WO2008010573A1

WO2008010573A1 - Microimplement, process for manufacturing the same, and method of assembling sugar material part

Info

Publication number: WO2008010573A1
Application number: PCT/JP2007/064346
Authority: WO
Inventors: Yoshikazu Tobinaga; Tomoya Kitagawa; Kentaro Ohshima
Original assignee: Elegaphy, Inc.; Maruho Co., Ltd.
Priority date: 2006-07-21
Filing date: 2007-07-20
Publication date: 2008-01-24
Also published as: JP2009232873A; JP4821993B2

Abstract

A microimplement for insertion in skin surface that ensures high safety, no pain and easy use, and that is less in the quantitative limitation or variety restriction as to functional material, etc., realizing high structure strength, high stability and high machining precision, and that in disposal thereof, is very low in environmental load; a process for manufacturing the microimplement; and a relevant method of assembling sugar material parts. There is provided a microimplement for insertion in skin surface having minute cantilevers of a material soluble into the skin, disposed on an upper edge portion of side face of substrate or on a surface of substrate sheet, wherein each of the cantilevers has roughly a half-split cone configuration and has a given dimension. Further, there are provided a process for manufacturing the above microimplement and a relevant method of assembling sugar material parts.

Description

Specification

Micro-implement, manufacturing method thereof, and sugar material component assembling method

Technical field

TECHNICAL FIELD [0001] The present invention relates to a technique for inserting a pharmaceutical agent for the purpose of treatment or health into a human skin surface, that is, a transdermal dosage technology, and a functional material for beauty in the human skin surface. Technology for the introduction of skin care materials, that is, transdermal nutritional supplements and supplemental administration technology, skin cosmetics and modification technology, and in-vivo information extraction and individual identification signals within the human skin surface. TECHNICAL FIELD The present invention relates to a technique for inserting a functional chip for sensing, that is, a technique for mounting a functional chip in the skin surface, and relates to a micro-implement for insertion in the skin surface to be used for the technique and a manufacturing method thereof. In addition, the present invention provides a sugar material for bringing a sugar material part into contact with each other or bringing a sugar material part into contact with each other or a substrate or a substrate sheet composed of pullulan or a composite sugar material of pullulan and maltose. It relates to the parts assembly method.

Background art

[0002] Conventionally, for transdermal administration, a drug is applied to the surface of a metal or plastic microneedle (hereinafter referred to as "fine needle"), and the microneedle is inserted into the skin surface. The method of penetrating the applied drug into the skin has been followed. However, in the case of microneedles based on industrial materials made of insoluble materials in the skin such as metal or blast, there are not a few accidents in which microneedles remain in the body due to carelessness during administration. It was a worrisome problem. Even if a pharmaceutical agent or a functional material is applied to a fine needle or a mixture thereof is mixed, there are quantitative limits on the pharmaceutical agent or functional material that can be physically mounted on the fine needle. There was a limit to the penetration of a sufficient amount of pharmaceutical agents and functional materials into the skin. Furthermore, as represented by the problem of disposal of medical instruments, there is a problem that disposal of fine needles takes a large environmental load.

[0003] In addition, with regard to cosmetic techniques, conventionally, the application of a cosmetic agent (functional material) to the skin surface, ultrasonic assistance for promoting the transdermal administration, and transdermal administration by electrophoresis, etc. However, in any case, due to the protective properties of the skin, a sufficient amount of cosmetics could not be applied, which was an important issue. As for skin surface modification technology, coloring materials have been administered to the surface of the skin on the outer side of the upper arm or the eyebrows since ancient times. However, this treatment is very painful and uses a needle. It required skilled skills and there were also safety issues. In addition, in the technique of administration of nutrients and nutritional supplements into the body, administration was limited to oral administration, so if they are solid due to problems with taste, chewing, gastrointestinal digestion and absorption, etc. The degree of freedom of nutrients, etc. is limited due to sugar coating and fine granulation, and when it is in liquid form, its use is almost limited to low-concentration water-soluble solubilizers. There was a problem that nutrients and nutritional supplements could not be added.

[0004] Furthermore, skin-embedded electronic chips, so-called functional chips, that are used to extract in-vivo information and sense individual identification signals, have conventionally used a medical instrument such as a scalpel to open the skin. As a result, the tip is pushed out of the body as the skin surface is healed, making it difficult to keep the functional tip in the skin in a stable state. It was.

[0005] On the other hand, it is safe for the human body and environmentally friendly! / For fine needles based on sugar, which is a material! / Injection molding method often used for resin processing as its manufacturing method Because of the characteristics of the manufacturing method and the crystallinity, physical, and chemical properties of the sugar used, the fine needles with high processing accuracy and high strength were used. Molding was almost impossible and this was a big problem. The strength mentioned here is the strength required when the fine needle is used on the human body, which is comparable to the strength required for the metal or plastic fine needle used for the human body.

[0006] Under such a development situation, as a development example, there is a micropile in which fine needles for skin mainly composed of a carbohydrate such as maltose are assembled and a manufacturing method thereof (for example, Patent Document 1). reference). This micropile is certainly easy to dispose of, and has a high level of safety, a force that is a fine needle. Since it is composed mainly of carbohydrates such as general maltose, it is caused by grain boundaries. There was a problem in that the strength of the structure was small and the stability was poor and the processing accuracy was low! / And! /. Patent Document 1: Japanese Patent Laid-Open No. 2003-238347

[0007] As another development example, a micro-perforator including a needle based on a water-soluble polymer such as polybutyl alcohol (PVA) and sodium carboxymethylcellulose (CMC-Na) (for example, see Patent Document 2) However, it is almost impossible to perform micro-processing to keep the needle tip to a diameter of 300 m or less due to the polymer material. Without pressurization, it is difficult to insert into the skin surface. Even if it can be painfully inserted by pressurization, it is equivalent to dissolution in the skin surface because the base material is a polymer material. If it took time!

Patent Document 2: Japanese Translation of Special Publication 2006—500973

Disclosure of the invention

Problems to be solved by the invention

[0008] In the above prior art, in the case of the transdermal dosage technique, there is a serious safety problem that a fine needle made of an insoluble material such as metal or blast material remains in the living body. However, there is a problem that there are quantitative limits on the pharmaceutical agents and functional materials that can be mounted on the fine needles, and there is a problem that a large environmental load is required for the disposal process. Also, in the case of cosmetic technology, there is a problem that a sufficient amount of cosmetic agent cannot be administered to the skin due to the protective properties of the skin even by application to the skin, and in the case of skin surface modification technology However, in the case of a technique for administration of nutrient supplements and nutritional supplements into the body, administration was limited to oral administration, even though demanding skilled techniques, and these were solid. The degree of freedom of nutrients, etc. is limited when it is in a liquid state, and when it is in a liquid state, its use is almost limited to a low-concentration water-soluble lysate. There was a problem. Furthermore, in the case of a technique for mounting a skin-embedded functional chip used for in-vivo information extraction or the like, the chip is pushed out of the body as the skin surface is healed, and the functional chip is removed from the skin in a stable state. There was a problem that it was difficult to keep it inside.

