JP6525017B2 - Microneedle device - Google Patents

Description

  The present invention is capable of efficiently administering a drug using a microneedle, and is capable of satisfactorily applying a drug to the microneedle by a simple method, and is manufactured by a more simple manufacturing method. It relates to possible microneedle devices.

  Conventionally, a microneedle device has been proposed as a device for promoting transdermal absorption of a drug. The microneedle device punctures the skin with several tens of μm to several hundreds of μm into the skin, provides a through hole in the stratum corneum of the outermost layer, and reaches the microneedle from the through hole to the surface layer of the stratum corneum layer The drug is administered into the body by In addition, the method of administering a drug using a microneedle device is expected as a non-invasive method of administering a drug because the drug can be administered by puncturing a microneedle that is very small compared to injection etc. There is.

As said microneedle, the thing of various shapes according to the administration method of a chemical | medical agent is proposed. Specifically, it has a hollow pyramidal three-dimensional shape in which the injection needle is reduced to several tens μm to several hundreds μm, and the medicine is injected into the body from the hollow portion (hole type) (eg, Patent Document 1) ), Having a pyramidal three-dimensional shape capable of puncturing the skin and applying the drug on the surface thereof, the drug is dissolved in the body by puncturing the skin (solid type) (for example, Patent Document 2) The above-described three-dimensional shape of a cone made of a material that can be decomposed in vivo, and the necessary amount of medicine is mixed in advance in the material to puncture the skin and then microneedles in the body Three types have been developed: those that dissolve drugs in the body by decomposition (biodegradable type) (for example, Patent Document 3).
Among them, solid-type microneedles are stable against drugs because mass production at the time of molding and processing is easy and that a drug application process can be provided in a process separate from the manufacturing process of the above-mentioned microneedles. It is attracting attention because it is possible to select various production processes.

Here, when a drug is administered using the above-mentioned solid type microneedle, the distribution of the drug on the surface of the microneedle greatly affects the efficiency of administration of the drug. Specifically, since the microneedle is administered to the body by causing the drug held on the surface to reach the lower layer of the stratum corneum from the through-hole of the stratum corneum, it is more in the lower layer of the stratum corneum. It is preferable that the amount of drug retained on the surface of the tip side of the microneedle to be reached is larger. Also, when the microneedle punctures the skin, the root portion of the microneedle is held in contact with the surface of the stratum corneum surface or the surface on the root side of the microneedle because it is located outside the stratum corneum surface Since it is difficult to administer the drug into the body, it is preferable that the amount of drug retained on the surface on the root side of the microneedle be small.
However, as illustrated in FIG. 32, the microneedle 102 used in the conventional microneedle device 110 has a three-dimensional shape of a pyramid (a square pyramid in FIG. 32), ie, from the tip to the root on the substrate 101 side. As a material having a continuous slope on the side is used, when a drug is applied to the microneedle 102 using a normal discharge method or immersion method, as shown in FIG. 33, the microneedle is exemplified. There is a problem that more medicine 40 is applied to the root portion than to the tip portion 102. Therefore, when a drug is administered using such a microneedle device 110, as illustrated in FIG. 34, the drug 40 held at the root portion is likely to adhere to the surface of the stratum corneum, and the through holes of the stratum corneum There is a problem that it becomes difficult to reach a sufficient amount of drug 40 from the lower layer to the lower layer of the stratum corneum.
32 is a schematic perspective view showing an example of a conventional microneedle device, FIG. 33 is a schematic view showing a microneedle exemplified in FIG. 32 with a drug applied, and FIG. It is explanatory drawing explaining an example of the administration method of the chemical | medical agent using the microneedle device illustrated to these.

Then, when apply | coating a chemical | medical agent to the said microneedle, the method of selectively apply | coating a chemical | medical agent to the front end side of a microneedle is tried (for example, nonpatent literature 1). However, in this case, since the viscosity of the drug and the application conditions are limited, there is a problem that some drugs can not be applied or the process of applying the drug becomes complicated.
In addition, when the drug is selectively applied to the distal end side, the amount of drug held per microneedle is limited, which may make it difficult to apply the amount of drug required for administration. is there. In order to solve this problem, it has been considered to increase the number of microneedles per unit area formed in the microneedle device to increase the drug retention of the entire microneedle device. However, in the microneedle device, since the three-dimensional shape of each microneedle needs to be formed to satisfy a certain level, defects tend to be more likely to occur as the number of microneedles increases. In addition, the microneedle device after the application of the drug also needs to be applied with the drug on the individual microneedles, and when there is a portion where the drug is not applied, it may not be used at the time of administration. Therefore, when the number of microneedles is increased, there is a problem that the manufacturing process of the microneedle device itself becomes complicated, and a problem that the inspection after applying the medicine to the obtained microneedle device becomes complicated.

JP, 2011-78654, A WO 2008/139648 brochure Japanese Patent Application Publication No. 2009-507573

Pham. Res, 2012, Volume 29, Number 1, Pages 170-177

  The present invention has been made in view of the above-mentioned circumstances, and the administration of the drug can be efficiently performed, the application of the drug to the microneedle can be favorably performed by a simple method, and the simple manufacturing method Main object is to provide a microneedle device that can be manufactured by

  In order to solve the above problems, the present invention comprises a substrate and a microneedle formed on the substrate and including a pyramidal structure capable of piercing the skin, the microneedle having a root from its tip The microneedle device is characterized by having a cross-sectional area increasing surface formed in a portion where the rate of increase in cross-sectional area parallel to the substrate surface increases discontinuously.

According to the present invention, since it has the above-mentioned cross-sectional area increasing surface, it becomes possible to deposit the medicine applied from the tip to the root of the microneedle on the cross-sectional area increasing surface. More drug can be applied to the surface from the surface to the distal side. In addition, since the flow of the drug from the tip to the root can be suppressed in the cross-sectional area increasing surface, the application of the drug to the root portion of the microneedle can be suppressed. Therefore, when a drug is administered using the microneedle device of the present invention, the amount of drug retained on the tip side of the microneedle to be punctured inside the stratum corneum of the skin can be increased, and the stratum corneum surface Since the amount of drug retained on the root side of the microneedle in contact with can be reduced, waste of the drug can be reduced and administration can be performed efficiently.
Further, by adjusting the height of the cross-sectional area increasing surface, it is possible to adjust the amount of the drug held on the surface on the tip side from the cross-sectional area increasing surface of the microneedle.
Further, according to the present invention, since the above-mentioned cross-sectional area increasing surface is applied, when applying the drug from the tip to the root of the microneedle, the flow of the drug from the tip to the root is suppressed by the cross-sectional area increasing surface. Therefore, it is possible to selectively apply the drug to the surface on the tip side from the cross-sectional area increasing surface. Moreover, since it becomes possible to apply a drug selectively by relaxing restrictions such as viscosity and application conditions of the drug as compared with the conventional drug application method, the drug application process is performed by a simple method It becomes possible.
In addition, since the surface area of the microneedle itself can be increased by having the cross-sectional area increasing surface, the amount of drug retained per microneedle can be increased. Therefore, even when the number of microneedles formed in the microneedle device is reduced, it is possible to make the amount of drug held by the microneedle device itself desired. Therefore, since the number of microneedles formed in the microneedle device can be reduced, it is possible to simplify the manufacturing process of the microneedle device and the inspection process of the microneedle device after the application of a drug. Become.

  In the present invention, the entire microneedle has the above-described pyramidal structure, and a removal portion formed by removing the side surface of the above-mentioned microneedle in the axial direction of the above-mentioned pyramidal structure It is preferable to have By having the removal portion, it is possible to have the cross-sectional area increasing surface described above. In addition, by having the removal portion, when the microneedle is punctured into the skin, the drug can be held inside the surface of the microneedle in contact with the stratum corneum of the skin, so the drug adhering to the stratum corneum at the time of puncture The amount of the drug can be reduced, and more drugs can be administered from the through holes of the stratum corneum.

  In the present invention, at least one stepped portion formed on the base material and having the cross-sectional area increasing surface as a stepped surface, and formed on the stepped surface of the uppermost stepped portion and having the pyramidal structure It is also preferred to have the top. By having the above-mentioned level difference part, it becomes possible to have the above-mentioned cross-sectional area increase part. In addition, when the medicine is applied to the microneedle by having the stepped portion, the flow of the medicine from the tip to the root can be suitably suppressed on the step surface which is the cross-sectional area increasing surface. In addition, since the three-dimensional shape of the top can be made more sharp, it is possible to easily puncture the stratum corneum of the skin. Therefore, it becomes possible to penetrate the stratum corneum well and to administer the drug efficiently.

  The present invention comprises a substrate and a microneedle formed on the substrate and including a pyramidal structure capable of piercing the skin, the microneedle being a side of the microneedle with respect to the axis of the microneedle. There are at least two places where the slope of the slope changes, and the portion where the absolute value of the slope of the side of the microneedle is small is sandwiched by the portion where the absolute value of the slope of the side of the microneedle is large Provided is a characterized microneedle device.

  According to the present invention, by having the above-described structure of the microneedle, the amount of drug retained at the tip of the microneedle can be increased, and the amount of drug retained at the root can be reduced. It becomes.

