JP2009220350A - Needle-like mold - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a means for forming a needle-like body having a fine projection precisely. <P>SOLUTION: A mold 31 for making the needle-like body has a base plate and a projection formed on the first surface of the base plate wherein the mold has a recess-projection inversed transfer pattern of the first surface of the needle-like body, and further has grooves 34a and 34b in at least the areas corresponding to the projection of the transfer pattern. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a mold for producing a fine needle-like body.

  In recent years, as a method for administering a physiologically active substance into a living body, a method of transdermal administration using a fine needle-like body has attracted attention. Penetration of the stratum corneum with high barrier properties using a needle-like body having a plurality of fine needles to form a passage route for the physiologically active substance, thereby allowing higher penetration of the physiologically active substance compared to general transdermal administration. Efficiency can be obtained. At this time, by designing the needle portion of the fine needle-like body so as not to penetrate the stratum corneum and reach the capillaries and nerves, it is possible to prevent bleeding and pain during use.

  When a fine needle-like body is used for the purpose of transdermal administration, the needle part of the needle-like body penetrates through the stratum corneum, which is thin enough to pierce the skin, and the tip corner, the outermost layer of the skin. It is desirable that the needle part has a length that does not reach the nerve layer. Specifically, the diameter of the needle part is about several μm to 100 μm, the tip of the needle part is sharp, and the angle is 30 degrees or less. The length of the needle part is preferably about several tens of μm to several hundreds of μm.

  The material constituting the needle-shaped body is preferably a material that does not adversely affect the human body even if the damaged needle part remains in the body, such as medical silicone resin, maltose, polylactic acid, Biocompatible materials such as dextran are considered promising (Patent Document 1).

  In addition, as a method for manufacturing the fine needle-like body described above, a manufacturing method has been proposed in which an original plate of a needle-like body is produced by X-ray lithography, a duplicate plate is made from the original plate, and transfer processing is performed (Patent Document). 2).

In addition, a manufacturing method has been proposed in which a needle-shaped original plate is manufactured by machining, a replica plate is formed from the original plate, and transfer processing is performed (Patent Document 3).
Japanese Patent Laid-Open No. 2005-21677 JP 2005-246595 A JP-T-2006-513811

  When a needle-like body having these fine protrusions is produced by a resin molding method such as a hot press method or an injection molding method, the transfer obtained by reversing the shape of the surface having the protrusions of the needle-like body Use the plate. The diameter of the protrusion is about several to 100 μm, the tip is sharp, the angle is 30 degrees or less, and the length is preferably about several tens to several hundreds of μm. It is required to form a fine shape with a high aspect ratio (ratio between the vertical direction and the horizontal direction of the structure) with high accuracy.

  However, it is not easy to accurately form the needle-like body having the fine needle portion by the resin molding method.

  Accordingly, an object of the present invention is to provide means for accurately forming a needle-like body having a fine protrusion.

Means for achieving the above object are as follows:
(1) A mold for producing a needle-like body having a substrate and a protrusion formed on the first surface of the substrate,
It has a transfer pattern in which the first surface of the needle-like body is inverted in irregularities,
Furthermore, a needle-shaped mold for producing a needle-like object, comprising a groove in a region corresponding to at least the protrusion of the transfer pattern:
(2) The groove for forming the needle-shaped body according to (1), wherein the groove is formed at least in a region corresponding to the tip of the protrusion.
(3) The mold for producing a needle-like body according to (1) and (2), wherein the groove has a width of 100 nm or less:
(4) The groove-shaped mold for producing a needle-like body according to any one of (1) and (2), wherein the groove has a width that does not allow a molding material to enter.
(5) The groove is continuous from the region corresponding to the protrusion to the outside of the region where the molding material comes into contact with the mold during molding of the needle-shaped body. ) The mold for producing needles according to any one of the following:
(6) A needle comprising obtaining a needle-like body by transferring a pattern of a mold to a molding material using the needle-shaped body-producing mold according to any one of (1) to (5) Manufacturing method of the body:
(7) A needle-shaped body produced by the production method according to (6):
It is.

  The needle-shaped mold of the present invention is characterized in that a fine groove is formed on the mold surface separately from the transfer pattern. According to the configuration of the present invention, it is possible to produce a resin needle having a desired shape with high accuracy and high productivity.

  Hereinafter, the needle-shaped body and the method for producing the needle-shaped body of the present invention will be described in detail based on the embodiments.