On the other hand, an injection molding method or the like has been used as a method for producing microneedles using sugar as a base material, but due to the characteristics of the production method and the properties of the sugar to be used, the processing accuracy is high. The problem is that it is almost impossible to mold microneedles with high strength. It was a title. In addition, there is a micropile that is a collection of microneedles for skin that contains only carbohydrates such as maltose as the main ingredient. This is because the main ingredient is only carbohydrates such as general maltose. Due to the grain boundaries, there was a problem that the strength as a structure was low and the processing accuracy was low and the stability was low. Furthermore, there are fine needles for transcutaneous using water-soluble polymers, but this is almost impossible and fine needle insertion is difficult. However, since the base material is a polymer material, there is a problem in that considerable time is required for dissolution within the skin surface. The conventional mold was for injection molding, and was molded by pushing it into a needle hole that was reversed with respect to the needle. Also in casting (casting method), the shape of the molding was shaped on the bottom of the mold. In any case, the accuracy of the needle tip is limited to about 30 m due to limitations due to fluid phenomena during molding (not flowing into details, turbulence or vortex phenomenon, ie, vortex phenomenon), which was a problem. . Furthermore, since it is usually a single mold, injection molding and casting cannot be performed with fine protrusions due to mechanical blurring at the time of release, which is also a problem.

[0010] The present invention is a structure having a fine cantilever made of a soluble material in the skin at the upper end of the side surface of the substrate or the surface of the substrate sheet. Micro-implement for insertion, micro-implement for insertion in skin surface with functional chip mounted on fine cantilever, and functional materials such as pharmaceutical agents, nutrients and their supplements, cosmetic materials, color materials, etc. It is an object of the present invention to provide a microimplement for penetration into the skin surface and a method for producing the same. It is another object of the present invention to provide a simple assembling method for sugar material parts such as micro-implements composed of these sugars as a base material.

Means for solving the problem

[0011] The present invention provides a means for solving the problem to achieve the above-described object,

(1) In a micro-implement having a structure having one or more fine cantilevers made of a soluble material in the skin at the upper end of the side surface of the substrate, the cantilever has a substantially truncated cone shape, The long width of the fine tip of the cantilever is 0.1 m to 100 μm A microimplement for insertion into the skin surface, characterized in that the length from the tip to the end of the cantilever is 50 m to 5 mm, and

(2) A micro-implement having a structure in which one or more fine cantilevers made of a soluble material in the skin are provided on the surface of the substrate sheet. The length of the fine tip of the cantilever is 0.1 μm to 100 μm, and the length from the tip to the end of the cantilever is 50,1 m to 5 mm. Micro-implementation, and

(3) The microimplement for insertion into the skin surface according to (1) or (2), wherein the cantilever has a constricted shape part, and

(4) Any of (1) to (3) above, wherein the base material of the substrate is one or more selected from saccharides, cellulose, solid starch, paper, wood, plastic, metal, force, etc. Kano's micro-implement for penetration into the skin surface,

(5) The microimplement for insertion into the skin surface of (2) or (3) above, wherein the base material of the substrate sheet is pullulan or a complex sugar material of pullulan and maltose, and

(6) The microimplement for insertion into the skin surface according to any one of (1) to (5) above, wherein the soluble material strength S in the skin is anhydrous amorphous maltose, and

(7) The microimplement for insertion into the skin surface according to any one of (1) to (5) above, wherein the soluble material in the skin is a complex sugar material of anhydrous amorphous maltose and pullulan, and

(8) The cantilever contains one or more selected from protein, DNA, pharmaceutical agent, nutritional agent, nutritional supplement, cosmetic material, color material, metal, metal oxide, microcapsule, force. (1) to (7) the microimplement for insertion into the skin surface, and

(9) The microimplement for insertion into the skin surface according to any one of (1) to (8) above, wherein a functional chip is mounted on the surface of the cantilever, and

(10) The microimplement for insertion into the skin surface according to any one of (1) to (8), wherein the cantilever has a structure in which a functional chip is mounted; and (11) The functional chip is a semiconductor chip, integrated circuit chip, temperature sensor chip, protein chip, DNA-containing chip, pharmaceutical agent-containing chip, nutrient-containing chip, nutritional supplement-containing chip, cosmetic material-containing chip, color material (9) or (10) the micro-implement for insertion into the skin surface, characterized in that it is 1 or 2 or more selected from a containing chip, a metal-containing chip, a micro-power chip, a force, and the like, and

(12) The surface of the functional chip is covered with a composite sugar material of maltose, maltose and pullulan, polyethylene, polypropylene, and one material of which force is also selected. Micro-implementation, and

(13) For micro-implement, which consists of a cantilever micro mold head having one or two or more fine cantilever inversion-shaped recesses on the upper surface end and a substrate mold having a substrate inversion-shaped recess The micro-implement mold has a temperature control mechanism, and the micro-mold head for the cantilever and the mechanism for allowing the substrate mold to move independently. (1) or (3), a method for producing a microimplement for insertion into the skin surface, and

(14) In a micro mold head for a cantilever having a reversal-shaped concave portion of one or more fine cantilevers at an upper end, the micro mold head has a temperature control mechanism and is on the surface of the substrate sheet. (2) or (3) the method for producing a microimplement for insertion into the skin surface, wherein the microimplement head is manufactured using a micro mold head having a vertically movable mechanism, and

(15) It is composed of at least one of the two sugar material parts S, pullulan, or a composite sugar material of pullulan and maltose, and the two sugar material parts are brought into contact with each other and welded together. A method for assembling sugar material parts, and

(16) The pullulan of (15) or a complex sugar material of pullulan and maltose

V. The sugar material component is a substrate or a substrate sheet, and the other sugar material component is brought into contact with and welded to the upper end of the side surface of the substrate or the surface of the substrate sheet. The other sugar material part is the cantilever of (3), and the soluble material in the skin of the cantilever is anhydrous amorphous maltose or a complex sugar material of anhydrous amorphous maltose and pullulan (16) Sugar material parts assembly method,

It is what.

The invention's effect

[0012] In the micro-implement for insertion into the skin surface of the present invention, since the fine cantilever inserted into the skin surface is based on the soluble material in the skin, it is dissolved quickly within the skin surface. Is painless, easy to use, and can contain functional materials such as pharmaceutical agents, beauty agents, nutritional supplements and adjuvants, and color materials in a fine cantilever. There are few kind restrictions and quantitative limits in these agents and materials, and the cantilever has a constricted shape part, so that when the microimplement is inserted into the skin surface, the cantilever easily breaks in the constricted shape part. It has the characteristic effect that it is possible to easily and safely insert the microimplement into the skin surface. If a cantilever equipped with a functional chip is used, the functional chip can be easily and painlessly attached to the skin surface in a stable state, and the skin solubilizer, which is the base material of the cantilever, is anhydrous and amorphous. By using a complex sugar material of maltose or anhydrous amorphous maltose and pullulan, the safety of the human body is high, the strength as a structure without crystal grain boundaries is high, the processing accuracy is high, and the stability is high. Furthermore, by making the substrate of the substrate or the substrate sheet into saccharides, the water-solubility of the substrate can be used to reduce the environmental impact due to the waste treatment! /, And! / Has a positive effect.

[0013] In addition to the above effects, in the micro-implement of the present invention, since the cantilever has a substantially pyramid-shaped split shape, it is easy to mount a functional chip on a split surface that forms a horizontal plane at room temperature. Furthermore, the heat resistance of the functional chip is not so required because it is mounted at room temperature, and further, the functional chip is covered with a composite sugar material of maltose, maltose and pullulan, polyethylene, etc. This has the effect of strengthening the adhesion between the cantilever and the one-sided surface of the cantilever (the mounting surface of the functional chip). Further, in the microphone mouth implementation of the present invention, the cantilever is encapsulated with a functional chip, thereby It is possible to reduce the penetration resistance of the chiller into the skin surface. In this case, although the heat resistance of the functional chip is required, the surface of the functional chip described above is combined with maltose, maltose and pullulan. Heat protection is possible by coating with sugar material, polyethylene, etc. Furthermore, since the functional chip is contained in the cantilever, it has a characteristic effect that it is hardly damaged.

