JP6943517B2 - Microneedle and microneedle array - Google Patents

Description

The present invention relates to microneedles and microneedle arrays that reduce mechanical irritation on the skin surface or stratum corneum of the user upon insertion.

As a method for transdermally administering useful components such as drugs, vaccines, and skin-beautifying components into the body, a method using a microneedle array in which minute microneedles are dispersed and arranged on a base sheet has become widespread in recent years (for example, Patent Document 1). , 2). In transdermal administration, it is known that the stratum corneum functions as a barrier layer, but by penetrating the stratum corneum with microneedles, it becomes possible to efficiently administer useful components into the body. As a method of imparting a useful component for administration to a microneedle, a method of supporting the useful component on the surface of the microneedle, a method of containing the useful component in a material constituting the microneedle, and the like are known. Further, dissolved microneedles (for example, Patent Document 3) using a biodegradable polymer that can be a useful component by itself such as hyaluronic acid are also spreading.

The microneedle is long enough to pass through the stratum corneum, which does not allow substances to pass through, and does not reach the dermis layer, which has many pain points, and is less than 1/10 the outer diameter of a general injection needle. Therefore, the greatest advantage is that the pain when a hole is formed in the skin is suppressed as compared with the method of administering the drug subcutaneously using an injection needle.

However, when the microneedles are inserted into the surface layer of the skin or the stratum corneum, mechanical irritation is generated due to friction between the side surface of the microneedles and the body tissue, which causes discomfort and pain.
To further reduce the mechanical irritation of the microneedles, there is a method of making the microneedles thinner, but the disadvantage is that the microneedles lack mechanical strength and break at the epidermis when the microneedles are pierced into the skin. There is. In addition, when the microneedles are made thinner, there is a drawback that the thinner the microneedles, the less useful components are in the type of microneedles in which the constituent materials contain useful components and the dissolved microneedles in which the constituent materials themselves also act as useful components. There was also.
There is also a method of coating the surface of the microneedle with a lubricating component in order to suppress mechanical irritation (for example, Patent Document 4), but this method has not been a complete solution either.

JP-A-2017-143963 Japanese Unexamined Patent Publication No. 2016-195651 Japanese Patent No. 6634623 Japanese Unexamined Patent Publication No. 2010-29634

As described above, in order to suppress the mechanical stimulation when the microneedle is inserted, the actual situation is that there are the above-mentioned problems.
Under such circumstances, an object of the present invention is to provide microneedles and microneedle arrays that reduce mechanical irritation in the skin surface layer or the skin stratum corneum when the microneedles are inserted.

As a result of intensive research to solve the above problems, the present inventor has found that if a groove (recess) is provided on the side surface of the microneedle, the contact area in the body is reduced and the mechanical stimulation is reduced. It led to the invention.

That is, the present invention relates to the following invention.
<1> A dissolution-type microneedle for piercing the skin to absorb useful components into the body, and a groove is formed on the side surface of the microneedle to reduce the contact area.
<2> The microneedle according to <1>, wherein the material is a biodegradable polymer.
<3> The microneedle according to <1> or <2>, wherein the number of grooves is 2 or more.
<4> The microneedle according to <3>, wherein the grooves have the same shape and are formed at equal intervals.
<5> The microneedle according to any one of <1> to <4>, wherein the shape of the microneedle is a cone or a cone-shaped column.
<6> The microneedle according to <5>, wherein the groove portion is formed so that a part of the side surface of the cone or the cone-shaped prism is recessed in the axial direction of the cone or the cone-shaped prism.
<7> The microneedle according to <6>, wherein the shape of the microneedle is conical.
<8> The microneedle according to <7>, wherein the groove portion is formed radially from the middle of the side surface of the cone to the bottom portion centering on the tip end.
<9> The microneedle according to <6>, wherein the shape of the microneedle is a conical prism, and the groove is formed radially from the middle of the side surface of the conical prism to the bottom centering on the tip.
<10> A microneedle array in which the microneedles according to any one of <1> to <9> are dispersed and arranged on a base sheet.
<11> The microneedle array according to <10>, wherein the microneedle and the base sheet are integrally molded.
<12> A microneedle patch comprising the microneedle array according to <10> or <11>.