  FIG. 1 is a schematic view showing an example of an embodiment of the present invention. Fig.1 (a) is a top view of the needle | hook 1 for needle-shaped object production, FIG.1 (b) is sectional drawing which cut | disconnected Fig.1 (a) along line II, FIG.1 (c) is FIG. 2 is a cross-sectional view of a needle-like body 5 manufactured with a mold 1. FIG. As shown in FIGS. 1A to 1C, a needle-shaped mold for producing a needle-like body (hereinafter also referred to as “mold”) 1 according to the present invention has a protrusion 7 that functions as a needle for piercing the skin. Is a mold for producing the needle-like body 5 having the first surface of the substrate 6 (FIG. 1C), and has a transfer pattern in which the surface of the needle-like body 5 having the protrusions 7 is inverted. However, in addition to the transfer pattern, the projection pattern 3 which is at least a region corresponding to the projection 7 has a fine groove 4.

  In this embodiment, as shown in FIG. 1, the plurality of grooves 4 are arranged in parallel to one side constituting the first surface of the substrate 2 and through the center of the protrusion pattern 3.

  The groove 4 may be formed with a width that does not allow the molding material to enter. Therefore, when the needle-shaped body 5 is manufactured, if the molding material for the needle-shaped body 5 is applied to the mold 1 having such a structure, the air that has entered the protrusion pattern 3 of the mold 1 together with the molding material. Passes through the groove 4 and is discharged to the outside of the mold 1. Thereby, the molding material is sufficiently filled in the projection pattern at the time of resin molding, and it is possible to suppress the occurrence of resin filling defects in the needle-like body that is the obtained molded product, which is preferable. Moreover, since the groove | channel 4 is the width | variety into which a molding material does not enter, it does not need to be transcribe | transferred to the form of the acicular body 5 obtained by transcription | transfer.

  The groove formation pattern may be determined as desired. For example, the patterns described in FIGS. 2A and 2B may be used. FIGS. 2A and 2B are plan views for further explaining the groove according to the present invention. A mold 21 shown in FIG. 2A includes a plurality of protrusion patterns 23 on a substrate 22, and further passes through the center of the protrusion pattern 23 and forms one side of the first surface of the substrate 22. And a groove 24b perpendicular to the groove 24a. The mold 25 shown in FIG. 2B includes a plurality of protrusion patterns 27 on the substrate 26, and further passes through the center of the protrusion patterns 27 and is parallel to the diagonal line of the first surface of the substrate 26. Groove 28 is provided. The groove formation pattern is not limited to this, and may be determined as desired. For example, in addition to the groove 28 in FIG. 2B, a further groove that goes straight to the groove 28 and passes through the center of the protrusion pattern 27 may be provided.

  FIG. 3 (a) is a view showing a further embodiment of the mold of the present invention. The first surface of the mold 31 has a transfer pattern in which the uneven shape of the surface of the first surface having the protrusions of the desired needle-like body is inverted. The transfer pattern includes a flat portion 33 and a protrusion pattern 32 corresponding to the protrusion, and the first surface of the mold 31 includes a groove 34. The groove 34 a is parallel to one side constituting the first surface of the mold 31, passes through the wall surface and the tip portion 36 constituting the protrusion pattern 32, and is disposed completely across the plane portion 33. The mold 31 further includes a groove 34b that is orthogonal to the groove 34a on the first surface thereof. The groove 34a and the groove 34b intersect at an intersection point 35. Accordingly, when the molding material is applied to the mold 31 and the needle-like body is transferred and formed, the air that has entered the projection pattern 32 together with the molding material is not only from the end point of the groove 34a but also from the end point of the groove 34b. Can also escape efficiently to the outside. Therefore, the groove 34b is not directly introduced into the wall surface of the projection pattern 32, but functions as a diffusion path. The mold according to the present invention may be provided with such a diffusion path.

  FIG. 4 shows a further example of an embodiment of the invention. In this example, in the mold 41 having the protrusion pattern 42 on the first surface of the substrate 43, a groove 44 is further provided in a region corresponding to the protrusion of the transfer pattern, that is, on the wall surface of the protrusion pattern 42. . Thus, the metal mold | die according to this invention should just provide a groove | channel at the area | region corresponding to the projection part of a transfer pattern at least. Due to the presence of the groove 44, the air that has entered the protrusion pattern 42 of the mold 41 together with the molding material is taken into the groove 44, and the protrusion pattern 42 is sufficiently filled with the molding material during resin molding. It is possible to suppress the occurrence of defective resin filling in the needle-shaped body that is a molded product. The arrangement of the grooves is not limited to this, and a plurality of grooves may be provided. The groove 44 may or may not pass through the tip 45 of the protrusion pattern 42, but more preferably passes through the tip 45 of the protrusion pattern 42.

