JP2022133864A - Manufacturing method for microneedle array and microneedle array - Google Patents

Abstract

To simplify a manufacturing step of a through hole in a microneedle array.SOLUTION: A manufacturing method for a microneedle array has: a tip of pins formation step which forms a plurality of tips of pins that are minute projections projecting from the surface as a microneedle array; a back hole formation step which has back holes that do not go through to the surface at an opposite position facing the tips of pins on a rear surface opposite the surface; and a through hole formation step which forms a through hole going through from the surface to the back hole by laser ablation using laser beam.SELECTED DRAWING: Figure 2

Description

INDUSTRIAL APPLICABILITY The present invention is suitable for application to, for example, capsules with needles for medical or cosmetic use and percutaneous administration applicators for medical use using microneedles.

BACKGROUND ART In recent years, microneedles using polymer compounds such as bioabsorbable polymers have been widely known for cosmetic purposes (see, for example, Patent Document 1). This microneedle has a configuration in which the needle itself holds a drug, and is expected to be used mainly for cosmetic purposes.

On the other hand, since microneedles are almost painless, highly safe, and can reduce the burden on patients, hollow-type microneedles with through holes for the purpose of transdermal administration have attracted attention. As a method for forming through holes in the microneedles, a method using laser ablation using laser light has been proposed (see, for example, Patent Document 2).

Patent No. 5495034 JP 2011-072695 A

However, laser ablation requires heating until the molecules sublime, and it takes time to form the through-holes, which complicates the manufacturing process.

The present invention was made to solve such problems, and an object thereof is to provide a method for manufacturing a microneedle array and a microneedle array that can simplify the manufacturing process.

In order to solve such a problem, in the method for producing a microneedle array of the present invention, a needle ridge forming step of forming a plurality of needle ridges, which are micro-sized protrusions protruding from the surface, as a microneedle array;
a back hole forming step that has a back hole that does not penetrate to the front surface at a position facing the needle thread on the back surface opposite to the front surface;
and a through-hole forming step of forming a through-hole penetrating from the surface to the back hole by laser ablation using a laser beam.

In the microneedle array of the present invention, a microneedle array having a plurality of needle ridges, which are micro-sized protrusions protruding from the surface, as a microneedle array,
a back hole that does not penetrate to the front surface at a position facing the needle thread on the back surface opposite to the front surface;
a through hole penetrating from the surface to the back hole and having a smaller cross-sectional area than the back hole.

INDUSTRIAL APPLICATION This invention can implement|achieve the manufacturing method and microneedle array of a microneedle array which can simplify a manufacturing process.

1 is a flow chart for explaining a method for manufacturing a microneedle array of the present invention. It is the schematic where it uses for description of the manufacturing method of the microneedle sheet in 1st Embodiment. It is the schematic where it uses for description of the manufacturing method of the microneedle sheet in 2nd Embodiment. FIG. 10 is a schematic diagram for explaining the configuration (1) of the microneedle sheet in the third embodiment; FIG. 11 is a schematic diagram for explaining the configuration (2) of the microneedle sheet in the third embodiment; It is the schematic where it uses for description of the manufacturing method of the microneedle sheet in other embodiment.

<Overview of the present invention>
As shown in FIG. 1, in the method of manufacturing a microneedle array of the present invention, needle ridges (microprotrusions) are formed on the front surface in step S11, and back holes are formed on the back surface in step S12. These steps S11 and S12 may be executed at the same time or may be separate processes. Further, step S11 may be executed after step S12.

Finally, in step S13, laser ablation using a laser beam forms a through hole penetrating from the tip of the needle thread or the vicinity of the tip (the center of the through hole is within 30% of the height of the needle thread from the tip) to the back hole. It is formed. Laser ablation may be performed from either the tip side or the back hole side of the pincushion. In step S13, the length of the through hole to be formed can be reduced by the length of the back hole formed in step S12, and the process can be shortened.

In the present invention, the method of forming the microneedle array is not limited. For example, needle ridges and back holes are integrally formed by injection molding using a mold, or needle ridges are formed by an optical vortex laser having a helical phase. The back hole may be formed in a separate process from the pincushion by shaving or stamping (pressing using a mold after heating). After forming the back hole in advance, the needle thread may be formed. Further, through-holes may be formed in all of the needle ridges, or may be formed in only some of the needle ridges.