According to the present invention, there are provided microneedles and microneedle arrays that reduce mechanical irritation when inserted into the body and suppress pain.

It is a schematic perspective view of the microneedle array which concerns on embodiment of this invention. It is explanatory drawing of the microneedle which comprises the microneedle array which concerns on embodiment of this invention, (a) is a plan view, (b) is a schematic perspective view. It is a modification of the microneedle according to this embodiment, (a) is a plan view, and (b) is a schematic perspective view. It is another modification of the microneedle according to this embodiment, (a) is a plan view, and (b) is a schematic perspective view. It is another modification of the microneedle according to this embodiment, (a) is a plan view, and (b) is a schematic perspective view. It is another modification of the microneedle according to this embodiment, (a) is a plan view, (b) is a front view, and (c) is a schematic perspective view. It is another modification of the microneedle according to this embodiment, (a) is a plan view, and (b) is a schematic perspective view. It is another modification of the microneedle according to this embodiment, (a) is a plan view, and (b) is a schematic perspective view. It is the schematic perspective view of the other modification of the microneedle which concerns on this embodiment. It is another modification of the microneedle according to this embodiment, (a) is a plan view, (b) is a front view, and (c) is a schematic perspective view. It is the schematic perspective view of the other modification of the microneedle which concerns on this embodiment. It is an optical microscope photograph of the master mold which concerns on Example 1, (a) is a plan view (magnification 80 times), (b) is a perspective view (magnification 30 times). It is an optical micrograph (magnification 80 times) of the convex part (needle) of the master mold which concerns on Example 1. It is an optical micrograph of the microneedle array of Example 1, (a) is a plan view (magnification 80 times), (b) is a perspective view (magnification 30 times). It is an optical micrograph (magnification 80 times) of the microneedle formed in the microneedle array of Example 1. FIG. It is an optical micrograph of a microneedle patch to which the microneedle array of Example 1 is attached, (a) is a plan view, and (b) is an enlarged view (magnification 15 times) of a microneedle array. It is an optical micrograph of the master mold which concerns on Example 2, (a) is a plan view (magnification 80 times), (b) is a perspective view (magnification 30 times). It is an optical micrograph (magnification 80 times) of the convex part (needle) of the master mold which concerns on Example 2. It is an optical micrograph of the microneedle array of Example 2, (a) is a plan view (magnification 80 times), (b) is a perspective view (magnification 30 times). It is an optical micrograph (magnification 80 times) of the microneedle formed in the microneedle array of Example 2. FIG. It is an optical micrograph of a microneedle patch to which the microneedle array of Example 2 is attached, (a) is a plan view, and (b) is an enlarged view (magnification 15 times) of a microneedle array.

Hereinafter, the present invention will be described in detail with reference to examples and the like. When the expression "-" is used in the present specification, it is used as an expression including numerical values before and after the expression.

The present invention is a dissolution type microneedle for piercing the skin to absorb useful components into the body, and a microneedle having a groove formed on a side surface of the microneedle to reduce the contact area (hereinafter referred to as “microneedle”). It is referred to as "the microneedle of the present invention").

The microneedles of the present invention are used to pierce the skin to reach the surface layer and the stratum corneum (and the lower layer of the stratum corneum) of the skin with useful components. The microneedle of the present invention is characterized in that a groove for reducing the area is formed on the side surface thereof. The non-removed portion of the microneedle that comes into contact with the surface layer of the skin and the stratum corneum (and the lower layer of the stratum corneum) when the microneedle is pierced into the skin by this groove (a portion other than the groove on the side surface, detailed in the embodiment). Since the area of the skin is reduced and the mechanical irritation is reduced, the pain when piercing the skin can be reduced.
The non-removed portion of the microneedle is, for example, 95% or less, 90% or less, 80% or less, 70% or less, 60% or less, assuming that the area of the side surface of the basic shape of the microneedle is 100%. It tends to reduce pain when piercing the skin. The lower limit of the area of the non-removed portion of the microneedle is not particularly limited as long as the mechanical strength is maintained, but the area of the side surface of the basic shape of the microneedle is 100%, for example, 10% or more, 20% or more. , 30% or more, 40% or more, 50% or more.

