WO2006075716A1

WO2006075716A1 - Drug delivery instrument and method of producing the same

Info

Publication number: WO2006075716A1
Application number: PCT/JP2006/300398
Authority: WO
Inventors: Koji Omichi; Kensuke Shima; Munehisa Fujimaki; Seiji Tokumoto; Hirotoshi Adachi
Original assignee: Fujikura Ltd.; Hisamitsu Pharmaceutical Co., Inc.
Priority date: 2005-01-14
Filing date: 2006-01-13
Publication date: 2006-07-20
Also published as: JPWO2006075716A1; JP5053645B2

Abstract

It is intended to provide a drug delivery instrument by which drug administration or blood extraction under sucking can be efficiently carried out. Namely, a drug delivery instrument characterized by consisting of a base and convexes which are provided at a first angle to the surface of the base and a second angle differing from the first angle and have a shape selected from the group consisting of roughly columnar, roughly conical and roughly spindle shapes. A method of producing a drug delivery instrument characterized by comprising the step of forming convexes which are provided at a first angle to the surface of the base and have a shape selected from the group consisting of roughly columnar, roughly conical and roughly spindle shapes and the step of forming an inclined plane in each of the convexes which has a second angle differing from the first angle as described above.

Description

Medicinal product carrying device and method for producing the same

Technical field

[0001] The present invention relates to a drug delivery device for use in a drug delivery system such as administration of a drug to a living body or aspiration extraction of blood from a living body, and is particularly painless and can be inserted under the skin. In addition, the present invention relates to a device for transporting a pharmaceutical product capable of providing a wide range of effective pharmaceutical products.

This application claims priority to Japanese Patent Application No. 2005-7327 filed on January 14, 2005, the contents of which are incorporated herein by reference.

Background art

[0002] In recent years, in order to suppress drug overdose and side effects, and to administer medical drugs more safely and effectively, “minimum necessary medicines can be placed where needed and when needed. Drug delivery systems (DDS) are actively researched with the mission of “supply”. And in this DDS, (1) so-called “sustained release of the drug” that releases the drug at a constant rate over a period of time, and (2) selectively transports the drug to the target affected area. It has two major goals for so-called “targeting”.

[0003] By the way, in order to achieve these target propositions and put them to practical use, it is difficult to improve the pharmaceuticals alone, and it is indispensable to develop transport equipment for carrying and transporting the pharmaceuticals.

For example, there is a technique, which is generically called a transdermal therapeutic system (TTS), which administers a skin force pharmaceutical product and realizes the expression of the pharmaceutical product in a part of the body or the whole body. Conventionally, pharmaceuticals that can be applied to TTS have been limited to those with high skin permeability, such as -troglycerin, isosorbide nitrate, and clozine. In recent years, however, there has been a growing demand for more effective absorption of the drug with high skin permeability into the body and application of drug with low skin permeability to TTS. Drug delivery devices have been proposed.

Non-Patent Document 1 describes that the surface of Si, which is the base, is dry-etched with a mixed gas of SF and O. Disclosed is a device for transporting a pharmaceutical product obtained by forming an array of needles having a height of about 100 m (which is described as “micro mouth-one dollar” in Non-Patent Document 1). ing. This Non-Patent Document 1 discloses puncturing the skin using this array of needle-like bodies, transporting a pharmaceutical product from the needle-like body and transporting it to the human body (see Non-Patent Document 1).

[0004] In addition, Patent Documents 1 to 3 disclose a technique for forming an array of needle-like bodies (in Patent Document 1, described as microneedles V). Furthermore, in Patent Document 1, a through-hole passage penetrating from the back surface of the base portion to the surface is formed at the center of the needle-shaped body to form a hollow needle-shaped body (described as a hollow microneedle in Patent Document 1). Is disclosed. Non-Patent Document 1: DV McAllister et al, "MICRO FABRICATED MICRONEEDLES: AN OVEL APPROACH TO TRANSDERMALDRUG DELIVERY", Proceed. Int'l. Symp. Control. Rel. Bioact. Mater., 25 ( 1998) Controlled Release Society. Inc.

Patent Document 1: Pamphlet of International Publication No. 99Z64580

Patent Document 2: Pamphlet of International Publication No. 00Z05166

Patent Document 3: Patent No. 3696513

Disclosure of the invention

Problems to be solved by the invention

[0005] However, the structure of the arrayed needle-like body disclosed in Non-Patent Document 1 that actually transports a pharmaceutical product has been clarified.