  According to the present invention, by having the cross-sectional area increasing surface, the drug can be efficiently administered, the application of the drug to the microneedle can be favorably performed by a simple method, and the simple production is possible. There is an effect that the microneedle device which can be manufactured by a method can be provided.

It is a schematic perspective view which shows an example of the microneedle device of this invention. It is an enlarged view of A part in FIG. 1, and is explanatory drawing explaining an example of the microneedle in this invention. FIG. 3 is a schematic cross-sectional view of the microneedle device illustrated in FIG. 2; It is explanatory drawing explaining the cross-sectional area increase surface in the microneedle device illustrated in FIG. It is explanatory drawing explaining an example of the application | coating method of the chemical | medical agent to the microneedle device of this invention. It is explanatory drawing explaining the other example of the application method of the chemical | medical agent to the microneedle device of this invention. It is the schematic which shows an example of what apply | coated the chemical | medical agent to the microneedle device of this invention. It is explanatory drawing explaining an example of the administration method of the chemical | medical agent using the microneedle device of this invention. It is explanatory drawing explaining the other example of the microneedle device in this invention. It is explanatory drawing explaining the other example of the microneedle in this invention. It is explanatory drawing explaining the other example of the microneedle in this invention. It is explanatory drawing explaining the other example of the microneedle in this invention. It is explanatory drawing explaining the other example of the microneedle in this invention. It is explanatory drawing explaining the front-end | tip shape of the microneedle in this invention. It is process drawing shown about an example of the manufacturing method of the microneedle device of this invention. It is a schematic perspective view which shows the other example of the microneedle device of this invention. It is an enlarged view of E part in FIG. FIG. 18 is a schematic cross-sectional view of the microneedle device illustrated in FIG. 17; It is explanatory drawing explaining the cross-sectional area increase surface in the microneedle device illustrated in FIG. It is a schematic perspective view which shows the other example of the microneedle device of this invention. It is an enlarged view of G part in FIG. It is the HH sectional view taken on the line in FIG. It is explanatory drawing explaining the other example of the application method of the chemical | medical agent to the microneedle device of this invention. It is explanatory drawing explaining the other example of the application method of the chemical | medical agent to the microneedle device of this invention. It is the schematic which shows the other example of what apply | coated the chemical | medical agent to the microneedle device of this invention. It is explanatory drawing explaining the other example of the administration method of the chemical | medical agent using the microneedle device of this invention. It is explanatory drawing explaining the other example of the microneedle in this invention. It is explanatory drawing explaining the other example of the microneedle in this invention. It is the photograph which image | photographed the microneedle formed in the master plate of the plate for microneedle devices in Example 1 using the optical microscope. It is the photograph which image | photographed the microneedle formed in the master plate of the version for microneedle devices in a comparative example using an optical microscope. It is the photograph which image | photographed what apply | coated the chemical | medical agent to the microneedle in the microneedle device of Example 1 and a comparative example using the optical microscope. It is a schematic perspective view which shows an example of the conventional microneedle device. It is the schematic which shows an example of what apply | coated the chemical | medical agent to the conventional microneedle device. It is explanatory drawing explaining an example of the administration method of the chemical | medical agent using the conventional microneedle device.

Hereinafter, the microneedle device of the present invention will be described.
The microneedle device of the present invention comprises a substrate and a microneedle formed on the substrate and including a pyramidal structure capable of piercing the skin, the microneedle being directed from its tip to its root, It is characterized by having a cross-sectional area increase surface formed in a portion where the rate of increase of the cross-sectional area parallel to the substrate surface is discontinuously increased.

The “cone structure” in the present invention is a three-dimensional shape having at least a part of a side surface continuous from the apex to the bottom of the cone, or a solid sharing one bottom of the cylinder and the bottom of the pyramid (hereinafter These three-dimensional shapes have side faces continuous from the top of the pyramid to the bottom).
In addition, “the rate of increase in cross-sectional area parallel to the substrate surface increases discontinuously” means that the cross-sectional area of the microneedle is taken along the horizontal axis (x-axis) and the height of the microneedle is taken along the vertical axis In the graph taken on the (y-axis), there are two or more places where the slope of the above graph changes, and a small value of the cross-sectional area is a downward convex part, and a large cross-sectional area is a convex upward. It means that there is one part having a part that becomes.
Moreover, the cross-sectional area increase surface in this invention shows the change of the cross-sectional area contained between two parts in the said graph.

According to the present invention, since it has the above-mentioned cross-sectional area increasing surface, it becomes possible to deposit the medicine applied from the tip to the root of the microneedle on the cross-sectional area increasing surface. More drug can be applied to the surface from the surface to the distal side. In addition, since the flow of the drug from the tip to the root can be suppressed in the cross-sectional area increasing surface, the application of the drug to the root portion of the microneedle can be suppressed. Therefore, when a drug is administered using the microneedle device of the present invention, the amount of drug retained on the tip side of the microneedle to be punctured inside the stratum corneum of the skin can be increased, and the stratum corneum surface Since the amount of drug retained on the root side of the microneedle in contact with can be reduced, waste of the drug can be reduced and administration can be performed efficiently.
Further, by adjusting the height of the cross-sectional area increasing surface, it is possible to adjust the amount of the drug held on the surface on the tip side from the cross-sectional area increasing surface of the microneedle.
Further, according to the present invention, since the above-mentioned cross-sectional area increasing surface is applied, when applying the drug from the tip to the root of the microneedle, the flow of the drug from the tip to the root is suppressed by the cross-sectional area increasing surface. Therefore, it is possible to selectively apply the drug to the surface on the tip side from the cross-sectional area increasing surface. Moreover, since it becomes possible to apply a drug selectively by relaxing restrictions such as viscosity and application conditions of the drug as compared with the conventional drug application method, the drug application process is performed by a simple method It becomes possible.
In addition, since the surface area of the microneedle itself can be increased by having the cross-sectional area increasing surface, the amount of drug retained per microneedle can be increased. Therefore, even when the number of microneedles formed in the microneedle device is reduced, it is possible to make the amount of drug held by the microneedle device itself desired. Therefore, since the number of microneedles formed in the microneedle device can be reduced, it is possible to simplify the manufacturing process of the microneedle device and the inspection process of the microneedle device after the application of a drug. Become.

Here, the microneedle device of the present invention is roughly divided into two modes depending on the form of the microneedle. Specifically, the entire microneedle has the above-mentioned pyramidal structure, and a removal portion formed by removing the side surface of the above-mentioned microneedle in the axial direction of the above-mentioned pyramidal structure And at least one stepped portion formed on the base material and having the cross-sectional area increasing surface as a stepped surface, and the stepped surface of the uppermost stepped portion, It is divided roughly into two modes with the mode (the second mode) having the top with the pyramidal structure (the second mode).
Each aspect will be described below.

I. First aspect First, the first aspect of the microneedle device of the present invention will be described.
The microneedle device of the present embodiment has a substrate and a microneedle formed on the substrate and including a pyramidal structure capable of piercing the skin, the microneedle being directed from its tip to its root, A cross-sectional area increasing surface formed in a portion where the rate of increase in cross-sectional area parallel to the substrate surface is discontinuously increased, and the entire microneedle has the above-described pyramidal structure, It is characterized by having a removal part formed by removing the side of the above-mentioned microneedle in the direction of an axis of the above-mentioned pyramid structure on the tip side from the above-mentioned cross-sectional area increase side.

  In the present embodiment, the “axis of the pyramidal structure” refers to a perpendicular (Y in FIG. 3 or the like described later) drawn from the top of the pyramidal structure to the bottom surface thereof. Moreover, an axial direction means the direction which goes to the said center from the side surface centering on the said perpendicular line.

Here, the microneedle device of the present embodiment will be described with reference to the drawings. FIG. 1 is a schematic perspective view showing an example of the microneedle device of the present embodiment, and FIG. 2 is an enlarged view of a portion A in FIG. 1 and an explanatory view for explaining the microneedle illustrated in FIG. 3 is a schematic cross-sectional view of the microneedle illustrated in FIG. 2, and FIGS. 3 (a) and 3 (b) are the tip side in the cross section along the cross-sectional area increasing surface of the microneedle device illustrated in FIG. 3 (c) is a cross-sectional view of the microneedle device illustrated in FIG. 2 taken along line B-B, and FIG. 3 (d) is a cross-sectional view of the microneedle device illustrated in FIG. It is a C line sectional view. FIG. 4 is a figure for demonstrating the cross-sectional area increase surface in the microneedle illustrated in FIG.
As illustrated in FIGS. 1 to 4, the microneedle device 10 of the present embodiment has a substrate 1 and a microneedle 2 formed on the substrate 1 and including a pyramidal structure capable of piercing the skin. Further, the microneedle 2 has a cross-sectional area increasing surface 21 formed in a portion where the cross-sectional area of the cross section parallel to the surface of the base material 1 discontinuously increases from the tip to the root. In addition, the entire microneedle 2 has a pyramidal structure, and has a removal portion 22 formed by removing the side surface of the microneedle 2 in the axis Y direction of the pyramidal structure from the cross-sectional area increasing surface 21 to the tip side. It is characterized by
As illustrated in FIGS. 3A and 3B, in the microneedle 2 in this embodiment, the cross-sectional area increasing surface 21 and the surface of the base material 1 are parallel, and the root along the cross-sectional area increasing surface 21 The cross-sectional area of the cross-section on the side (FIG. 3 (b)) is larger than the cross-sectional area of the cross-section on the tip side (FIG. 3 (a)).
Further, the microneedle 2 illustrated in FIG. 2 has a side surface continuous from the top to the bottom of the pyramid as illustrated in FIG. 3C in its entirety. In this example, an example in which the three-dimensional shape of the prototype of the microneedle 2 is a quadrangular pyramid is shown.
In FIGS. 2, 3 (d) and 4, the side surface 22 a of the microneedle 2 in the removal portion 22 as the removal portion 22 on the side surface of the microneedle 2 from the cross-sectional area increasing surface 21 to the tip side An example is shown in which a groove 22 'is formed in which the side surface 22a of the removing portion may be referred to as a curved surface. Further, in this example, the groove 22 'has a semi-elliptical cross-sectional shape parallel to the surface of the base material 1, and the groove 22' on the side has a substantially triangular shape.

