JP6304431B2 - Microneedle device - Google Patents

Description

  The present invention can efficiently administer a drug using a microneedle, and can be satisfactorily applied to the microneedle by a simple method. It relates to a possible microneedle device.

  Conventionally, a microneedle device has been proposed as a device for promoting percutaneous absorption of a drug. The microneedle device punctures the skin with a microneedle of several tens to several hundreds of μm to provide a through hole in the outermost stratum corneum, and the microneedle reaches the epidermis layer under the stratum corneum from the through hole. To administer drugs to the body. In addition, since a drug administration method using a microneedle device can be administered by puncturing a very small microneedle compared to injection or the like, it is expected as a noninvasive drug administration method. Yes.

As the above-mentioned microneedle, those having various shapes have been proposed according to the administration method of the drug. Specifically, it has a hollow cone-shaped three-dimensional shape in which an injection needle is reduced to several tens to several hundreds of μm, and injects a drug from the hollow part into the body (hole type) (for example, Patent Document 1) ), Which has a three-dimensional shape of a cone that can puncture the skin, and in which the drug is applied to the surface, the drug is dissolved in the body by puncturing the skin (solid type) (for example, Patent Document 2) The cone has a three-dimensional shape composed of a material that can be decomposed in a living body, and a necessary amount of medicine is mixed in the material in advance, so that the microneedle is inserted into the body after puncturing the skin. Three types have been developed which dissolve drugs in the body by decomposing (biodegradation type) (for example, Patent Document 3).
Among these, solid microneedles are easy to mass-produce at the time of molding, and can be provided with a drug application process that is separate from the microneedle manufacturing process. It is attracting attention because it can select a simple production process.

Here, when a drug is administered using the solid type microneedle, the distribution of the drug on the surface of the microneedle greatly affects the efficiency of the drug administration. Specifically, the microneedle is administered into the body by allowing the drug held on its surface to reach the lower layer of the stratum corneum from the through-hole of the stratum corneum, and therefore more into 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 reaching microneedle is larger. In addition, when the microneedle is punctured into the skin, the root portion of the microneedle is in contact with the stratum corneum surface or is located outside the stratum corneum surface, and is thus retained on the root surface of the microneedle. Since it becomes difficult to administer the drug into the body, it is preferable that the amount of the drug retained on the surface on the root side of the microneedle is small.
However, as the microneedle 102 used in the conventional microneedle device 110, as exemplified mainly in FIG. 32, a conical solid shape (a quadrangular pyramid in FIG. 32), that is, from the tip to the base on the base 101 side. Since those having a continuous slope on the side face are used, when a drug is applied to the microneedles 102 using a normal discharge method or dipping method, as illustrated in FIG. There is a problem that more medicine 40 is applied to the root portion than the tip portion of 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 easily adheres to the stratum corneum surface, and the through-hole of the stratum corneum Therefore, there is a problem that it is difficult to reach a sufficient amount of the drug 40 from the skin 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 drug applied to the microneedle exemplified in FIG. 32, and FIG. It is explanatory drawing explaining an example of the administration method of the chemical | medical agent using the microneedle device illustrated to.

Therefore, when applying a drug to the microneedle, a method of selectively applying the drug to the tip side of the microneedle has been attempted (for example, Non-Patent Document 1). However, in this case, since the viscosity of the medicine and the application conditions are limited, there is a problem that the medicine cannot be applied or the process of applying the medicine becomes complicated.
In addition, when a drug is selectively applied to the distal end side, the amount of drug held per microneedle is limited, and therefore it may be difficult to apply a drug necessary for administration. is there. In response, it has been studied to increase the number of microneedles per unit area formed in the microneedle device to increase the amount of drug retained in the entire microneedle device. However, in the microneedle device, since the three-dimensional shape of each microneedle needs to be formed so as to satisfy a certain level, defects tend to occur more easily as the number of microneedles increases. In addition, for the microneedle device after the drug application, the drug needs to be applied to each microneedle, and if it has 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 are problems that the manufacturing process of the microneedle device itself is complicated, and that the inspection after applying the drug to the obtained microneedle device is complicated.

JP 2011-78654 A International Publication No. 2008/139648 Pamphlet Special table 2009-507573

Pham.Res, 2012, Volume29, Number1, Pages 170-177

  The present invention has been made in view of the above circumstances, can administer a drug efficiently, can favorably apply a drug to a microneedle by a simple method, and is a simple production method The main object is to provide a microneedle device that can be manufactured by the method described above.

  In order to solve the above-mentioned problems, the present invention has a base material and a microneedle formed on the base material and including a cone structure that can puncture the skin, and the microneedle is rooted from the tip. A microneedle device 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 the cross-sectional area increasing surface is provided, it is possible to deposit the drug applied from the tip of the microneedle toward the root on the cross-sectional area increasing surface, and thus the cross-sectional area of the microneedle is increased. More drugs can be applied from the surface to the surface on the tip side. Moreover, since the flow of the medicine from the tip toward the root can be suppressed by the cross-sectional area increasing surface, it is possible to suppress the medicine from being applied to the root portion of the microneedle. Therefore, when a drug is administered using the microneedle device of the present invention, the amount of drug held on the tip side of the microneedle punctured inside can be increased more than the stratum corneum of the skin, and the stratum corneum surface Since the amount of the drug held on the base side of the microneedle that contacts the needle can be reduced, waste of the drug can be reduced and administration can be performed efficiently.
In addition, by adjusting the height of the cross-sectional area increasing surface, it is possible to adjust the amount of the drug held on the tip side surface from the cross-sectional area increasing surface of the microneedle.
Further, according to the present invention, since the cross-sectional area increasing surface is provided, the flow of the medicine from the tip toward the root is suppressed by the cross-sectional area increasing surface when the drug is applied from the tip of the microneedle toward the base. Therefore, it is possible to selectively apply the drug from the cross-sectional area increasing surface to the tip side surface. Also, compared to conventional drug application methods, the drug application process can be performed by a simple method because the drug viscosity and application conditions can be relaxed and the drug can be selectively applied. It becomes possible.
In addition, since the surface area of the microneedles itself can be increased by having the cross-sectional area increasing surface, it is possible to increase the amount of drug held per microneedle. Therefore, even when the number of microneedles formed in the microneedle device is reduced, it is possible to make the amount of drug retained in the microneedle device itself desired. Therefore, since the number of microneedles formed on the microneedle device can be reduced, the manufacturing process of the microneedle device, the inspection process of the microneedle device after applying the drug, and the like can be performed more easily. Become.

  In the present invention, the entire microneedle has the cone structure, and is a removal portion formed by removing the side surface of the microneedle in the axial direction of the cone structure from the cross-sectional area increasing surface to the tip side. It is preferable to have. By having the removal portion, it is possible to have the above-described cross-sectional area increasing surface. In addition, by having a removal part, when the microneedle is punctured into the skin, the drug can be held inside the surface of the microneedle that contacts the stratum corneum of the skin, so that the drug adheres to the stratum corneum at the time of puncture It is possible to reduce the amount of the drug, and it becomes possible to administer more drug from the through-hole of the stratum corneum.

  In the present invention, at least one step portion formed on the base material and having the cross-sectional area increasing surface as a step surface, and formed on the step surface of the uppermost step portion, the cone structure is provided. It is also preferred to have a top. By having the step portion, the cross-sectional area increasing portion can be provided. In addition, by providing the step portion, when the drug is applied to the microneedle, the flow of the drug from the tip toward the root can be suitably suppressed at the step surface that is the cross-sectional area increasing surface. Further, since the uppermost three-dimensional shape can be made sharper, it is possible to easily puncture the stratum corneum of the skin. Therefore, it is possible to efficiently penetrate the stratum corneum and efficiently administer the drug.