In addition, the hollow needle-like bodies disclosed in Patent Documents 1 to 3 disclose means for transporting pharmaceuticals and blood through the through-holes, but the present technology has a small opening diameter (in the examples) The diameter is limited to 15 m). Since ordinary medicines and blood have a very high viscosity, there is a problem that they do not flow in a through-hole having such a small opening diameter. Increasing the opening diameter (for example, 50 m in diameter) can be easily performed with this technology, but in this technology, it means that the tip diameter of the needle-like body also increases, making it impossible to puncture the skin. End up. In these conventional technologies, there are two further problems in reducing the needle tip diameter. That is, the mechanical strength of the needle-like body is weak because the thickness of the needle-like portion is limited, and the allowable range of the position accuracy of the through hole is reduced due to the limitation of the thickness, and the yield is reduced. Mari is a very bad point.

[0006] The present invention has been made in view of the above circumstances, and "controlled release of a pharmaceutical product" in which a pharmaceutical product is regulated and released at a constant rate over a certain period of time, and the pharmaceutical product is selectively transported to the affected area. The purpose of the present invention is to provide a drug delivery device that can perform drug administration or blood suction extraction efficiently, while being able to be `` targeted for pharmaceutical products '' and being able to be inserted under the skin without pain. To do.

Means for solving the problem

[0007] In order to achieve the above object, the present invention provides a substantially columnar shape, a substantially cylindrical shape, a base portion, a first angle with respect to the surface thereof, and a second angle different from the first angle. There is provided a device for transporting a pharmaceutical product characterized by having a convex portion having a shape selected from the group consisting of a frustum shape and a substantially frustum shape.

[0008] Further, the present invention includes a base and a convex portion having a shape selected from the group consisting of a substantially columnar shape, a substantially frustum shape, and a substantially frustum shape standing at a first angle with respect to the surface thereof. And a convex portion having an inclined surface having a second angle different from the first angle.

[0009] In the drug delivery device of the present invention, the second angle is preferably smaller than the first angle.

The first angle is preferably 70 degrees to 90 degrees, and the second angle is preferably 50 degrees to 80 degrees.

In the drug delivery device of the present invention, it is preferable that a through-hole that penetrates from the back of the base to the tip of the convex is formed.

The opening area of the through hole is preferably ² ^{× 10_3} mm ² or more. In the drug delivery device of the present invention, it is preferable that the convex part and the base part are made of a silicon material! /.

[0010] Further, the present invention includes a step of forming a convex portion having a shape selected from the group consisting of a substantially columnar shape, a substantially frustum shape, and a substantially frustum-like shape standing at a first angle with respect to the surface of the base portion. And a step of forming an inclined surface having a second angle different from the first angle on the convex portion. [0011] Further, the present invention provides a step of forming an opening serving as a through hole path penetrating from the rear surface of the base portion to the tip of the convex portion, and standing on the surface of the substrate at a first angle with respect to the surface. Forming a convex portion having a shape selected from the group consisting of a substantially columnar shape, a substantially frustum shape, and a substantially conical shape, and the convex portion having a second angle different from the first angle. And a step of forming an inclined surface. A method for producing a drug delivery device is provided.

[0012] In the manufacturing method of the present invention, the step of forming the inclined surface having the second angle is preferably performed by selectively irradiating the base material surface with ionized gas.

[0013] In the drug delivery device of the present invention, the convex portion and the base portion are preferably made of a polylactic acid material among the thermoplastic polymers which may be made of a thermoplastic polymer.

[0014] In the present invention, a mold having pores for forming a convex portion and a base material are disposed to face each other, and at least one of the mold and the base material is heated and then applied to the base material. There is provided a method for producing a pharmaceutical product transporting device, characterized by comprising a step of applying pressure to transfer the shape of a mold to a substrate and a step of cooling to release the substrate.

The invention's effect

[0015] The drug delivery device of the present invention is a substantially columnar, substantially frustum that is erected with a base, a first angle with respect to the surface thereof, and a second angle different from the first angle. And a convex portion having a shape selected from the group consisting of substantially conical shapes, the tip of the convex portion can be sharply formed, and the puncture property to the skin can be improved.

In addition, a through-hole having a large opening diameter can be formed on the convex portion having a shape selected from the group consisting of a substantially columnar shape, a substantially frustum shape, and a substantially frustum shape without impairing the puncture property to the skin. Can effectively carry medicines into the body. In addition, the types of pharmaceutical products that can be applied also increase. Furthermore, the puncture property can be maintained regardless of the thickness of the convex portion formed at this time.

In addition, since the convex portion having a shape selected from the group consisting of a substantially columnar shape, a substantially frustum shape, and a substantially conical shape is formed with an inclined surface having a second angle, the thickness of the bottom bottom portion of the convex portion Increases the mechanical strength.

Brief Description of Drawings

FIG. 1A is a plan view of an array of painless needles according to a first embodiment of the present invention.

