturing Apparatus] The manufacturing apparatus 100 used in this embodiment will be described below. Figure 1 is a schematic diagram showing an example of a microneedle formation process in which the manufacturing apparatus 100 individually and sequentially forms a plurality of microneedles 2 (see Figures 4A and 4B) on the surface 1a of the substrate 1 while fluctuating the temperature of the micro process head 120 with rising and falling temperatures based on a specific temperature profile control. Figures 2A to 2F are diagrams illustrating an example of a micro mold head used as the micro process head 120 shown in Figure 1, and are perspective views showing micro mold heads 120A, 120B, 120C, 120D, 120E, and 120F, respectively. Figures 3A and 3B illustrate an example of a microheater head used as the microprocess head 120 shown in Figure 1. Figure 3A is a schematic diagram showing a microheater head 120G in which a material supply space S that functions as a reservoir for a small amount of maltose is secured by winding a heating wire 128 in a coil shape. Figure 3B is a schematic diagram showing the procedure for melting pure maltose or a maltose composite material (indicated as M in Figure 3B) using the microheater head 120G shown in Figure 3A.

[0085] As shown in Figure 1, the manufacturing apparatus 100 is generally configured to include a support unit 110, a micro-process head 120, a head mounting unit 130, and a drive unit 140.

[0086] The support unit 110 supports the substrate 1 such that its surface 1a faces the micro-process head 120. In the illustrated example, the support unit 110 is configured so that the back surface 1b of the substrate 1 is attached to the mounting surface 111. The support unit 110 is also equipped with an electric heater (not shown), and is configured to heat the substrate 1 as the support unit 110 heats up. The support unit 110 is not particularly limited, but a heat-resistant plate-shaped member can be used.

[0087] As described above, the micro-process head 120 sequentially supplies solid maltose or maltose composite material for forming the micro-needles 2 toward the surface 1a side of the substrate 1, while fluctuating its temperature so that the temperature rises and falls, for example, by repeating heating and cooling a predetermined number of times. In the example shown in Figure 1, the micro-process head 120 is mounted on a head mounting unit 130 and is configured to reciprocate in the X-X direction in the figure by a drive unit 140, which will be described in detail later.

[0088] Examples of the micro-process head 120 described above include any of the micro-mold heads 120A, 120B, 120C, 120D, 120E, and 120F shown in Figures 2A to 2F, which have a concave cavity 122 or cavity 123 for freely forming a micro-needle 2. These micro-mold heads 120A to 120F have, for example, a total volume of 10 mm² including the cavity 122 or cavity 123. ３ It is described as a small cubic structure made of the following metal materials.

[0089] Furthermore, as an example of the micro-process head 120, there is also a micro-heater head 120G, which consists of a heating coil in which a heating wire 128 is wound so as to gradually decrease in diameter toward the substrate 1, and a material supply space S for freely arranging and forming micro-needles 2 is secured within the coil.

[0090] As described above, the micro-mold heads 120A to 120F shown in Figures 2A to 2F have a concave cavity 122 or cavity 123 for forming a fine needle 2 from solid maltose or a maltose composite material. In the micro-mold heads 120A, 120C, 120E, and 120F shown in Figures 2A, 2C, 2E, and 2F, the opening side of the cavity 122 is an end face 121 facing the surface 1a of the substrate 1. In the micro-mold head 120B shown in Figure 2B, the opening side of the cavity 123 is an end face 121B facing the surface 1a of the substrate 1, and in the micro-mold head 120D shown in Figure 2D, the opening side of the cavity 122 is an end face 121D facing the surface 1a of the substrate 1. The cavities 122 and 123 described above supply solid maltose or maltose composite material onto the surface 1a of the substrate 1 while melting it.

[0091] The micro mold heads 120A, 120C to 120F shown in Figures 2A, 2C to 2F form a space consisting of a roughly triangular pyramidal recess in the cavity 122, which has a top portion 122a and a side 122b extending from the top portion 122a toward the end face 121, with the end face 121 being the bottom surface. In other words, when the micro mold heads 120A, 120C to 120F are applied to the micro process head 120 in the manufacturing apparatus 100 shown in Figure 1, the cavity 122 is arranged to expand toward the end face 121 facing the surface 1a of the substrate 1.

[0092] On the other hand, the micro mold head 120B shown in Figure 2B has a cavity 123 that, in plan view, has a curved top portion 123a and a conical surface 123b extending from the top portion 123a toward the end face 121, forming a space consisting of a roughly apexless semi-conical recess with the end face 121 being the bottom surface. In other words, by applying the micro mold head 120B to the micro process head 120 in the manufacturing apparatus 100 shown in Figure 1, the cavity 123 is arranged to expand toward the end face 121 facing the surface 1a of the substrate 1.

[0093] The micro mold head 120C shown in Figure 2C is made of an alloy material that can generate heat when an electric current E is supplied, and has current supply units 124a and 124b to which the electric current E is supplied. The micro mold head 120C is configured so that the main body 124, which is provided with a cavity 122, can generate heat due to the electric current E supplied to the current supply units 124a and 124b. Furthermore, since the current supply units 124a and 124b are provided so as to branch off from the main body 124, the current supply units 124a and 124b also function as heat sinks to promote cooling of the main body 124.

[0094] As the metal material capable of generating heat when an electric current is applied to constitute the micro mold head 120C, it is preferable to use, for example, conventionally known nichrome alloy (nickel-chromium alloy) or Kanthal alloy (iron-chromium-aluminum alloy). On the other hand, the metal material used for the micro mold head 120C is not limited to the above-mentioned alloy materials, and other alloy materials such as stainless steel or metal materials with the same heat generation function from among various single metals can be adopted. Furthermore, the micro mold head 120C can be made of the above-mentioned metal material and can be an ultra-compact design that takes into account the ability to cool down in a short time.