In the present invention, the "useful ingredient" may be any ingredient that can be administered transdermally and is useful, and all chemical substances (raw materials for drugs and cosmetics, etc.) that can be used for percutaneous absorption are targeted, depending on the purpose. Can be selected as appropriate.

The shape, size, and material of the microneedle of the present invention may not impair the effect of the present invention (reduction of pain when piercing the skin) and may satisfy the purpose of use (for example, the amount of the desired useful component). Details of the microneedle of the present invention will be described later together with the embodiment.

It is preferable that the microneedle of the present invention is a soluble type and the material is a biodegradable polymer. In addition to the biodegradable polymer, the microneedle of the present invention may contain other useful components as long as the object and effect of the present invention are not impaired. Details will be described later.

In the microneedle of the present invention, at least one groove may be formed on the side surface of the microneedle, but it is preferable that two or more (s) are formed, and more preferably three or more and four or more. The upper limit of the number of grooves is not particularly limited as long as it can maintain mechanical strength and can be stably formed, but is, for example, 30 or less, 10 or less, and 8 or less.

In the microneedles of the present invention, the shapes of the grooves may be the same or different, but they are preferably the same. Further, the intervals of the grooves may be the same or different, but they are preferably the same (equal intervals).

The microneedle of the present invention is usually used as a microneedle array (hereinafter, referred to as "microneedle array of the present invention") dispersed and arranged on a base sheet.
In the microneedle array of the present invention, the shape, dimensions, and number of microneedles to be arranged, and the method of arranging the microneedles on the base sheet and the conditions of the arrangement range are the effects of the present invention (on the skin). It is not particularly limited as long as it does not impair (reduction of pain at the time of stinging) and can satisfy the purpose of use (for example, the amount of the target useful ingredient).
In addition, in the microneedle array of the present invention, it is preferable that the microneedles to be arranged and the base sheet are integrally molded using the same material. An example in which hyaluronic acid is used as a material will be described later in Examples.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings, but the present invention is not limited to the following embodiments, and can be arbitrarily modified and implemented without departing from the gist of the present invention. ..

<Microneedle array>
FIG. 1 shows a schematic schematic diagram of a microneedle array according to a typical embodiment of the present invention.
As shown in FIG. 1, in the microneedle array 1 according to the embodiment of the present invention, a plurality of microneedles 20 are dispersedly arranged (erected in a predetermined arrangement pattern) on the base sheet 10. In FIG. 1, in order to facilitate understanding of the structure of the microneedle array 1, the microneedles 20 with respect to the base sheet 10 are shown larger than they actually are, and the number (density) is shown to be smaller than the actual size.

The base sheet 10 may have a plurality of microneedles 20 erected in a predetermined arrangement pattern, and the size, thickness, and shape can be selected according to the purpose.

The material of the base sheet 10 may be appropriately selected depending on the intended use of the microneedle array 1 as long as the microneedles 20 can be erected in a predetermined arrangement pattern.
For example, the microneedle array can be used as a so-called microneedle patch. Here, the patch means a sheet to which the microneedle array according to the present invention is attached and the surface to which the microneedle array is attached is attached to the skin. The patch that secures the microneedle array is made of a flexible material, and also has an adhesive sheet for adhesion to the skin and protection to protect the adhesive sheet and support the microneedle array when it is attached to the skin. It can also be used by adding a release sheet or the like. The patch material is arbitrary as long as the object of the present invention is not impaired. For example, a resin such as polyethylene, polypropylene or polystyrene, or a bionon-degradable material such as paper, non-woven fabric or cloth may be used. Biodegradable materials such as polylactic acid, polyethylene glycol and polypropylene glycol may be used.

The size and thickness of the patch that fixes the microneedle array is not particularly limited, and depends on the size, material, and placement density of the microneedle in the microneedle array, and the part where the microneedle patch is used (the part where the skin is attached). It can be adjusted as appropriate. Further, the shape can be various shapes such as a circular shape, an elliptical shape, a magatama shape, and a face-shaped mask.