FIG. 1B is a cross-sectional view taken along the line A-B in FIG. 1A. 1C is an enlarged perspective view of the convex portion of FIG. 1A.

FIG. 2 is a diagram showing each part a to e and angles 0 1, 0 2 of the array of painless needles of the first embodiment.

FIG. 3 is a cross-sectional view sequentially illustrating manufacturing steps of the array of painless needles of the first embodiment.

4 is a configuration diagram showing an example of a dry etching apparatus used in step C in FIG. 3.

FIG. 5A is a plan view of an array of painless needles according to a second embodiment of the present invention.

FIG. 5B is a cross-sectional view taken along the line A-B in FIG. 5A.

FIG. 5C is an enlarged perspective view of the convex portion of FIG. 5A.

FIG. 6 is a diagram showing each part f˜; j and angles 0 1, 0 2 of the arrayed painless needle of the second embodiment.

FIG. 7 is a cross-sectional view sequentially showing manufacturing steps of the array of painless needles of the second embodiment.

FIG. 8 is a configuration diagram showing an example of a focused ion beam etching apparatus used in FIG. 7.

FIG. 9A is a plan view of an array of painless needles according to a third embodiment of the present invention.

FIG. 9B is a cross-sectional view taken along the line A-B in FIG. 9A.

FIG. 9C is an enlarged perspective view of the convex portion of FIG. 9A.

FIG. 10 is a diagram showing each part k to p and angles 0 1 and 0 2 of the arrayed painless needle of the third embodiment.

FIG. 11 is a cross-sectional view sequentially showing manufacturing steps of the array of painless needles of the third embodiment.

FIG. 12A is a cross-sectional view sequentially illustrating manufacturing steps of the array of painless needles of the fourth embodiment.

FIG. 12B is a cross-sectional view sequentially illustrating manufacturing steps of the array of painless needles of the fourth embodiment.

[FIG. 12C] FIG. 12C is a cross-sectional view sequentially illustrating manufacturing steps of the arrayed painless needle of the fourth embodiment.

Explanation of symbols

[0017] 1, 12, 19, 32 ··· Arrayed painless needles (medicine delivery devices), 2, 13, 20, 33… Base, 3, 14, 21, 34 ··· Convex, 3A, 14A, 21A, 34Α ··· Inclined surface, 22 ··· through hole, θ 1 ··· first angle, 0 2 ··· second angle.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described with reference to the drawings. However, the present invention is not limited to the following examples. For example, the components of these examples are appropriately combined. You may combine them.

1A to 1C are views showing a first embodiment of the present invention, in which FIG. 1A is a plan view, FIG. 1B is a cross-sectional view between A and B in FIG. 1A, and FIG. 1C is an enlarged perspective view of a convex portion in FIG. FIG. In the present embodiment, an array of painless needles is illustrated as an example of the drug delivery device of the present invention. 1A to 1C, reference numeral 1 denotes an array of painless needles, 2 denotes a base material, 3 denotes a convex portion, and 3A denotes an inclined surface.

In the present embodiment, the array of painless needles 1 has a base 2 and a first angle θ 1 with respect to the surface thereof and a second angle Θ 2 different from the first angle θ 1. It has a configuration having a protruding portion 3 having a substantially conical shape standing upright. In this example, the first angle θ 1 is substantially perpendicular to the surface of the base 2, and a second angle Θ 2 different from θ 1 is appropriately set on a part of the convex portion 3 so that the inclined surface 3A By forming this, the tip of the convex part 3 is sharply formed.

[0020] In this array of painless needles 1, the dimensions a to e of each part in Fig. 2 can be set within the following range, for example. In FIG. 2, (a) is a cross-sectional view of the main part of the array of painless needles 1, and (b) is a perspective view of the convex part 3.

, Base thickness &: 200-1000 111.

• Convex height b: 50-500 μm.

'Projection pitch. : 30-1000 1! 1 (sneak, c> d).

-Convex bottom 1: φ20-100 πι.

'Convex top 6: () 3 111 or less.

In the present invention, the size of the device is limited in particular, and the size can be changed in any way by the initial design and the manufacturing process thereof.

In the example of the convex portion 3 shown in FIG. 2 (b), the first angle θ 1 is about 90 degrees and the second angle Θ 2 is about 70 degrees. Is merely an example, and the present invention is not limited to this example. In the present invention, it is preferable that these angles θ 1 and θ 2 have a relationship of first angle θ 1> second angle θ 2. Further, the first angle θ 1 is 70 degrees to More preferably, it is in the range of 90 degrees, and the second angle Θ 2 is 50 degrees to 80 degrees.