  The present invention has a base material and a microneedle including a cone structure formed on the base material and capable of puncturing the skin, and the microneedle has a side surface of the microneedle with respect to the axis of the microneedle. That there are at least two places where the inclination of the microneedle changes and a portion where the absolute value of the inclination of the side surface of the microneedle is small is sandwiched between portions where the absolute value of the inclination of the side surface of the microneedle is large A microneedle device is provided.

  According to the present invention, since the microneedle has the above-described structure, it is possible to increase the amount of drug held at the tip portion of the microneedle and to decrease the amount of drug held at the root portion. It becomes.

  According to the present invention, by having the cross-sectional area increasing surface, the drug can be efficiently administered, the drug can be satisfactorily applied to the microneedles by a simple method, and simple manufacturing. There exists an effect that the microneedle device which can be manufactured by the method can be provided.

It is a schematic perspective view which shows an example of the microneedle device of this invention. FIG. 2 is an enlarged view of a portion A in FIG. 1 and is an explanatory diagram illustrating an example of a microneedle in the present invention. It is a schematic sectional drawing of the microneedle device illustrated in FIG. 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 coating method of the chemical | medical agent to the microneedle device of this invention. It is explanatory drawing explaining the other example of the coating method of the chemical | medical agent to the microneedle device of this invention. It is the schematic which shows an example which 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. It is a schematic sectional drawing of the microneedle device illustrated in FIG. 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 coating method of the chemical | medical agent to the microneedle device of this invention. It is explanatory drawing explaining the other example of the coating method of the chemical | medical agent to the microneedle device of this invention. It is the schematic which shows the other example which 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. 2 is a photograph of microneedles formed on a master plate of a microneedle device plate in Example 1 taken using an optical microscope. It is the photograph which image | photographed the microneedle formed in the master plate of the plate for microneedle devices in a comparative example using the optical microscope. It is the photograph which image | photographed what applied 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 which 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 has a base material and a microneedle including a cone structure formed on the base material and capable of puncturing the skin, and the microneedle is directed from the tip toward the 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 increases discontinuously.

The “conical structure” in the present invention is a three-dimensional shape having at least a part of a side surface continuous from the top to the bottom of the cone, or a solid that shares one bottom surface of the column and the bottom surface of the cone (hereinafter, referred to as “conical structure”). A solid shape having at least a part of a side surface continuous from the apex to the bottom.
Further, “the rate of increase in the cross-sectional area parallel to the substrate surface increases discontinuously” means that the cross-sectional area of the microneedle is on the horizontal axis (x-axis) and the height of the microneedle is on the vertical axis In the graph taken on the (y-axis), there are two or more portions where the slope of the graph changes, and a portion that protrudes downward when the cross-sectional area is small and protrudes upward when the cross-sectional area is large. This means that there is one part having a part.
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 the cross-sectional area increasing surface is provided, it is possible to deposit the drug applied from the tip of the microneedle toward the root on the cross-sectional area increasing surface, and thus the cross-sectional area of the microneedle is increased. More drugs can be applied from the surface to the surface on the tip side. Moreover, since the flow of the medicine from the tip toward the root can be suppressed by the cross-sectional area increasing surface, it is possible to suppress the medicine from being applied to the root portion of the microneedle. Therefore, when a drug is administered using the microneedle device of the present invention, the amount of drug held on the tip side of the microneedle punctured inside can be increased more than the stratum corneum of the skin, and the stratum corneum surface Since the amount of the drug held on the base side of the microneedle that contacts the needle can be reduced, waste of the drug can be reduced and administration can be performed efficiently.
In addition, by adjusting the height of the cross-sectional area increasing surface, it is possible to adjust the amount of the drug held on the tip side surface from the cross-sectional area increasing surface of the microneedle.
Further, according to the present invention, since the cross-sectional area increasing surface is provided, the flow of the medicine from the tip toward the root is suppressed by the cross-sectional area increasing surface when the drug is applied from the tip of the microneedle toward the base. Therefore, it is possible to selectively apply the drug from the cross-sectional area increasing surface to the tip side surface. Also, compared to conventional drug application methods, the drug application process can be performed by a simple method because the drug viscosity and application conditions can be relaxed and the drug can be selectively applied. It becomes possible.
In addition, since the surface area of the microneedles itself can be increased by having the cross-sectional area increasing surface, it is possible to increase the amount of drug held per microneedle. Therefore, even when the number of microneedles formed in the microneedle device is reduced, it is possible to make the amount of drug retained in the microneedle device itself desired. Therefore, since the number of microneedles formed on the microneedle device can be reduced, the manufacturing process of the microneedle device, the inspection process of the microneedle device after applying the drug, and the like can be performed more easily. Become.

Here, the microneedle device of the present invention is roughly divided into two modes according to the form of the microneedle. Specifically, the entire microneedle has the cone structure, and is a removal portion formed by removing the side surface of the microneedle in the axial direction of the cone structure from the cross-sectional area increasing surface to the tip side. The first step, and at least one step portion formed on the base material and having the cross-sectional area increasing surface as a step surface; and the step surface of the step portion at the uppermost step, It is roughly divided into two modes, that is, a mode (second mode) having a top portion having a cone structure.
Hereinafter, each aspect will be described.

I. 1st aspect First, the 1st aspect of the microneedle device of this invention is demonstrated.
The microneedle device of this aspect has a base material and a microneedle including a cone structure formed on the base material and capable of puncturing the skin, and the microneedle is directed from the tip toward the root. The cross-sectional area increasing surface formed in a portion where the rate of increase in the cross-sectional area of the cross-section parallel to the substrate surface increases discontinuously, the entire microneedle has the cone structure, It has a removal part formed by removing the side surface of the microneedle in the axial direction of the cone structure on the tip side from the cross-sectional area increasing surface.

  In this embodiment, “the axis of the cone structure” means a perpendicular line (Y in FIG. 3 or the like described later) drawn from the apex of the cone structure to the bottom surface thereof. The axial direction refers to a direction from the side surface toward the center with the perpendicular as the center.

Here, the microneedle device of this aspect is demonstrated using figures. 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 is 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. 3A and 3B are front end sides in a cross section along the cross-sectional area increasing surface of the microneedle device illustrated in FIG. FIG. 3C is a schematic cross-sectional view of the root side, FIG. 3C is a cross-sectional view of the microneedle device illustrated in FIG. 2, and FIG. 3D is a cross-sectional view of the microneedle device illustrated in FIG. FIG. FIG. 4 is a diagram for explaining a cross-sectional area increasing surface in the microneedle illustrated in FIG.
1-4, the microneedle device 10 of this aspect has the base material 1 and the microneedle 2 which is formed on the base material 1 and contains the cone structure which can puncture skin. Moreover, the microneedle 2 has the cross-sectional area increase surface 21 formed in the part which the cross-sectional area of a cross section parallel to the base material 1 surface increases discontinuously toward the base from the front-end | tip. Further, the entire microneedle 2 has a cone structure, and has a removal portion 22 formed by removing the side surface of the microneedle 2 in the direction of the axis Y of the cone structure from the cross-sectional area increasing surface 21 to the tip side. It is characterized by.
As illustrated in FIGS. 3A and 3B, the microneedle 2 in this embodiment has a cross-sectional area increasing surface 21 and a surface of the base material 1 that are parallel to each other. The cross-sectional area of the cross section on the side (FIG. 3B) is larger than the cross-sectional area of the cross section on the tip side (FIG. 3A).
Moreover, the microneedle 2 illustrated in FIG. 2 has a side surface continuous from the apex to the bottom surface of the cone, as illustrated in FIG. 3C as a whole. In this example, an example in which the original three-dimensional shape of the microneedle 2 is a quadrangular pyramid is shown.
Further, in FIGS. 2, 3 (d) and 4, the side surface 22 a (hereinafter referred to as the side surface 22 a) of the microneedle 2 in the removing unit 22 is used as the removing unit 22 on the side surface of the microneedle 2 from the cross-sectional area increasing surface 21. An example is shown in which a groove 22 ′ having a curved surface (which may be referred to as a side surface 22a of the removal portion) is formed. Further, in this example, the groove portion 22 ′ has a semi-elliptical cross-sectional shape parallel to the surface of the substrate 1, and the groove portion 22 ′ on the side surface has a substantially triangular shape.