  In this aspect, by having the removal portion, it is possible to have the cross-sectional area increasing surface described above. Therefore, when the drug is applied in the direction of the root from the tip of the microneedle, the drug can be selectively applied to the surface on the tip side from the cross-sectional area increasing surface of the microneedle. In addition, the amount of medicine applied to the root portion can be reduced. Therefore, the amount of drug retained on the surface on the tip side from the cross-sectional area increasing surface of the microneedle in this embodiment can be increased, and the amount of drug retained on the root can be reduced. It becomes possible to do efficiently.

  Here, the case where a drug is applied to the microneedle in the microneedle device of the present embodiment will be described with reference to the drawings. FIG. 5 is an explanatory view for explaining an example of a method of applying a drug to the microneedle device of this embodiment. As illustrated in FIG. 5, when the application is performed by discharging the drug 40 using the nozzle 30 or the like from above the tip of the microneedle 2 using a discharge method such as an inkjet method, the discharged drug 40 Is applied to the surface of the microneedle 2 by flowing along the side of the microneedle 2 and flowing from the tip to the root direction when the tip of the microneedle 2 is reached. In the present embodiment, by having the cross-sectional area increasing surface 21, it is possible to receive the drug 40 flowing from the tip in the direction of the root toward the cross-sectional area increasing surface 21 and deposit it on the surface. Therefore, it is possible to increase the amount of the drug 40 applied from the cross-sectional area increasing surface 21 to the surface on the tip side of the microneedle 2. Further, since the flow of the drug 40 from the tip to the root can be suppressed by having the cross-sectional area increasing surface 21, the amount of the drug 40 deposited on the root portion can be reduced.

  FIG. 6 is an explanatory view for explaining another example of the method for applying a drug to the microneedle device of this embodiment. As illustrated in FIG. 6, when coating is performed by dipping the drug 40 with the tip of the microneedle 2 facing downward using an immersion method such as dip method, the drug 40 is the tip of the microneedle 2. It is applied while being sucked up along the side from the to the root direction. In this aspect, by having the cross-sectional area increasing surface 21, the flow of the medicine 40 due to being sucked up from the tip toward the root can be stopped at the cross-sectional area increasing surface 21. Therefore, it becomes possible to selectively apply the medicine 40 to the surface on the tip side from the cross-sectional area increasing surface 21. Further, since the flow of the medicine 40 can be stopped at the cross-sectional area increasing surface 21, it is possible to reduce the amount of the medicine 40 deposited at the root portion.

  As described above, in the present embodiment, since the microneedle 2 can have the cross-sectional area increasing surface 21 by having the removing portion 22, the microneedle 2 can selectively be provided on the surface on the tip side from the cross-sectional area increasing surface 21. Since the drug can be applied, as illustrated in FIGS. 7A and 7B, the amount of the drug 40 held on the surface on the tip side from the cross-sectional area increasing surface 21 of the microneedle 2 is increased. The amount of drug 40 retained at the root portion can be reduced.

Next, administration of a drug using the microneedle device of this embodiment is also described with reference to the drawings.
FIG. 8 is an explanatory diagram for explaining an example of a method of administering a drug using the microneedle device of the present embodiment. When a drug is administered using the microneedle device 10 of this embodiment, the microneedle 2 to which the drug 40 is applied punctures the stratum corneum of the skin to make a through hole in the stratum corneum, and the microneedle 2 is The administration is performed by reaching the epidermis or the like under the stratum corneum. In the microneedle device 10 of the present embodiment, the microneedle 2 has the removal portion 22 having the cross-sectional area increasing surface 21, whereby the amount of the drug 40 held on the tip side of the microneedle 2 is large. Since the amount of the drug 40 retained on the root side can be reduced, the amount of the drug 40 reaching the lower layer of the stratum corneum can be increased, and the amount of the drug 40 attached to the stratum corneum surface can be reduced. be able to. In addition, since the drug 40 can be held by the removal unit 22, the drug 40 can be held inside the surface of the microneedle 2 in contact with the stratum corneum, so the drug adhering to the stratum corneum at the time of puncturing The amount of 40 can be smaller and the amount of drug 40 reaching the interior of the stratum corneum can be more.

  Therefore, in the present embodiment, by having the removal portion, it is possible to have the cross-sectional area increasing surface, and therefore, the drug is applied to the tip side of the microneedle by a simple method as compared to the microneedle in the conventional microneedle device. It becomes possible to apply selectively. In addition, since a large amount of the drug can be held on the surface on the tip side of the microneedle and the amount of the drug held on the surface on the root side can be reduced, the drug can be efficiently administered.

  Hereinafter, the details of the microneedle device of the present embodiment will be described.

1. Microneedle First, the microneedle in this embodiment will be described. Here, when the drug is administered into the body using the microneedle device of this embodiment, the microneedle is a drug to be applied, and the skin is punctured in the skin to provide a through hole in the stratum corneum, and It is used to allow drugs to reach the lower layer of the stratum corneum.

(1) Structure of Microneedle The structure of the microneedle in this aspect will be described.
The microneedle in this aspect has a cross-sectional area increasing surface formed in a portion where the rate of increase in cross-sectional area parallel to the surface of the base material increases discontinuously from the tip to the root The entire microneedle has the above-described pyramidal structure, and has a removal portion formed by removing the side surface of the above-mentioned microneedle in the central direction of the above-mentioned pyramidal structure on the tip side from the above-mentioned cross section It is.

The microneedle in this aspect is formed such that the whole has a pyramidal structure by forming the removal portion on the side surface, and the three-dimensional shape of the microneedle in a state without the removal portion , And may be referred to as an original three-dimensional shape)) having a pyramid or pyramidal body.
Further, as the three-dimensional shape of the above prototype, more specifically, when the three-dimensional shape of the above prototype is a cone, a cone or a polygonal pyramid can be mentioned, and when it is a cylinder having a cone, a cylinder The thing which has a cone in one bottom face of, and the thing which has a polygon pyramid in one bottom face of a polygonal column can be mentioned. Further, in the present embodiment, one in which the axis of the cone or pyramidal body passes through the center of the bottom surface of the pyramid or pyramidal body can be suitably used, but it is not limited thereto.

(A) Cross-sectional area increase surface The cross-sectional area increase surface in this aspect will be described.
In the present embodiment, the cross-sectional area increasing surface is formed in a portion where the rate of increase in cross-sectional area parallel to the substrate surface increases discontinuously from the tip to the root of the microneedle .
Further, the cross-sectional area increasing surface is located at an end portion on the root side of the removing portion formed on the side surface of the microneedle.

  Such a cross-sectional area increasing surface can suppress the flow of the drug from the tip of the microneedle to the root direction, and is not particularly limited as long as the drug can be deposited on the surface, even if it is a curved surface Although it may be flat, it is preferably flat. It has the advantage that it is easy to adjust the area etc. of the cross-sectional area increasing surface and to adjust the amount of drug held in the microneedle.

In addition, as the angle between the cross-sectional area increasing surface and the substrate surface, it is possible to suppress the flow of the drug from the tip of the microneedle to the root direction, and it is particularly limited if the drug can be deposited on the surface Although not preferred, it is preferably within the range of ± 45 °, more preferably within the range of ± 30 °, and particularly preferably within the range of ± 15 °.
By setting the angle between the cross-sectional area increasing surface and the substrate surface to be equal to or less than the above range, the flow of the above-described drug can be more suitably suppressed, and the drug can be suitably deposited on the surface. is there. Further, in this embodiment, it is preferable that the angle between the cross-sectional area increasing surface and the substrate surface be 0 °, that is, the cross-sectional area increasing surface be parallel to the substrate surface. It is because it becomes possible to control the flow of medicine efficiently. The angle between the cross-sectional area increasing surface and the substrate surface is, for example, the angle shown by θ in FIG. 9 (b). Although FIG. 9 (b) shows an example in which the angle between the cross sectional area increasing surface and the substrate surface takes a value of +, although not shown, the cross sectional area increasing surface with the substrate surface The formed angle may have a value of-, that is, the inclination of the cross-sectional area increasing surface may be opposite to the inclination illustrated in FIG.