  According to the most preferable embodiment, the groove is formed in the mold so that the air inside the projection pattern flows out to the outside during resin molding. Therefore, it is preferable that the groove is continuous not only on the wall surface of the projection pattern, but also outside the region where the molding material contacts the mold during needle-shaped body molding.

  The example shown in FIGS. 1 and 2 shows a conical projection, and the example shown in FIGS. 3 and 4 shows a quadrangular pyramid. However, the shape of the projection is not limited to this. , Any cone or pyramid shape. That is, the bottom surface of the protrusion provided on the needle-shaped body manufactured by the mold according to the present invention may have an arbitrary shape such as a circle, an ellipse, or a rectangle. Further, the shape of the substrate of the needle-like body, the arrangement of the protrusions, and the number of protrusions per area of the first surface of the substrate are not limited to this, and may be designed as desired.

  5 (a) to 5 (c) are partial explanatory views for explaining a further embodiment of the present invention. With reference to FIGS. 5A to 5C, the positional relationship when the mold comes into contact with the molding material will be described. FIG. 5A is a schematic view of the mold according to the present invention as viewed from above the surface on which the transfer pattern is formed. FIGS. 5B and 5C are cross-sectional views taken along line II-II of FIG. 5A, and the positional relationship when forming a needle-like body on the molding material using the mold. FIG. As shown in FIG. 5A, the mold 51 includes a substrate 52, a protrusion pattern 53 formed on the first surface of the substrate 52, and the center of the protrusion pattern 53. A groove 54a parallel to one side of one surface and a groove 54b perpendicular to the groove 54a are provided. All the grooves 54 including the grooves 54 a and 54 b are arranged in the groove forming region 55 so as to cross the region 55.

  As shown in FIG. 5B, the molding material 58 is applied to the mold 51 so as to be located inside the region 55, for example, within the region 56, at the time of forming the needle-like body. Just do it. That is, the groove 54 may be formed continuously from the protrusion pattern 53 to the outside of the region 56. In such a structure, the groove 54 is continuous from the area corresponding to the needle-like protrusion of the mold 51, that is, from the protrusion pattern 53 to the outside of the area where the molding material 58 contacts the mold 51. Therefore, the air taken into the groove 54 is easily discharged to the outside, and a desired needle-like body is formed well.

  On the other hand, as shown in FIG. 5C, when the molding material 59 is disposed in a region outside the groove forming region 55, for example, the region 57, and the resin molding is performed, the groove 54 is a mold. Since it does not reach the outer peripheral portion of the molding material 59 in contact with 51, air may not be sufficiently discharged from the pattern provided in the mold 51, which may lead to molding defects. For this reason, it is preferable that the groove | channel of this invention is continuing to the outside of the area | region where the molding material which transfers a pattern contacts a metal mold | die at the time of needle-shaped object shaping | molding. FIG. 5 shows an example of the embodiment of the present invention. The shape and arrangement of the needle-like body pattern, the outer shape of the mold, the region where the groove is arranged, the region where the molding material is arranged, etc. It is not limited to the illustrated form.

  The groove produced in the mold according to the present invention is preferably formed with a minute width so that the molding material does not flow during resin molding. The optimum groove width varies depending on the type of the molding material, the fluidity of the molding material at the time of molding, the temperature, and the like, but in the case of a linear groove, the width is typically preferably 100 nm or less. . However, when the groove width is about 100 nm, traces of the groove may remain on the surface of the molded needle-like body, and therefore, preferably, the groove width of the mold is 60 nm or less. Although there is no restriction | limiting in particular about the depth of a groove | channel, in order to raise the effect of the air bleeding at the time of shaping | molding, the deeper one is preferable and it is preferable to make it at least equivalent to the width | variety of a groove | channel.

  The material of the mold according to the present invention is not particularly limited, and may be nickel, an aluminum alloy, a zinc alloy, or the like.

  Although there is no restriction | limiting in particular about the manufacturing method of the said metal mold | die, You may use a well-known manufacturing method suitably according to the shape of the acicular body to produce. For example, a mold having a desired pattern shape may be manufactured by a fine processing technique, or a mold having a needle-like body formed by a micro processing technique, and the shape is inverted from the original by transfer molding. May be formed.

  Here, as the fine processing technique, for example, a lithography method, a wet etching method, a dry etching method, a sand blast method, a laser processing method, a precision machining method, or the like may be used.

  There is no particular limitation on the method of forming the groove in the mold. For example, a mold in which a desired needle-like body shape is inverted is prepared, and fine grooves may be formed on the mold surface by a fine processing technique. Here, as a fine processing technique, for example, a focused ion beam method, a wet etching method, a dry etching method, a laser processing method, a precision machining method, or the like may be used.