  In this aspect, it becomes possible to have the cross-sectional area increase surface mentioned above by having the said removal part. Therefore, when the drug is applied in the root direction from the tip of the microneedle, the drug can be selectively applied from the cross-sectional area increasing surface of the microneedle to the surface on the tip side. In addition, the amount of drug applied to the root portion can be reduced. Therefore, since 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 at the root portion can be decreased, It becomes possible to carry out efficiently.

  Here, the case where a chemical | medical agent is apply | coated to the microneedle in the microneedle device of this aspect is demonstrated using figures. FIG. 5 is an explanatory view illustrating an example of a method of applying a drug to the microneedle device of this embodiment. As illustrated in FIG. 5, when coating is performed by ejecting 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 surface of the microneedle 2 from the tip toward the root when the tip of the microneedle 2 is reached. In this aspect, by having the cross-sectional area increasing surface 21, it is possible to receive the drug 40 flowing in the root direction from the tip by the cross-sectional area increasing surface 21 and deposit it on the surface. Therefore, it is possible to increase the amount of the medicine 40 applied from the cross-sectional area increasing surface 21 to the surface on the tip side of the microneedle 2. In addition, since the cross-sectional area increasing surface 21 is provided, it is possible to suppress the flow of the medicine 40 from the tip to the root, so that the amount of the medicine 40 deposited on the root portion can be reduced.

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

  As described above, in this embodiment, since the microneedle 2 has the removal portion 22, it can have the cross-sectional area increasing surface 21. Therefore, the microneedle 2 can be selectively transferred from the cross-sectional area increasing surface 21 to the tip side surface. Since the medicine can be applied, as illustrated in FIGS. 7A and 7B, the amount of the medicine 40 held on the surface on the distal end side from the cross-sectional area increasing surface 21 of the microneedle 2 is increased. Thus, the amount of the medicine 40 held at the root portion can be reduced.

Next, the case where a drug is administered using the microneedle device of this embodiment will be described with reference to the drawings.
FIG. 8 is an explanatory view illustrating an example of a method for administering a drug using the microneedle device of this embodiment. When a drug is administered using the microneedle device 10 of this embodiment, the microneedle 2 coated with the drug 40 is punctured into the stratum corneum of the skin to open a through hole in the stratum corneum, and the microneedle 2 is removed from the through hole. Administration is carried out by reaching the epidermis or the like below the stratum corneum. In the microneedle device 10 of this aspect, the microneedle 2 has the removal part 22 having the cross-sectional area increasing surface 21, thereby increasing the amount of the drug 40 held on the tip side of the microneedle 2. Since the amount of the drug 40 held 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 adhering to the stratum corneum surface can be decreased. be able to. Further, since the medicine 40 can be held in the removing portion 22, the medicine 40 can be held inside the surface of the microneedle 2 that comes into contact with the stratum corneum. Therefore, the medicine that adheres to the stratum corneum at the time of puncture The amount of 40 can be reduced, and the amount of the drug 40 that reaches the inside of the stratum corneum can be increased.

  Therefore, in this aspect, since it can have a cross-sectional area increase surface by having a removal part, compared with the microneedle in the conventional microneedle device, a medicine is put on the tip side of the microneedle by a simple method. It becomes possible to apply selectively. In addition, since a large amount of drug can be held on the surface on the tip side of the microneedle and the amount of 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 this embodiment will be described.

1. Microneedle First, the microneedle in this aspect is demonstrated. Here, the microneedle is a drug applied when the drug is administered into the body using the microneedle device of this embodiment. The microneedle is punctured into the skin to provide a through hole in the stratum corneum. It is used to make a drug reach the lower layer of the stratum corneum.

(1) Structure of microneedle The structure of the microneedle in this aspect is demonstrated.
The microneedle in this aspect has a cross-sectional area increasing surface formed in a portion where the rate of increase in the cross-sectional area of the cross section parallel to the substrate surface increases discontinuously from the tip to the base. The whole microneedle has the cone structure, and has a removal portion formed by removing the side surface of the microneedle in the central direction of the cone structure from the cross-sectional area increasing surface to the tip side. It is.

The microneedle in this aspect is formed so that the whole has a cone structure by forming a removal portion on the side surface thereof, and the three-dimensional shape of the microneedle (hereinafter referred to as the microneedle) without the removal portion. , Which may be referred to as the original three-dimensional shape).
More specifically, as the original three-dimensional shape, when the original three-dimensional shape is a cone, a cone and a polygonal pyramid can be cited, and when the original three-dimensional shape is a column having a cone, a cylinder One having a cone on one bottom surface and one having a polygonal pyramid on one bottom surface of a polygonal column. Moreover, in this aspect, although the axis | shaft of a cone or a cone-shaped column can pass the center of the bottom face of a cone or a cone-shaped column can be used suitably, it is not limited to this.

(A) Cross-sectional area increase surface The cross-sectional area increase surface in this aspect is demonstrated.
The cross-sectional area increasing surface in this aspect is formed in a portion where the rate of increase in the cross-sectional area of the cross section parallel to the substrate surface increases discontinuously from the tip of the microneedle to the base. .
Moreover, the said cross-sectional area increase surface is located in the edge part by the side of the base of the removal part formed in the side surface of a microneedle.

  Such a cross-sectional area increasing surface is not particularly limited as long as the flow of the drug from the tip of the microneedle to the root direction can be suppressed, and the drug can be deposited on the surface thereof. It may be a flat surface, but is preferably a flat surface. There are advantages that it is easy to adjust the area of the cross-sectional area increasing surface and the like, and it is easy to adjust the amount of drug retained in the microneedle.

Further, the angle formed by the cross-sectional area increasing surface and the substrate surface is particularly limited as long as it is possible to suppress the flow of the drug from the tip of the microneedle to the root direction and to deposit the drug on the surface. However, it is preferably within a range of ± 45 °, in particular within a range of ± 30 °, particularly preferably within a range of ± 15 °.
By making the angle formed by the cross-sectional area increasing surface and the substrate surface equal to or less than the above range, the above-described flow of the drug can be more suitably suppressed, and the drug can be suitably deposited on the surface. is there. In this embodiment, it is further preferable that the angle formed by the cross-sectional area increasing surface and the substrate surface is 0 °, that is, the cross-sectional area increasing surface and the substrate surface are parallel. This is because the flow of the medicine can be controlled efficiently. The angle formed by the cross-sectional area increasing surface and the substrate surface is, for example, an angle indicated by θ in FIG. FIG. 9B shows an example in which the angle formed by the cross-sectional area increasing surface and the base material surface takes a positive value. Although not shown, the cross-sectional area increasing surface and the base material surface The angle formed may be a negative value, that is, the inclination of the cross-sectional area increasing surface may be opposite to the inclination illustrated in FIG. 9B.