  In addition, when the cross-sectional area increasing surface and the substrate surface are parallel, the cross-sectional area on the root side is larger than the cross-sectional area on the tip side of the microneedle cut along the cross-sectional area increasing surface.

  The number of such cross-sectional area increasing surfaces is not particularly limited as long as one or more microneedles are formed, and is appropriately determined according to the number of removed portions described later. In this aspect, since it is preferable that a plurality of the removal portions be formed, it is preferable that a plurality of the removal portions are also formed as the number of the cross-sectional area increasing surfaces. Moreover, when multiple cross-sectional area increase surfaces are formed, it is preferable that the form of each cross-sectional area increase surface is the same.

In the present embodiment, when a plurality of cross-sectional area increasing surfaces are formed, the heights of the respective cross-sectional area increasing surfaces 21 (the distance in the vertical direction from the substrate surface to the cross-sectional area increasing surface) are illustrated in FIG. It may be equivalent, and may differ as illustrated in FIG. 9 (a). In the present embodiment, it is preferable that the height of the cross-sectional area increasing surface 21 be equal among them. In this embodiment, by adjusting the height of the cross-sectional area increasing surface, it is possible to adjust the amount of the drug held by the microneedle, but the heights of the cross-sectional area increasing surface in the plurality of cross-sectional area increasing surfaces By making the same, it is possible to more simply adjust the amount of drug.
FIG. 9 is an explanatory view for explaining another example of the microneedle device in this aspect, and FIG. 9A is a schematic perspective view showing another example of the microneedle device in this aspect, b) is a cross-sectional view taken along the line D'-D 'in FIG. Further, in FIGS. 9A and 9B, the heights of the cross-sectional area increasing surfaces formed on the two opposing surfaces are equal, and the heights of the cross-sectional area increasing surfaces formed on the adjacent surfaces are different. Is illustrated. Further, since the reference numerals not described in FIGS. 9A and 9B can be the same as the reference numerals in FIG. 2 and the like, the description here is omitted. Further, the height of the cross-sectional area increasing surface refers to the distance indicated by p1 in FIG. 3 (d). Also, when the cross-sectional area increasing surface has a slope, it refers to the distance in the vertical direction from the substrate surface to the midpoint of the height of the cross-sectional area increasing surface, for example, the distance shown by p1 'in FIG. I shall say.

  Further, the microneedle device 10 exemplified in FIGS. 9A and 9B has a base 1 and a microneedle 2 formed on the base 1 and including a pyramidal structure capable of piercing the skin. The microneedle 2 has at least two places where the inclination of the side surface of the microneedle 2 changes with respect to the axis Y of the microneedle, and the absolute value of the inclination of the side surface of the microneedle 2 is small Is a microneedle device 10 characterized in that it is sandwiched between the portions 2a and 22a where the absolute value of the inclination of the side surface of the microneedle 2 is large. As illustrated in FIG. 9, the axes of the microneedles and the axes of the pyramidal structures are generally coincident.

  The specific height of the cross-sectional area increasing surface is appropriately determined according to the use of the microneedle, etc., but the height of the microneedle (the distance in the vertical direction from the substrate surface to the tip of the microneedle It is preferable that the ratio of the height of the cross-sectional area increasing surface to the above is 10% or more, more preferably 20% or more, particularly 30% or more, and the ratio is 90% or less, particularly 80 % Or less, particularly preferably 70% or less. If the above ratio is less than the above range, the cross-sectional area increasing surface is present at a position close to the root, which may increase the amount of drug that can not be dissolved in the body when the microneedle device punctures the stratum corneum of the skin. If the ratio exceeds the above range, the desired amount of drug may not be applied to the tip of the microneedle even when the cross-sectional area increasing surface is formed. The height of the microneedle refers to the distance indicated by q in FIG. 3 (d).

  The specific height of the cross-sectional area increasing surface is appropriately selected depending on the form of the microneedle, etc., for example, within the range of 50 μm to 450 μm for the microneedle having a height of about 500 μm, Among them, the thickness is preferably in the range of 100 μm to 400 μm, and more preferably in the range of 150 μm to 350 μm.

The area of the cross-sectional area increasing surface is not particularly limited as long as a drug can be deposited on the cross-sectional area increasing surface, as long as a desired amount of the drug can be held in the removing portion. It is possible to select suitably according to the form of the, the use, etc.
The area of the specific cross-sectional area increase surface, but those selected appropriately by steric shape of the prototype of the microneedles, 1000 .mu.m ² within the ～225000Myuemu ^2, within inter alia the 10000μm ² ~150000μm ^2, In particular, the thickness is preferably in the range of 17500 μm ^{2 to} 125000 μm ² .

  The shape of the cross-sectional area increasing surface is determined according to the shape of the bottom of the three-dimensional shape of the microneedle prototype, the form of the removal portion, and the like, and thus the description thereof is omitted here.

(B) Removal part The removal part which removed the side of the above-mentioned microneedle in the direction of an axis of the above-mentioned pyramid structure was formed on the tip side from the above-mentioned cross-sectional area increase side.

As such a removal part, a microneedle can be made into the pyramid structure which can be pierced to skin, and if it can have the cross-sectional area increase surface mentioned above, it will not be limited in particular. In the present embodiment, it is preferable that the removal portion 22 be a groove 22 'as illustrated in FIG. 2 and FIGS.
Here, the groove portion means that the side surface of the removal portion is a concave portion with respect to the side surface of the microneedle not having the removal portion, and the side surface of the removal portion is a curved surface or two or more surfaces.
In the case where the removal portion is a groove, as described above, when the drug is administered using the microneedle in the present embodiment, the drug can be more easily held inside the surface of the microneedle in contact with the stratum corneum of the skin. As a result, less drug adheres to the stratum corneum when punctured into the skin, and it becomes possible to administer more drugs into the body through the pores of the stratum corneum opened by puncture. .

(I) Groove part Hereinafter, the groove part in this aspect is demonstrated.
Examples of the shape of the groove on the side surface of the microneedle (hereinafter sometimes referred to as the shape of the groove) include, for example, a substantially polygonal shape. Further, when the shape of the groove portion is a substantially polygonal shape, it is preferable that the shape of the groove portion 22 'is a substantially three shape as illustrated in FIGS. 1 and 10A. Because the volume of the groove can be increased, it is possible to hold more medicine. The substantially polygonal shape includes not only a polygon but also a case where a part of a corner is formed in a curved shape as illustrated in FIG. 1.
Further, as the shape of the groove 22 ′, a linear shape can be mentioned as exemplified in FIG. 11 (a) and FIG. Further, when the shape of the groove portion is linear, although not shown, the width may be constant, or the width may be partially different. When the width of the groove portion is partially different, it is preferable that the width decreases from the root side to the tip side as illustrated in FIG. 11A and FIG. In addition, when the shape of the groove 22 'is linear, it may be formed linearly on the side of the microneedle from the tip to the root as illustrated in FIG. It may be formed in a spiral shape.

  The cross-sectional shape of the cross section parallel to the base material surface of the groove portion is not particularly limited as long as it can be formed on the side surface of the microneedle, and for example, semicircular (not shown), semielliptic Shapes (FIG. 4), triangles (FIG. 10 (b)), quadrilaterals (FIG. 11 (b)), polygonal shapes (not shown) and the like can be mentioned.

  The position of the end on the tip end side of the groove is not particularly limited as long as it is located in the portion from the cross-sectional area increasing surface to the tip, and as illustrated in FIGS. It may be located between them, and may coincide with the tip as illustrated in FIGS. 10 (a) and 11 (a).

  10 is an explanatory view for explaining another example of the microneedle in this aspect, and FIG. 10 (a) is a schematic perspective view showing another example of the microneedle in this aspect, and FIG. FIG. 10 is an explanatory view for explaining the shape of the cross-sectional area increasing surface in FIG. Further, FIG. 10 shows an example in which the three-dimensional shape of the microneedle prototype is a cone. 11 is an explanatory view for explaining another example of the microneedle in this aspect, and FIG. 11 (a) is a schematic perspective view showing another example of the microneedle in this aspect, and FIG. FIG. 11 is an explanatory view for explaining the shape of the cross-sectional area increasing surface in FIG. Further, FIG. 11 shows an example in which the original three-dimensional shape of the microneedle is a conical cylinder composed of a cone and a cylinder. FIG. 12 is an explanatory view for explaining another example of the microneedle in this aspect. Moreover, about the code | symbol which is not demonstrated in FIGS. 10-12, since it can be made the same as that of FIG. 1 etc., description here is abbreviate | omitted.

  The width of the groove is not particularly limited as long as a desired cross-sectional area increasing surface can be formed, and may be appropriately selected depending on the shape of the groove and the like, but within a range of 1 μm to 450 μm, Among them, the thickness is preferably in the range of 1 μm to 350 μm, and more preferably in the range of 1 μm to 250 μm. If the width of the groove is less than the above range, it may be difficult to stably form the groove on the side of the microneedle. If the width of the groove exceeds the above range, the groove may not be formed. This is because the formation may significantly reduce the strength of the microneedles. The width of the groove refers to the distance indicated by r in FIG.