FIG. 3 is a cross-sectional view showing an example of a method for manufacturing the array of painless needles 1 in the order of steps. As shown in FIG. 3, the array of painless needles 1 includes a step B of forming a substantially columnar convex portion 8 erected at a first angle Θ 1 with respect to the surface of the Si base material 4; On the convex part 8, the first Forming a tilted surface 3 mm having a second angle Θ 2 different from the angle θ 1 and covering the convex portion 3 having a sharp tip as shown in FIG. ing.

Further, in step (b), a Si substrate is prepared, (b) a Cr layer is formed on the surface, and (c) a photoresist is formed on the Cr layer by a photolithography technique to form a convex pattern. (D) The Cr layer is wet-etched using this photoresist as a mask to form a Cr pattern, and (e) a substantially columnar protrusion is formed using the Cr pattern as a mask. An example of manufacturing the array-shaped painless needle 1 of the first embodiment according to FIGS. 3 (a) to 3 (f) is described in detail in the following Manufacturing Example 1. This Manufacturing Example 1 is merely an example, and the present invention It is not intended to limit this.

In the examples of the following embodiments, the base material indicates a material for forming the convex portion and the base portion, and the definition is different from the base portion that is one constituent portion of the drug delivery device.

[0023] (Production Example 1)

FIG. 3 (a) shows a 1000 m thick single crystal silicon (Si) wafer (hereinafter referred to as Si substrate 4) used as a substrate in Production Example 1 and mirror-polished on one side. Hereinafter, the mirror-polished surface is referred to as the surface.

FIG. 3 (b) shows the formation of a Cr layer 5 serving as an etching mask on the surface of the Si substrate 4. A Cr layer 5 of about 1 μm is formed on the surface of the Si substrate 4 by sputtering.

[0025] Fig. 3 (c) shows the formation of a photoresist pattern on the convex portion. By one photolithography technique, a negative pattern of the convex portion on the surface of the Si substrate 4, that is, a photoresist on the convex portion. 6 is left and a pattern is formed by removing the non-convex photoresist. In Production Example 1, the diameter of the photoresist 6 was set to 50 μm.

FIG. 3 (d) shows the formation of a Cr pattern, and the Cr layer 5 disposed under the photoresist 6 is etched using the photoresist 6 formed in the step (c) as a mask. Cr pattern 7 is formed. Etching of Cr was performed by wet etching using an aqueous solution mainly composed of ceric nitrate and perchloric acid.

[0027] Fig. 3 (e) shows the formation of the convex portion, and the substantially patterned columnar convex portion 8 is formed on the surface of the Si base 4 using the Cr pattern 7 formed in the step (d) as a mask. To do. The convex portion 8 is formed by a dry etching process. Si substrate 4 with Cr pattern 7 formed on dry etching equipment Installed in the chamber, evacuated, then mixed SF and O as etching gas

Etching was performed using 6 2 gas.

Considering that the Si etching rate is about 6 μmZmin, the etching time was set to 25 minutes. As a result, a convex part 8 with an etching depth (convex part height) of about 150 m could be formed. Even after etching at about 150 / zm, the Cr layer as a mask had a thickness of 0.7 / zm or more. The etching rate ratio (selection ratio) between Si and _Cr is 500: 1 or more.

Note that the shape of the convex portion 8 can be changed to a substantially cylindrical force to a substantially conical shape depending on the etching conditions at this time (for example, the process pressure, the flow rate of the etching gas, and the amount of electric power applied to the high frequency). In Production Example 1, the convex portion 8 was formed in a substantially cylindrical shape having a diameter of 50 m. Finally, Cr pattern 7 remaining on the Si surface was removed by wet etching using an aqueous solution mainly composed of ceric nitrate and perchloric acid.

Fig. 3 (f) shows the completion of the tool (arrayed painless needle 1) from the convex processing, and this (f) convex processing step is performed by ionizing Si substrate 4 with convex 8 formed. The etching was performed by placing the film at an arbitrary angle with respect to the gas flow and performing dry etching. FIG. 4 is a configuration diagram showing an outline of the dry etching apparatus. In FIG. 4, reference numeral 9 is a chamber of the dry etching apparatus, 10 is a high-frequency power source, and 11 is a jig for tilting at an arbitrary angle. This chamber 9 is connected to an evacuation system, and the inside can be evacuated. The chamber 9 is provided with an Ar gas supply pipe through which argon (Ar) gas, which is an ion gas source, flows between the electrodes. As shown in FIG. 4, the Si base material 4 on which the convex portions 8 are formed is disposed at an arbitrary angle with respect to the electrodes in the chamber 19 of the dry etching apparatus. The jig 11 for tilting the Si substrate 4 at an arbitrary angle may be any one as long as it is made of a conductive material such as aluminum (A1).

A Si base material 4 having a substantially cylindrical convex portion 8 formed thereon was placed on the jig 11, the chamber 9 was evacuated, and etching was performed using Ar gas as an etching gas.