[0095] The micro mold head 120D shown in Figure 2D has a structure in which concave notches 125a, 125a are provided on both sides of the side (outer) surfaces 125D, 125D. With the micro mold head 120D, the presence of the notches 125a, 125a increases the effective surface area, and the circulation of air inside the concave notches 125a, 125a promotes the cooling of the micro mold head 120D.

[0096] In the example shown in Figure 2E, the micro mold head 120E is provided with fin portions 126a and 126b that protrude outward from both sides of the side (outer) surfaces 125E, 125E. The fin portions 126a and 126b function as cooling fins to promote cooling of the micro mold head 120E. In the illustrated example, an example is shown in which two fin portions 126a and 126b are provided, but the example is not limited to this, and it is sufficient for the fin portion to be provided in at least one location on the outer surface of the micro mold head 120E.

[0097] In the example shown in Figure 2F, the micro mold head 120F is provided with ventilation holes 127 that penetrate between the side surfaces 125F, 125F. The ventilation holes 127 have the effect of promoting the cooling of the micro mold head 120F by allowing air to circulate inside them, for example. Furthermore, if water is circulated through the ventilation holes 127, it becomes possible to cool the micro mold head 120F more effectively.

[0098] In the illustrated example, a ventilation hole 127 is provided so as to penetrate between the side surfaces 125F, 125F, but the location of the ventilation hole is not limited to this, and the ventilation hole may be provided so as to penetrate at least a part of the other surfaces.

[0099] Of the micro mold heads 120A to 120F, all except micro mold head 120C, which uses an alloy material that can generate heat when energized, can be made of the same metal material as molds conventionally used in this field, have one cavity 122 or cavity 123 corresponding to one micro needle 2, and are ultra-compact and designed to cool down in a short time.

[0100] The micro mold heads 120A to 120F are configured such that, for example, an electric heater (not shown) is integrally provided, or the head mounting unit 130 to which the micro mold heads 120A to 120F are attached has an electric heater (not shown) inside, allowing for rapid repetition of heating by energization and cooling by current interruption. In other words, the micro mold heads 120A to 120F are configured to allow for temperature rise and fall based on temperature profile control, which will be described in detail later, for example, rapid repetition of heating and cooling a predetermined number of times.

[0101] When micro-mold heads 120A to 120F are used as the micro-process head 120, solid maltose or maltose composite material is sequentially supplied in a molten state from cavity 122 or cavity 123 toward the surface 1a side of the substrate 1. This allows the micro-needles 2 to be formed so as to grow sequentially from the base end 21 on the substrate 1 side.

[0102] As described above, the microheater head 120G is composed of a heating coil around which a heating wire 128 is wound, so that the microheater head 120G itself can generate heat when an electric current is passed through it. That is, as shown in Figure 3A, the microheater head 120G is constructed with the heating wire 128 wound so that it gradually decreases in diameter with the tip 128c as the apex, and the heating wires 128 protruding from the end opposite the tip 128c are the current supply lines 128a and 128b. Note that in Figure 3A, for illustrative purposes, the overlapping parts of the heating wire 128 (including the current supply lines 128a, 128b and the tip 128c) are shown with hidden lines indicating breaks, but in reality, the heating wire 128 is constructed as a single continuous wire.

[0103] The microheater head 120G is configured to rapidly repeat heating and cooling in accordance with the application and interruption of current from current supply lines 128a and 128b, based on temperature profile control which will be described in detail later.

[0104] In the microheater head 120G, the space surrounded by the wound heating wire 128 is designated as the material supply space S. As shown in Figure 3B, molten solid maltose or maltose composite material is supplied to the material supply space S from the outside. Specifically, solid maltose or maltose composite material is supplied to the material supply space S from the large coil formed on the current supply line 128a and 128b side of the wound heating wire 128, and molten solid maltose or maltose composite material (indicated as M) is supplied toward the surface 1a of the substrate 1 from the small coil formed on the tip side 128c.

[0105] As the heating element 128 constituting the micro heater head 120G, for example, a general nichrome wire made of the nichrome alloy described above can be used, but it is also possible to use a Kanthal wire made of the Kanthal alloy described above, which has superior heating characteristics. Furthermore, the metal material used for the heating element 128 is not limited to the alloy material described above, and as with the micro mold head 120C, it is also possible to use other alloy materials such as stainless steel, or a metal material with the same heating function from among various single metals.

[0106] When a microheater head 120G is used as the microprocess head 120, the tip 128c side is positioned on the substrate 1 side as shown in Figure 1, and solid maltose or maltose composite material is sequentially supplied in a molten state from the position of the tip 128c toward the surface 1a of the substrate 1. This makes it possible to form fine needles 2 that grow sequentially from the base end 21 on the substrate 1 side.

[0107] The manufacturing method for the microimplement in this embodiment involves rapidly repeating the heating and cooling of the micro-process head 120 based on a specific temperature profile control. Therefore, it is particularly important to improve the cooling efficiency of the micro-process head 120. From this perspective, in the manufacturing apparatus 100 illustrated in this embodiment, when micro-mold heads 120A to 120F are used as the micro-process head 120, the total volume including the cavities 122 and 123 is 10 mm² in order to suppress the heat capacity, as described above. ３The following rectangular parallelepiped structure is preferable. By making the micro mold heads 120A to 120F into a miniaturized rectangular parallelepiped structure, it becomes possible to repeat heating and cooling at high speed and efficiency. Furthermore, by integrally providing an electric heater (not shown) to the micro mold head, or by configuring the micro mold head itself to generate heat, as exemplified by the micro mold head 120C in Figure 2C, it becomes possible to repeat heating and cooling at even higher speed and efficiency, in conjunction with the miniaturization of the micro mold head.