  Moreover, 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 the cross-sectional area increasing surfaces is not particularly limited as long as one or more microneedles are formed on the microneedles, and is appropriately determined according to the number of removing portions described later. In this aspect, since it is preferable that a plurality of the removal portions are formed, it is preferable that a plurality of the increased cross-sectional areas are formed. Further, when a plurality of cross-sectional area increasing surfaces are formed, it is preferable that the shape of each cross-sectional area increasing surface is the same.

In this embodiment, when a plurality of cross-sectional area increasing surfaces are formed, the height of each cross-sectional area increasing surface 21 (the distance in the vertical direction from the substrate surface to the cross-sectional area increasing surface) is illustrated in FIG. As illustrated in FIG. 9A, they may be equivalent. In this embodiment, the height of the cross-sectional area increasing surface 21 is preferably the same. In this aspect, it is possible to adjust the amount of drug held by the microneedles by adjusting the height of the cross-sectional area increasing surface, but the height of the cross-sectional area increasing surface in a plurality of cross-sectional area increasing surfaces By making them equal, the amount of the drug can be adjusted more easily.
FIG. 9 is an explanatory diagram for explaining another example of the microneedle device according to this embodiment, and FIG. 9A is a schematic perspective view showing another example of the microneedle device according to this embodiment. FIG. 9B is a sectional view taken along line D′-D ′ in FIG. 9A and 9B, the heights of the cross-sectional area increasing surfaces formed on the two opposing surfaces are the same, and the cross-sectional area increasing surfaces formed on the adjacent surfaces are different in height. It is illustrated about. Moreover, since the reference numerals not described in FIGS. 9A and 9B can be the same as those in FIG. 2 and the like, description thereof is omitted here. Further, the height of the cross-sectional area increasing surface means a distance indicated by p1 in FIG. Further, when the cross-sectional area increasing surface has an inclination, it refers to the vertical distance from the base material surface to the midpoint of the height of the cross-sectional area increasing surface, for example, the distance indicated by p1 ′ in FIG. 9B. It shall be said.

  9A and 9B includes a base 1 and a microneedle 2 that is formed on the base 1 and includes a cone structure that can puncture 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 portion 21 where 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 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 axis of the microneedle and the axis of the cone structure usually coincide with each other.

  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 vertical distance 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 10) is 10% or more, especially 20% or more, particularly 30% or more, and the ratio is 90% or less, especially 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, so that when the microneedle device is punctured into the stratum corneum of the skin, the amount of drug that cannot be dissolved into the body may increase. This is because if the ratio exceeds the above range, a desired drug amount may not be applied to the tip portion 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.

  In addition, the specific height of the cross-sectional area increasing surface is appropriately selected depending on the form of the microneedle and the like. For example, the height of the microneedle having a height of about 500 μm is within a range of 50 μm to 450 μm. Especially, it is preferable that it exists in the range of 100 micrometers-400 micrometers, especially in the range of 150 micrometers-350 micrometers.

The area of the cross-sectional area increasing surface is not particularly limited as long as the drug is deposited on the cross-sectional area increasing surface so that a desired drug amount can be retained in the removal portion. It is possible to select appropriately according to the form, application and the like.
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, it is preferably within a 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 surface in the original three-dimensional shape of the microneedle, the form of the removal portion, and the like, and thus the description thereof is omitted here.

(B) Removal part It has the removal part formed by removing the side surface of the said microneedle in the axial direction of the said cone structure from the said cross-sectional area increase surface to the front end side.

Such a removal portion is not particularly limited as long as the microneedle can have a cone structure that can puncture the skin and can have the above-described cross-sectional area increasing surface. In this embodiment, it is preferable that the removal portion 22 is a groove portion 22 ′ as illustrated in FIG. 2 and FIGS.
Here, the groove portion means that the side surface of the removal portion becomes a concave portion with respect to the side surface of the microneedle having no removal portion, and the side surface of the removal portion becomes a curved surface or two or more surfaces.
When the removal part is a groove part, as described above, when the drug is administered using the microneedle in this embodiment, it becomes easier to hold the drug inside the surface of the microneedle that contacts the stratum corneum of the skin. Therefore, it is possible to reduce the amount of drug adhering to the stratum corneum when puncturing the skin, and it is possible to administer more drug into the body through the hole in 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 a substantially polygonal shape. Moreover, when the shape of the said groove part is a substantially polygonal shape, it is preferable that the shape of the said groove part 22 'is a substantially three shape so that it may illustrate in FIG. 1, FIG. 10 (a). This is because it is possible to increase the volume of the groove, and thus it is possible to hold more medicine. The term “substantially polygonal” 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.
Further, as the shape of the groove 22 ', a linear shape can be exemplified as illustrated in FIG. 11 (a) and FIG. Moreover, when the shape of a groove part is linear, although not shown in figure, the width | variety may be made constant and a width | variety may differ partially. When the widths of the groove portions are partially different, it is preferable that the width decreases from the root side to the tip side as illustrated in FIGS. When the shape of the groove 22 ′ is linear, it may be formed linearly from the tip to the root direction as illustrated in FIG. 11A on the side surface of the microneedle, as illustrated in FIG. You may form in a spiral shape.

  The cross-sectional shape of the cross section parallel to the substrate surface of the groove is not particularly limited as long as it can be formed on the side surface of the microneedle, and is, for example, semicircular (not shown), semielliptical Shapes (FIG. 4), triangle shapes (FIG. 10B), quadrilateral shapes (FIG. 11B), polygonal shapes (not shown), and the like.

  The position of the end portion on the tip side of the groove is not particularly limited as long as it is located in a portion from the cross-sectional area increasing surface to the front end, 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).

  FIG. 10 is an explanatory diagram for explaining another example of the microneedle according to the present embodiment, and FIG. 10A is a schematic perspective view illustrating another example of the microneedle according to the present embodiment. ) Is an explanatory view for explaining the shape of the cross-sectional area increasing surface in FIG. FIG. 10 shows an example in which the original three-dimensional shape of the microneedle is a cone. Moreover, FIG. 11 is explanatory drawing explaining the other example of the microneedle in this aspect, FIG.11 (a) is a schematic perspective view which shows the other example of the microneedle in this aspect, FIG.11 (b) ) Is an explanatory diagram 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 columnar body composed of a cone and a cylinder. FIG. 12 is an explanatory view illustrating another example of the microneedle in the present embodiment. Also, reference numerals not described in FIGS. 10 to 12 may be the same as those in FIG.

  The width of the groove is not particularly limited as long as a desired cross-sectional area increasing surface can be formed, and is appropriately selected depending on the shape of the groove, etc., but in the range of 1 μm to 450 μm, Especially, it is preferable to be in the range of 1 μm to 350 μm, particularly 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 surface of the microneedle. If the width of the groove exceeds the above range, This is because there is a possibility that the strength of the microneedles may be remarkably reduced. In addition, the width | variety of a groove part refers to the distance shown by r in FIG.

  The depth of the groove is not particularly limited as long as a desired cross-section increasing surface can be formed, and depends on the height of the cross-sectional area increasing surface and the size of the original three-dimensional shape of the microneedle. It is determined as appropriate. Moreover, it should just be a grade which does not impair the front-end | tip of a cone structure, and is normally formed below the distance from a side surface to an axis | shaft. 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. If the depth of the groove portion is less than the above range, even when a cross-sectional area increasing surface is formed, it is difficult to maintain a desired amount of drug on the surface of the microneedle from the cross-sectional area increasing surface to the tip. This is because there is a possibility that the strength of the microneedle may be significantly reduced when the depth of the groove exceeds the above range. In addition, the depth of a groove part means the distance shown 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 formed by the side surface and the cross-sectional area increasing surface of the groove, and the original three-dimensional shape of the microneedle, Further, it can be appropriately selected depending on 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 groove is formed on the side surface of the microneedle, but a plurality of grooves are preferably formed. This is because the surface area of the microneedle can be increased. In addition, when a plurality of grooves are formed, if the original three-dimensional shape of the microneedle is a cone or a cylinder having a cone, the grooves having the same shape can be formed radially at equal intervals around the tip. preferable. In addition, when the original three-dimensional shape of the microneedle is a polygonal pyramid or a polygonal column having a polygonal pyramid, it is preferable to form the same number of grooves having the same shape on each side surface. By forming the groove portion in this way, when the drug is held on the microneedle, it is possible to reduce the deviation of the drug on the surface on the tip side from the cross-sectional area increasing surface of the microneedle. Moreover, it is because the fall of the intensity | strength of the microneedle by forming a groove part can be made small.