  Further, a linear protrusion having a shape in which the fine groove of the mold is inverted is formed on the original plate having the protrusion pattern, and the mold having the fine groove is formed by performing transfer molding on the original plate. It may be produced. Examples of the microfabrication technique used in such a mold manufacturing method include a lithography method, a focused ion beam method, a sputtering method, a CVD method, a laser deposition method, and a precision machining method.

  You may design the shape of a projection part freely by a use. For example, for the purpose of promoting percutaneous absorption of a physiologically active substance or for the purpose of percutaneously extracting a substance in a living body to the outside of the living body, from the viewpoint of skin puncture performance, the tip of the protrusion has a sharp cone shape. The base width is several μm to several hundred μm, the length is about several tens μm to several hundred μm, and it is desirable that the side wall of the protrusion has no constriction or step.

  The molding material for forming the needle-like body according to the present invention may be a resin such as a polymer material, polycarbonate, polyethylene terephthalate and a biocompatible material. Moreover, it is preferable that at least the protrusion is formed of a material having biocompatibility. By using a material having biocompatibility, even if the needle-like body is damaged when applied to living body skin and a part of the needle-like body is left in the living body, the influence on the living body can be reduced. Examples of the material having biocompatibility have biocompatibility and biodegradability such as polylactic acid, polyglycolic acid, polylactic acid glycolic acid copolymer, polycitric acid, polymalic acid, polyamino acid, maltose, and dextran. Examples thereof include polymers.

  Moreover, you may perform a mold release process to a metal mold | die etc. in order to improve the mold release property of the metal mold | die and resin after shaping | molding. The mold release process may be any process known per se.

[Example]
Hereinafter, an example of the method for manufacturing the needle-shaped body of the present invention will be described with reference to FIG. Naturally, the manufacturing method of the needle-shaped body of the present invention is not limited to the following examples, and includes other manufacturing methods that can be analogized. Moreover, the metal mold | die and needle-shaped object of this invention are not limited to the needle-shaped object produced in the following Example.

<Preparation of the needle plate precursor>
First, a 4-inch silicon substrate having a thickness of 525 μm is processed using precision machining, and a regular quadrangular pyramidal protrusion 62 (height: height) is formed at the center of the substrate 61 as schematically shown in FIG. An acicular body original plate 64 having a projection array 63 in which 100 pieces of 150 μm, bottom surface: 60 μm × 60 μm) are arranged in a 10-column, 10-row lattice pattern at 1 mm intervals was produced. The 100 protrusions 62 were arranged in a square region having a side of about 9 mm.

<Formation of structure with inverted fine grooves>
Next, in order to form a groove of the mold on the surface of the first surface having the protrusion 62 of the needle-shaped body original plate 64, a fine protrusion pattern in which the groove was inverted was formed. That is, as shown in FIG. 6B, a negative electron beam resist 65 is formed to a thickness of about 100 nm by spray coating on the entire surface of the needle body original plate 64 on which the projections 62 are formed. It was applied as follows. Subsequently, only a desired region was scanned with the electron beam on the entire surface of the resist 65 using an electron beam drawing apparatus. Scanning with an electron beam was performed in a vertical and horizontal grid pattern with an electron beam having a width of about 60 nm, the grid spacing was 500 μm, and the intersection of the vertical and horizontal lines was positioned at the tip of the projection 62 of the needle-shaped original plate 64. . Next, the exposed resist 65 on the needle-shaped original plate 64 was developed to obtain a needle-shaped original plate 67 having a fine lattice pattern 66 as shown in FIG. The lattice pattern 66 was formed on the acicular body original plate 67 at a pitch of 500 μm. The obtained fine lattice pattern 66 was observed with an electron microscope, and it was confirmed that the width of the lattice pattern 66 was about 60 nm and the height of the lattice pattern 66 was about 100 nm. When such a lattice pattern 66 is concavo-convex transferred, grooves according to the present invention are formed.

<Production of mold having fine grooves>
Next, a nickel conductive layer having a thickness of 100 nm was formed on the acicular body original plate 67 having the fine lattice pattern by sputtering (not shown). This conductive layer becomes a seed layer in the subsequent electrolytic plating. Next, as shown in FIG. 6D, a nickel film 68 having a thickness of 500 μm was formed on the seed layer by electrolytic plating. Next, the acicular body original plate 67 made of silicon and resist is completely removed by wet etching with a 30% by weight potassium hydroxide aqueous solution heated to 90 ° C., as shown in FIG. A needle-shaped mold 71 made of nickel having a groove 69 and a projection array pattern 70 was produced. The obtained groove 69 was observed with an electron microscope, and it was confirmed that the groove width was about 60 nm and the groove depth was about 100 nm.