[0108] Furthermore, in the manufacturing apparatus 100 illustrated in this embodiment, if a microheater head 120G is used as the microprocess head 120, the extremely fine heating wires 128 are wound around it and spaced apart from each other, making it possible to repeat heating and cooling at a higher speed and more efficiently.

[0109] In this embodiment, by using a configuration that includes the micro mold heads 120A to 120F or the micro heater head 120G described above, the processing speed for growing the fine needles 2 can be increased, and thus the production efficiency can be significantly improved.

[0110] As described above, the head mounting unit 130 has functions such as being a support base on which the micro-process head 120 is attached. The head mounting unit 130 moves back and forth in the X-axis direction shown in Figure 1 by means of a drive shaft 141 provided in the drive unit 140, which will be described later, thereby causing the micro-process head 120 to move back and forth in the same direction. The material of the head mounting unit 130 is not particularly limited, but considering that the micro-process head 120, which undergoes repeated heating and cooling, is attached to it, and that the electric heater described above is incorporated inside, a metal such as stainless steel can be used. Alternatively, it is possible to use an alloy material that can generate heat when an electric current is supplied to the head mounting unit 130, thereby configuring the head mounting unit 130 itself to generate heat.

[0111] On the other hand, if the micro mold head 120 is configured to generate heat through current supply, it is preferable that the head mounting unit 130 has a structure that allows for heat insulation between it and the micro mold head 120, from the viewpoint of accelerating the temperature rise and fall of the micro mold head 120. This is because, in order to accelerate the temperature rise and fall of the micro mold head 120, it is necessary to minimize the capacity of the micro mold head 120, but if the temperature change caused by the head mounting unit 130 is added, its heat capacity will also be added, which may hinder rapid temperature rise and fall.

[0112] Furthermore, if the micro mold head 120 is configured to generate its own heat, the head mounting unit 130 can also be configured to have a function of supplying current to the micro mold head 120.

[0113] The drive unit 140 reciprocates the fine process head 120 in the X-axis direction shown in Figure 1 so as to move it closer to and further away from the substrate 1. In the illustrated example, the drive unit 140 has a drive shaft 141 that protrudes from the main body and its tip is connected to the head mounting unit 130. The reciprocating motion of the drive shaft 141 allows the fine process head 120, which is mounted on the head mounting unit 130, to reciprocate at high speed.

[0114] The drive unit 140 is not particularly limited, but for example, a configuration that uses an electromagnetic valve or motor to reciprocate the drive shaft 141 can be adopted. In the manufacturing apparatus 100 described in this example, the drive unit 140 is configured such that the fine process head 120 reciprocates in conjunction with the reciprocating movement of the head mounting unit 130, and at the same time, the fine process head 120 is able to rapidly repeat heating and cooling.

[0115] Furthermore, although not shown in Figure 1, the manufacturing apparatus 100 is also provided with an X-Z stage unit that allows the support unit 110 to be freely moved vertically and horizontally along the planar direction of the substrate 1 in the Y-axis and Z-axis directions in Figure 1. By providing the X-Z stage unit (not shown), the manufacturing apparatus 100 moves the substrate 1 freely vertically and horizontally along the planar direction, and the micro-process head 120 continuously forms multiple micro-needles 2 one by one at high speed on the surface 1a of the substrate 1.

[0116] [Example of Manufacturing Method (Procedure and Conditions)] As an example of the manufacturing method of this embodiment, the procedure and conditions for manufacturing the microimplementation 10 shown in Figures 4A and 4B using the manufacturing apparatus 100 shown in Figure 1 will be described in detail below. In this embodiment, an example will be described that further includes a component mixing step in which a functional component is mixed with maltose to prepare a maltose composite material, prior to the microneedle formation step described above.

[0117] (Component mixing process) First, using a component preparation device (not shown), maltose is dissolved, and components selected from the above-mentioned functional components are mixed in an amount such that the mass ratio to maltose is within a predetermined range. This mixture is then stirred so that the functional components are uniformly distributed, or kneaded uniformly in a manner similar to kneading dough for a pastry. This allows for the preparation of a maltose composite material.

[0118] The prepared maltose composite material is then supplied to the next step, the micro-needle formation step. That is, the molten maltose composite material prepared in a component preparer (not shown) is discharged and supplied to the micro-process head 120 using a nozzle (not shown). Specifically, the molten maltose composite material is supplied to the inside of the cavity 122 or cavity 123 of the micro-mold heads 120A to 120F, or to the inside of the material supply space S of the micro-heater head 120G. At this time, the maltose composite material can be supplied little by little and continuously in an amount corresponding to approximately one micro-needle 2, in accordance with the reciprocating movement in the X-axis direction of the micro-mold heads 120A to 120F or the micro-heater head 120G in the next step. Alternatively, the supply timing, supply speed, and supply amount of the maltose composite material may be adjusted in accordance with the high-speed temperature rise and fall (fluctuation) of the micro-process head 120, for example, the repetition of heating and cooling a predetermined number of times, based on temperature profile control, which will be explained in more detail later.

[0119] Furthermore, if the fine needles 2 are formed from pure maltose, the component mixing step does not need to be included. That is, when forming the fine needles 2 from pure maltose material, the pure maltose is heated to a melted state and then sent directly to the next step, the fine needle formation step.

[0120] (Microneedle Formation Process) Next, in the microneedle formation process, a plurality of microneedles 2 made of maltose composite material are formed on the surface 1a of the substrate 1 using the manufacturing apparatus 100 described above.