The microneedle 20 is a needle-like body whose diameter decreases toward the tip side, and a plurality of grooves for reducing the area of the side surface of the microneedle are formed. Details of the microneedle will be described later.

Each condition regarding the shape and size of the microneedle 20 and the arrangement pattern of the microneedle 20 on the base sheet 10 is particularly limited as long as the intended use of the microneedle array 1 (for example, the amount of the desired useful component) can be satisfied. It can be selected as appropriate.

The number (density) of microneedles 20 arranged on the base sheet 10 is appropriately selected according to the intended use of the microneedle array 1. For example, there are 10 to 5000 ^{sheets in a range of 1 cm 2 of the base sheet 10.}

The arrangement region 30 is a region of the base material sheet 10 in which a group of microneedles composed of a plurality of microneedles 20 exists.

The shape and size (area) of the arrangement region 30 are appropriately determined according to the purpose of the microneedle array. In FIG. 1, in the arrangement region 30, the microneedles 20 are dispersedly arranged vertically and horizontally on the base sheet 10 so as to form a rectangle in a plan view, but the present invention is not limited to this, and the microneedle array 1 Depending on the purpose of use, other regular arrangements (arranged in a circular or elliptical shape in a plan view) may be used, or randomly distributed arrangements may be made. The arrangement may be different in each arrangement area 30.

Further, the shape and size of the non-arranged region 40, which is the region on the base sheet 10 where the microneedles 20 do not exist, are appropriately determined according to the purpose of use of the microneedle array 1.

(Microneedle)
The microneedle of the present invention will be described. Here, the microneedle is used to pierce the skin and reach the surface layer and the stratum corneum (and the lower layer of the stratum corneum) of the skin when the useful component is administered into the body using the microneedle array. It is a thing.

The microneedle according to the present invention has a basic shape of a needle-like body that tapers toward the tip side, and a groove portion for reducing the area of the side surface of the microneedle is provided on the side surface thereof.

In the present specification, the "basic shape (of the microneedle)" means the three-dimensional shape of the microneedle in a state without a groove.

The shape of the microneedle of the present invention is a cone shape or a cone-shaped pillar shape as a basic shape. In the present specification, the "pyramid shape" is a shape that gathers from the bottom surface to the apex, and includes a conical shape and a polygonal pyramid. Further, the "pyramid prism shape" means a three-dimensional shape that shares one bottom surface of the prism and the bottom surface of the pyramid, and has a shape having a cone on one bottom surface of the prism and one bottom surface of a polygonal prism. Includes a shape with a polygonal pyramid.

When the basic shape of the microneedle of the present invention is a cone shape or a cone-shaped pillar shape, it is drawn from the axis of the cone or the cone-shaped pillar (the tip (apical) of the cone or the cone-shaped pillar to the bottom surface). It is preferable that the vertical line passes through the center of the bottom surface of the cone or the cone-shaped column, but the present invention is not limited to this.

The height of the microneedles (the vertical distance from the surface of the base sheet to the tip of the microneedles) is appropriately determined according to the application of the microneedles, and is, for example, in the range of 0.5 to 1000 μm. It is typically 30 to 500 μm.

The diameter of the bottom surface (contact surface between the base sheet and the microneedles) of the microneedles is appropriately determined according to the application of the microneedles, and is typically about 0.1 to 500 μm. Is 10 to 200 μm. The "diameter of the bottom surface of the microneedle" means the diameter when the bottom surface of the microneedle is a circle, the major axis when the bottom surface is an ellipse, and the diameter of the circumscribed circle when the bottom surface is a polygon.

Further, the shape of the tip of the microneedle in this embodiment may be any shape as long as it is possible to pierce the skin and provide a through hole in the surface layer or the stratum corneum of the skin. That is, it may have a curved surface or a flat surface capable of piercing the tip-shaped skin.

In the present specification, the "groove portion" is a recess (dent) with respect to the side surface of the microneedle (the basic shape of the microneedle when there is no groove), and the surface forming the recess is a curved surface or 2 It shall mean something that is more than a surface.