<Needle transfer molding>
Next, as shown in FIGS. 6 (f) and 6 (g), a polylactic acid is formed by a thermal imprint method using a sheet-like needle molding material 72 made of polylactic acid having a thickness of about 400 μm and the mold 71. The needle-like body transfer molding to was carried out. Next, the transfer-molded needle-shaped body molding material 73 is peeled off from the mold 71 and includes a substrate 76 and a protrusion 74 formed on the first surface of the substrate 76 shown in FIG. A needle-shaped body 77 made of polylactic acid having a projection array 75 was obtained. The needle-like body 77 has a square pyramid (height: 150 μm, bottom: 60 μm × 60 μm) projections 74 on a square substrate 76 having a side of about 18 mm in a 10-column, 10-row grid at 1 mm intervals. It was produced in a form in which 100 lines were arranged. The obtained needle-like body 77 was observed with an electron microscope, and it was confirmed that no defect due to poor resin filling occurred in all 100 protrusions 74. Also, it was confirmed by electron microscope observation that no transfer marks due to the fine grooves were observed.

[Comparative Example 1]
A mold having a fine groove having a width of about 160 nm and a depth of about 200 nm was produced in the same manner as in the example, and polylactic acid was transferred by thermal imprinting under the same conditions as in the example. . The obtained acicular body was observed with an electron microscope, and it was confirmed that there was no defective filling of the resin. On the other hand, it was confirmed that lattice-like projections were formed on the acicular body surface corresponding to the fine grooves. did. It was confirmed that the grid-like projections had a width of about 160 nm and a height of about 200 nm, and were projections corresponding to the fine grooves formed in the mold. Further, the lattice-like protrusions were formed so that the resin was partially extended.

[Comparative Example 2]
A mold without a groove was produced by the same method as in the example, and polylactic acid was transferred by thermal imprinting under the same conditions as in the example. The obtained needle-like body was observed with an electron microscope, and it was confirmed that defective resin filling occurred in almost all of the 100 protrusions.

The needle-shaped body of the present invention is not only a needle-shaped body for transdermal administration, but also medical, drug discovery, cosmetics, MEM.
It can be utilized as a fine needle-like body used in various fields such as S devices.

The figure which shows an example of embodiment of this invention. The figure which shows an example of embodiment of this invention. The figure which shows an example of embodiment of this invention. The figure which shows an example of embodiment of this invention. The figure which shows an example of embodiment of this invention. The figure which shows an example of this invention.

Explanation of symbols

1, 21, 25, 31, 41, 51, 71 ... Mold 2, 6, 22, 26, 43, 52, 61, 76 ... Substrate 3, 23, 27, 32, 42, 53 ... Projection Patterns 4, 24, 28, 34, 44, 54, 69 ... grooves 5, 77 ... needle-like bodies 7, 62, 74 ... projections 33 ... planes 35 ... intersections 36, 45 ... tips 55... Groove forming regions 56 and 57... Regions 58, 59, 72 and 73... Forming material 64... Needle needle plate 63 and 75. Acicular body original plate 68 having a lattice pattern ... Nickel film 70 ... Projection array pattern

Claims (7)

A mold for producing a needle-like body having a substrate and a protrusion formed on the first surface of the substrate,
It has a transfer pattern in which the first surface of the needle-like body is inverted in irregularities,
Furthermore, a groove for forming a needle-like body, comprising a groove in at least a region corresponding to the protrusion of the transfer pattern.   The said groove | channel is formed in the area | region corresponding to the said front-end | tip part at least, The needle-shaped object production metal mold | die of Claim 1 characterized by the above-mentioned.   The needle-shaped mold for manufacturing a needlelike object according to claim 1 or 2, wherein the groove has a width of 100 nm or less.   3. The mold for producing a needle-like body according to claim 1, wherein the groove has a width that does not allow a molding material to enter.   5. The method according to claim 1, wherein the groove is continuous from a region corresponding to the protrusion to an outside of a region where the molding material contacts the mold during molding of the needle-like body. 2. A mold for producing a needle-like body according to item 1.   A method for producing a needle-like body comprising obtaining a needle-like body by transferring a pattern of a mold onto a molding material using the needle-shaped body-producing mold according to any one of claims 1 to 5. .   A needle-shaped body produced by the manufacturing method according to claim 6.

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