Materials for the microneedle array are not limited, and known inorganic/organic materials can be used as appropriate. For example, natural or artificial polymer materials, bioabsorbable inorganic materials mainly composed of minerals such as calcium, and the like are used. In particular, bioabsorbable polymeric materials such as hyaluronic acid, polylactic acid, polyglycolic acid, and collagen, which are highly safe for the human body, are preferably used. This is because even if the needle thread 2 is broken and remains in the body, it is naturally absorbed into the body and is harmless to the human body.

In the microneedle array, the height from the root of the needle (the surface position of the base surface where no unevenness is formed) to the tip is about 100 to 990 μm, and the diameter at the root is about 100 to 500 μm. Although the size of the through-hole is not limited, it is preferable that the diameter is about 10 to 60 μm (about 1/20 to 1/5 of the diameter of the pincushion) in order to prevent clogging and maintain the strength of the pincushion.

Although the shape of the needle thread is not limited, it is preferably tapered from the root side to the tip side. The shape and size of the back hole are not limited, and can be appropriately changed according to the method and material for forming the back hole.

The microneedle array has a liquid storage space for storing liquids such as medicines and cosmetics on the back side. It is envisioned that the drug will be applied to the surface of the human body. The shape and configuration of this liquid storage space are not particularly limited, and various configurations are applicable.

<First Embodiment>
BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments for carrying out the present invention will be described with reference to the drawings.

As used herein, the term "microneedle array" means a region in which microprojections are formed in a component having a plurality of microprojections (microneedles), and there is no limit to the number or shape of the microprojections.

In the present embodiment, a method for manufacturing a sheet-like component (microneedle sheet) having three needle threads and one through hole will be described. The present invention can also be applied to forming microneedle arrays on parts having various shapes.

As shown in FIG. 2A, the first mold 11 has a needle thread recess 11A corresponding to the needle thread 14 and a substrate recess 11B corresponding to the substrate portion 15. As shown in FIG. The second mold 12 includes a back hole base convex portion 12A and a back hole tip convex portion 12B (back hole convex portion) corresponding to the back hole base portion 16A and the back hole tip portion 16B of the back hole 16, respectively, and a base material portion. 15 and a substrate recessed portion 12C corresponding to the recessed portion 12C.

The back hole protrusions are provided corresponding to only some of the needle thread recesses 11A (one in the figure), and the center of the pinion thread recesses 11A and the back hole protrusions extending in the opposite direction (vertical direction on the page). Axes are the same.

As shown in FIG. 2B, the first mold 11 and the second mold 12 are set, and after the resin material is injected into the formed space, the resin is cooled and solidified. As a result, a microneedle sheet 13 is formed as shown in FIG. 2(C).

The surface 15A of the microneedle sheet 13 is formed with a plurality of needle threads 14 protruding from the base material portion 15 and a back hole 16 opening from the back surface. The back hole 16 is formed corresponding to the needle thread 14 in which the through hole 17 is to be formed, and the back hole 16 is not formed in the back surface corresponding to the pin thread 14 in which the through hole 17 is not formed. A back hole 16 is formed at a position facing the pinion 14 , that is, at a position overlapping the pinion 14 in the axial direction of the pinion 14 . The position of the back hole 16 facing the pincushion 14 means that the central axis of the back hole 16 is located within the range of the pincushion 14 in the axial direction of the pincushion 14 .

A through hole 17 is formed from the tip 14A of the needle thread 14 toward the back hole tip 16B by laser ablation using a laser beam. Here, if the back hole 16 is not formed, it is necessary to form the through hole 17 by the sum of the thickness T1 of the base portion 15 + the height T2 of the needle thread 14. The length of the through-hole 17 is (thickness T1 of the base portion 15 + height T2 of the needle ridge 14 - depth T3 of the back hole 16), and the distance to form the through-hole 17 is the depth T3 of the back hole 16. can be reduced.

Here, as shown in FIGS. 2(C) and (D), the back hole 16 has a back hole base portion 16A having a truncated cone shape and a back hole leading end portion 16B having a cylindrical shape from the back surface 13B side. there is The tip (smallest diameter) portion of the back hole base portion 16A and the diameter of the back hole tip portion 16B are the same. The diameter D2 of the back hole tip portion 16B is smaller than the diameter D1 of the base of the needle thread 14 and larger than the diameter of the through hole 17. As shown in FIG. The base (thickest diameter) portion of the back hole base portion 16A is formed to be larger than the diameter D1 of the root.

As a result, the back hole leading end portion 16B is arranged only at the portion where the pincushion 14 is present, so that the depth T3 of the back hole 16 can be maximized and the reduction in strength caused by the back hole 16 can be suppressed. In addition, the peelability of injection molding can be improved as compared with the case where the back hole 16 is simply formed in a cylindrical shape. Furthermore, the shape of the back hole base portion 16A can enhance the visibility of the needle thread 14 in which the through-hole 17 is formed or will be formed in the future, which can be utilized in the manufacturing process and quality control.