By having the groove, when the microneedle is pierced into the skin, the surface area of the microneedle that comes into contact with the surface layer of the skin and the stratum corneum (and the lower layer of the stratum corneum) is reduced, and the mechanical irritation is reduced. You can reduce the pain at the time.

In the present invention, the number and arrangement of grooves in the microneedle are not particularly limited as long as the object of the present invention can be achieved. The number of grooves is preferably 2 or more, and 3 or more and 4 or more. The upper limit of the number of grooves is not particularly limited as long as it can maintain mechanical strength and can be stably formed, but is, for example, 30 or less, 10 or less, and 8 or less. Further, the intervals of the grooves may be the same or different, but they are preferably the same (equal intervals).

The shape of the groove on the side surface of the microneedle is not particularly limited as long as the object of the present invention can be achieved. For example, it is preferable that the groove portion is formed so that a part of the side surface of the cone or the cone-shaped prism constituting the microneedle is recessed in the axial direction of the cone or the cone-shaped prism. Here, the "axial direction of the cone or the pyramidal prism" is the direction drawn from the tip of the cone or the pyramidal prism to the bottom surface (the direction of the perpendicular line).
Further, the cross-sectional shape parallel to the base sheet of the groove portion is preferably a substantially semicircular shape or a substantially polygonal shape. Here, the substantially semicircular shape includes not only a circle but also an ellipse, and the substantially polygonal shape includes not only a polygon but also a case where a part of a corner portion is formed in a curved shape. The width of the groove is appropriately determined according to the size and application of the microneedle, and is, for example, about 0.05 to 100 μm, typically 5 to 50 μm. Further, the shape of the groove may be the same or different, but it is preferable that the grooves are the same.

One of the preferred embodiments of the groove shape is a substantially triangular shape. FIG. 2 shows a plan view and a perspective view of the microneedle 20 having a substantially triangular groove shape. In FIG. 2, the basic shape of the microneedle is a cone. Further, in FIG. 2, in the microneedle 20, five groove portions 21 are provided at equal intervals, but the present invention is not limited to this.

The microneedle 20 in the present embodiment is a conical needle-like body that tapers toward the tip side, and a plurality of groove portions 21 are provided on the side surface of the microneedle 20 radially from the tip of the cone to the bottom centering on the tip. (5 in FIG. 2). As shown in FIG. 2, the groove 21 is formed so that a part of the side surface of the cone is recessed in the axial direction of the cone, and the width is reduced from the root side to the tip side of the cone.

The groove portions 21 illustrated in FIG. 2 are formed by removing the side surfaces of the microneedle 20 so as to be recessed in the axial direction of the cone, and are formed at substantially equal intervals. Between each groove 21 and the groove 21, there is a non-removed portion 22 in which the side portion of the cone is not removed and remains.

The shape of the groove 21 is not particularly limited as long as it can be formed on the side surface of the microneedle. FIGS. 2 to 6 show a modified example (basic shape: conical shape) of the groove portion according to the microneedle of the present invention. These modified examples also have a plurality of groove portions 21 provided radially from the tip of the cone to the bottom of the cone with the tip as the center.
When the shape of the groove is expressed as a cross-sectional shape parallel to the base sheet (that is, the bottom surface of the microneedle), in addition to the triangular shape illustrated in FIG. 2, the curved surface shape (semicircular shape) exemplified in FIG. (Including semi-elliptical shape), substantially polygonal shape (not shown) and the like can be mentioned. In each microneedle, a part of the side surface is removed in the axial direction of the cone to form a groove portion 21, and the side portion of the cone is not removed and remains between the groove portion 21 and the groove portion 21. Part 22 is present.
The substantially polygonal shape includes not only a polygonal shape but also a case where a part of a corner portion is formed in a curved shape as illustrated in FIG. In FIGS. 3 and 4, five groove portions 21 on the side surface of the microneedle 20 are provided at equal intervals, but the present invention is not limited to this.