[0014] In the microimplement manufacturing method of the present invention, in the microimplement mold constituted by the micromold head for cantilever and the substrate mold having the concave portion having the inverted shape of the substrate, Has a temperature control mechanism, and has a mechanism that allows the parenthesis micro mold head and substrate mold to move independently, making it easy to manufacture substrate-type micro-implements with high processing accuracy and high structural strength. Is possible. Further, in this manufacturing method, the micro mold head for cantilever having a temperature control mechanism has a mechanism that can move vertically with respect to the surface of the substrate sheet, so that the processing accuracy is high and the substrate sheet has high structural strength. This has the effect that the micro-implement of the mold can be easily manufactured. Furthermore, in the present invention, the bottom of the casting mold is not used, the limit of the fluid is avoided, and the protrusion is opened using the end (surface part) of the mold so that the fluid can flow. In addition, the projection (needle part) and the base part are separated, the mechanical mold is eliminated, the fine part is formed in advance (release), and the separation mold is used to release the base part. This has the characteristic effect of overcoming the problems of conventional molds.

[0015] In the method for assembling a sugar material part of the present invention, the sugar material part is composed of at least one of the two sugar material parts, or a complex sugar material of pullulan and maltose, and therefore uses the adhesiveness of pullulan. Thus, these sugar material parts can be brought into contact with each other and welded, and the sugar material parts having a high structural strength can be easily assembled. In the assembling method of the present invention, the sugar material component is a substrate or a substrate sheet made of pullulan or the like, so that the other sugar material component is brought into contact with the upper end portion of the substrate side surface or the substrate sheet surface. It has the effect that it can be welded and a sugar material part having a high structural strength can be easily assembled. Furthermore, in this assembly method, the other sugar material part is a cantilever, and the soluble material in the skin of this cantilever is anhydrous amorphous maltose. Or a complex sugar material of anhydrous amorphous maltose and pullulan, it is possible to easily assemble a microimplement for insertion into the skin surface with high structural accuracy and high processing accuracy! It also has a characteristic effect.

Brief Description of Drawings

1] It is an outline drawing showing a substrate type micro-implement of the present invention.

2] An outline view showing a substrate sheet type micro-implement of the present invention.

Garden 3] An enlarged perspective view of a cantilever having a half-conical shape of a cone in the present invention. 4) An enlarged perspective view of a cantilever having a half-shaped shape of a quadrangular pyramid in the present invention.

5] It is a schematic diagram showing a cross section of a substrate type micro-implement.

[Fig. 6] Schematic diagram showing a cross section of a substrate type micro-implement having a constricted portion. 7] Schematic diagram showing a cross section of a substrate type micro implement having a functional chip. 8] Functional chip mounting type. FIG. 3 is a schematic diagram when the microimplement is inserted into the skin surface.

9] It is a schematic diagram after insertion of a functional-chip-mounted microimplement into the skin surface.

10] This is a schematic diagram of the functional material mixed type micro-implement when it is inserted into the skin surface.

11] This is a schematic diagram of the functional material mixed type micro-implement after insertion into the skin surface.

12] It is a schematic diagram showing the state of functional material diffusion and penetration into the skin.

FIG. 13 is a schematic diagram showing a combination of a micro mold head for a cantilever and a mold for a substrate.

FIG. 14 is a schematic diagram showing a driving micro mold head and a cantilever on a substrate sheet. Explanation of symbols

1 Cantilever

2 Board

3 Side of the board

4 Board sheet

5 Cantilever with half-cut shape of cone

6 Cantilever with a half-cut shape of a quadrangular pyramid

7 One side of cantilever

8 Board top surface

9 Cantilever with constricted shape

10 Functional chips

11 Skin surface

12 Substrate type micro-implement with functional chip

13 Substrate-type micro-implement with a constricted part with a functional chip 14 Functional chip remaining in the skin surface

15 Functional chips remaining on the skin surface (when using a cantilever with a constricted part)

16 Substrate-type micro-implement of functional material-containing cantilevers

17 Cantilever substrate type micro-implement with functional material and constricted shape

18 Cantilevers containing functional materials

19 Cantilever with constricted shape containing functional material

20 Cantilevers containing functional materials remaining in the skin

21 Cantilevers with constricted shapes containing functional materials remaining in the skin

22 Diffusion penetration area of functional materials

23 Diffusion penetration area for functional materials (when using cantilevers with constricted parts) 24 Micro mold head

25 PCB mold 26 Heater for temperature control

27 Drive stage

BEST MODE FOR CARRYING OUT THE INVENTION

[0018] In the following, embodiments of the micro-implement for insertion into the skin surface according to the present invention, a manufacturing method thereof, and a sugar material component assembling method will be described. However, the present invention is not limited to the following embodiments. Is not to be done.

In the present invention, the cantilever means structurally a cantilever, and the tip of the cantilever is a free end, and the end where the cantilever is in contact with the substrate or the substrate sheet is a fixed end. The shape of the cantilever is a half of a pyramid that is close to a quadrangular pyramid, polygonal pyramid, cone, etc. (that is, a substantially pyramid) cut by a plane that passes through a perpendicular extending from the apex of the cone to the bottom of the cone. It is in the form of a single-sided crack, which is referred to as a substantially conical piece in the present invention. However, the cutting of the substantially cone in the plane is cut so that its volume is almost halved, in other words, the plane is divided so that the bottom of the cone is divided almost in half of its bottom area. Just go down. For example, if the cone is almost a cone, the bottom of the cone is almost circular.If the plane passes through a line indicating the diameter of the circle, its half-cracked shape (the cantilever shape at this time is shown in Fig. 3). (Shown) is about half the volume of the cone. Also, for example, when the substantially pyramid is a substantially quadrangular pyramid, the bottom surface of the cone is almost rectangular, and if the above plane passes through the diagonal of the square, its half-broken shape (the cantilever shape at this time is shown in FIG. The volume is almost half that of the pyramid. However, if the cone bottom area and cone volume are halved, the above plane can pass through any line other than the diagonal line of the cone base. Good. Therefore, since the one-side crack surface of the one-sided shape of the substantially pyramid is horizontal, it is possible to easily mount a functional chip on the one-side crack surface.

[0020] The size of the cantilever in the present invention is the longest diameter in the shape (substantially polygonal or substantially circular) of the long width of the fine tip of the cantilever, that is, when the apex of the approximate cone is viewed directly in front. However, it is preferably in the range of 0.1〃111 to 100、111, but this is physically impossible at less than 0.1 l 、 m, and physically into the skin surface at more than 100 in. This is because there is a great deal of resistance and a stinging sensation. Also, the length from the tip to the end of the cantilever ( In other words, the length of the above normal line) is preferably in the range of 50 mm to 5 mm. However, if it is 50 mm or less, the cantilever cannot reach the deep part of the skin surface. This is because it is too long to ensure structural strength. In the present invention, the insertion of the micro-implement into the skin surface substantially means that the cantilever is inserted into the skin from the skin surface, and the skin (keratin) located on the surface of the skin is called the skin. Layer)), the underlying dermis, and the underlying subcutaneous tissue. The insertion site in the skin is identified according to the insertion purpose, and the cantilever tip force is adjusted accordingly. If you decide the length of