For example, the thickness T1 of the base portion 15 = 0.5 mm, the height T2 of the needle thread 14 = 0.2 mm, the depth T3 of the back hole 16 = 0.37 mm, the diameter D1 of the root of the needle thread 14 = 0.3 mm, The diameter D2 of the tip portion 16B of the back hole is 0.15 mm, the diameter D3 of the bottom side of the base portion 16A of the back hole is 0.55 mm, and the diameter of the through hole 17 is 0.03 mm. Also, the center axis of the back hole 16 is positioned on the extension line of the through hole 17 .

<Second Embodiment>
Next, a second embodiment will be described with reference to FIG. In addition, in the second embodiment, the reference numerals corresponding to those in the first embodiment are added by 10, and the description of the same parts is omitted.

As shown in FIG. 3A, the microneedle sheet 23 is formed with needle ridges 24 that protrude from the surface 25A of the base material portion 25 .

As shown in FIG. 3B, a back hole 26 is formed from the rear surface 25B of the base member 25 by cutting using a drill DS such that the needle thread 24 and the central axis are aligned with each other.

As shown in FIG. 3C, through holes 27 are formed by laser ablation using laser light LS.

As shown in FIG. 3(D), a through hole 27 is formed at a position offset from the center axis of the needle thread 24 . The center axis of the back hole 26 coincides with the extension line of the through hole 27, and although the center axes of the pincushion 24 and the back hole 26 are deviated, the pincushion 24 and the back hole 26 are aligned in the axial direction of the pincushion 24. , and the back hole 26 is positioned opposite the needle thread 24 .

For example, the thickness T1 of the base portion 25 = 0.6 mm, the height T2 of the needle thread 24 = 0.8 mm, the depth T3 of the back hole 26 = 0.4 mm, the diameter D1 of the root of the needle thread 24 = 0.2 mm, The diameter D2 of the back hole 26 is 0.1 mm, and the diameter of the through hole 27 is 0.05 mm. Also, the central axis of the back hole 26 is positioned on the extension line of the through hole 27 .

<Operation and effect>
Hereinafter, the features of the group of inventions extracted from the above-described embodiments will be described while presenting problems, effects, and the like as necessary. In the following description, for ease of understanding, configurations corresponding to the above-described embodiments are appropriately shown in parentheses or the like, but are not limited to the specific configurations shown in parentheses or the like. Also, the meanings and examples of terms described in each feature may be applied as the meanings and examples of terms described in other features described with the same wording.

In the above configuration, in the method of manufacturing a microneedle array of the present invention, a plurality of needle ridges (pink ridges 14), which are micro-sized protrusions protruding from the surface (surface 15A), are formed as a microneedle array (microneedle sheet 13). a pincushion forming step (step S11);
a back hole forming step (step S12) having a back hole (back hole 16) that does not penetrate to the front surface at a position facing the pincushion on the back surface (back surface 15B) opposite to the front surface;
and a through-hole forming step (step S13) of forming a through-hole (through-hole 17) penetrating from the surface to the back hole by laser ablation using a laser beam.

As a result, the distance for forming the through-holes can be shortened, so the time required for the through-hole forming step can be shortened, and the manufacturing process can be simplified.

In the method for manufacturing a microneedle array, the needle thread forming step and the through hole forming step are performed simultaneously by injection molding.

As a result, the needle thread and the back hole can be formed at the same time, so the manufacturing process can be simplified.

In the method for manufacturing a microneedle array, the cross-sectional area of the back holes is larger than the cross-sectional area of the through holes. The cross-sectional area of the back holes means the average value of the cross-sectional areas of the back holes.

As a result, even if the through-hole is slightly displaced in the planar direction of the substrate, the through-hole can be reliably connected to the back hole. In addition, since the visibility from the back side (existence of through-holes) can be enhanced, the subsequent manufacturing process and quality control can be simplified.

In the method for manufacturing a microneedle array, the back hole has, on the front surface side, a planar portion (surface at the tip of the tip portion 16B of the back hole) that is larger than the cross-sectional area of the through hole.

As a result, even if the through holes are slightly displaced in the planar direction of the substrate, the back holes and the through holes can be connected by forming the through holes with the same distance.

In the method for manufacturing a microneedle array, at least a part of the back hole has a columnar shape with a constant cross-sectional area (back hole tip portion 16B).