Further, the groove portion is not limited to a cone (or one formed up to the apex described later), and the groove portion may be formed from the middle of the side surface of the microneedle as illustrated in FIG. 5. In FIG. 5, the root side may be formed. Although the shape of the groove portion whose width is reduced from the to the tip side of the cone is shown, it may be formed in a straight line having a constant width (not shown). In each microneedle, the groove portion 21 and the groove portion 21 There is a non-removed portion 22 that remains without removing the side portion of the cone. In FIG. 5, five groove portions 21 on the side surface of the microneedle 20 are provided at equal intervals. Not limited to.

Further, the shape of the microneedle of the present invention may be a conical shape having a conical top portion 20A and a conical body portion 20B as shown in FIG. The "cone top" in the microneedle of the present invention is a portion including the apex of the cone in the microneedle, and the "cone body" is a portion continuous with the cone top and constituting the microneedle, and is a pedestal (base material). It is a part including the sheet) and the contact portion. In the microneedle shown in FIG. 6, since the connecting portion between the top of the cone and the body of the cone is smoothly formed, the resistance when pierced into the skin is reduced and pain is less likely to occur.
In the microneedle shown in FIG. 6, the groove portion 21 is formed by removing the groove portion 21 from the middle of the side surface of the cone top portion 20A to the bottom portion (root) of the cone body portion 20B so as to be recessed in the axial direction of the cone. Is not limited to this, and may be formed only on the conical body. Further, in FIG. 5, four groove portions 21 on the side surface of the microneedle 20 are provided at equal intervals, but the present invention is not limited to this.

Further, the basic shape of the microneedle may be a polygonal pyramid. Typical polygonal pyramids are triangular pyramids, quadrangular pyramids, pentagonal pyramids, hexagonal pyramids, and octagonal pyramids, but are not limited thereto. When the basic shape of the microneedle is a polygonal pyramid, it is preferable to form a groove on each side surface. FIG. 7 shows an example in which the basic shape of the microneedle is a quadrangular pyramid. In the microneedle illustrated in FIG. 7, groove portions having a narrow width from the root side to the tip side of the quadrangular pyramid are formed on each side surface of the quadrangular pyramid. Further, as illustrated in FIG. 8, a plurality of grooves may be provided on each side surface of the quadrangular pyramid in parallel with the bottom surface. In each microneedle, there is a non-removed portion 22 between the groove portion 21 and the groove portion 21 in which the side portion of the pyramid is not removed and remains.

Further, the basic shape of the microneedle may be a conical column. Specific examples of the pyramidal column include a shape composed of a cone and a cylinder, and a shape composed of a polygonal prism and a corresponding polygonal prism. When the shape of the microneedle is a conical prism, it is preferable that the grooves are radially formed from the middle of the side surface of the conical prism to the bottom centering on the tip as shown in FIGS. 9 to 11 described below.

FIG. 9 shows an example of a cone-shaped column composed of a cone portion 20a (cone) and a column portion 20b (cylinder). As shown in FIG. 9, when the basic shape of the microneedle is a conical prism, the groove 21 is formed by being removed from the side of the prism 20b so as to be recessed in the axial direction of the cone 20b. Is preferable. Further, as shown in FIG. 10, the groove portion 21 may be formed by being removed not only from the pillar portion 20b but also from the middle of the cone portion 20a so as to be recessed in the axial direction. In each microneedle, there is a non-removed portion 22 between the groove portion 21 and the groove portion 21 in which the side portion of the prism portion is not removed and remains.
In FIGS. 9 and 10, four groove portions 21 on the side surface of the microneedle 20 are provided at equal intervals, but the present invention is not limited to this.

Further, FIG. 11 shows an example of a cone-shaped pillar composed of a cone portion 20a (square pyramid) and a pillar portion 20b (square pillar). As shown in FIG. 11, when the basic shape of the microneedle is a conical prism, it is preferable that the groove is formed in the prism 20b. Further, although not shown, the groove portion may be formed not only from the prism portion 20b but also from the middle of the cone portion 20a.
In FIG. 11, four groove portions 21 on the side surface of the microneedle 20 are provided at equal intervals, but the present invention is not limited to this.