Since Ar ions are chemically inert, they are etched only with physical energy when Ar ions collide with the surface of the Si substrate 4. Since Ar ions are incident perpendicularly to the electrodes, one surface of the convex portion can be selectively etched by tilting the Si base 4. [0029] Through the above steps, with respect to the surface of the base 2, a first angle θ 1 (for example, about 90 degrees) and a smaller second angle Θ 2 (for example, about 70 degrees) An array of painless needles 1 having a substantially cone-shaped convex part 3 standing up can be formed.

[0030] The array of painless needles 1 of the present embodiment has a substantially conical shape erected with a base 2 and a first angle θ 1 and a smaller second angle Θ 2 relative to the surface thereof. Therefore, by appropriately setting the first angle Θ and the second angle Θ2, the tip of the convex portion 3 can be sharply formed, and the puncture property to the skin is improved. be able to.

FIGS. 5A to 5C are views showing a second embodiment of the present invention, FIG. 5A is a plan view, FIG. 5B is a cross-sectional view between A and B in FIG. 5A, and FIG. 5C is a convex portion of FIG. FIG. In the present embodiment, an array of painless needles is illustrated as an example of the drug delivery device of the present invention. 5A to 5C, reference numeral 12 denotes an array of painless needles, 13 denotes a base, 14 denotes a convex portion, and 14A denotes an inclined surface.

[0032] In the present embodiment, the array of painless needles 12 includes a base portion 13 and a group of substantially columnar, substantially frustum, and substantially conical shapes that are erected with a first angle Θ1 with respect to the surface thereof. And a convex portion 14 having a selected shape, and an inclined surface 14A having a second angle Θ 2 different from the first angle θ 1 is formed on the convex portion.

In this array of painless needles 12, the dimensions f˜; j of each part in FIG. 6 can be set within the following range, for example. In FIG. 6, (a) is a cross-sectional view of the main part of the array of painless needles 12, and (b) is a perspective view of the convex part 14.

• Base thickness f: 200-1000 μm.

• Convex height g: 50-500 μm.

'Protrusion formation pitch 11: 30 to 1000 111 (weighing, h> j).

'Bottom bottom of convex part i: φ20-100 πι.

'Upper base of convex part j: φ 3 / ζ πι or less.

In the example of the convex portion 14 shown in FIG. 6 (b), the first angle θ 1 is about 90 degrees and the second angle Θ 2 is about 70 degrees. Is merely an example, and the present invention is not limited to this example. In the present invention, these angles θ 1 and Θ 2 are defined as the first angle Θ 1> the first The first angle θ 1 is preferably in the range of 70 degrees to 90 degrees, and the second angle Θ 2 is in the range of 50 degrees to 80 degrees. Is more preferable.

FIG. 7 is a cross-sectional view showing an example of a method for manufacturing the array of painless needles 12 in the order of steps.

An example of manufacturing the array of painless needles 12 of the second embodiment according to FIG. 7 is described in detail in the following Manufacturing Example 2. This Manufacturing Example 2 is merely an example and is intended to limit the present invention. There is no. Note that the description of the same parts as those in Production Example 1 is omitted.

[0036] (Production Example 2)

FIG. 7 (a) shows the process of forming a substantially cylindrical convex portion 8 on the surface of the Si substrate 4, and the convex portion 8 is formed in the same manner as in the steps of FIGS. 3 (a) to (e). The details can be omitted. 3A to 3E, which are the same as in the case of Manufacturing Example 1, the substantially cylindrical convex portion 8 erected with the first angle θ 1 with respect to the surface of the Si base 4 is formed. It is formed.

[0037] FIG. 7 (b) shows the completion of the convex part processing force instrument (array-shaped painless needle 12), and this process is performed by a focused ion beam (FIB) etching apparatus schematically shown in FIG. To do. In the etching apparatus of FIG. 8, an XYZ (three-dimensional) precision stage 16 is provided in a chamber 15 that can be evacuated, and the Si substrate 4 is tilted at an arbitrary angle on the XYZ precision stage 16. A jig 17 for placement is provided. Further, an ion gun shutter 18 is provided at a Ga ion introduction part connected to the chamber 19 so that the introduction part can be opened and closed. As shown in FIG. 8, a Si substrate 4 having a substantially cylindrical convex portion 8 is disposed in a chamber 115 of a FIB etching apparatus provided with an ion gun and an XYZ precision stage 16. At this time, the Si substrate 4 is tilted at an arbitrary angle with respect to the ion gun using the jig 11. This jig 11 can be made of any material as long as it is made of a conductive material such as A1! /. Next, the ion ion microscope (Scanning Ion Microscope: SIM) and XYZ precision stage 16 provided in the device are moved so that the part (projection tip) where you want to selectively irradiate ions comes to a predetermined position. Irradiate gallium (Ga) ions from a gun.