[0121] Specifically, in the microneedle formation process of this embodiment, by rapidly repeating the adhesion process and growth solidification process shown in (A) and (B) below, a plurality of microneedles 2 are formed on the surface 1a of the substrate 1 sequentially and individually at high speed. (A) Adhesion process: When the micro-process head 120 is close to the substrate 1, the heated micro-process head 120 adheres the maltose composite material to the surface 1a of the substrate 1 in a molten state. When the microneedles 2 are formed from maltose alone, in the adhesion process, pure maltose is adhered to the surface 1a of the substrate 1 in a molten state. (B) Growth and solidification process: As the micro-process head 120 gradually detaches from the substrate 1, the temperature of the micro-process head 120 is varied by repeatedly heating and cooling the micro-process head 120 based on the temperature profile control represented by the general formula (1) above. Maltose composite material is sequentially supplied from the micro-process head 120 toward the surface 1a of the substrate 1, thereby solidifying the maltose composite material attached to the surface 1a of the substrate 1 while it grows sequentially from the base end 21, thereby forming the micro-needles 2. When the micro-needles 2 are grown from solid maltose, in the growth and solidification process, the solid maltose attached to the surface 1a of the substrate 1 is sequentially grown and solidified.

[0122] In the microneedle formation process, in the adhesion process described in (A) above, an appropriate amount of dissolved to melted maltose composite material is deposited on the surface 1a of the substrate 1 in an amount that can be contained in the cavity 122 or cavity 123 of the micro mold heads 120A to 120F, in a shape corresponding to the internal shape of the cavities 122 and 123. Alternatively, in the adhesion process described in (A) above, an appropriate amount of dissolved to melted maltose composite material is deposited on the surface 1a of the substrate 1 in an amount that can be contained in the material supply space S of the micro heater head 120G, in a shape corresponding to the shape of the material supply space S.

[0123] Next, in the growth and solidification process described in (B) above, with the molten maltose composite material adhering to the surface 1a of the substrate 1, the micro-mold heads 120A to 120F or the micro-heater head 120G constituting the micro-process head 120 are gradually released from the substrate 1. In this way, when the micro-mold heads 120A to 120F or the micro-heater head 120G are released from the maltose composite material adhering to the substrate 1, a portion of the molten maltose composite material is grown by the micro-mold heads 120A to 120F or the micro-heater head 120G moving in the direction of release from the substrate 1. At this time, the maltose composite material is sequentially supplied toward the surface 1a side of the substrate 1 while repeatedly heating and cooling the micro-mold heads 120A to 120F or the micro-heater head 120G based on the temperature profile control represented by the general formula (1) above. Then, the maltose composite material attached to the surface 1a of the substrate 1 is solidified while being grown sequentially from the base end 21 to form the fine needles 2.

[0124] In the process described above, the maltose composite material grown on the surface 1a of the substrate 1 solidifies upon cooling, with the tip 24 becoming sharp. This allows for the formation of a fine needle 2 with a roughly conical tip 24, as shown in Figures 4A and 4B.

[0125] In the growth solidification process included in the microneedle formation process, the above general formula (1), i.e., the following formula {F(L ｎ , T ｎ ,t ｎ ) = Σn(L ｎ , T ｎ ,t ｎ The operation of repeatedly heating and cooling the micro mold heads 120A to 120F or the micro heater head 120G based on the temperature profile control represented by ) will be described.

[0126] In the manufacturing method of this embodiment, by repeatedly heating and cooling based on the temperature profile control described above, the shape of the formed microneedles can be made into various desired shapes. That is, when forming the microneedles 2 of the microimplementation 10 illustrated in Figure 4B, the growth height is defined as the length of the microneedles 2 that grow sequentially on the surface 1a of the substrate 1, i.e., the length of the needle from the base end 21 to the tip end 24, and any growth height H can be set. ｎ and growth height H ｎ＋１ The growth regions between them are each called growth region L. １ ~L ｎ And so, growth area L １ ~L ｎ Temperature T of the micro-process head 120 in each of the following locations １ ~T ｎ , and the required time t for the micro-process head 120 １ ~t ｎ By appropriately applying each of these conditions, any shape can be obtained. In the illustrated example, the microimplement 10 has a total of seven arbitrary growth heights H in the longitudinal direction as the solid maltose or maltose composite material grows at the positions of the body portion 22 and the needle-shaped needle portion 23 of the fine needle 2. １ ~H ７ , and also, Growth Area L １ ~L ７ It is set.

[0127] In the microimplementation 10 illustrated in Figure 4B, any growth height H in the longitudinal direction (needle length) of the microneedle 2 is １ ~H ７ Growth regions L are located adjacent to each other. １ ~L ７ This corresponds to the growth height H １ From growth height H ２ The area moving towards growth is growth area L １ It is said that, and the growth height H ２ ~H ７ and growth area L ２ ~L ７ The relationship with the other is similar. On the other hand, growth height H ７ Since it is at the same level as the tip 24 of the microneedle 2, the growth region L ７ Strictly speaking, this area cannot be called a growth area, but this growth area L７ The conditions for temperature profile control in [description of the context] are such that while completing the shaping up to the tip 24 of the fine needle 2 and creating a sharp vertex at the position of the tip 24, it becomes the conditions when the fine process head 120 completely releases from the mold. Also, the growth height H １ becomes the same level as the surface 1a of the substrate 1, so for the temperature profile control conditions in the growth region L １ as the conditions for temperature profile control, the initial conditions for growing pure maltose or a maltose composite material are set.