  The depth of the groove is not particularly limited as long as it is possible to form a desired cross-sectional increase surface, and the height of the cross-sectional increase surface and the size of the three-dimensional shape of the prototype of the microneedle etc. It is determined appropriately. In addition, it is sufficient that the tip of the pyramidal structure is not damaged, and it is usually formed with a distance from the side surface to the axis or less. Specifically, the depth of such a groove is preferably in the range of 1 μm to 250 μm, more preferably in the range of 1 μm to 200 μm, and particularly preferably in the range of 1 μm to 180 μm. When the depth of the groove is less than the above range, it is difficult to maintain the desired amount of the drug on the surface of the microneedle from the cross-sectional area increasing surface to the tip even when the cross-sectional area increasing surface is formed This is because there is a possibility that if the groove depth exceeds the above range, the strength of the microneedle may be significantly reduced. The depth of the groove means the distance indicated by s in FIG.

  The length of the groove is not particularly limited as long as a desired drug can be held in the space constituted by the side surface of the groove and the cross-sectional area increasing surface, and the three-dimensional shape of the microneedle prototype And the height of the cross-sectional area increasing surface, the shape of the groove, and the like.

  The number of grooves in this embodiment is not particularly limited as long as at least one is formed on the side surface of the microneedle, but a plurality of grooves are preferably formed. This is because it is possible to further increase the surface area of the microneedles. When a plurality of grooves are formed, if the three-dimensional shape of the original microneedle is a cone or a cylinder having a cone, grooves of the same shape may be formed at equal intervals radially about the tip. preferable. Further, when the three-dimensional shape of the microneedle prototype is a polygonal pyramid or a polygonal prism having a polygonal pyramid, it is preferable to form the same number of groove portions in each side surface. By forming the groove in this manner, when the microneedle is made to hold the drug, it is possible to reduce the bias of the drug on the surface on the tip side from the cross-sectional area increasing surface of the microneedle. In addition, the reduction in the strength of the microneedle due to the formation of the groove can be reduced.

The microneedle in this aspect forms the removal portion so that the surface area of the microneedle from the cross-sectional area increasing surface to the tip thereof is greater than the surface area on the tip side from the position corresponding to the cross-sectional area increasing surface in the three-dimensional shape of the prototype. Also because it can be enlarged, it makes it possible to increase the amount of drug held by the microneedles.
In the removal section in this aspect, the surface area on the tip side from the cross-sectional area increasing surface of the microneedle is 1.2 or more times the surface area on the tip side from the position corresponding to the cross-sectional area increasing surface in the three-dimensional shape of the prototype It is preferable to form so that it may become in the range of 1.2 times-2.0 times especially in the range of 1.2 times-1.5 times especially. By forming the removal portion so that the surface area on the tip side from the cross-sectional area increasing surface of the microneedle falls within the above-described range, the amount of drug per microneedle in this embodiment can be increased. The number of microneedles formed on the material can be reduced. Therefore, it becomes possible to simply perform the manufacturing process of the microneedle device of this aspect, the inspection process of the microneedle device after drug application, and the like.

(Ii) Other Removal Portions In the above description, the groove portion was described as an example of the removal portion, but in this aspect, removal portions other than the groove portion can also be used. As such a removal part 22, as illustrated in FIG. 13, for example, it is possible to cite a notch 22 ′ ′ in which the side face 22a of the removal part has one flat surface. Is not particularly limited as long as it does not impair the tip of the pyramidal structure.
13 is an explanatory view for explaining another example of the microneedle in this aspect, and FIG. 13 (a) is a schematic perspective view showing another example of the microneedle in this aspect, and FIG. b) is the schematic which shows the cross-sectional area increase surface of the microneedle illustrated to Fig.13 (a).

  Moreover, in this aspect, it may have both a groove part and a notch part as a removal part.

(C) Three-dimensional shape of microneedle The microneedle in this aspect is a thing in which the whole has a pyramid structure. More specifically, the three-dimensional shape of the microneedle is a three-dimensional shape having at least a part of the side surface continuous from the apex to the bottom of the cone, and at least a part of the side surface continuous from the apex to the bottom of the pyramidal cylinder It has a three-dimensional shape.

  In addition, the microneedle in this aspect is one in which the original three-dimensional shape is the above-described cone or pyramidal body.

Further, the shape of the tip of the microneedle in this embodiment is not particularly limited as long as it is possible to puncture the skin and provide a through hole in the stratum corneum, and a complete vertex as exemplified in FIG. In addition to the case of having a surface, it may have a curved surface capable of puncturing the skin as illustrated in FIG. 14 (b), and the surface may be punctured as illustrated in FIG. 14 (c). It may have a plane.
In addition, FIG. 14 is explanatory drawing explaining the front-end | tip shape of the microneedle in this aspect.

Examples of the base area of the microneedle, but those selected appropriately depending on the application of the microneedle device of the present embodiment, in the range of 1500μm ² ~250000μm ^2, within inter alia of 7500μm ² ~200000μm ^2, particularly preferably in the range of 10000μm ² ~100000μm ^2. If the bottom area of the microneedle is less than the above range, it may be difficult to provide the microneedle with a puncturing strength to the skin, and the bottom area of the microneedle is in the above range. If the size of the microneedle device is larger than the size of the microneedle device, it may be difficult to handle when puncturing the skin.

  The height of the microneedle is not particularly limited as long as the skin can be punctured and the drug can be administered to the inside of the stratum corneum. Specifically, the thickness is preferably in the range of 20 μm to 1000 μm, more preferably in the range of 50 μm to 800 μm, and particularly preferably in the range of 150 μm to 750 μm. If the height of the microneedles is less than the above range, it may be difficult to stably puncture the skin with the microneedles. If the height of the microneedles exceeds the above range, This is because the microneedles come in contact with nerves in the dermal layer, and administration of the drug may be painful.

(D) Others The number of microneedles formed in the microneedle device of the present embodiment is not particularly limited as long as it can hold a desired drug, and it is appropriately determined according to the application of the microneedle device, etc. Although it is selected, the number per unit area of the substrate is in the range of 1 / cm ^{2 to} 5000 / cm ² , in particular in the range of 25 / cm ^{2 to} 2500 / cm ² ,
In particular, it is preferable to be in the range of 50 / cm ^{2 to} 1000 / cm ² .
Further, in the present embodiment, for ease of manufacture of the microneedle device and easiness of inspection of the microneedle after drug application, it is preferable that the number is particularly small in the above-mentioned range.

(2) Material of Microneedle The material of the microneedle used in the present embodiment is not particularly limited as long as it can form a desired microneedle, and is the same as that used in a general microneedle device can do.
Specifically, inorganic materials and resin materials can be mentioned.
Specific examples of the inorganic material include silicon, silicon dioxide, ceramic and the like. In addition, metals such as stainless steel, titanium, nickel, molybdenum, chromium, cobalt and the like can be mentioned.
On the other hand, examples of resin materials include biodegradable polymers such as polylactic acid, polyglycolide, polylactic acid-co-polyglycolide, pullulan, capronolactone, polyurethane, polyanhydride and the like. Other examples include non-degradable polymers such as polycarbonate, polymethacrylic acid, ethylene vinyl acetate, polytetrafluoroethylene, polyoxymethylene, cycloolefin polymer (COP) and cycloolefin copolymer (COC).

  In the present embodiment, among the above-described materials, a liquid repellent material exhibiting liquid repellency is more preferable. If the microneedle is made of a material having high wettability as a whole, the progress of the drug flowing in the direction of the substrate can not be suppressed by the cross-sectional area increasing surface, and a large amount of drug is applied near the root. It is because the possibility is increased. Therefore, when the liquid repellent property is given to the surface of the microneedle, when the medicine is applied to the microneedle, it is possible to more suitably suppress the progress of the medicine flowing from the tip toward the base material in the cross sectional area increasing surface. .

  Here, the liquid repellency in the present embodiment is not particularly limited as long as the drug can be prevented from being applied to the portion from the cross-sectional area increasing surface to the root, but the microneedle has a surface tension of 72 The contact angle with a liquid (generally water) of about 75 mN / m is preferably 45 ° or more, more preferably 50 ° or more, and particularly preferably 70 ° or more. By setting the liquid repellency of the above-mentioned microneedles to the above-mentioned value, it is possible to apply the medicine more easily from the cross-sectional area increasing surface to the tip portion. The contact angle with the liquid is measured by dropping a droplet from the microsyringe using a contact angle measuring device (DM500 manufactured by Kyowa Interface Science Co., Ltd.). Seconds), and can be obtained from the result or by graphing the result.

  Specific examples of materials having such liquid repellency include polycarbonate, polymethacrylic acid, ethylene vinyl acetate, polytetrafluoroethylene, polyoxymethylene, cycloolefin polymer (COP), cycloolefin copolymer (COC) and the like. Can be mentioned. Moreover, in order to give liquid repellency, what performed additional processings, such as a fluorine treatment, may be used.

(3) Method of Forming Microneedle The microneedle used in the present embodiment is usually formed integrally with the substrate. The specific forming method will be described in the section “4. Method of manufacturing microneedles” described later, and thus the description thereof is omitted here.