As a result, by arranging the pillar-shaped portion particularly at or near the tip portion (a position within 1/10 of the thickness of the base material from the tip of the back hole), a thin back hole portion can be formed, and the microneedle The intensity of the entire array can be maintained.

In the method for manufacturing a microneedle array, the back hole is characterized in that it has a diverging shape (back hole base portion 16A) in which the cross-sectional area increases toward the back surface.

As a result, the cross-sectional area of the back hole in the vicinity of the rear entrance can be increased, so that the formation of the back hole can be facilitated. In particular, when the injection molding method is used, the peelability can be improved.

In the method for manufacturing a microneedle array, the back hole has a tapered portion that tapers from the back surface to the front surface and a pillar portion whose cross-sectional area does not change, and the surface side of the tapered portion and the back surface side of the pillar portion. are connected in the same shape.

As a result, the strength of the base material of the microneedle array can be ensured, and the visibility of the back holes and the through holes from the back surface can be enhanced by enlarging the opening. Moreover, when injection molding is performed, the releasability can be improved, and the elongated projecting portion of the mold can be shortened, so that the durability of the mold can be improved.

A microneedle array having a plurality of needle ridges that are micro-sized protrusions protruding from the surface, and a back hole that does not penetrate to the surface at a position opposite to the needle ridge on the back surface opposite to the surface, and a back hole that does not penetrate to the surface A microneedle array, comprising a through-hole that penetrates to the back hole and has a smaller cross-sectional area than the back hole.

As a result, the length of the through-hole, which is the thinnest portion, can be shortened, so that the risk of liquid clogging or clogging of the through-hole can be minimized. In addition, since the visibility of the through-holes from the rear surface can be enhanced, the manufacturing process can be simplified in the subsequent manufacturing process and quality control.

<Third Embodiment>
Next, a third embodiment will be described with reference to FIGS. 4 and 5. FIG. In addition, in the third embodiment, reference numerals obtained by adding 20 are assigned to portions corresponding to those in the first embodiment, and descriptions of the same portions are omitted.

The microneedle sheet 33 of the present invention is a microneedle sheet on which a plurality of micro-sized needle ridges projecting from the surface are formed, and the needle ridges are through-hole needle ridges formed with through-holes penetrating from the front side to the back side. (through pincushion 33) and a dummy pincushion (dummy pincushion 39) in which the through hole is not formed. As a result, the microneedle sheet can improve the ease of pricking by the effect of pulling the skin of the dummy pinion.

As shown in FIG. 4, the microneedle sheet 33 has, as needle ridges, a through needle ridge 34 having a through hole 37 and a dummy needle ridge 39 having no through hole. The microneedle sheet 33 is a circular sheet with an overall diameter R3 of 6 mm, and has four penetrating needle ridges 34 and eight dummy needle ridges 39 formed on the surface 35A.

The four through needle ridges 34 and the four dummy pin ridges 39 are arranged alternately and at regular intervals (45°) such that the centers of the through needle ridges 34 and the four dummy pin ridges 39 are positioned on a circle RG1 having a diameter R1 of 2 mm. , are arranged concentrically. The remaining four dummy pinholes 39 are arranged at equal intervals (90°) on a circle RG2 having a diameter R2 of the through pinhole 34 of 3.4 mm. It is located in a straight line. Therefore, the penetrating pincushion 34 is surrounded by the three dummy pincushions 39 .

5A shows a cross-sectional view taken along line XX' in FIG. 4, and FIG. 5B shows an enlarged view of a portion (indicated by a dashed line) in FIG. 5A. Although the description is omitted, in this embodiment as well, the through holes 37 are formed by laser light after the microneedle sheet 33 having the back holes 36 is formed by injection molding.

The microneedle sheet 33 has an edge step 35C with rounded corners, and a back hole 36C having a diameter R4 of 4 mm from the back surface 35B. A hole tip portion 36A and a through hole 37 are formed. The back hole pedestal 36 has a shape that tapers in a curved line as it goes to the tip, for example, R is set to 0.2 mm, and is smoothly connected to the cylindrical back hole tip 36A. . The tip of the back hole tip portion 36A is at the same position as the surface 35A of the microneedle sheet 33 . The tip surface of the back hole tip portion 36A is formed to have a diameter of 110 μm, for example.

The diameter D1 and the diameter D5 of the root portions of the penetrating needle thread 34 and the dummy needle thread 39 are the same, 300 μm, and the tips 34A and 39A are formed flat. The tip of the dummy pinion 39 is thinner than that of the through pincushion 34, that is, the through pinion 34 and the dummy pinion 39 are formed to have the same height but different tip diameters.