In the microneedle in this aspect, by forming the removal portion, the surface area of the microneedle from the cross-sectional area increasing surface to the tip thereof is made larger than the surface area on the front end side from the position corresponding to the cross-sectional area increasing surface in the original three-dimensional shape. Since the size can be increased, it is possible to increase the amount of the drug held by the microneedles.
As the removal portion in this aspect, the surface area on the tip side from the cross-sectional area increasing surface of the microneedle is 1.2 times or more than the surface area on the front end side from the position corresponding to the cross-sectional area increasing surface in the original three-dimensional shape, Especially, it is preferable to form so that it may become in the range of 1.2 times-2.0 times, especially 1.2 times-1.5 times. Since the removal portion is formed so that the surface area on the tip side from the cross-sectional area increasing surface of the microneedle is 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, the manufacturing process of the microneedle device of this aspect, the inspection process of the microneedle device after applying the drug, and the like can be easily performed.

(Ii) Other removal portion In the above description, the groove portion is described as an example of the removal portion. However, in this embodiment, a removal portion other than the groove portion can also be used. An example of such a removal portion 22 is a notch portion 22 ″ in which the side surface 22a of the removal portion has one plane, as illustrated in FIG. 13. About the depth and width of the notch portion. Is not particularly limited as long as the tip of the cone structure is not damaged.
FIG. 13 is an explanatory diagram for explaining another example of the microneedle according to the present embodiment, and FIG. 13A is a schematic perspective view illustrating another example of the microneedle according to the present embodiment. FIG. 13B is a schematic diagram illustrating a cross-sectional area increasing surface of the microneedle illustrated in FIG.

  Moreover, in this aspect, you 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 has a cone structure as a whole. More specifically, the three-dimensional shape of the microneedle is a three-dimensional shape having at least part of a side surface continuous from the top to the bottom of the cone, and at least part of a side surface continuing from the top to the bottom of the cone column. It has a three-dimensional shape.

  In addition, the microneedle in the present embodiment has the original three-dimensional shape that is the above-described cone or cone column.

In addition, the tip shape of the microneedle in this embodiment is not particularly limited as long as it can puncture the skin and provide a through-hole in the stratum corneum. As illustrated in FIG. 14 (b) may have a curved surface capable of puncturing the skin, and the skin may be punctured as illustrated in FIG. 14 (c). You 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 give the microneedle strength sufficient to puncture the skin. This is because the microneedle device itself becomes large when it exceeds 1, and may be difficult to handle when puncturing the skin.

  The height of the microneedle is not particularly limited as long as it can puncture the skin and administer the drug inside the stratum corneum. Specifically, it is preferably in the range of 20 μm to 1000 μm, in particular in the range of 50 μm to 800 μm, particularly in the range of 150 μm to 750 μm. If the height of the microneedle is less than the above range, it may be difficult to stably puncture the microneedle into the skin. If the height of the microneedle exceeds the above range, This is because the microneedles may be in contact with nerves in the dermis layer, and the 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 a desired drug can be retained, and is appropriately determined depending on the use of the microneedle device. Although those selected, per unit area of the substrate, one ^/ cm 2 ~ 5000 present / cm ² in the range, among them 25 present ^/ cm 2 to 2500 present in the range of / cm ^2,
In particular, it is preferably within the range of 50 / cm ^{2 to} 1000 / cm ² .
Moreover, in this aspect, it is preferable that the number is particularly small in the above-described range for easy manufacture of the microneedle device and easy inspection of the microneedle after application of the drug.

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

  In this embodiment, among the materials described above, a liquid repellent material exhibiting liquid repellency is more preferable. If the microneedle is made of a material with high wettability as a whole, the progress of the drug flowing toward the base material cannot be suppressed on the cross-sectional area increasing surface, and a large amount of drug is applied in the vicinity of the root. This is because the possibility increases. Therefore, when liquid repellency is imparted to the surface of the microneedle, it is possible to more suitably suppress the progress of the drug flowing from the tip toward the substrate when the drug is applied to the microneedle in terms of increasing the cross-sectional area. .

  Here, the liquid repellency in the present embodiment is not particularly limited as long as the drug can be suppressed from being applied to the portion from the cross-sectional area increasing surface to the base, but the microneedle has a surface tension of 72. It is preferable that the contact angle with a liquid (generally water) of about .75 mN / m is 45 ° or more, in particular, the contact angle is 50 ° or more, particularly the contact angle is 70 ° or more. This is because, by setting the liquid repellency of the microneedle to the above-described value, it is possible to easily apply the drug from the cross-sectional area increasing surface to the tip portion. Note that the contact angle with the liquid is 30 by measuring the contact angle with the liquid having the surface tension using a contact angle measuring device (DM500 manufactured by Kyowa Interface Science Co., Ltd.). Seconds later) and can be obtained from the result or as a graph of the result.

  Specific examples of such a material having liquid repellency include polycarbonate, polymethacrylic acid, ethylene vinyl acetate, polytetrafluoroethylene, polyoxymethylene, cycloolefin polymer (COP), and cycloolefin copolymer (COC). Is mentioned. Moreover, in order to give liquid repellency, you may perform what performed additional processes, such as a fluorine process.

(3) Formation method of microneedle The microneedle used for this aspect is normally formed integrally with a base material. Since a specific formation method will be described in the section “4. Manufacturing method of microneedle” described later, description thereof is omitted here.

2. Base material The base material used in this embodiment holds the above-described microneedles.
Such a substrate may be integrated with the above-described microneedle or may be a separate body, but usually the microneedle and the substrate are formed integrally.

  The thickness of the base material is such that the above-described microneedle can be held, and the microneedle device of this aspect can have a strength that can puncture the stratum corneum of the skin. There is no particular limitation. 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. If the thickness of the substrate is less than the above range, it may be difficult to stably form the substrate with a certain thickness when the microneedle and the substrate are formed integrally. When 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 increase. Because there is.

  About the magnitude | size, shape, etc. of the said base material, it can select suitably according to the use etc. of a microneedle device.

  Since the material of the base material can be the same as the material used for the microneedle described above, description thereof is omitted here.

3. Microneedle device The microneedle device of this aspect will not be specifically limited if it has the base material and microneedle which were mentioned above, It is possible to select and add a required structure other than the above suitably.

  The microneedle device of this embodiment is used when various drugs are transdermally administered.

4). Production method of microneedle device The production method of the microneedle device of this embodiment is not particularly limited as long as it is a production method capable of forming the above-described microneedle on a substrate, and production of a general microneedle A manufacturing method similar to the method can be used.

  Specifically, a method of manufacturing a microneedle device by directly forming a microneedle by performing etching processing or mechanical cutting processing on the surface of a base material composed of a microneedle material, and a microneedle and a base material A method of manufacturing a microneedle device by processing a material of the microneedle using a plate for a microneedle device such as a stamper or a mold having a recess corresponding to the above. In the present embodiment, the production method using the microneedle device plate is particularly preferable. This is because the microneedle device can be mass-produced with high accuracy.