Since Ga ions are chemically inert, etching is performed only with physical energy when Ga ions collide with the tip of the convex portion. Since Ga ions are incident parallel to the ion gun, the tip of the convex portion can be selectively etched by tilting the Si base 4. Thereafter, the movement by the XYZ precision stage 16 and the FIB selective etching are repeated. By etching the tips of all the convex portions 8, an inclined surface 14A having a second angle Θ 2 smaller than the first angle θ 1 is formed at the tips of the substantially cylindrical convex portions 8, and the tips are An array of painless needles 12 having pointed projections 14 are produced.

[0038] The array of painless needles 12 according to the second embodiment has a second column that is smaller than the first angle θ1 and has a substantially columnar convex portion 14 erected on the base at a first angle θ1. Since the inclined surface 14A with an angle Θ2 is formed, it is possible to form a needle-like part with a thick bottom bottom part that does not impair the ability to puncture the skin, thus improving the mechanical strength of the instrument. Can be made.

FIGS. 9A to 9C are views showing a third embodiment of the present invention, FIG. 9A is a plan view, FIG. 9B is a cross-sectional view between A and B in FIG. 9A, and FIG. 9C is a convex portion of FIG. FIG. In the present embodiment, an array of painless needles is illustrated as an example of the drug delivery device of the present invention. 9A to 9C, reference numeral 19 denotes an array of painless needles, 20 denotes a base, 21 denotes a convex portion, 21A denotes an inclined surface, and 22 denotes a through hole.

In the present embodiment, the array of painless needles 19 stands with a base 20 and a first angle θ 1 and a second angle Θ 2 different from the first angle θ 1 with respect to the surface thereof. The projection has a substantially cone-shaped projection 21 and a through-hole path 22 penetrating from the back surface of the base 20 to the tip of the projection 21. This through-hole path 22 is used for the purpose of supplying a medicine from the back surface of the base 20 and transporting the medicine into the living body or taking out body fluid such as blood aspirated and extracted from the living body from the back surface of the base 20. be able to.

In this array of painless needles 19, the dimensions k to p of each part in FIG. 10 can be set within the following range, for example. In FIG. 10, (a) is a cross-sectional view of the main part of the array of painless needles 19, and (b) is a perspective view of the convex part 21.

• Base thickness k: 200-1000 μm.

'Convex height 1: 50-500 111.

'Protrusion formation pitch 111: 30 to 1000 111 (denoted, m> n).

'Lower bottom of convex part η: φ 50 ~: ί00 πι.

• Through hole diameter ο: φ 50-80 μm. -Top of convex part: 0 3 1! 1 or less.

Further, in the example of the convex portion 21 shown in FIG. 10 (b), the first angle θ 1 is about 90 degrees and the second angle Θ 2 is about 70 degrees. Is merely an example, and the present invention is not limited to this example. In the present invention, it is preferable that these angles θ 1 and Θ 2 have the relationship of first angle Θ 1> second angle Θ 2. Further, the first angle θ 1 is 70 degrees to More preferably, it is in the range of 90 degrees, and the second angle Θ 2 is 50 degrees to 80 degrees.

Further, the opening area of the through-hole path 22 is preferably ² ^{× 10_3} mm ² or more. If the opening area of the through-hole path 22 is 2 ^{× 10_3} mm ² or more, it is possible to efficiently administer a pharmaceutical product or perform blood suction extraction through the through-hole path 22.

FIG. 11 is a cross-sectional view showing an example of a method for manufacturing the array of painless needles 19 in the order of steps. An example of manufacturing the arrayed painless needle 19 of the third embodiment according to FIG. 11 will be described in detail in the following Manufacturing Example 3. This Manufacturing Example 3 is merely an example and is intended to limit the present invention. Absent. Note that the description of the same parts as those in Production Example 1 is omitted.

[0044] (Production Example 3)

The method of manufacturing the arrayed painless needles 19 having the through-hole paths 22 is selected from the group of the step A for forming the opening portions 24 to be the through-hole paths 22, the substantially columnar shape, the substantially frustum shape, and the substantially conical shape. Forming a convex portion 25 and then forming the opening 24 as a through-hole path 22 and a step C forming an inclined surface 21A having a second angle on one surface of the convex portion 25. .

[0045] FIG. 11 (a) is a Si wafer having a thickness of 500 m (hereinafter referred to as Si base material 23) having both surfaces mirror-polished for use as a base material in Production Example 3. Hereinafter, both sides of the Si base material 23 are distinguished as a surface A and a surface B.