The shape of the groove with respect to the microneedle may be the same or different, but it is preferable that the groove has the same shape.

The width of the groove is not particularly limited as long as it can maintain the mechanical strength of the microneedle and can be stably formed, and is appropriately selected depending on the size of the microneedle, the shape of the groove, and the like.

The depth of the groove is not particularly limited as long as it can maintain the mechanical strength of the microneedle and can be stably formed, and is appropriately selected depending on the size of the microneedle, the shape of the groove, and the like.

The number of grooves is not particularly limited as long as it can maintain the mechanical strength of the microneedles and can be stably formed, and is appropriately selected depending on the size of the microneedles, the shape of the grooves, and the like.
In the microneedle of the present invention, at least one groove may be formed on the side surface of the microneedle (for example, a spiral groove), but it is preferable that two or more (s) are formed, and more preferably 4. That is all. The upper limit of the number of grooves is not particularly limited as long as it can maintain mechanical strength and can be stably formed, but is, for example, 30 or less, 10 or less, and 8 or less.

When a plurality of grooves are formed and the basic shape of the microneedle is a cone, it is preferable to form grooves of the same shape at equal intervals radially centered on the tip. If the grooves have the same shape at equal intervals in a radial pattern, the decrease in the strength of the microneedles due to the formation of the grooves can be reduced. The groove may be formed radially from the middle of the side surface of the cone to the bottom with the tip as the center.

When the basic shape of the microneedle is a polygonal pyramid, it is preferable to form the same number of grooves having the same shape on each side surface.
When the shape of the microneedle is a conical prism, it is preferable that grooves having the same shape are formed radially from the middle of the side surface of the conical prism to the bottom centering on the tip.

(Microneedle material)
The material of the microneedle of the present invention is not particularly limited as long as it is a biocompatible material and it is possible to form a microneedle having a desired shape. Here, the "in vivo compatible material" may be any material that can coexist with the living body while fulfilling its original function without giving an adverse effect or a strong stimulus to the living body for a long period of time, and only a material having in vivo solubility. However, a material having no in vivo solubility may be contained, but it is preferable that only the in vivo soluble material is used.

As the biocompatible material, either an inorganic material or an organic material can be selected.

Specific examples of the biocompatible material composed of a polymer substance include polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer, polycaprolactone, polycarbonate, nylon, polyvinyl alcohol, silicone (organosiloxane), polyester, and the like. Synthetic polymers such as polyurethane, polyethylene, polyethylene terephthalate, polystyrene, polypropylene, polytetrafluoroethylene, polymethylmethacrylate, poly2-hydroxyethyl methacrylate, various proteins such as collagen, gelatin, albumin, cellulose, amylose, dextran , Natural polymers such as polysaccharides such as chitin, chitosan and hyaluronic acid. These may be used by mixing polymer substances of the same type but having different degrees of polymerization, or may be used alone or in combination of two or more.

Hyaluronic acid is one of the suitable materials for the microneedle of the present invention.
Hyaluronic acid is a kind of glycosaminoglycan (mucopolysaccharide) and has a structure in which N-acetylglucosamine and glucuronic acid disaccharide units are linked.

As the hyaluronic acid, either biological hyaluronic acid or culture-derived hyaluronic acid can be used.

When a biosoluble polymer substance is used as the biocompatible material, the weight average molecular weight is usually preferably 50 to 2 million. If the weight average molecular weight is too small, the mechanical strength is lowered and it is easy to break during storage or when it is inserted into the skin. On the contrary, if the weight average molecular weight is too large, the hardness is lowered and it becomes difficult to pierce the skin.

Further useful ingredients may be added to the biocompatible material. Examples of the method of imparting the useful component to the biocompatible material include a method of kneading the biocompatible material and the useful component to form a microneedle using the raw material, and a method of forming a microneedle with the biocompatible material. Examples thereof include a method of adsorbing and absorbing useful components on a biocompatible material after forming the above.