  Here, the specific example of the manufacturing method of the microneedle device using the plate for microneedle devices is demonstrated using figures. FIG. 15 is a process diagram showing an example of a manufacturing method of the microneedle device of this embodiment, and is a manufacturing method using an imprint method. In this example, as illustrated in FIG. 15A, a microneedle device plate 50 having a concave portion corresponding to a microneedle and a microneedle material such as a thermoplastic resin is first used. A substrate 10 ′ is prepared. Next, as illustrated in FIG. 15B, the microneedle device substrate 50 is pressed on the surface of the heated microneedle device substrate 10 ′, and then cooled, etc. By curing ', the microneedle 2 is formed on the surface of the substrate 10' for microneedle device, as illustrated in FIG. 15 (c). Next, although not shown, the microneedle device substrate is peeled from the microneedle device substrate, and the microneedle device substrate is molded as necessary. By performing the above process, the microneedle device 10 illustrated in FIG. 15D can be manufactured.

  As the plate for the microneedle device, known stampers and molds used for the microneedle device can be used. For example, it may be formed by subjecting the surface of a metal substrate or the like to mechanical cutting, etc., and after performing etching or cutting on the metal substrate or the like to form a master plate of a microneedle device, The master plate may be formed by electroforming or the like.

  As a processing method using the microneedle device plate, a known processing method used in a microneedle device manufacturing method can be employed. Specific examples include a method of filling a resin such as an imprint method and an injection molding method. Since a specific method for manufacturing a microneedle device using each method is the same as a known method, description thereof is omitted here.

5. Method for Applying Drug to Microneedle As a method for applying a drug to the microneedle in the microneedle device of this aspect, any method can be used as long as the drug can be applied from the tip of the microneedle toward the root portion. It is not limited. For example, a discharge method such as an inkjet method or a dispenser method, or an immersion method such as a dip method can be given.

II. Second Aspect Next, a second aspect of the microneedle device of the present invention will be described.
The microneedle device of this aspect has a base material and a microneedle including a cone structure formed on the base material and capable of puncturing the skin, and the microneedle is directed from the tip toward the root. A cross-sectional area increasing surface formed at a portion where the rate of increase in cross-sectional area parallel to the base material surface increases discontinuously, the cross-sectional area increasing surface being formed on the base material, It has at least 1 level | step-difference part which is a surface, and the uppermost part which is formed in the said level | step surface of the said level | step difference part of the uppermost step, and has the said cone structure.

  Here, “the cross-sectional area increasing surface is a stepped surface” means that the solid side surface above the cross-sectional area increasing surface and the solid side surface below are continuous from the apex to the bottom surface of the cone or columnar column. The side surface of the upper solid and the side surface of the lower solid are not continuous with the cross-sectional area increasing surface as a boundary. Further, it means that there is an upper solid bottom surface inside the outer periphery of the cross-sectional area increasing surface.

Here, the microneedle device of this aspect is demonstrated using figures. FIG. 16 is a schematic perspective view showing an example of the microneedle device of the present embodiment, and FIG. 17 is an enlarged view of a portion E of FIG. 16 and is an explanatory diagram for explaining an example of the microneedle of the present embodiment. FIG. 18 is a schematic cross-sectional view of the microneedle device illustrated in FIG. 18A and 18B are schematic cross-sectional views of the tip side and the root side in the cross section including the cross-sectional area increasing surface of the microneedle illustrated in FIG. 17, and FIG. 18C is a cross-sectional view of FIG. It is the FF sectional view taken on the line of the illustrated microneedle device. FIG. 19 is an explanatory diagram for explaining a cross-sectional area increasing surface in the microneedle device illustrated in FIG. 17.
As illustrated in FIGS. 16 to 19, the microneedle device 10 of this aspect includes a base material 1 and a microneedle 2 that is formed on the base material 1 and includes a cone structure that can puncture the skin. 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 increases discontinuously from the tip to the base. At least one step portion 23 formed on the material 1 and having the above-mentioned cross-sectional area increasing surface 21 as a step surface 23a, and an uppermost portion 24 formed on the step surface 23a of the uppermost step portion 23 and having a cone structure, It is characterized by having.
As illustrated in FIGS. 18A and 18B, the cross-sectional area increasing surface 21 is parallel to the surface of the base material 1, and the cross section including the cross-sectional area increasing surface 21 is a 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 front end side (FIG. 18 (a)).
In addition, the microneedle 2 illustrated in FIG. 17 has a four-sided bottom shape, a stepped portion 23 having a trapezoidal cross-sectional shape in a direction perpendicular to the substrate surface, and a pyramid of a quadrangular pyramid. An example having a top 21 with a structure is shown.
Further, as illustrated in FIG. 19, the uppermost bottom surface exists inside the outer periphery of the cross-sectional area increasing surface 21 that 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 in FIG. FIG. 22 is a cross-sectional view taken along line HH in FIG. In this aspect, 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 stepped portion 231.

  In this aspect, it becomes possible to have the cross-sectional area increase surface mentioned above by having the said level | step-difference part. Therefore, when the drug is applied in the root direction from the tip of the microneedle, the drug can be selectively applied from the cross-sectional area increasing surface to the tip side surface, that is, the cross-sectional area increasing surface and the uppermost surface. In addition, the amount of drug applied to the root portion can be reduced. Therefore, the amount of the drug held on the uppermost surface from the cross-sectional area increasing surface of the microneedle in this embodiment can be increased, and the amount of the drug held on the root portion can be decreased.

Here, the case where a chemical | medical agent is apply | coated to the microneedle in the microneedle device of this aspect is demonstrated using figures. FIG. 23 and FIG. 24 are explanatory diagrams for explaining an example of a method for applying a drug to the microneedles in this embodiment, FIG. 23 is an explanatory diagram for explaining a coating method using a discharge method, and FIG. It is explanatory drawing explaining the coating method using a method.
Also in this aspect, since the microneedle 2 has the stepped portion 23 and thus has the cross-sectional area increasing surface 21, as described in the above-mentioned section “I. First aspect”, The flow can be suppressed by the cross-sectional area increasing surface 21. Therefore, also in this aspect, it is possible to increase the amount of drug applied to the surface on the tip 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 uppermost portion 24. Moreover, in this aspect, since it has the level | step-difference part 23, since the side surface of the uppermost part 24 and the side surface of the level | step-difference part 23 do not have a continuous part, the flow of the medicine which goes to a root from a front end more effectively It becomes possible to suppress. Further, as illustrated in FIG. 23 and FIG. 24, by forming a plurality of stepped portions 23, even if the drug flows from the stepped surface 231 a of the stepped portion 231 formed with the uppermost portion 24 in the root direction, Since the step surface 232a of the step portion 232 positioned at the position can further suppress the flow of the drug in the root direction, the amount of the drug applied to the root portion of the microneedle can be further reduced. .

  As described above, in this embodiment, since the microneedle 2 has the stepped portion 23, the cross-sectional area increasing surface 21 can be provided, so that the microneedle 2 is selectively selected from the cross-sectional area increasing surface 21 to the front surface. The drug can be applied to the skin. Therefore, as illustrated in FIG. 25, the amount of the drug retained on the surface on the distal end side from the cross-sectional area increasing surface 21 of the microneedle 2 can be increased, and the amount of the drug retained on the root portion can be decreased. be able to.