[0128] As described above, when each position in the length direction of the fine needle 2 is divided by the growth regions L １ to L ｎ , the stacking relationship in which the fine needle 2 grows sequentially, as represented by the following formula {(L １ , T １ , t １ ) + (L ２ , T ２ , t ２ ) +... + (L ｎ , T ｎ , t ｎ ), is obtained. And by summarizing this stacking relationship, the function represented by the above general formula (1), that is, the temperature profile control represented by the following formula {F(L ｎ , T ｎ , t ｎ ) = Σ ｎ (L ｎ , T ｎ , t ｎ )} is obtained. By appropriately setting such temperature profile control and performing control to repeatedly heat and cool the micro mold heads 120A to 120F or the micro heater head 120G, it becomes possible to form the fine needle 2 into various arbitrary shapes.

[0129] Based on the above temperature profile control, in the growth region L ｎ (including the growth height H ｎ etc.) in the above general formula (1), the temperature T ｎ , and the "n" in the required time t ｎ is set to infinity (that is, substantially L ｎWhen set to = 0, the shape of the body portion 22 and the needle-shaped needle portion 23 of the micro-needle 2 can be made to approach a shape that changes continuously. On the other hand, in practice, it is not necessary to make "n" infinite, and a shape that changes continuously and smoothly can be obtained by adopting molding conditions in which the maltose composite material (or pure maltose) melts.

[0130] Here, for example, when forming the microneedles 2 of the microimplementation 10 illustrated in Figure 4B, the conditions for temperature profile control based on the above general formula (1) can be set to the conditions described below. First, the growth region L of the microneedles 2 １ , L ３ , L ５ , L ７ Each temperature T １ , T ３ , T ５ , T ７ at the same temperature (T １ = T ３ = T ５ = T ７ ) and growth area L １ , L ２ , L ４ , L ６ Temperature T in each of the following locations １ , T ２ , T ４ , T ６ The following equation { T １ >T ２ , T ４ , T ６ Let the relationship be represented by}. In this way, the growth region L ７ Temperature T ７ Growth area L ６ Temperature T ６ By making it higher, it becomes possible to form a thinner tip portion 24.

[0131] Furthermore, the growth region L of the microneedle 2 １ ~L ７ The time required for each in t １ ~t ７ That is, when a maltose composite material (or solid maltose) grows, each growth region L １ ~L ７The time required for the micro-process head 120 to move is set appropriately. Then, by programming each of these temperature profile control conditions in a control unit (not shown) provided in the manufacturing apparatus 100, it is possible to form a three-layered hump structure micro-needle 2 having a constricted shape in which thick needle regions 23a, 23c, 23e and thin needle regions 23b, 23d are alternately arranged, as shown in Figure 4B.

[0132] In the manufacturing method of this embodiment, as described above, the heating and cooling of the micro-process head 120 are repeated based on the temperature profile control represented by the general formula (1) above. Therefore, from the viewpoint of effectively performing cooling in a short time, it is preferable to suppress the specific heat of the micro-process head 120 as much as possible and minimize the heat capacity. From this viewpoint, in this embodiment, a small micro-process head 120 is used, specifically a micro-mold head 120A to 120F or a micro-heater head 120G is employed.

[0133] By employing micro-mold heads 120A to 120F, which consist of small molds, as the micro-process head 120, the heat capacity can be minimized compared to using a large mold to form many micro-needles in one process. This improves the heating and cooling efficiency of the micro-mold heads 120A to 120F, allowing for high-speed and precise temperature control. Furthermore, if an electric heater (not shown) is integrated into the micro-mold heads 120A to 120F, the heating efficiency can be further improved, enabling faster heating and cooling cycles. This allows for high-speed temperature changes to follow the temperature profile control represented by the general formula (1) above, making it possible to precisely grow the micro-needles 2 in a more diverse and intricate shape, and with a tapered shape that becomes smaller towards the tip.

[0134] Furthermore, by employing a microheater head 120G as the microprocess head 120, the base is made of a thin heating element 128, which further minimizes the heat capacity, significantly improves heating and cooling efficiency, and enables faster and more precise temperature control. As a result, it is possible to follow the temperature profile control represented by the general formula (1) above with even faster temperature changes, making it possible to grow the microneedle 2 with even more diverse and intricate shapes, and with a tapered shape that becomes smaller in diameter towards the tip, with high precision.

[0135] Generally, when controlling the temperature of molds and the like, heating is relatively easy to control because it is forced heating by applying electric current, but cooling by air cooling tends to take a long time. On the other hand, in the manufacturing method of this embodiment, by using the above-mentioned micro mold heads 120A to 120F or micro heater head 120G, their heat capacity is minimized, and both heating efficiency and cooling efficiency are increased. As a result, it is possible to follow the temperature profile control represented by the above-mentioned general formula (1) with high-speed temperature changes, and the effect of growing the fine needles 2 with a variety of fine shapes with high precision is obtained.

[0136] Furthermore, in the manufacturing method of this embodiment, by using the above-mentioned micro mold heads 120A to 120F or micro heater head 120G and varying the temperature by heating and cooling based on the temperature profile control represented by the above-mentioned general formula (1), it is possible to form micro needles of various shapes. Specifically, for example, when using the micro mold head 120A having a triangular pyramidal cavity 122, it is possible to form a triangular pyramidal micro needle according to the shape of the cavity 122, while by adjusting the above-mentioned temperature profile control, it is possible to form the micro needle into various conical shapes such as a cone. That is, by optimally setting the above-mentioned temperature profile, it is possible to form the overall outline (rough outer shape) of the micro needle from the base to the tip not only into a roughly conical shape, but also into various conical shapes such as a triangular pyramid, a square pyramid, a bullet shape, and a polygonal pyramid of pentagonal pyramid or more.