In the present invention, the substrate and the substrate sheet refer to a force that is necessary for the above-mentioned cantilever to fix the end portion thereof. When the cantilever fixes the end portion to the upper end portion of the side surface of the substrate, (Shown in Fig. 1) and the cantilever that fixes the end of the substrate sheet surface (shown in Fig. 2). This is called a micro-implement for penetration into the skin surface. Fig. 3 shows an enlarged perspective view of a part of the cantilever in the substrate type micro-implement shown in Fig. 1. This is a case where the cantilever is almost in the shape of a half piece of a cone, and its bottom surface is almost the same. Shows a semicircle. Fig. 4 shows an enlarged perspective view of a part of the cantilever in the substrate sheet type micro-implement shown in Fig. 2. This is a case where the cantilever has a substantially half-pyramidal shape, and its bottom surface. Indicates a triangle. The cross-section of the cantilever shown in FIG. 3 is the force S shown in FIG. 5, particularly in the case of a substrate type microimplement, the cantilever's half-break surface 7 and the substrate top surface 8 are connected with almost no step as shown in FIG. In addition, in the substrate sheet type micro-implement, the force S that is preferable to make the one side of the cantilever split vertically with respect to the surface of the substrate sheet, and the contact surface with the substrate sheet in the mold head for the cantilever and the substrate sheet The surface is normally parallel. By tilting this parallel contact surface with respect to the substrate sheet surface, it is possible to make the one-side crack surface of the cantilever stand at an angle other than perpendicular to the substrate sheet surface. It should be noted that the shape and size of the substrate and the substrate sheet are not particularly limited, and the shape and size may be specified according to the intended use of the micro-implement for insertion into the skin surface. Further, the micro-implement of the present invention can be mounted on the cantilever according to the purpose of use. Alternatively, it may be a structure having one or two or more in the substrate sheet. In the present invention, the term “implement” is used to mean mounting and mounting in the design field of a semiconductor integrated circuit, but in the present invention, a tool (that is, a tool used for mounting a cantilever on a skin surface) In other words, it means wearing equipment).

[0022] As shown in Fig. 6, the cantilever according to the present invention preferably has a constriction-shaped portion between its distal end portion and the distal end portion. In order to leave the cantilever inserted in the skin surface more easily, more stably and in the skin when inserting the mouth implement, the constricted part between the tip and the end of the cantilever This is to make the cantilever easy to break at this shape. This makes it possible to insert the microimplement into the skin surface easily and safely, and then the cantilever, which is a solubilizing agent in the skin, quickly dissolves in the skin surface. This constriction shape has a stepped constriction or a curved constriction. The constriction shape is not particularly limited.

[0023] The substrate sheet in the present invention refers to a substrate in the form of a sheet, and therefore the base material which is the material thereof is the same as the substrate. The substrate in the present invention and the substrate in the substrate sheet are preferably one or more selected from saccharides, cellulose, solid starch, paper, wood, plastic, metal, force and the like. Examples of the saccharide include glucose, fructose, galactose for monosaccharides, and maltose, sucrose, ratatoose, cellobiose, trehalose for disaccharides, and other oligosaccharides such as trisaccharides and tetrasaccharides. Examples thereof include sugar alcohols such as xylitol, maltitol, and reduced starch syrup, and polysaccharides such as pullulan. However, water-soluble saccharides are preferable from the viewpoint of easy disposal. Of these, the substrate sheet is preferably composed of pullulan or a complex sugar material of pullulan and maltose among saccharides! /, But it is preferable to use the adhesiveness of pullulan. This is because the cantilever can be firmly fixed. The reason for using maltose is that it is easy to make a complex sugar material by mixing with pullulan, and it is cheap and easily available. In this case, the mixing ratio of pullulan and maltose is not particularly limited.

[0024] The skin-soluble material in the present invention literally means a material that can be dissolved in the skin. For example, biocompatible materials such as saccharides, chitin and chitosan, and biodegradation of polylactic acid and the like. Among them, saccharides having the highest dissolution rate in vivo are preferable. Among saccharides, anhydrous amorphous maltose or a complex sugar material of anhydrous amorphous maltose and pullulan is preferred in terms of safety to the human body and immediate solubility in the skin, and there is no grain boundary. Therefore, it is preferable because a cantilever with high processing accuracy can be obtained. Here, anhydrous amorphous maltose refers to maltose from which water of crystallization has been removed and it is amorphous (amorphous), but this anhydrous amorphous maltose is low molecular weight and anhydrous. It is easy to mix with polysaccharide aqueous solutions such as pullulan, that is, when anhydrous amorphous maltose and pullulan aqueous solution are mixed, pullulan hydrated molecules are easily taken into maltose, and a complex sugar material with a good mixing state is obtained. It is easy to be done. When this is used as a base material for cantilevers, as in the case of using anhydrous amorphous maltose alone, there is no crystal grain boundary, so it is possible to obtain a cantilever with high processing accuracy and solubility within the skin surface. In addition, the pullulan adhesiveness makes it extremely easy to bond the bottom surface of the cantilever to the side surface of the substrate or the surface of the substrate sheet. In this case, the mixing ratio of anhydrous amorphous maltose and pullulan is not particularly limited, but 1: 0 to; 1: 9 is preferred, and in order to emphasize the characteristics of pullulan, 1: 1 or more is preferable. The immediate solubility in the skin means that the dissolution in the skin is extremely fast. From the viewpoint of safety and convenience after inserting a cantilever made of a soluble material in the skin into the skin surface, The cantilever is preferably dissolved in about 60 seconds at the latest, and more preferably in about 30 seconds at the latest.