FIG. 11 (b) shows the formation of the opening 24 that becomes the through-hole path 22, and this formation of the opening 24 is performed using the photolithography technique and the dry etching process described in Production Example 1. Using this, the opening 24 to be the through-hole path 22 is formed on the surface B of the Si base material 23 (see Step B in FIG. 3). O The etching technique for forming this opening 24 is the Bocsh process. Alternately known etching gas (e.g. SF) and deposition gas (e.g. CF) Therefore, a process in which plasma is generated and an etching process and a deposition process are repeated is preferable. At this time, the Cr mask described in Process B of Production Example 1 is not necessary, and the opening 24 can be formed using the resist as a mask.

Through the above steps, openings 24 having an opening diameter of 50 μm, a depth of 470 μm, and a pitch of 500 μm were formed on the Si surface B.

[0047] FIG. 11 (c) shows the formation of the convex portion, and after passing through the same process as Process B of Production Example 1 described above, Table A of Si base material 23 [this diameter is 80 μm, Protrusions with a height of 150 μm and a pitch of 500 μm were formed. At this time, the 基材 and Β double-sided patterns of the Si base material 23 were aligned at the same time of photolithography, and the center of the opening 24 and the center of the convex part 25 were aligned.

[0048] FIG. 11 (d) shows the formation of the through-hole path 22. After removing the Cr mask, the A surface of the Si base material 23 is etched again by a dry etching process, thereby opening the opening. The portion 24 becomes a through-hole path 22 penetrating from the back surface of the base material to the tip of the convex portion.

[0049] FIG. 11 (e) shows the completion of the tool (array-shaped painless needle 19) from the convex processing, and the back surface of the base 20 is obtained by performing the same process as in Step C of Production Example 1 described above. An array-shaped hollow painless needle 19 having a through-hole path 22 penetrating to the tip of the convex portion 21 is obtained. Of course, the array of hollow painless needles 19 can also be obtained by using the step C ′ described in Production Example 2 described above.

[0050] In the array of hollow painless needles 19 produced through the above steps, the tip of the convex portion 21 can be sharpened even if the diameter of the through-hole path 22 is increased (that is, the opening area is increased). Therefore, the fluidity of the pharmaceutical product is high and the through-hole path can be formed while maintaining the puncture property to the skin.

The opening area of the through-hole passage 22 that can sufficiently secure the fluidity of the drug is usually about 2 X 10 ^_3 mm ^{2 although} it depends on the viscosity of the drug product. For roads, a diameter of about 50 μm is sufficient.

Further, even if the diameter of the convex portion 21 is increased with respect to the diameter of the through-hole path 22, the puncture property to the skin does not change, so that the thickness of the hollow convex portion 21 can be increased, and the mechanical strength is increased. improves. In addition, it is not possible to accurately align the center of the opening 24 and the center of the convex portion 25 by aligning the 基材 and Α double-sided patterns of the Si substrate 23 at the same time of photolithography, and the yield is high. In the present invention, the diameter of the convex portion 21 is set to be different from the diameter of the through-hole path 22 in the present invention. Since it can be increased, the tolerance of positional accuracy is increased and the yield is improved.

[0051] FIGS. 12A to 12C are cross-sectional views showing an example of a method for producing an array of painless needles made of a thermoplastic polymer material according to the fourth embodiment of the present invention in the order of steps.

As shown in FIGS. 12A to 12C, in the array of painless needles, a mold having pores for forming convex portions and a thermoplastic polymer base material that becomes the array of painless needles are arranged to face each other ( Fig. 12A) Heats at least one of the mold and the thermoplastic polymer substrate, holds the thermoplastic polymer substrate under pressure (Fig. 12B), cools after molding, then cools the thermoplastic polymer substrate This is done by the process of releasing the material (Figure 12C).

[0052] A mold having pores for forming convex portions used for molding is produced by the following method.

That is, the pharmaceutical product transportation device exemplified in Production Example 1 is a master type, and then the surface of the master type is made conductive by sputtering a metal such as Ni, and then the shape of the master type is formed by Ni electroplating. Transcript.

[0053] After the transfer, by selectively removing the master mold, a mold having pores for forming convex portions can be produced.

[0054] An example of producing an array of painless needles composed of the thermoplastic polymer material according to the fourth embodiment according to Figs. 12A to 12C will be described in detail in Production Example 4 below. Is merely an example and is not intended to limit the present invention.

[Production Example 4]

FIG. 12A shows a Ni electroplating mold 30 having pores for forming convex portions used as molds in Production Example 4 and a plate-shaped polylactic acid having a thickness of 1000 m (hereinafter referred to as polylactic acid substrate 31). is there. Note that the array-shaped painless needle 1 exemplified in Production Example 1 was used as the master mold used for the manufacture of the Ni electric mold 30.