[0137] Furthermore, by adjusting the temperature profile control using the micro mold head 120A, it is possible to form thorn-shaped micro-needles that curve while shrinking in size towards the tip. Moreover, by optimally adjusting the temperature profile control represented by the general formula (1) above, it is possible to form various shapes, such as hourglass shapes, bowling pin shapes, and jewel shapes, which have a constricted portion in the middle of the length direction where the cross-sectional area is smaller than at other positions.

[0138] Here, the maltose used in the micro-needle 2 has a low melting point of 108°C in its anhydrous form, which is significantly lower than other materials conventionally used for micro-needles, such as starch (256-258°C) and hyaluronic acid (209°C or higher). When using such a low-melting-point maltose as the material for micro-needles and molding them using a mold, if a large mold with multiple cavities is used, the heat capacity is too large, making it difficult to lower the mold temperature. This presents a problem in that it is difficult to form the maltose attached to the substrate into the desired shape.

[0139] In the manufacturing method of this embodiment, a method is employed to form the fine needles 2 using the single-cavity micro mold heads 120A to 120F or micro heater head 120G described above, and the heating and cooling of the micro mold heads 120A to 120F or micro heater head 120G are performed at high speed and continuously. By employing such a method, even when easily melted maltose is used as the material for the fine needles, it becomes possible to continuously form the fine needles 2 of the desired shape with excellent precision. Furthermore, by using the micro mold heads 120A to 120F or micro heater head 120G with a high cooling rate, it becomes possible to form the fine needles 2 using maltose composite materials containing functional components with low heat resistance, such as amino acids, proteins, or unheated biomaterials.

[0140] Furthermore, according to the manufacturing method of this embodiment, by employing a method using the manufacturing apparatus 100 described above, the shape of the micro-needle can be freely set and formed using a method with 3D printing functionality, and its arrangement and positioning can also be freely determined. As a result, the micro-needle 2 can be freely formed in a desired arrangement, and changes in the arrangement specifications can be easily accommodated without requiring the replacement of the micro-process head 120, thus further improving productivity. In addition, by employing a method using the micro-mold heads 120A to 120F or the micro-heater head 120G described above, high-speed heating and cooling become possible, and the micro-needle 2 can be formed under conditions that are essentially equivalent to having a high-speed temperature rise and fall function, so that the tip 24 of the micro-needle 2 can be formed with superior shape quality so that it becomes sharper.

[0141] [Other examples of manufacturing methods] The manufacturing method of this embodiment is not limited to the method employing the above-described procedure and conditions. Detailed illustrations are omitted, but for example, it is also possible to employ the following procedure and conditions, and to employ a method that includes other steps (refer to the microimplements 10, 10B shown in Figures 4A and 4B, 6 and 7 as appropriate, if necessary).

[0142] (Method for preparing multiple maltose composite materials in the component mixing step) In the manufacturing method of this embodiment, in the component mixing step, for example, multiple maltose composite materials are prepared using two or more different functional components so that different functional components are mixed in each, and in the microneedle formation step, a method is also adopted in which multiple microneedles are continuously formed so that each contains one of the two or more different functional components.

[0143] In the manufacturing method of this embodiment, if a method comprising the component mixing step and the microneedle formation step described above is adopted, it becomes possible to manufacture microimplements with multiple functions.

[0144] (Method with a spraying step) In this embodiment, for example, a spraying step may be added before the microneedle formation step to further adhere fine clumps of functional components to the surface 1a of the substrate 1, and the microneedle formation step may be a method in which multiple microneedles are formed by overlapping the functional components that have adhered to the surface 1a of the substrate 1. Furthermore, in the above-mentioned spraying step, two or more different functional components may be adhered to the surface 1a of the substrate 1 at different positions.

[0145] In this embodiment, when a method comprising the above-described spraying step and microneedle formation step is employed, even if, for example, multiple different functional components each have different, unspecified shapes (solids) and it is difficult to manufacture and arrange them uniformly, it becomes possible to manufacture microimplements as shown in Figures 4A and 4B, etc.

[0146] (Method with a micro-protrusion forming step) In this embodiment, if necessary, a method may be adopted in which a micro-protrusion forming step is performed in advance to form a plurality of micro-protrusions, not shown, on the surface 1a of the substrate 1, and in the micro-needle forming step, micro-needles are formed on the micro-protrusions. As the material for such micro-protrusions, for example, the same material as the substrate 1 or a maltose composite material similar to that used for the micro-needles 2, etc. may be used. Furthermore, in the above-mentioned micro-protrusion forming step, a plurality of micro-protrusions containing any one of two or more different functional components may be formed on the surface 1a of the substrate 1. In such cases, pure maltose can be used as the material for the micro-needles formed on the micro-protrusions.

[0147] In this embodiment, by employing a method comprising the above-described micro-protrusion forming step and micro-needle forming step, it becomes possible to manufacture a microimplement that has the function of gradually penetrating the superficial and / or deep layers of the skin through the micro-protrusions after creating micropores on the user's skin surface with multiple micro-needles.

[0148] (Method for arranging functional component chips on micro-protrusions) In this embodiment, for example, after forming a plurality of micro-protrusions on the surface 1a of the substrate 1 in the micro-protrusion formation step described above, a method can be adopted in which micro-needles are formed on these micro-protrusions by a micro-needle formation step, and functional component micro-chips are arranged thereon.

[0149] In this embodiment, by employing the method of arranging functional component microchips on the micro-protrusions as described above, it becomes possible to manufacture microimplements that, like the above, have easily soluble micro-needles, excellent biosafety, and a high rate of functional component administration from the micro-needles.