The cantilever in the present invention preferably contains one or more selected from protein, DNA, pharmaceutical agent, nutrient, nutritional supplement, cosmetic material, color material, metal, metal oxide, and microcapsule. . Here, in the case of proteins, there are general proteins such as albumin, actin, and myosin, and pharmaceutical proteins for treatment, etc. In the case of DNA, there are cells that are not encapsulated! /, Pure DNA, etc. In the case of transdermal administration! /, An effective analgesic agent, insulin effective in treating diabetes, lidocaine as a local anesthetic, chlorhexine dalconate effective in periodontal disease, etc. There is a force that is not particularly limited. In the case of nutritional supplements, there are various sugars such as glucose and dextrin. In the case of nutritional supplements, vitamins such as vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, Casein has a calcium absorption promoting effect. In the case of cosmetics, moisturizer such as hyaluronic acid, anti-smudge agent such as α-arbutin, ascorbic acid phosphate phosphate, ellagic acid, and melanin pigment removal ability In the case of a color material, there are various natural pigments such as pigments for internal use, tartardin, cosmetic pigments, gardenia red pigments, gardenia yellow pigments, etc. In the case of metal oxides, there are titanium oxide, iron oxide, barium sulfate, etc. In the case of microcapsules, microcapsules containing various pharmaceutical agents, various nutrients, and various color materials are encapsulated. Force S with capsules, these are not particularly limited. FIG. 10 is a schematic diagram showing a state in which a normal cantilever 18 and a cantilever 19 having a constricted portion are inserted into the skin surface of a substrate-type microimplement containing a functional material. However, the direction force of the cantilever 19 having the constricted portion is easier to penetrate into the skin surface than the normal cantilever 18 because the resistance of the constricted portion is less. FIG. 11 is a schematic diagram showing the state after insertion of both cantilevers. However, before the cantilevers are dissolved in the skin, a cantilever having a constricted portion is naturally used. The cantilever remains deeper in the skin surface than when a normal cantilever is used, that is, the cantilever 21 remains deeper in the skin surface than the cantilever 20. Furthermore, after these cantilevers dissolve and disappear, the functional material diffuses and permeates, but the area is naturally proportional to the insertion position of the cantilever, and the diffusion permeation area 23 is more than the diffusion permeation area 22. There are two types of cantilevers according to the present invention, which have a structure in which a functional chip is mounted on the surface (see FIG. 7) and a structure in which a functional chip is mounted inside. In the case of the former, it is easy to mount the functional chip on one side that forms a horizontal plane at room temperature, and the thermal resistance of the functional chip is not so required for mounting at normal temperature. By covering the surface of the chip with maltose, maltose and pullulan complex sugar material, polyethylene, etc., there is a feature that the adhesion between the functional chip and the cantilever becomes strong. In the latter case, it is possible to reduce the insertion resistance of the force cantilever into the skin surface by enclosing the functional tip in the cantilever. Although the heat resistance of the functional chip is required, it is possible to take heat countermeasures by coating the surface of the functional chip with maltose, maltose and pullulan complex sugar material, polyethylene, etc. Since it is contained in the cantilever, it has a characteristic effect that it is less susceptible to physical damage. The functional chip in the present invention includes a semiconductor chip, an integrated circuit chip, a temperature sensor chip, a protein chip, a DNA-containing chip, a medicine-containing chip, a nutrient-containing chip, a nutritional supplement-containing chip, a cosmetic material-containing chip, and a color material-containing chip. A chip, a metal-containing chip, a microcapsule-containing chip, or one or more functional chips selected is preferable. Furthermore, the surface force of the functional chip is preferably coated with one material selected from maltose, maltose and pullulan complex sugar materials, polyethylene, polypropylene, and force. The base material of the above chip is not particularly limited, but from the viewpoint of the affinity of the base material used in the present invention, a saccharide is used as a base and it contains a pharmaceutical agent, a functional material and the like. As sugars that can be used, for example, maltose, anhydrous amorphous maltose, and complex sugar materials thereof with pullulan can be used. FIG. 8 is a schematic diagram showing a state in which a normal force cantilever 12 and a cantilever 13 having a constricted portion are inserted into the skin surface of a substrate-type microimplement. A cantilever 13 having a force constricted portion 13 is shown. 1S As the constriction-shaped part has less resistance, it is easier to penetrate the skin surface deeper than a normal cantilever 12. FIG. 9 is a schematic diagram showing the state after insertion of both cantilevers. Both cantilevers dissolve and disappear in the skin, and then leave their chips. Of these tips, when a cantilever having a constricted part is used, the tip remains naturally at a deeper position in the skin surface than when a normal cantilever is used. Also remains deep within the skin surface.

In the microimplement manufacturing method of the present invention, a micro mold head for a cantilever having a concave portion of a fine cantilever at the upper surface end in a micro cantilever manufacturing method is an anhydrous amorphous maltose or a composite of anhydrous amorphous maltose and pullulan. A fine mold for molding cantilevers as sugar materials, and a mold that can be used to mold fine cantilevers with a mechanism that can be finely driven to release cantilevers. A substrate mold having a concave portion with an inverted shape of the substrate is a substrate mold that can be formed into a substrate that can support a cantilever and can be incorporated into a micro mold head. FIG. 13 shows a schematic diagram of a cantilever mold head and a substrate mold. The temperature control mechanism of the micro-implement mold is a temperature control mechanism capable of rapidly heating and melting the above-mentioned base material formed by the micro-mold head and cooling and solidifying it. The micro-mold head for cantilever and the substrate The mechanism that can move the mold independently can prioritize the molding of the fine cantilever shape and drive only the micro mold head in advance. After the cantilever is released and molded, the substrate can be released by separate drive. This is the mechanism. As a result, the substrate type micro-implement can be manufactured. Furthermore, the mechanism that the micro mold head for cantilevers can move vertically with respect to the surface of the substrate sheet means that one or more cantilevers are provided perpendicularly to the surface of the substrate sheet. After forming, the method of moving to the formation of the next cantilever is a mechanism in which the micro mold head is once retracted in the direction perpendicular to the sheet and then moved to the position of the next cantilever. FIG. 14 shows a schematic diagram of a micro mold head and a substrate sheet. In the figure, a temperature control heater is used as the temperature control mechanism, and a drive stage is used as the movable mechanism. As a result, the substrate sheet type micro-implement can be manufactured. Although the temperature control mechanism in the present invention is not particularly limited, any temperature control mechanism can be used as long as it can control the temperature from 50 ° C. to about 200 ° C. and can maintain a constant temperature, for example. it can.

According to the method of the present invention described above, since the cantilever can be manufactured and assembled separately from the substrate or the substrate sheet, the tip can be sharp! /, The cantilever can be manufactured with high accuracy, and the shape of the sword mountain shape. It becomes possible to easily manufacture a micro implement having a large number of cantilevers within a certain area. Also, the material of the cantilever and the material of the substrate or the substrate sheet can be different.

In other words, if a material is poured into a mold in which the needle mold and the substrate mold are in communication like a micropile, and the fine needle and the substrate are integrally formed, the surface tension, the material at the time of molding will inevitably occur. The flow of (maltose, etc.) and other substrate manufacturing conditions affect needle manufacturing conditions that require high accuracy, and tend to degrade important needle tip accuracy. That is, the above In a conventional mold, the volume of the substrate is large, so there is a pressure limit for filling the material to the tip of the fine needle, and the manufacturing limit of the long width of the tip of the fine needle is 10 to 20 m. . In addition, the materials of the substrate and the fine needle are always the same, and even when a plurality of fine needles are provided, the drug that can be mixed with the fine needles is monolithic, which is limited to a single item. In this method, fine needles cannot be formed on the surface of the sheet-like base material, and a very large restriction is imposed on the shape of the microimplement.

On the other hand, according to the method of the present invention, it is possible to introduce an assembly method in which the substrate is manufactured in advance and only the cantilever-shaped microneedles can be manufactured later, which is different from the case where the substrate and the microneedles are integrally formed. The needle tip accuracy can be maintained without being affected by the substrate. This makes it possible to manufacture cantilevers with a fine tip of less than 10 m, and it is possible to accurately manufacture even cantilevers with a fine tip length of 2 to 3 m. For this reason, it was possible to reduce the pressure applied when the cantilever was inserted into the skin, and to achieve sufficient pain-freeness. Further, by providing a mechanism which is adapted to drive the mold cantilever as Heddode device enables ideal sword mountain shape fabrication as shown in FIG. 2, a high density of needle (cantilever such 1 cm ² per 100 or more Even a micro-implement with) can be manufactured. Furthermore, since the cantilever can be formed regardless of the shape of the substrate, it is possible to use a sheet-like substrate or the like that is only a plate-like substrate, and the degree of freedom of the shape of the micro-implement is increased. In addition, since the cantilever is assembled on the substrate, the base material and the fine needle material can be made different, and different cantilevers can be incorporated in each cantilever.

The sugar material part assembling method of the present invention comprises at least one of the two sugar material parts, S, pullulan, or a composite sugar material of pullulan and maltose. Force to contact and weld S is suitable. Further, the sugar material component composed of pullulan, or a composite sugar material of pullulan and manoletose is a substrate or a substrate sheet, and the other sugar material component is brought into contact with the upper end of the side surface of the substrate or the surface of the substrate sheet for welding. It is preferable to let this occur. Further, in the method of assembling the microimplement for insertion into the skin surface, the other sugar material component is a fine cantilever, and the soluble material in the skin of the cantilever is anhydrous amorphous maltose, or anhydrous amorphous maltose and pullulan. of A complex sugar material is preferred.

Hereinafter, the present invention will be specifically described with reference to examples. However, the present invention is not limited to the following examples.