2. Substrate The substrate used in the present embodiment is for holding the above-described microneedles.
Such a substrate may be integral with or separate from the above-described microneedle, but usually, the microneedle and the substrate are integrally formed.

  As the thickness of the above-mentioned base material, the above-mentioned microneedle can be held, and the microneedle device of this aspect can be punctured into the stratum corneum of the skin to such an extent that the strength can be achieved. It is not particularly limited. Specifically, the thickness described above is preferably in the range of 10 μm to 1500 μm, more preferably in the range of 50 μm to 750 μm, and particularly preferably in the range of 100 μm to 500 μm. When the thickness of the substrate is less than the above range, it may be difficult to stably form the substrate with a constant thickness when the microneedle and the substrate are integrally formed. If the thickness of the base material exceeds the above range, the microneedle device becomes large. Therefore, when it is necessary to administer the drug by puncturing for a certain period of time, the burden on the human body may be large. It is because there is.

  The size, shape, and the like of the above-described base material can be appropriately selected according to the application and the like of the microneedle device.

  The material of the base material can be the same as the material used for the above-described microneedles, and thus the description thereof is omitted here.

3. Microneedle Device The microneedle device of the present embodiment is not particularly limited as long as it has the above-described base material and microneedle, and it is possible to appropriately select and add necessary configurations other than the above.

  The microneedle device of this embodiment is used in transdermal administration of various drugs.

4. Method of Manufacturing Microneedle Device The method of manufacturing the microneedle device of the present embodiment is not particularly limited as long as it is a manufacturing method capable of forming the above-described microneedles on a substrate, and general microneedle manufacturing The same manufacturing method as the method can be used.

  Specifically, a method of manufacturing a microneedle device by directly forming a microneedle by etching or mechanical cutting on the surface of a substrate composed of the material of the microneedle, a microneedle and a substrate The method of manufacturing a microneedle device can be mentioned by processing the material of a microneedle using the template for microneedle devices, such as a stamper and a mold, etc. which have a crevice corresponding to. In the present embodiment, among others, a manufacturing method using a microneedle device plate is preferable. This is because microneedle devices can be mass-produced with high accuracy.

  Here, a specific example of a method of manufacturing a microneedle device using a microneedle device plate will be described with reference to the drawings. FIG. 15 is a process chart showing an example of a method of manufacturing the microneedle device of this embodiment, which is a manufacturing method using an imprint method. In this example, first, as illustrated in FIG. 15A, a microneedle device plate 50 having a recess corresponding to the microneedle, and a microneedle device composed of a material of a microneedle such as a thermoplastic resin. Prepare a substrate 10 '. Next, as illustrated in FIG. 15 (b), the microneedle device plate 50 is pressed on the surface of the heated microneedle device substrate 10 ′ and then cooled or the like to perform the microneedle device substrate 10. By curing ', as illustrated in FIG. 15C, the microneedles 2 are formed on the surface of the substrate 10' for a microneedle device. Next, although not shown, the microneedle device plate is peeled off from the microneedle device substrate, and the microneedle device substrate is molded if necessary. By performing the above steps, the microneedle device 10 illustrated in FIG. 15D can be manufactured.

  As the plate for the microneedle device, a stamper used for the microneedle device and a well-known template can be used. For example, it may be formed by subjecting the surface of a metal substrate or the like to mechanical cutting or the like, and after etching or cutting the metal substrate or the like to form a master plate of a microneedle device, It may be formed by subjecting the above master plate to electroforming or the like.

  As a processing method using a microneedle device plate, a known processing method used in a method of manufacturing a microneedle device can be adopted. Specifically, the method of filling resin, such as an imprint method and an injection molding method, etc. can be mentioned. About the manufacturing method of the specific microneedle device using each system, since it is the same as that of a well-known method, description here is abbreviate | omitted.

5. Method of applying a drug to a microneedle As a method of applying a drug to a microneedle in the microneedle device of this aspect, it is particularly a coating method that can apply a drug from the tip of the microneedle to the root portion It is not limited. For example, an ink jet method, a discharge method such as a dispenser method, or an immersion method such as a dip method can be mentioned.

II. Second Aspect Next, a second aspect of the microneedle device of the present invention will be described.
The microneedle device of the present embodiment has a substrate and a microneedle formed on the substrate and including a pyramidal structure capable of piercing the skin, the microneedle being directed from its tip to its root, It has a cross-sectional area increasing surface formed in a portion where the rate of increase in cross-sectional area parallel to the substrate surface is discontinuously increased, and is formed on the substrate, and the cross-sectional area increasing surface is a step It is characterized in that it has at least one step portion which is a surface, and a top portion which is formed on the step surface of the top step portion and which has the above-mentioned pyramidal structure.

  Here, "the cross-sectional area increasing surface is a step surface" means that the side surface of the solid above the cross-sectional surface increasing surface and the side surface of the lower solid are continuous from the apex to the bottom of the pyramid or pyramidal cylinder. It means that the side surface of the upper solid and the side surface of the lower solid below become discontinuous at the boundary of the cross-sectional area increasing surface. Also, it means that there is a solid bottom surface above the outer periphery of the cross-sectional area increasing surface.

Here, the microneedle device of the present embodiment will be described with reference to the drawings. FIG. 16 is a schematic perspective view showing an example of the microneedle device of this embodiment, and FIG. 17 is an enlarged view of a portion E of FIG. 16 and an explanatory diagram for explaining an example of the microneedle in this embodiment. FIG. 18 is a schematic cross-sectional view of the microneedle device illustrated in FIG. 18 (a) and 18 (b) are schematic cross-sectional views of the distal end side and the root side in a cross section including the cross-sectional area increasing surface of the microneedle illustrated in FIG. 17, and FIG. It is a FF sectional view taken on the line of the illustrated microneedle device. FIG. 19 is an explanatory view for explaining a cross-sectional area increasing surface in the microneedle device illustrated in FIG.
As illustrated in FIGS. 16 to 19, the microneedle device 10 of this embodiment includes a substrate 1 and a microneedle 2 formed on the substrate 1 and including a pyramidal structure capable of piercing the skin. Further, the microneedle 2 has a cross-sectional area increasing surface 21 formed in a portion where the cross-sectional area of the cross section parallel to the surface of the substrate 1 discontinuously increases from its tip to the root, At least one stepped portion 23 formed on the material 1 and having the cross-sectional area increasing surface 21 as the stepped surface 23a, and the uppermost portion 24 formed on the stepped surface 23a of the uppermost stepped portion 23 and having a pyramidal structure It is characterized by having.
As illustrated in FIGS. 18A and 18B, in the cross section including the cross-sectional area increasing surface 21 which is parallel to the cross-sectional area increasing surface 21, the cross section on the root side (FIG. 18). The cross-sectional area of (b) is larger than the cross-sectional area of the cross-section on the tip end side (FIG. 18A).
Further, the microneedle 2 illustrated in FIG. 17 has a quadrangular bottom shape, and has a single step portion 23 whose cross-sectional shape in the direction perpendicular to the substrate surface has a trapezoidal shape, and a pyramidal pyramid An example is shown having a top 21 with a structure.
Further, as illustrated in FIG. 19, the bottom surface of the uppermost portion exists inside the outer periphery of the cross-sectional area increasing surface 21 which is the step surface 23.

  FIG. 20 is a schematic perspective view showing another example of the microneedle device of this embodiment, and FIG. 21 is an enlarged view of a portion G of FIG. FIG. 22 is a sectional view taken along the line HH in FIG. In the present embodiment, the microneedle may have a plurality of step portions 23 (two step portions 231 and 232 in FIGS. 21 and 22). In this case, the uppermost portion 24 is formed on the step surface of the uppermost step portion 231.

  In this aspect, by having the above-described step portion, it is possible to have the above-described cross-sectional area increasing surface. Therefore, when the drug is applied in the direction from the tip of the microneedle to the root, the drug can be selectively applied to the surface on the tip side from the cross-sectional area increasing surface, that is, the cross-sectional area increasing surface and the uppermost surface. In addition, the amount of medicine applied to the root portion can be reduced. Thus, the amount of drug retained on the surface of the microneedle in the present embodiment from the cross-sectional area increasing surface of the microneedle can be increased, and the amount of drug retained in the root portion can be reduced.

Here, the case where a drug is applied to the microneedle in the microneedle device of the present embodiment will be described with reference to the drawings. 23 and 24 are explanatory diagrams for explaining an example of a method for applying a drug to a microneedle in this embodiment, and FIG. 23 is an explanatory diagram for explaining an application method using a discharge method, and FIG. It is an explanatory view explaining an application method using a method.
Also in this embodiment, since the microneedle 2 has the cross-sectional area increasing surface 21 by having the step portion 23, as described in the section of "I. First embodiment" described above, the medicine directed from the tip to the root The flow can be suppressed by the cross-sectional area increasing surface 21. Therefore, also in this embodiment, it is possible to increase the amount of drug applied to the surface on the tip end side from the cross-sectional area increasing surface 21 of the microneedle 2, that is, the surfaces of the cross-sectional area increasing surface 21 and the top 24. Further, in the present embodiment, since the step portion 23 is provided, the side surface of the top 24 and the side surface of the step portion 23 do not have a continuous portion, so the flow of the medicine from the tip to the root is more effectively performed. It becomes possible to suppress. Further, as illustrated in FIGS. 23 and 24, even if the medicine flows out from the stepped surface 231a of the stepped portion 231 where the uppermost portion 24 is formed by forming a plurality of stepped portions 23, the lower stage The step surface 232a of the step portion 232 located on the side makes it possible to further suppress the flow of the medicine in the direction of the root, so that the amount of medicine applied to the root portion of the microneedle can be further reduced. .