[0150] <Effects and Effects> As described above, the manufacturing method of the microimplement of this embodiment employs a method in which, when forming a plurality of fine needles 2 from solid maltose or maltose composite material so as to be arrangeable on the surface 1a of the substrate 1, the temperature of the fine process head 120, which is a fine jig, is fluctuated based on a specific temperature profile control, and the plurality of fine needles 2 are formed individually and sequentially. As a result, even when forming the fine needles 2 from solid maltose or maltose composite material, which is meltable at low temperatures, they can be formed with high precision in various shapes, and the fine needles 2 can be formed so as to be arrangeable in the desired shape and arrangement, and it is possible to easily respond to changes in specifications, etc. In this way, by forming the fine needles 2 in various shapes and arrangements, the administration rate of functional components from the fine needles is increased, and the fine needles can be easily inserted into the superficial and / or deep layers of the skin, so it is possible to produce microimplements that provide a better user experience and more pronounced effects from treatment and cosmetic procedures.

[0151] Furthermore, according to the microimplementation of this embodiment, a plurality of microneedles 2 provided on the substrate 1 are made of solid maltose or a maltose composite material, and the plurality of microneedles 2 are individually formed and freely arranged on the surface 1a of the substrate 1, and a structure is adopted in which one or more locations in the direction from the base end (base portion) 21 on the substrate 1 side toward the tip portion 24 or in the needle length direction are constricted, with thick needle regions and thin needle regions arranged alternately. As a result, compared to the case in which the microneedles 2 have a simple shape, the rate of administration of functional ingredients from the microneedles 2 is increased, and the microneedles 2 are made easier to insert into the superficial and / or deep layers of the skin, resulting in excellent biocompatibility, and for example, the effects of treatment and cosmetic procedures can be obtained more significantly.

[0152] <Modifications of the Invention> Although embodiments of the present invention have been described in detail above, the method for manufacturing a microimplement and the microimplement of the present invention are not limited to the embodiments described above, and can be implemented with various changes and modifications as long as they do not depart from the principles of the present invention and the scope of the appended claims.

[0153] Here, Figure 6 is a perspective view showing one of the multiple fine needles 2B provided on the surface 1a of the substrate 1 in a modified microimplementation 10B of the present invention, and Figure 7 is an overall perspective view showing the microimplementation 10B in which the multiple fine needles 2B are arranged irregularly on the surface 1a of the substrate 1.

[0154] In the present invention, a structure can also be adopted in which the needle-shaped portion 23B growing from the body portion 22 does not have a constricted shape, but is entirely conical, as exemplified by the microneedle 2B in Figures 6 and 7. Microimplements equipped with various shapes of microneedles, including such shapes, can be manufactured by the manufacturing method of the present invention.

[0155] Furthermore, according to the manufacturing method of the present invention, it is also possible to form a plurality of fine needles 2B on the surface 1a of the substrate 1 in an irregular arrangement, as exemplified by the microimplement 10B in Figure 7. In the example shown in Figure 7, a total of 10 fine needles 2B are irregularly arranged while leaving empty space in a part of the surface 1a of the substrate 1. In Figure 7, for the sake of clarity, the planned mounting locations 11 when the empty space on the surface 1a of the substrate 1 is filled with fine needles 2B in an irregular arrangement are shown, and a total of 6 locations are shown in the figure. That is, in the illustrated example, the microimplement 10B has a mixture of areas with and without fine needles 2B on the surface 1a of the substrate 1, resulting in a substantially irregular arrangement. According to the manufacturing method of the present invention, in addition to the arrangement of fine needles 2B exemplified in Figure 7, it is possible to form them in various ways, such as intermittently arranging the fine needles 2B based on the planned mounting locations 11.

[0156] Furthermore, it goes without saying that the irregular arrangement of multiple microneedles on the surface 1a of the substrate 1, as described above, is also applicable to the microimplementation 10 shown in Figures 4A and 4B.

[0157] The method for manufacturing microimplants of the present invention allows for the precise formation of microneedles in various shapes, and enables the formation of microneedles in desired shapes and arrangements, and can easily accommodate changes in specifications. Furthermore, the microimplants of the present invention have excellent administration rates of functional components from the microneedles and are easily inserted into the superficial and / or deep layers of the skin. Therefore, the method for manufacturing microimplants of the present invention is highly suitable for applications such as skin treatment, cosmetic and modification procedures, and advanced treatments such as the treatment of deep subcutaneous tissue and systemic immune system diseases. The microimplants of the present invention are highly suitable for the various applications of the above-mentioned treatments.

[0158] 10, 10A, 10B... Microimplement 1... Substrate 1a... Front surface 1b... Back surface 11... Mounting location 2, 2A, 2B... Fine needle 21... Base end 22... Body 23, 23A, 23B... Needle-shaped needle section 23a, 23c, 23e, 23f, 23h, 23j... Thick needle area (constricted shape) 23b, 23d, 23g, 23i... Fine needle area (constricted shape) 24... Tip 100... Microimplement manufacturing equipment 110... Support unit 111... Mounting surface 120... Microprocess head 120A, 120B, 120C, 120D, 120E, 120F... Micro mold head (microprocess head) 121... End face 122... Cavity 122a... Top 122b...Side 123...Cavity 123a...Top 123b...Conical surface 120G...Microheater head (micro-process head) 128...Heating wire 128a...Current supply line 128b...Current supply line 128c...Tip S...Material supply space M...Maltose (maltose composite material) 130...Head mounting unit 140...Drive unit 141...Drive shaft