FIG. 12B shows a process of transferring the shape of the Ni electroplating mold 30 to the polylactic acid substrate 31. After heating the Ni electroplating mold 30 and the polylactic acid substrate 31 to 100 ° C., the polylactic acid substrate 31 is pressed from above the Ni electromolding mold 30 with a pressure of about lOMPa. By holding for 10 minutes in the pressed state, the shape of the Ni electroplating mold 30 is transferred to the polylactic acid substrate 31 almost accurately.

FIG. 12C shows a process of releasing the polylactic acid base material. After cooling the Ni electric mold 30 and the polylactic acid substrate to 50 ° C, the polylactic acid substrate is released. [0058] Through the above steps, an array of painless needles 32 made of a polylactic acid material can be formed. Although not described in detail, this array-shaped painless needle is substantially the same shape as the shape of the array-shaped painless needle 1, which is a master type. And base 3 3.

[0059] The substrate used in this production example may be basically any thermoplastic polymer, but polylactic acid is non-toxic to living organisms and is bioabsorbable. For example, even if the convex portion 34 of the array of painless needles 32 is broken and remains in the body, it is preferable because it is decomposed in the body.

[0060] Each of the above-described embodiments is merely an example of the present invention, and the present invention is not limited to these embodiments, and various modifications can be made.

For example, the shape of the convex portion is not limited to the examples of the above-described embodiments, and any shape may be used as long as the shape and size can be punctured without pain on the skin or the like. Other examples of the shape of the convex portion include a substantially cylindrical shape, a substantially truncated cone shape, a substantially prismatic shape (triangular pyramid, quadrangular pyramid, etc.), a substantially truncated pyramid shape, and a substantially truncated pyramid shape. These can be changed in any way depending on the convex pattern of temporary photolithography and dry etching conditions when forming the convex.

Further, the through hole formed in the array of hollow painless needles is not limited to a circular shape, and may have a square shape (triangle, square, etc.). This can also be changed in any manner by the opening pattern of temporary photolithography.

Claims

The scope of the claims

[1] A group consisting of a substantially columnar shape, a substantially frustum shape, and a substantially conical shape standing upright with a base, a first angle with respect to the surface, and a second angle different from the first angle And a convex part having a shape selected from the above.

[2] having a base and a convex portion having a shape selected from the group consisting of a substantially columnar shape, a substantially frustum shape, and a substantially frustum shape standing at a first angle with respect to the surface thereof. An instrument for transporting a pharmaceutical product, characterized in that an inclined surface having a second angle different from the first angle is formed in the part.

[3] The drug delivery device according to claim 1 or 2, wherein the second angle is smaller than the first angle.

[4] The drug delivery according to any one of claims 1 to 3, wherein the first angle is 70 degrees to 90 degrees, and the second angle is 50 degrees to 80 degrees. Instruments.

[5] The drug delivery device according to any one of claims 1 to 4, wherein a through-hole passage penetrating from the back surface of the base portion to the tip of the convex portion is formed.

[6] The device for transporting a pharmaceutical product according to [5], wherein an opening area of the through hole is 2 ^{× 10_3} mm ² or more.

[7] The instrument for transporting a pharmaceutical product according to any one of [1] to [6], wherein the base and the convex are made of a silicon material.

[8] A step of forming a convex portion having a shape selected from the group consisting of a substantially columnar shape, a substantially frustum shape, and a substantially frustum shape standing at a first angle with respect to the surface of the base portion; The method for producing a drug delivery device according to claim 1, further comprising: forming an inclined surface having a second angle different from the first angle.

[9] A step of forming an opening serving as a through-hole path penetrating from the rear surface of the base portion to the tip of the convex portion, and a substantially columnar shape substantially extending upright at a first angle with respect to the surface of the base portion A step of forming a convex portion having a shape selected from the group consisting of a truncated cone shape and a substantially conical shape, and a step of forming an inclined surface having a second angle different from the first angle on the convex portion. The method for producing a pharmaceutical product transporting device according to claim 5, characterized by comprising:

[10] The drug delivery according to claim 8 or 9, wherein the step of forming the inclined surface having the second angle is performed by selectively irradiating a gas ionized on the convex portion. A method for manufacturing appliances.

[11] The device for transporting a pharmaceutical product according to any one of [1] to [6], wherein the base portion and the convex portion are made of a thermoplastic polymer material.

12. The drug delivery device according to claim 11, wherein the base part and the convex part are made of a polylactic acid material.

[13] A mold having pores for forming the convex portions and a base material are arranged to face each other, and at least one of the mold and the base material is heated, and pressure is applied to the base material. The method for producing a drug delivery device according to claim 11 or 12, comprising: a step of transferring the shape of the mold to the base material; and a step of cooling and releasing the base material. Method.