Example 1

[0031] In manufacturing the substrate-type micro-implement having the shape shown in FIG. 1, first, the bottom surface has a diameter of 200 μm, and the perpendicular length from the apex to the bottom surface is 550 μm. On the vertical side of a stainless steel plate (vertical length: 15 mm, horizontal length: 5 mm, thickness: 1 mm) that produces a cantilever with a semi-conical split shape (the bottom is a semicircle with a diameter of 200 m) At the upper end, the four inverted concavities of the above-mentioned substantially conical cracked shape are dug by machining so that the shape of the fine tip of the cantilever is almost circular (diameter 0. S ^ m) Then, the innermost end of the digging portion was finely processed using a focused ion beam, and a mold head for a cantilever was produced. Next, based on a predetermined stainless steel plate for producing a rectangular parallelepiped substrate having a length of 10 mm, a width of 50 mm, and a thickness of 1 mm, a substrate mold having a concave portion having a reverse shape of the above-mentioned substrate is manufactured. A combination of cantilever mold head and substrate mold having the shape shown in Fig. 13 was produced. If you look directly at the substrate mold with the mold head removed, you will see a U-shape. Next, this U-shaped mold substrate was combined with the above-mentioned cantilever mold head to form a concave-shaped substrate mold. As the substrate material, a mixture of saccharide maltose and pullulan (50% by weight maltose and 50% by weight pullulan dissolved in 105 ° C) was used, and the above-mentioned mouth shape maintained at 105 ° C. The substrate raw material was poured into a substrate mold until the substrate had a thickness force of S lmm, and was slowly cooled to 80 ° C. to produce a substrate. Next, remove the mold head from the substrate mold and remove the mold head. Combine the cantilever mold head with the substrate mold including the substrate, and hold only the mold head at 105 ° C. An anhydrous amorphous maltose dissolved at 105 ° C was poured into the recess of the mold head to produce a cantilever, and then slowly cooled to room temperature to produce the microimplement shown in FIG. As described above, the length of the vertical line from the apex to the bottom is 550 m at the top of the side of the substrate, which is 10 mm long, 50 mm wide, and 1 mm thick, at the top of the side of the substrate, with a bottom diameter of 200 m. A cantilever with a roughly conical piece (its bottom is a semicircle with a diameter of 200 m), and its fine tip A cantilever force S having a substantially circular shape (diameter 0.3 m), and four substrate-type micro-implements arranged in the longitudinal direction of the substrate were assembled and manufactured. However, since FIG. 1 is a schematic diagram, the size of the cantilever and the substrate are not relatively matched. In this production, the force used by dissolving the substrate and the cantilever raw material at 105 ° C was put into the mold and die head held at 105 ° C in the above-mentioned state in the state of particles. It's okay. From the beginning, the cantilever mold head and substrate mold having the shape shown in FIG. 13 are used, and these are held at 105 ° C., and the raw material is poured into the cantilever mold and substrate. In this case, the cantilever and the substrate are made of the same material.

Example 2

To manufacture the substrate sheet type micro-implement with the shape shown in Fig. 2, first, 30% by weight of pullulan and 30% by weight of maltose were mixed together, and then 40% of water was added to create a viscous state. Furthermore, it is stretched into a sheet shape and dried. A substrate sheet of 10 mm in length, 10 mm in width, and 0.5 mm in thickness (with a composition ratio of 50% by weight of pullulan and 50% by weight of maltose, the substrate sheet is square when viewed from directly above. ) Was produced. Next, it is a rhombus that is a combination of two equilateral triangles with a bottom of 150 m on one side, and the vertical length from the apex to the bottom is 500 m. On the upper end along the vertical side of a stainless steel plate (vertical length 5 mm, horizontal length 5 mm, thickness lm m) for producing a cantilever with a regular triangle) Using a focused ion beam at the deepest end of the digging part, the shape of the cantilever tip is semicircular (0.4 m in diameter). Then, a cantilever mold head was fabricated. After attaching a predetermined temperature control mechanism and a movable mechanism to the mold head, the mold head held at 80 ° C was brought into contact with the substrate sheet surface, and anhydrous amorphous maltose dissolved at 105 ° C and A composite sugar material with pullulan (anhydrous amorphous 50% by weight, pullulan 50% by weight composition ratio) is poured into the mold head, and after forming the cantilever, the mold head is retracted in a direction perpendicular to the substrate sheet surface. Then, a cantilever was fabricated on the surface of the substrate sheet as shown in FIG. Next, the mold head is moved laterally at a pitch interval of 250 μm, and this mold head is placed on the substrate sheet surface. The mold head is moved forward and brought into contact, the above complex sugar material dissolved at 105 ° C is poured into the mold head, and after the cantilever is formed, the mold head is moved backward in a direction perpendicular to the substrate sheet surface, A second cantilever was fabricated on the substrate sheet surface. By repeating the above series of operations, the cantilever for a total of 30 on the surface of the substrate sheet with a total pitch of 5 and 6 with a pitch interval of 250 m (having the above-mentioned substantially quadrangular pyramid piece shape) A substrate sheet type micro-implement having the structure shown in Fig. 2 and a structure in which cantilevers were arranged was assembled and manufactured. However, since FIG. 2 is a schematic diagram, the size of the cantilever and the substrate sheet are not relatively matched. In this manufacturing example, the force S that required the above-mentioned repetitive operation 30 times using a die head for producing one cantilever was used, and six cantilevers for the die head in the vertical direction. When using an inversion-shaped concave part, it is only necessary to repeat the operation five times, and it is possible to produce a micro-implement very efficiently.

Example 3

[0033] When the substrate-type microimplement of Example 1 was inserted into the skin surface of the back of the hand, it was painless, and it was confirmed by observation with a microscope that the cantilever melted and disappeared in about 1 minute. Furthermore, when the surface of the skin was observed with a microscope, it was confirmed that four almost semicircular holes with a diameter of about 150 m were opened in the skin surface. When a finger was pressed near the hole, a small amount of blood came out of the hole, so it was possible to measure the blood glucose level by collecting a few mg of the blood.

Example 4

[0034] When the substrate sheet type microimplement of Example 2 was inserted into the skin surface of the back of the hand, it was confirmed that the cantilever melted and disappeared in about 1 minute by observation with a microscope. Furthermore, when the skin surface was observed with a microscope, it was confirmed that approximately ellipsoidal holes with a diameter of about 100 m were opened at 30 locations on the skin surface. After pressing these points with your finger and wiping the blood that has come out with absorbent cotton, applying an aqueous solution of sodium ascorbate phosphate 1% to the skin surface of those locations, the aqueous solution quickly spills into those holes. Was able to penetrate the aqueous solution into the skin surface. In this way, the cantilever The force used for opening this is because vitamin C, which is easily decomposed by heating, such as sodium ascorbate phosphate, cannot be included in cantilevers formed by overheating. As a result, vitamin C was able to penetrate into the skin more effectively.

Example 5

A substrate-type microimplement was produced in the same manner as in Example 1 using anhydrous amorphous maltose containing 1% by weight of lidocaine, which is a kind of local anesthetic, as a base material of the cantilever. This microimplement was inserted into the skin surface of the abdomen of the rat, and as a result of plasma analysis, it was found that lidocaine was present in the plasma, which confirmed the penetration of lidocaine into the whole body of the rat.

Example 6

[0036] Substrate-type microimplementation in the same manner as in Example 1, using non-aqueous amorphous maltose containing 0.03 wt% of chlorhexine dalconate having a healing effect on periodontal abscess as a base material of cantilever Two were produced. Insertion of these microimplements into the surface of the skin near the gums affected by periodontal disease and between the gums and the teeth results in insertion experiments. Periodontal leakage was improved after 24 hours.