Claims

1. A method for manufacturing a micro-imprint that forms a plurality of fine needles on a substrate using pure maltose or a maltose composite material in which one or more functional components are mixed on the surface of the substrate, wherein the substrate is made of a polymer material, a biodegradable material, a water-soluble material, or a mixture thereof to which the maltose can adhere, and a fine process head, which is a fine jig for forming the fine needles so that they can be arranged from the pure maltose or the maltose composite material, is provided with a fine needle forming step of forming the plurality of fine needles individually and sequentially, the fine needle forming step is based on temperature profile control represented by the following general formula (1), and while varying the temperature of the fine process head so as to rise and fall, the pure maltose or the maltose composite material is sequentially supplied from the fine process head toward the surface side of the substrate, whereby the fine needles are formed so as to grow sequentially from the base end portion on the substrate side. A method for manufacturing a micro-imprint, characterized in that. F(L ｎ , T ｎ , t ｎ ) = Σ ｎ (L ｎ , T ｎ , t ｎ ) ······ (1) However, in the general formula (1), L ｎ : The direction from the base end portion to the tip portion of the fine needle or the needle length direction, when the growth height at which the fine needle grows sequentially is taken as an arbitrary growth height H ｎ and the growth height H ｎ＋１ and the growth region between the growth heights H ｎ : The temperature of the fine process head in the growth region L ｎ t ｎ : The time required for the fine process head to move through the growth region L ｎ where n is an integer of 1 or more that increases sequentially from the base end portion side as the fine needle grows.

2. The microneedle formation step comprises: an adhesion process in which, when the microprocess head is in close proximity to the substrate, the heated microprocess head adheres the maltose or maltose composite material to the surface of the substrate in a molten state; and a growth solidification process in which, as the microprocess head gradually detaches from the substrate, and while repeatedly heating and cooling the microprocess head based on the temperature profile control represented by the general formula (1), the solid maltose or maltose composite material attached to the surface of the substrate is sequentially grown and solidified from the base end, and the method for manufacturing a microimplement according to claim 1 is characterized in that a plurality of microneedles are continuously formed on the surface of the substrate by repeating the adhesion process and the growth solidification process.

3. The micro-process head is a micro-mold head having a concave cavity for freely arranging the micro-needles, and the total volume of the micro-mold head, including the cavity, is 10 mm². ３ A method for manufacturing a microimplement according to claim 1 or 2, characterized in that it is a rectangular parallelepiped made of the following metal materials.

4. The method for manufacturing a microimplement according to claim 3, characterized in that the micro-mold head consists of a triangular pyramidal recess in which the cavity is arranged to expand toward the end face facing the surface of the substrate.

5. The method for manufacturing a microimplement according to claim 3, characterized in that the micro-mold head consists of a semi-conical recess in which the cavity is arranged to expand toward the end face facing the surface of the substrate.

6. The method for manufacturing a microimplement according to claim 3, characterized in that the micro mold head is made of a material capable of generating heat when an electric current is supplied to it, and has an electric current supply unit to which the electric current is supplied.

7. The method for manufacturing a microimplement according to claim 3, characterized in that the micro-mold head has a concave notch at at least one location on its outer surface.

8. The method for manufacturing a microimplement according to claim 3, characterized in that the micro mold head is provided with a fin portion at least at one location on its outer surface that protrudes outward from the outer surface.

9. The method for manufacturing a microimplement according to claim 3, characterized in that the micro-mold head has ventilation holes provided so as to penetrate at least a portion of the micro-mold head.

10. The method for manufacturing a microimplement according to claim 1 or 2, characterized in that the microprocess head is a microheater head consisting of a heating coil in which a heating wire is wound so as to gradually decrease in diameter toward the substrate side, and a material supply space for forming the microneedles can be freely arranged is secured within the coil.

11. A method for producing a microimplement according to claim 1 or 2, characterized in that, prior to the microneedle formation step, the method comprises a component mixing step of mixing a functional component with the maltose to prepare the maltose composite material.

12. The method for manufacturing a microimplement according to claim 11, characterized in that the component mixing step involves preparing a plurality of maltose composite materials using two or more different functional components, each of which contains a different functional component, and the microneedle formation step involves continuously forming the plurality of microneedles, each containing one of the two or more different functional components.

13. The method for manufacturing a microimplement according to claim 1 or 2, further comprising a spraying step of attaching the functional component to the surface of the substrate before the microneedle formation step, wherein the microneedle formation step is characterized in that the plurality of microneedles are formed by overlapping them at the positions of the functional component attached to the surface of the substrate.

14. The method for manufacturing a microimplement according to claim 13, characterized in that the spraying step involves attaching two or more different functional components to the surface of the substrate at different positions.

15. A microimplement comprising: a substrate made of a polymer material, biodegradable material, water-soluble material, or a mixture thereof to which maltose can adhere; and a plurality of fine needles arranged on the surface of the substrate, wherein the maltose is used in its pure form or a maltose composite material mixed with one or more functional components is used, wherein the plurality of fine needles are individually formed and can be freely arranged on the surface of the substrate, and one or more locations in the longitudinal direction from the base end to the tip on the substrate side are constricted, consisting of a thick needle region and a thin needle region.

16. The microimplement according to 15, wherein each of the plurality of fine needles has multiple thick needle regions and thin needle regions arranged alternately, so that multiple locations in the longitudinal direction are constricted, and each of the plurality of thick needle regions is made of a maltose composite material mixed with different functional components, and each of the thin needle regions is a region in which the different functional components change continuously.

17. The microimplement according to claim 15, characterized in that each of the plurality of microneedles is a mixture of two or more different functional components.

18. The microimplement according to claim 15 or 16, characterized in that the functional component is one or a combination of two or more selected from the group consisting of vitamins, hyaluronic acid, collagen, proteins, DNA, peptides, vaccines, drugs, nutritional supplements, cosmetic materials, antibody test agents, body-use color materials, body-use metals, body-use metal oxides, and body-use magnetic materials.

19. The microimplement according to claim 15 or 16, characterized in that the material used for the substrate is any one of polyvinyl alcohol, pullulan, hyaluronic acid, collagen, ceramic, or paper.

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