  As described above, in the present embodiment, since the microneedle 2 can have the cross-sectional area increasing surface 21 by having the step part 23, the microneedle 2 can selectively be on the surface on the tip side from the cross-sectional area increasing surface 21. The drug can be applied to Therefore, as illustrated in FIG. 25, the amount of drug retained on the surface on the tip side from the cross-sectional area increasing surface 21 of the microneedle 2 can be increased, and the amount of drug retained on the root portion is decreased. be able to.

Next, administration of a drug using the microneedle device of this embodiment is also described with reference to the drawings.
FIG. 26 is an explanatory view showing an example of a method of administering a drug using the microneedle device of this embodiment. In the microneedle device 10 of the present embodiment, since the microneedle 2 can have the cross-sectional area increasing surface 21 by having the step portion, the amount of the drug 40 held on the tip side of the microneedle 2 Because the amount of the drug 40 retained on the root side of the microneedle can be reduced, the amount of the drug 40 reaching the lower layer of the stratum corneum can be increased, and the drug adhering to the surface of the stratum corneum The amount of 40 can be reduced. Further, in the present embodiment, by making the shape of the top 24 a sharper shape, it is possible to puncture the skin more easily to form a through hole, so that the drug 40 is better administered into the body. Is possible.

  Therefore, in the present embodiment, since the cross-sectional area increasing surface can be provided by having the step portion, the drug is applied to the tip side of the microneedle by a simple method as compared with the microneedle in the conventional microneedle device. It becomes possible to apply selectively. In addition, since a large amount of drug can be held on the tip side of the microneedle and the amount of drug held on the root side can be reduced, the drug can be efficiently administered.

  Hereinafter, the details of the microneedle device of the present embodiment will be described.

1. Microneedle (1) Structure of Microneedle First, the structure of the microneedle in this embodiment will be described.
The microneedle in this aspect has a cross-sectional area increasing surface formed in a portion where the rate of increase in cross-sectional area parallel to the substrate direction increases discontinuously from the tip to the root And at least one stepped portion formed on the base material and having the cross-sectional area increasing surface as a stepped surface, and the uppermost surface having the above-described pyramidal structure formed on the stepped surface of the uppermost stepped portion. The

(A) Cross-sectional area increasing surface The cross-sectional area increasing surface in this aspect is a portion where the rate of increase of the cross-sectional area of the cross section parallel to the substrate direction increases discontinuously from the tip of the microneedle to the root. It was formed in
Further, the cross-sectional area increasing surface is located on the step surface of the step portion to be described later.

  Such a cross-sectional area increasing surface can suppress the flow of the drug from the tip of the microneedle to the root direction, and is not particularly limited as long as the drug can be deposited on the surface, even if it is a curved surface Although it may be flat, it is preferably flat. In addition, about this reason, since it can be made to be the same as the reason demonstrated in the term of the above-mentioned "I. 1st aspect", description here is abbreviate | omitted.

  The angle formed between the cross-sectional area increasing surface and the surface of the base can be the same as the reason described in the section of “I. First aspect” described above, and thus the description thereof is omitted here.

  The number of such cross-sectional area increasing surfaces is not particularly limited as long as one or more microneedles are formed, and the number is appropriately determined according to the number of step portions described later.

The specific height of the cross-sectional area increasing surface is appropriately determined according to the use of the microneedle and the like. The ratio of the height of the cross-sectional area increasing surface to the height of the microneedle and the height of the specific cross-sectional area increasing surface may be the same as those described in the section "I. First embodiment" described above. Since it can be done, the explanation here is omitted.
In the present embodiment, when the microneedle has a plurality of stepped portions, the height refers to the height of the cross-sectional area increasing surface on which the uppermost portion is formed, and the distance shown by p2 in FIG. Say

  The area of the cross-sectional area increasing surface is not particularly limited as long as a drug can be deposited on the cross-sectional area increasing surface, as long as a desired amount of the drug can be held in the removing portion. It is possible to select suitably according to the form of the, the use, etc. The specific area of the cross-sectional area increasing surface can be the same as that described in the section “I. First aspect” described above, so the description here is omitted.

  The shape of the cross-sectional area increasing surface is appropriately selected in accordance with the cross-sectional shape parallel to the surface of the base portion of the step portion and the uppermost portion described later.

(B) Stepped part The stepped part in this aspect is formed on a base material, and makes the cross-sectional area increase surface mentioned above a stepped surface. In addition, an uppermost portion to be described later is formed on the uppermost step surface.

  The bottom surface shape of the stepped portion is not particularly limited as long as it can be formed on the base material and can provide the microneedle with a strength capable of puncturing the skin. For example, circular shape and polygonal shape can be mentioned.

  The cross-sectional shape in the direction perpendicular to the base of the stepped portion is not particularly limited as long as it is a shape capable of forming the uppermost portion described later, and is exemplified in FIGS. 16, 17, and 18 (c). As shown in FIGS. 27 (a) and 27 (b), the side surface of the step 23 may be perpendicular to the base material. It may be formed to be 27 is an explanatory view for explaining another example of the microneedle in this aspect, and FIG. 27A is a schematic perspective view showing another example of the microneedle in this aspect, and FIG. 27 is a cross-sectional view taken along the line I-I of FIG. The reference numerals not described in FIG. 27 can be the same as those in FIG. 17 and the like, and thus the description thereof is omitted here.

  Further, at least one stepped portion in the present embodiment may be formed, and one may be formed on the substrate 1 as illustrated in FIG. 16 and the like, and as illustrated in FIG. Multiple may be formed. In the present embodiment, it is preferable that a plurality of step portions be formed among them. Even when the drug applied from the tip of the uppermost portion can not be held on the cross-sectional area increasing surface (step surface) on which the uppermost portion is formed by having a plurality of stepped portions, the cross-sectional area of the stepped portion located in the lower layer is increased Since the drug can be received by the surface (step surface), it is possible to reduce the drug applied to the root side.

The number of steps in this embodiment is not particularly limited as long as it is at least one or more.
It is preferable that it is one or more, in particular in the range of 1 to 10, particularly in the range of 1 to 5. By setting the number of steps to the above range, it is possible to more selectively apply the drug to the tip portion of the microneedle.
Further, the upper limit of the number of steps is appropriately selected depending on the use of the microneedle and the like, and is about 50, for example. If the above value is exceeded, it may be difficult to form the microneedle stably.

(C) Top part The top part in this aspect is formed in the step surface of the level | step-difference part of the top step, and has a pyramid structure.

  The formation position of the top is not particularly limited as long as it is inside the outer periphery of the step surface, ie, the cross sectional area increasing surface, but the position where the axis of the pyramid structure of the top overlaps the center of the step surface described above Is preferred. This is because it becomes possible to stably puncture the microneedle into the skin.

  The three-dimensional shape of the top is not particularly limited as long as it has a pyramidal structure that can be punctured in the skin. Specifically, it may be a pyramid as illustrated in FIG. 16 or the like, or may be a pyramidal body although not shown. In addition, as illustrated in FIG. 28, a pyramid having a top removing portion 25 formed by forming the above-mentioned pyramid and pyramidal body into a three-dimensional shape of the original form and removing the side surface in the axial direction of the pyramid structure. It may be a body structure. In the present embodiment, it is preferable that the top three-dimensional shape be a pyramidal structure having a top removing portion. As described above, by having the removal portion, it is possible to hold more drug on the tip side of the microneedle, and it is possible to more efficiently administer the drug using the microneedle device of this embodiment. It is because

  Such a top removing portion is not particularly limited as long as it is formed on the side of the top, but as illustrated in FIG. 28, the position of the end on the root side of the top removing portion 25 is a step It is preferable to be formed on the tip side from the cross-sectional area increasing surface 21 which is coincident with the surface, that is, the step surface 23. Since the area of the cross-sectional area increasing surface on which the top is formed can be made wider, and the surface area on the tip side can be made wider from the cross-sectional area increasing surface of the microneedle, It is possible to increase the amount of drug that can be retained.

  The top removing portion can be the same as the removing portion described in the section “I. First aspect” described above, and thus the description thereof is omitted here.

  The shape of the bottom surface of the top is not particularly limited as long as it is possible to form the top on the step surface of the top step, and may have the same shape as the step surface, and is different It may be In the present embodiment, it is preferable that the shape of the bottom of the top or the bottom of the original three-dimensional shape of the top is, in particular, a shape similar to the shape of the step surface of the step. This is because the area of the surface of the step can be easily adjusted, and the top can be stably formed on the surface of the step.

(C) Three-Dimensional Shape of Microneedle The microneedle in this aspect has the above-described step portion and the uppermost portion. Such a three-dimensional shape of the entire microneedle does not constitute a pyramidal structure.