Next, the case where a drug is administered using the microneedle device of this embodiment will be described with reference to the drawings.
FIG. 26 is an explanatory diagram showing an example of a drug administration method using the microneedle device of this embodiment. In the microneedle device 10 of this aspect, since the microneedle 2 has the stepped portion, it becomes possible to have the cross-sectional area increasing surface 21, and thus the amount of the medicine 40 held on the tip side of the microneedle 2 Since the amount of the drug 40 held on the root side of the microneedle can be reduced, the amount of the drug 40 that reaches the lower layer of the stratum corneum can be increased, and the drug that adheres to the stratum corneum surface The amount of 40 can be reduced. Moreover, in this aspect, since the shape of the uppermost portion 24 is made sharper, it is possible to more easily puncture the skin and easily form a through-hole, so that the drug 40 can be administered better into the body. Is possible.

  Therefore, in this aspect, since it can have a cross-sectional area increasing surface by having a step part, compared with the microneedle in the conventional microneedle device, the drug is applied to the tip side of the microneedle by a simple method. 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 this 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 at a portion where the rate of increase in the cross-sectional area of the cross section parallel to the base material direction increases discontinuously from the tip to the base. And at least one step portion formed on the base material and having the cross-sectional area increasing surface as a step surface, and an uppermost portion formed on the step surface of the step portion at the uppermost step and having the cone structure. It is what has.

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

  Such a cross-sectional area increasing surface is not particularly limited as long as the flow of the drug from the tip of the microneedle to the root direction can be suppressed, and the drug can be deposited on the surface thereof. It may be a flat surface, but is preferably a flat surface. The reason for this can be the same as the reason described in the above-mentioned section “I. First Mode”, and will not be described here.

  In addition, the angle formed by the cross-sectional area increasing surface and the substrate surface can be the same as the reason described in the above-mentioned section “I. First Mode”, 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 is appropriately determined depending on 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 microneedles and the specific height of the cross-sectional area increasing surface may be the same as those described in the above section “I. First aspect”. Since it is possible, description here is abbreviate | omitted.
In addition, in this aspect, when the microneedle has a plurality of step portions, it means the height of the cross-sectional area increasing surface on which the uppermost portion is formed, and the distance indicated by p2 in FIGS. 18 (c) and 22 Say.

  The area of the cross-sectional area increasing surface is not particularly limited as long as the drug is deposited on the cross-sectional area increasing surface so that a desired drug amount can be retained in the removal portion. It is possible to select appropriately according to the form, application and the like. 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, and thus the description thereof is omitted here.

  About the shape of a cross-sectional area increase surface, it selects suitably according to the cross-sectional shape parallel to the level | step-difference part mentioned later and the uppermost base material surface.

(B) Level difference part The level difference part in this aspect is formed on a base material, and uses the cross-sectional area increase surface mentioned above as a level | step surface. Moreover, the uppermost part mentioned later is formed on the uppermost step surface.

  The shape of the bottom surface of the stepped portion is not particularly limited as long as it can be formed on a substrate and can give the microneedle strength enough to puncture the skin. For example, a circular shape and a polygonal shape can be mentioned.

  Further, the cross-sectional shape in the direction perpendicular to the base material 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). Thus, the side surface of the stepped portion may be formed in a trapezoidal shape so as to have an inclination, and the side surface of the stepped portion 23 is perpendicular to the substrate as illustrated in FIGS. It may be formed as follows. FIG. 27 is an explanatory diagram for explaining another example of the microneedle according to the present embodiment. FIG. 27A is a schematic perspective view illustrating another example of the microneedle according to the present embodiment, and FIG. ) Is a cross-sectional view taken along the line II of FIG. Also, reference numerals not described in FIG. 27 can be the same as those in FIG. 17 and the like, and thus description thereof is omitted here.

  In addition, at least one stepped portion in this aspect may be formed, and one step may be formed on the substrate 1 as illustrated in FIG. 16 and the like, as illustrated in FIG. 20 and the like. A plurality may be formed. In this aspect, it is preferable that a plurality of step portions are formed. By having a plurality of stepped portions, the cross-sectional area of the stepped portion located in the lower layer is increased even when the medicine applied from the top of the topmost portion cannot be held on the cross-sectional area increasing surface (step surface) on which the topmost portion is formed. Since the drug can be received by the surface (step surface), it is possible to reduce the drug applied to the base side.

The number of steps in this aspect is not particularly limited as long as it is at least 1 or more,
It is preferable that it is 1 or more, especially in the range of 1 to 10, particularly in the range of 1 to 5. By setting the number of steps to be in 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 according to the use of the microneedle, and is about 50, for example. It is because it may become difficult to form a microneedle stably when exceeding the said value.

(C) Uppermost part The uppermost part in this aspect is formed on the step surface of the uppermost step part and has a cone structure.

  The uppermost formation position is not particularly limited as long as it is on the inner side of the step surface, that is, the outer periphery of the cross-sectional area increasing surface. Is preferred. This is because the microneedle can be stably punctured into the skin.

  The uppermost three-dimensional shape is not particularly limited as long as it has a cone structure that can puncture the skin. Specifically, it may be a cone as illustrated in FIG. 16 or the like, and may be a pyramidal column, although not shown. Further, as illustrated in FIG. 28, a cone having an uppermost removal portion 25 formed by removing the cone and the columnar column from the original three-dimensional shape and removing the side surface in the axial direction of the cone structure. It may be a body structure. In this aspect, it is preferable that the uppermost three-dimensional shape has a cone structure having the uppermost removal portion. As described above, it is possible to hold more drug on the tip side of the microneedle by having the removal portion, and it is possible to administer the drug more efficiently using the microneedle device of this aspect. Because it becomes.

  The uppermost removal portion is not particularly limited as long as it is formed on the side surface of the uppermost portion. However, as illustrated in FIG. 28, the position of the end portion on the root side of the uppermost removal portion 25 is stepped. It is preferably formed on the tip side from the cross-sectional area increasing surface 21 which is the surface, that is, the stepped surface 23. Since the area of the cross-sectional area increasing surface on which the uppermost part is formed can be increased, and the surface area on the tip side from the cross-sectional area increasing surface of the microneedle can be increased, It becomes possible to increase the amount of drug that can be retained.

  The removal unit for the uppermost part can be the same as the removal unit described in the above-mentioned section “I. First Mode”, and thus the description thereof is omitted here.

  The shape of the uppermost bottom surface is not particularly limited as long as the uppermost portion can be formed on the step surface of the uppermost step portion, and may have the same shape as the step surface. It may be. In this aspect, it is preferable that the shape of the uppermost bottom surface or the uppermost original three-dimensional shape is similar to the shape of the stepped surface of the stepped portion. This is because the area of the step surface can be easily adjusted, and the uppermost portion can be stably formed on the step surface.

(C) Three-dimensional shape of microneedle The microneedle in this aspect has the step part mentioned above and the uppermost part. Such a three-dimensional shape of the entire microneedle does not constitute a cone structure.

  Further, in this aspect, usually, the top surface area and the surface area of the step surface on which the top portion is formed are a cone or a weight having the step surface of the top step portion as the bottom surface and the top vertex as the vertex. It is formed to be larger than the surface area of the columnar body. Regarding the relationship between the sum of the surface areas of the top and step surfaces and the surface area of the cones or spindles described above, the cross-sectional area increasing surface of the microneedle described in “I. First aspect” described above Since the surface area on the front end side and the surface area on the front end side from the position corresponding to the cross-sectional area increasing surface in the original three-dimensional shape can be made the same, description thereof is omitted here.

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

(2) Microneedle The microneedle can be the same as that described in the above-mentioned section “I. First aspect” except for the structure of the microneedle described above. To do.

2. Others Regarding the microneedle device of this aspect, the matters other than the above-described microneedle can be the same as those described in the item “I. First aspect” described above. To do.