For example, the diameter D4 of the flat portion of tip 34A is 60 μm (area is 11304 square μm), the diameter of the flat portion of tip 39A is 50 μm (area is 7850 square μm), and the diameter of through hole 37 is 30 μm (area is 2826 square μm). μm). That is, the contact area (11304-2826=8487 square μm) of the tip 34A of the penetrating needle thread 34 that contacts the skin excluding the through hole 37 and the contact area (7850 square μm) of the dummy needle thread 39 at 39A (7850 square μm) are almost the same (same area ±20%).

As a result, the puncturing timings of the penetrating needle thread 34 and the dummy needle thread 39 can be aligned, and the microneedle sheet 33 can be improved in puncture performance.

For example, the thickness T1 of the portion where the back hole 36C exists in the microneedle sheet 33 = 300 µm, the needle height T2 = 800 µm, the height T3 from the back hole 36C to the back hole tip 36A = 300 µm, and the thickness from the surface 35A to 100 µm. The diameter of the through needle ridge 34 and the dummy needle ridge 39 at the position (T4) is about 70 μm.

<Other embodiments>
In the above-described embodiment, the through hole 17 is formed from the surface 13A side, that is, from the vicinity of the tip of the needle thread 14 toward the back hole 16, but the present invention is not limited to this. For example, as shown in FIG. 6, the through holes can be formed by irradiating the laser beam LS from the rear surface side, or by irradiating the laser beam LS from both the rear surface side and the front surface side (not shown). In this case, the back hole 16x may have a shape in which two truncated cones with different inclination angles from the central axis of the side surfaces (the inclination angle on the back side is large) are overlapped. As a result, the peripheral portion of the converging laser beam can be prevented from being blocked as much as possible. Even in this case, from the viewpoint of maintaining strength, it is preferable that both the diameter D2a on the tip side and the diameter D2b on the bottom side of the back hole tip portion 16Ax are smaller than the diameter D1 at the base of the needle thread 14. . In addition, the tip portion of the truncated cone does not necessarily have to be flat, and may have a curved surface. Also, although not shown, the back hole may have a truncated cone shape or a conical shape with a curved tip. In this case, in order to maintain the strength, it is preferable that the diameter of the back hole is equal to or less than the diameter of the needle thread at half the depth of the back hole.

INDUSTRIAL APPLICABILITY The present invention can be applied when manufacturing a microneedle array having hollow needle ridges.

11: First mold 11A: Pincushion concave portions 11B, 12C: Substrate concave portion 12: Second mold 12A: Back hole base convex portion 12B: Back hole tip convex portion 13: Microneedle sheet 13A: Front surface 13B: Back surface 14: Pincushion 14A: tip 15: base material portion 15A: front surface 15B: back surface 16: back hole 16A: back hole base portion 16B: back hole tip portion 17: through hole

Claims (8)

a needle ridge forming step of forming a plurality of needle ridges, which are micro-sized protrusions protruding from the surface, as a microneedle array;
a back hole forming step that has a back hole that does not penetrate to the front surface at a position facing the needle thread on the back surface opposite to the front surface;
and a through-hole forming step of forming through-holes penetrating from the surface to the back holes by laser ablation using a laser beam. The needle thread forming step and the through hole forming step are
2. The method of manufacturing a microneedle array according to claim 1, wherein the method is carried out simultaneously by injection molding. The cross-sectional area of the back hole is
The method for manufacturing a microneedle array according to claim 1 or 2, wherein the cross-sectional area is larger than the cross-sectional area of the through-hole. The back hole is
4. The method for manufacturing a microneedle array according to claim 3, wherein the surface side has a planar portion larger than the cross-sectional area of the through-hole. The back hole is
4. The method of manufacturing a microneedle array according to claim 3, wherein at least a portion of the microneedle array has a columnar shape with a constant cross-sectional area. The back hole is
4. The method for producing a microneedle array according to claim 3, characterized in that it has a divergent shape in which the cross-sectional area increases toward the back surface. The back hole is
having a tapered portion that tapers from the back surface to the front surface and a column portion whose cross-sectional area does not change,
4. The method for producing a microneedle sheet according to claim 3, wherein the surface side of the tapered portion and the back surface side of the columnar portion are connected in the same shape. A microneedle array having a plurality of needle ridges that are micro-sized protrusions protruding from the surface,
a back hole that does not penetrate to the front surface at a position facing the needle thread on the back surface opposite to the front surface;
and a through hole penetrating from the surface to the back hole and having a smaller cross-sectional area than the back hole.

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