  Also, in this embodiment, usually, the surface area of the top surface and the surface area of the top surface is the cone or the weight having the bottom surface of the top level difference portion as the bottom and the top top apex as the top. It is formed to be larger than the surface area of the rod body. Regarding the relationship between the sum total of the surface area of the top and the surface of the step and the surface area of the above-described pyramid or pyramid, the cross-sectional area increasing surface of the microneedle described in the above-mentioned "I. The relationship between the surface area on the tip end side and the surface area on the tip end side from the position corresponding to the cross-sectional area increasing surface in the three-dimensional shape of the prototype can be the same, so the description here is omitted.

  The height of the microneedle and the bottom area of the microneedle can be the same as the height of the microneedle described in the section of “I. First embodiment” described above, and thus the description thereof is omitted here.

(2) Microneedle The microneedle can be the same as that described in the section "I. First aspect" except for the structure of the microneedle described above, so the description here is omitted. Do.

2. Others The microneedle device of the present embodiment can be the same as those described in the item of “I. First embodiment” above for matters other than the above-described microneedle, so the description here is omitted. Do.

III. Microneedle Device The microneedle device of the present invention may have any of the microneedles described in the first or second aspect described above, and the microneedle in the first aspect and the microneedle in the second aspect Both may be included, and the microneedles having a three-dimensional shape other than the microneedles in the first aspect or the second aspect may be included.

  This aspect is not limited to the above embodiment. The above embodiment is an exemplification, and it has substantially the same configuration as the technical idea described in the claims of the present embodiment, and exhibits the same operation and effect as the present embodiment. It is included in the technical scope of

  Hereinafter, the microneedle device of the present invention will be specifically described by way of examples and comparative examples.

Example 1
(Preparation of microneedle device version)
As shown in Fig. 29, a recess is formed on the side so that there is a step at the base of 0.35mm x 0.35mm, height 0.5mm, and height 0.25mm from the tip by cutting to metal. A master plate of 100 microneedles in which ten projections were arranged vertically and horizontally at a pitch of 1 mm was produced to obtain a master plate.
Next, in order to duplicate the microprotrusions of the microneedles of the master plate of the microneedle device created, electroforming is performed using nickel in order to make a duplicate master plate (plate for microneedle device) from the above master plate, and A plate for a microneedle device having an intaglio plate reverse to the master shape was obtained.

(Replication of resin microneedle device)
As a molding material for the microneedle device, a 2 mm-thick sheet of cycloolefin polymer Zeonoa (manufactured by Nippon Zeon Co., Ltd .: Model Zeonor 1060R), which is a cyclic olefin-based resin, was prepared. Incidentally, the glass transition temperature of the cycloolefin polymer 1060R used is 100 ° C., the MFR is 280 ° C., 21.18 N, and 60 g / min.
The Zeonoa sheet, which is the cycloolefin polymer, is heated to 120 ° C. above the glass transition temperature (100 ° C.), and the above-described microneedle device plate is heated to 120 ° C., the glass transition temperature, at a pressure of 12 MPa. The mold for the microneedle device is cooled in a press-pressed and press-pressed state, and the temperature is sufficiently lowered to around room temperature, and then a hot press (heat imprint) is performed to peel off in the cone length direction. Thus, a resin-made microneedle device having the same shape as the above-described master shape was obtained.

Example 2
A microneedle device was produced in the same manner as in Example 1 except that a microneedle device plate was produced as follows.
When cutting to metal, a step is formed at the base of 0.35 mm × 0.35 mm, height 0.5 mm, and at a height of 0.25 mm from the tip, and a square projection up to a height of 0.25 mm from the tip A mastering shape of 100 microneedles in which ten projections, each having a recess, are formed in the vertical and horizontal directions at a 1 mm pitch by further performing a counterbore treatment on the four side surfaces of the projection The master version was obtained.
Next, in order to duplicate the microprotrusions of the microneedles of the master plate of the microneedle device created, electroforming is performed using nickel in order to make a duplicate master plate (plate for microneedle device) from the above master plate, and A plate for a microneedle device having an intaglio plate reverse to the master shape was obtained.

[Comparative example]
A microneedle device was produced in the same manner as in the example except that a microneedle device plate was produced as follows.
A master shape of 100 microneedles, in which 10 square pyramidal protrusions with a base of 0.25 mm × 0.25 mm and a height of 0.5 mm are arranged vertically and horizontally at a pitch of 1 mm, are fabricated by metal cutting (Fig. 30). Next, in order to duplicate the microprotrusions of the microneedles of the master plate of the microneedle device created, electroforming is performed using nickel in order to make a duplicate master plate (plate for microneedle device) from the above master plate, and A plate for a microneedle device having an intaglio plate reverse to the master shape was obtained.

[Evaluation]
(The appearance of the surface of the microneedle after drug application)
The following chemical solutions were prepared, and a dispenser device (manufactured by Musashi Engineering Co., Ltd .: SHOTminiα) was employed, and the chemical solution was dispensed quantitatively to the chemical solution supply nozzle opening, to manufacture in Examples 1, 2 and Comparative Example The drug solution dispensed onto the microneedle of the microneedle device was contact-transferred and applied.
The prepared chemical | medical solution used what dissolved 0.02 g of polyvinyl pyrrolidone (The Nippon Shokuhin Co., Ltd. make: PVP K-90) 0.06g and caffeine (the Wako Pure Chemical Industries) in 1 g of purified waters was used.
The above drug solution is filled in the drug solution storage unit of the dispenser drug solution dispensing apparatus, the dispenser drug solution dispensing apparatus is set, and the dispenser drug solution dispensing is performed on the tip of 100 microneedles on the substrate of the microneedle device. The microneedle surface is brought into contact with a chemical solution that has been dispensed by a predetermined amount that can be discharged in 0.1 MPa and 0.05 sec to the nozzle of the device (Musashi Engineering Co., Ltd .: SN-LF series 32G, nozzle opening inner diameter: 0.1 mmφ) I was transferred to The coating process was performed once for one microneedle to obtain a drug-coated microneedle device.
The coating shape when applied was confirmed by an optical microscope. The results are shown in FIG. 31 (a) is a photograph of Example 1 taken by an optical microscope, and FIG. 31 (b) is a photograph of a comparative example taken by an optical microscope.

  In Example 1 and Example 2, coating by the dispensing method was carried out, and the tip holding was easy in the vicinity of the cross-sectional area increasing surface, and all 100 out of 100 could be coated. In Comparative Example 1, at the time of tip application, the drug may be applied to the vicinity of the root in 50 or more of the 100 in the dispensing method, and it is difficult to manufacture microneedles in which the drug is applied to the tip in all 100 The

(About the amount of drug held)
The amount of caffeine loaded on the surface from the tip of the microneedle to the height of 0.25 mm in Examples 1 and 2 and Comparative Example was determined as follows. First, the microneedle device after drug deposition is stirred overnight in methanol, quantified by high performance liquid chromatography (HPLC), and the average value per 100 microneedles on each device from the average value The drug loading was confirmed. The sample of the comparative example was measured using a sample that could be applied at a height of about 0.25 mm. The results are shown in Table 1. In addition, the surface area of the side surface of the top in Example 1 and the surface area of the side surface from the tip in the comparative example to a height near 0.25 mm can be made equal.

これらの結果から、断面積増大面を有する形状とすることで、断面積増大面から先端近傍にかけて薬剤の保持量が多いマイクロニードルデバイスを容易に製造可能になったことがわかる。

From these results, it can be seen that the microneedle device having a large amount of drug retention can be easily manufactured from the cross-sectional area increasing surface to the vicinity of the tip by using the shape having the cross-sectional area increasing surface.

DESCRIPTION OF SYMBOLS 1 ... Base material 2 ... Microneedle 10 ... Microneedle 21 ... Cross-sectional area increase surface 22 ... Removal part 23, 231, 232 ... Step difference part 23a, 231a, 232a ... Step surface 24 ... Top part

Claims (3)

A substrate,
A microneedle formed on the substrate and comprising a pyramidal structure capable of piercing the skin;
The microneedle has a cross-sectional area increasing surface formed in a portion where the rate of increase in cross-sectional area parallel to the substrate surface increases discontinuously from the tip to the root,
The entire microneedle has the pyramidal structure,
The cross-sectional area increasing surface is formed between the apex and the bottom of the pyramidal structure,
A plurality of removal parts formed by removing the side surface of the microneedle in the axial direction of the pyramidal structure only in the region on the tip side from the cross-sectional area increasing surface , and arranging in the circumferential direction of the pyramidal structure; A microneedle device characterized by having a non-removal part which remains without removing the side of said pyramidal structure among a plurality of removal parts .   The pyramidal structure is a polygonal pyramid shape,
  The removal portion is formed on the side surface of the polygonal pyramid shape,
  The microneedle device according to claim 1, wherein the non-removal portion is configured by a portion of a ridge line extending from the top to the bottom of the polygonal pyramid shape.   Said cone structure is conical in shape,
  The removal portion is configured such that a part of the side surface of the conical shape is recessed in the axial direction of the conical shape,
  The microneedle device according to claim 1, wherein the non-removal portion is configured by the side surface of the conical shape.

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