Example 7

[0037] A substrate sheet type micro-implement was prepared in the same manner as in Example 2 using a composite sugar material with anhydrous amorphous maltose containing 0.3% by weight of α-arbutin as a whitening cosmetic material and pullulan as a base material. Produced. However, each of the 30 cantilevers has a constricted portion at a position 150 m from the fine tip, and the cantilever is easily broken at the constricted portion. This micro-implementation was conducted once a day in a series of experiments in which the skin surface with brown spots on the face (within 200 m from the skin surface) was inserted. It was confirmed by visual observation that the thickness was thin.

Example 8 [0038] The complex sugar material with whitening cosmetic material in which vitamin C kind Asukorubin magnesium phosphate 1wt ^_0/0 containing anhydrous amorphous maltose and pullulan as a substrate material, in the same manner as in Example 2, A substrate sheet type micro-implement was produced. However, each of the 30 cantilevers has a constricted portion at a position 150 inches from the fine tip, and the cantilever is easily broken at the constricted portion. As a result of conducting an experiment in which the microimpregnation was inserted into the skin surface (within 200 m from the skin surface) with brown spots on the face once a day, about one month passed as in Example 7. As a result, the brownish stain on the face faded and was confirmed.

Example 9

[0039] As a result of lightly applying the substrate sheet type microimplement of Example 2 to the skin surface of the back of the hand 5 times, it was confirmed by observation with a microscope that a large number of holes were opened on the skin surface. An aqueous solution containing 1% by weight of hydroquinone, a whitening effect agent having the ability to remove melanin pigment, is applied to these holes with a glass rod. Hydroquinone was able to penetrate into the stratum corneum by imprinting on the skin.

Example 10

[0040] As a result of lightly applying the substrate sheet type microimplement of Example 2 to the skin surface of the back of the hand five times, it was confirmed by observation with a microscope that a large number of holes were opened on the skin surface. At a place open these holes have a whitening effect, a relatively unstable chemicals aqueous solution containing 1 weight ^_0/0 Asukorubin magnesium phosphate is more applied to the glass rod, using a glass rod By imprinting the liquid onto the skin, ascorbic acid magnesium phosphate was able to penetrate into the stratum corneum as in Example 9. Example 11

[0041] Using anhydrous amorphous maltose containing 5% by weight of a mixture of titanium oxide and oxidative iron (1: 1 composition ratio), which is a skin-colored cosmetic material, as a base material, in the same manner as in Example 2, A substrate sheet type micro-implement was produced. However, each of the 30 cantilevers has a constricted portion at a position 150 m from the fine tip, and the cantilever is easily broken at the constricted portion. This micro-implement is brown on the face As a result of experiments conducted within the surface of the skin where there was a stain (within 200 m from the surface of the skin), it was confirmed by visual observation that the brown stain on the face had faded and the skin color was strengthened. Example 12

[0042] A substrate-type microimplement was produced in the same manner as in Example 1 using anhydrous amorphous maltose containing 5% by weight of a natural gardenia red pigment, which is a pigment specified in the body. However, each of the four cantilevers similarly has a constricted portion at a location 100 inches from the fine tip, and the cantilever is easily bent at the constricted portion. When this microimplement was inserted into the skin surface of the back of the hand, it was confirmed by visual observation that a pigment was left in the skin stratum corneum. By using this microimplement, simple and safe tattooing became possible. Arbitrary notation within the stratum corneum became possible.

Example 13

[0043] A substrate type microimplement was produced in the same manner as in Example 1 using anhydrous amorphous maltose containing 1% by weight of orange dye tartardin as a base material. After inserting the microimplement into the skin surface of the abdomen of the rat, the cross section of the skin was observed with a microscope, and it was confirmed that the tartardin dye penetrated deep into the skin.

Example 14

[0044] A substrate-type micro-implement was prepared in the same manner as in Example 1, using anhydrous amorphous maltose containing 1% by weight of Coomassie brilliant blue (CBB), a blue pigment with strong adhesiveness to proteins. did. After inserting this microimplement into the skin surface of the abdomen of the rat, the cross-section of the skin was observed with a microscope, and it was confirmed that the CBB color reflected the cross-sectional shape of the microcantilever insertion. .

Example 15

[0045] Albumin, which is a kind of protein, is contained in 3% by weight of a disk-shaped chip (diameter 50 m, thickness 5 111) of pullulan and anhydrous amorphous maltose (1: 1 composition ratio). Substrate type micro-implementation of Example 1 (however, three of the four cantilevers were removed A microchip with a functional chip mounted type was fabricated by bonding it at room temperature on the one side of the chip. When the microimplement was inserted into the skin surface of the back of the hand, as a result of microscopic observation and chemical analysis of the extracted corneocytes, albumin remained in the stratum corneum! .

Example 16

[0046] Insulin effective in treating diabetes is contained in 1% by weight of a disk-shaped chip (diameter 50 m, thickness 5 111) of pullulan and anhydrous amorphous maltose (1: 1 composition ratio). Was bonded to one side of the cracked surface of the substrate-type micro-implement in Example 1 (but three of the four cantilevers were removed) to produce a micro-implement with a functional chip. . When the micro-implement was inserted into the skin surface of the back of the hand, it was confirmed that the insulin remained in the stratum corneum as a result of observation with a microscope and chemical analysis of the extracted corneocytes.

Example 17

[0047] Carotenoid, a type of vitamin A, a nutritional supplement, is added to a disc-shaped chip (diameter 50 m, thickness 5 m) of pullulan and anhydrous amorphous maltose (1: 1 composition). The chip is bonded to one side of the cracked surface of the substrate type micro-implement in Example 1 (however, three of the four cantilevers are removed) at room temperature, so that the functional chip mounted type A micro-implement was made. When the microimplement was inserted into the skin surface of the back of the hand, observations using a microscope and chemical analysis of the extracted corneocytes confirmed that the carotenoid remained in the stratum corneum.

Example 18

[0048] Hyaluronic acid as a humectant is contained in 3% by weight of a disk-shaped chip (diameter 50 m, thickness 5 m) of pullulan and anhydrous amorphous maltose (1: 1 composition ratio). A microchip (with a functional chip mounted type) in which the above chip is mounted inside the cantilever in the same manner as in Example 1 except that it is inserted into one recess of the mold head for the cantilever in Example 1. And only one cantilever). When the micro supplement was inserted into the skin surface of the back of the hand, hyaluronic acid, which was decomposed by heating as a result of observation with a microscope and chemical analysis of the extracted corneocytes, was found. It was confirmed that it stayed in the stratum corneum and was able to administer hyaluronic acid easily into the skin surface.

Example 19

[0049] Design rule An IC chip with a built-in 2 μm fine magnetic coil circuit is split into a substrate-type micro-implement of Example 1 (however, three of the four cantilevers are removed! /) An IC chip-mounted micro-implement was fabricated by bonding it to the surface at room temperature. When the microimplement was inserted into the skin surface of the back of the hand, it was confirmed by observation with a microscope that the IC chip remained 50 m below the skin surface.

Example 20

[0050] Adhesive consisting of a composite sugar material (1: 1 composition ratio) of pullulan and anhydrous amorphous maltose on the back of a so-called IC tag, an IC chip with a side of 200 μm and a thickness of 10 μm Then, the back surface of the substrate-type microimplement of Example 1 was bonded to the one side of the substrate-type microimplement at room temperature to produce an IC tag-mounted microimplement. When the microimplement was inserted into the skin surface of the back of the hand, observation with a microscope confirmed that the IC chip remained in the stratum corneum 100 m below the skin surface.