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

  This aspect is not limited to the above embodiment. The above-described embodiment is an exemplification, and this embodiment has substantially the same configuration as the technical idea described in the claims of this embodiment and exhibits any similar effect. Are included in the technical scope.

  Hereinafter, the microneedle device of the present invention will be specifically described with reference to Examples and Comparative Examples.

[Example 1]
(Preparation of microneedle device plate)
As shown in FIG. 29, a concave portion is formed on the side so that there is a step at a base of 0.35 mm × 0.35 mm, a height of 0.5 mm, and a height of 0.25 mm from the tip. A master plate of 100 microneedles having 10 protrusions arranged vertically and horizontally at a pitch of 1 mm was prepared to obtain a master plate.
Next, in order to duplicate the microprotrusions of the microneedle of the master plate of the prepared microneedle device, electroforming is performed using nickel to make a replica master (microneedle device plate) from the master plate, A plate for a microneedle device having an intaglio plate opposite 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 ZEONOR (manufactured by ZEON Corporation, model number Zeonor 1060R), which is a cycloolefin polymer, is a cyclic olefin resin. Incidentally, the glass transition temperature of the used cycloolefin polymer 1060R: 100 ° C., MFR: 280 ° C., 21.18 N, 60 g / min.
The zeonore sheet, which is the cycloolefin polymer, is heated to 120 ° C. that is equal to or higher than the glass transition temperature (100 ° C.), and the zeonore sheet is heated at 120 ° C. that is equal to or higher than the glass transition temperature. The above-mentioned microneedle device plate is cooled while being pressed and pressed, and after the temperature has been sufficiently lowered to near room temperature, hot pressing (thermal imprint) is performed to peel in the cone length direction. Thus, a resin microneedle device having the same shape as the master shape described above was obtained.

[Example 2]
A microneedle device was produced in the same manner as in Example 1 except that the microneedle device plate was produced as follows.
By cutting into metal, a step is formed at a base of 0.35 mm x 0.35 mm, a height of 0.5 mm, and a height of 0.25 mm from the tip. 100 microneedle master shapes in which 10 protrusions with 1 mm pitch are arranged vertically and horizontally on the four side surfaces of the shaped protrusions by carrying out counterbore processing by cutting. To obtain a master version.
Next, in order to duplicate the microprotrusions of the microneedle of the master plate of the prepared microneedle device, electroforming is performed using nickel to make a replica master (microneedle device plate) from the master plate, A plate for a microneedle device having an intaglio plate opposite to the master shape was obtained.

[Comparative example]
A microneedle device was produced in the same manner as in the example except that the microneedle device plate was produced as follows.
A master shape of 100 microneedles in which 10 pieces of square pyramid-shaped protrusions with a base of 0.25 mm x 0.25 mm and a height of 0.5 mm are arranged vertically and horizontally at a pitch of 1 mm by cutting into metal. (FIG. 30). Next, in order to duplicate the microprotrusions of the microneedle of the master plate of the prepared microneedle device, electroforming is performed using nickel to make a replica master (microneedle device plate) from the master plate, A plate for a microneedle device having an intaglio plate opposite to the master shape was obtained.

[Evaluation]
(Surface of microneedle after drug application)
The following chemical solutions were prepared, and dispensers (made by Musashi Engineering Co., Ltd .: SHOTminiα) were employed, and the chemical solutions were quantitatively dispensed into the chemical solution supply nozzle openings to produce in Examples 1, 2 and Comparative Examples. The chemical solution dispensed to the microneedle of the microneedle device was contact-transferred and applied.
The prepared chemical solution used was polyvinylpyrrolidone (manufactured by Nippon Shokubai Co., Ltd .: PVP K-90 0.06 g) and caffeine (manufactured by Wako Pure Chemical Industries, Ltd.) 0.02 g dissolved in 1 g of purified water.
The chemical solution is filled in the chemical solution container of the dispenser chemical solution dispensing device, the dispenser chemical solution dispensing device is set, and the dispenser chemical solution dispensing is performed on the tip portion of 100 microneedles on the substrate of the microneedle device. The surface of the microneedle is brought into contact with a nozzle (Musashi Engineering Co., Ltd .: SN-LF series 32G, nozzle opening inner diameter: 0.1 mmφ) with a predetermined amount of liquid dispensed in 0.1 MPa and 0.05 sec. The transfer was applied. The coating process was performed once for each microneedle, and a microneedle device coated with a drug was obtained.
The coating shape when applied was confirmed with an optical microscope. The results are shown in FIG. FIG. 31A is a photograph of Example 1 taken with an optical microscope, and FIG. 31B is a photograph taken with an optical microscope of a comparative example.

  In Example 1 and Example 2, application by the dispense method was performed, and it was easy to hold the tip near the cross-sectional area increasing surface, and all 100 out of 100 could be applied. In Comparative Example 1, when dispensing at the tip, 50 or more of the 100 may be applied to the vicinity of the root, and it is difficult to manufacture microneedles with the tip applied to the tip in all 100. It was.

(About drug retention)
The amount of caffeine mounted on the surface from the tip of the microneedle in Examples 1 and 2 and the comparative example to a height of 0.25 mm was determined as follows. First, the microneedle devices after drug application are stirred in methanol all day and night, quantified by high performance liquid chromatography (HPLC), and the average value per 100 microneedles on each device is determined. 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. The surface area of the uppermost side surface in Example 1 and the surface area of the side surface up to a height of about 0.25 mm from the tip in the comparative example can be made equal.

  From these results, it can be seen that a microneedle device having a large amount of drug retained from the cross-sectional area increasing surface to the vicinity of the tip can be easily manufactured by adopting 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 part 23a, 231a, 232a ... Step surface 24 ... Top part

Claims (4)

A substrate;
A microneedle comprising a cone structure formed on the substrate and capable of puncturing the skin and clogged inside ;
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 base,
The entire microneedle has the cone structure,
The cross-sectional area increasing surface is formed between the top and bottom of the cone structure,
The removal part formed by removing the side surface of the microneedle in the axial direction of the cone structure only in the tip side region from the cross-sectional area increasing surface,
The original three-dimensional shape of the microneedle is a shape having a polygonal pyramid, and as the removal portion, at least two or more grooves of the same shape are formed on the side surface so as to be pointed with the apex portion of the polygonal pyramid as a center point. Formed ,
The groove part has an exposed surface facing the outer peripheral side of the microneedle. A substrate;
A microneedle comprising a cone structure formed on the substrate and capable of puncturing the skin and clogged inside ;
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 base,
The entire microneedle has the cone structure,
The cross-sectional area increasing surface is formed between the top and bottom of the cone structure,
The removal part formed by removing the side surface of the microneedle in the axial direction of the cone structure only in the tip side region from the cross-sectional area increasing surface,
When the three-dimensional shape of the prototype of the microneedle is a shape having a cone, a plurality of grooves having the same shape are formed at equal intervals radially as the removal portion, and the prototype of the microneedle When the three-dimensional shape is a shape having a polygonal pyramid, the same number of groove portions of the same shape are formed on each side of the polygonal pyramid as the removal portion ,
The groove part has an exposed surface facing the outer peripheral side of the microneedle.   The microneedle has a surface area having the removal portion from the cross-sectional area increasing surface to the tip side 1.2 times the surface area on the front end side from a position corresponding to the cross-sectional area increasing surface in the original three-dimensional shape. It is the above, The microneedle device of Claim 1 or Claim 2 characterized by the above-mentioned.   4. The microneedle device according to claim 1, wherein a ratio of a height of the cross-sectional area increasing surface to a height of the microneedle is 10% or more. 5.

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