Example 21

[0051] A micro silicon substrate temperature sensor chip with a side of 150 μm and a thickness of 10 μm was covered with polyethylene and the lead wire was left on the substrate type micro-implementation of Example 1 (however, 4 (3 out of the cantilevers were removed) were bonded at room temperature to a micro-implement with a micro silicon substrate temperature sensor chip. When the microimplement was inserted into the skin surface of the back of the hand, as a result of observation with a microscope, it was confirmed that it remained in the stratum corneum 50 m below the skin surface, and the lead wire was externally exposed. In addition, the signal could be extracted through the lead wire, so that the temperature inside the body could be measured accurately.

Example 22

[0052] Human IgG antibody, a disk-shaped chip of pullulan and anhydrous amorphous maltose (1: 1 composition ratio) 0.25% by weight in a diameter of 50 111 and a thickness of 5 111), and the chip is divided into parts of the substrate type micro-implement of Example 1 (however, three of the four cantilevers are removed) A human IgG antibody-containing micro-implement was fabricated by bonding it at room temperature. After conducting an in-vivo experiment in which the microimplement was administered to the skin of the abdomen of the rat, the cross-section of the rat skin was observed with a microscope, and the presence of human IgG in the rat skin was confirmed.

Example 23

[0053] The DNA portion is contained in a disk-shaped chip (diameter 50 111, thickness 5 m) of pullulan and anhydrous amorphous maltose (1: 1 composition ratio), and the chip is used as the substrate type of Example 1 A micro-implement with a DNA-containing chip mounted was fabricated by bonding the micro-implant (however, three of the four cantilevers were removed) to one side of the cracked surface at room temperature. When the microimplement was inserted into the skin surface of the back of the hand, it was confirmed by observation with a microscope that the DNA part remained in the stratum corneum!

Example 24

[0054] A substrate-type microimplement was produced in the same manner as in Example 1 using anhydrous amorphous maltose containing 2 wt% of iron particles having a diameter of 25 Hm or less as a base material of the cantilever. After inserting this micro-implement into the skin surface of the back of the hand, the high-sensitivity time sensor can count the iron particles in the skin surface, and the number correspondence can be taken. Application of this method suggests the possibility of convenient use for inpatient numbering.

Example 25

[0055] A micro-force psell (particle size: 1 μm) containing 1% by weight of lidocaine and the base material is anhydrous amorphous maltose, a disk of pullulan and anhydrous amorphous maltose (1: 1 composition ratio) A chip-shaped chip (diameter 50 m, thickness 5 111) containing 5% by weight, and the chip is a single-sided surface of the board-type micro-implement of Example 1 (however, three of the four cantilevers are removed) The microcapsule-mounted microimplement was fabricated by bonding it at room temperature. After the microimplement was inserted into the skin surface of the abdomen of the rat, the cross-section of the skin was observed with a microscope, and as a result, lidocaine was present on the skin surface. Was confirmed.

Industrial applicability

The skin surface microimplement and the method for producing the same of the present invention have the above-mentioned various characteristic effects. By these, the medical field, the field of nutrients and supplements, the field of beauty, the field of cosmetics, the field of application of various functional materials. It can be used in application fields of microcapsules and functional chips. In addition, since the sugar material parts assembling method can easily and efficiently assemble sugar material parts, it can be used in the application fields of various sugar material parts.

Claims

The scope of the claims

[1] A micro-implement having a structure in which one or more fine cantilevers made of a soluble material in the skin are provided at the upper end portion of the side surface of the substrate, and the cantilever has a substantially fractal shape of a cone, and the cantilever The length of the fine tip of the cantilever is 0.1 m to 100 μm, and the length from the tip to the end of the cantilever is 50 Hm to 5 mm. implement.

[2] In a micro-implement having a structure having one or more fine cantilevers made of a soluble material in the skin on the surface of the substrate sheet! /, The cantilever has a substantially conical half-divided shape, and the cantilever The length of the fine tip of the cantilever is 0.1 μm to 100 μm, and the length from the tip to the end of the cantilever is 50,1 m to 5 mm. Micro-implementation.

[3] The microimplement for insertion into the skin surface according to claim 1 or 2, wherein the cantilever has a constricted shape.

[4] The substrate according to any one of claims 1 to 3, wherein the base material of the substrate is one or more selected from sugar, cellulose, solid starch, paper, wood, plastic, metal, force. The micro-implement for insertion into the skin surface.

5. The microimplement for insertion into the skin surface according to claim 2 or 3, wherein the base material of the substrate sheet is pullulan or a complex sugar material of pullulan and maltose.

[6] The microimplement for insertion into the skin surface according to any one of [1] to [5], wherein the soluble material in the skin is anhydrous amorphous maltose.

[7] The microimplement for penetration into the skin surface according to any one of [1] to [5], wherein the soluble material in the skin is a complex sugar material of anhydrous amorphous maltose and pullulan.

[8] The cantilever contains one or more selected from proteins, DNA, pharmaceutical agents, nutrients, nutritional supplements, cosmetics, color materials, metals, metal oxides, microcapsules, and force. A micro-implement for insertion into the skin surface according to any one of claims 1 to 7.

[9] A structure in which a functional chip is mounted on the surface of the cantilever. The micro-implement for insertion into the skin surface according to any one of claims 1 to 8.

[10] The microimplement for insertion into the skin surface according to any one of [1] to [8], wherein a functional chip is mounted inside the cantilever.

[11] The functional chip is a semiconductor chip, an integrated circuit chip, a temperature sensor chip, a protein chip, a DNA-containing chip, a pharmaceutical agent-containing chip, a nutrient-containing chip, a nutritional supplement-containing chip, a cosmetic material-containing chip, The micro-implement for insertion into the skin surface according to claim 9 or 10, wherein the color material-containing chip, the metal-containing chip, the micro-capsule-containing chip, and the force are selected 1 or 2 or more.

12. The surface of the skin according to claim 11, wherein the surface of the functional chip is covered with a maltose, maltose and pullulan complex sugar material, polyethylene, polypropylene, and a material of which force is also selected. Input micro-implementation.

[13] A micro-implement mold comprising a cantilever micro mold head having an inverted concave portion of one or two or more fine cantilevers at an upper surface end, and a substrate mold having an inverted concave portion of the substrate. The micro-implement mold has a temperature control mechanism, and the micro-implement mold has a mechanism that allows the cantilever micro-mold head and the substrate mold to move independently. The method for producing a microimplement for insertion into the skin surface according to claim 1 or claim 3, wherein

[14] In a micro mold head for a cantilever having a reversal-shaped concave portion of one or more fine cantilevers at the upper end, the micro mold head has a temperature control mechanism and is on the surface of the substrate sheet. 4. The method for producing a mic mouth implement for insertion into the skin surface according to claim 2 or 3, wherein the micro die head having a mechanism capable of moving vertically is used.

[15] It is composed of at least one of two sugar material parts, S, pullulan, or a composite sugar material of pullulan and maltose, and the two sugar material parts are brought into contact with each other and welded together. The sugar material parts assembly method.

[16] The pullulan according to claim 15, or the sugar material component comprising a composite sugar material of pullulan and maltose is a substrate or a substrate sheet, and an upper end portion of the substrate side surface or the substrate sheet 4. A method for assembling a sugar material part, wherein the other sugar material part is brought into contact with and welded to the surface. 4. The method for assembling a microimplement for insertion into the skin surface according to claim 3, wherein the other sugar material part is charged. 17. The cantilever according to claim 3, wherein the soluble material in the skin of the cantilever is anhydrous amorphous maltose or a complex sugar material of anhydrous amorphous maltose and pullulan. Method.