The useful ingredient may be a useful ingredient having an imparting property to a biocompatible material and may be a raw material for drugs and cosmetics conventionally used as a transdermal preparation, and can be appropriately selected depending on the purpose. Like the above-mentioned biosoluble polymer substance such as hyaluronic acid, it may be a substance that dissolves itself and functions as a useful component.

<Manufacturing method of microneedle>
The microneedles of the present invention are not particularly limited as long as they are a manufacturing method capable of forming the above-mentioned microneedles on a base sheet, and a manufacturing method similar to a general microneedle manufacturing method can be used. can.
As a suitable method, there is a method of using a replica mold in which a microneedle array having a desired shape is inverted and transferred (concavities and convexities are inverted and transferred). For example, a master mold having a convex portion in the shape and arrangement of microneedles having a desired shape is prepared, and the master mold is molded by metal plating or a curable silicone resin (typically, Polydimethylsiloxane (PDMS)). Examples thereof include a method of manufacturing the above-mentioned replica mold and producing a microneedle array by embedding and releasing a biocompatible material (for example, hyaluronic acid) in the replica mold. As described above, the microneedle and the base material sheet are used. In the case of manufacturing a microneedle array by integrally molding the microneedles, the microneedles and the base sheet are made of the same material.

Although the embodiments of the present invention have been described above with reference to the examples and drawings, the embodiments disclosed this time are examples in all respects and are not limiting. In particular, in the embodiments disclosed this time, matters not explicitly disclosed do not deviate from the scope normally implemented by those skilled in the art, and can be easily assumed by those skilled in the art. Values can be adopted.

In addition, the microneedles and microneedle arrays of the present invention are usually used for humans, but can also be applied to animals other than humans.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

<Example 1>
(Manufacturing of microneedle array)
Using the micro stereolithography method and 3D printing manufacturing technique, a resin master in which convex portions (needle) having a shape according to FIG. 10 are ^{arranged at a density of 625 needles / cm 2} (distance between needles (design value) 400 μm). A mold (convex mold) was manufactured. The observation results of the master mold and the convex portion (needle) with an optical microscope (Nikon-SMZ800N) are shown in FIGS. 12 and 13, respectively.
As shown in FIG. 13, the convex portion (needle) has a tip apex angle of 49 °, a tip diameter of 7 μm, an overall height (H) of 268 μm, a cone height of 99 μm, a prism height of 169 μm, and a base. The diameter (D) of the bottom surface of the portion was 94 μm, the width of the groove portion (bottom surface of the base portion) was 23 μm, and the height of the groove portion was 175.5 μm.

Liquid PDMS (Polydimethylsiloxane) was poured into the produced convex master mold, and after sufficiently drying and curing, the cured PDMS was peeled off to obtain a PDMS mold (concave mold).
A 4 wt% sodium hyaluronate aqueous solution, which is a material for microneedles, was supplied to the PDMS mold, allowed to stand at a predetermined temperature to be sufficiently dried and cured, and then the PDMS mold was removed to form the PDMS mold with hyaluronic acid. The microneedle array of Example 1 was obtained.
The observation results of the microneedle array and the microneedle portion by an optical microscope (Nikon-SMZ800N) are shown in FIGS. 14 and 15, respectively.
As shown in FIGS. 14 and 15, it was confirmed that in the microneedle array of Example 1, the formed microneedles were not broken or deformed, and the shape of the master mold was accurately transferred.

(Manufacturing of microneedle patches)
The microneedle array of Example 1 was fixed to the inner diameter portion of a Hydrocolloid band (outer diameter 14 cm, inner diameter 8 cm) to produce a microneedle patch of Example 1 capable of adhering to the skin. An optical micrograph of the microneedle patch of Example 1 is shown in FIG.

<Example 2>
(Manufacturing of microneedle array)
Using the micro stereolithography method and 3D printing manufacturing technique, a resin master in which convex portions (needle) having a shape according to FIG. 6 are ^{arranged at a density of 625 needles / cm 2} (distance between needles (design value) 400 μm). A mold (convex mold) was manufactured. The observation results of the master mold and the convex portion (needle) with an optical microscope (Nikon-SMZ800N) are shown in FIGS. 17 and 18, respectively.
As shown in FIG. 18, the convex portion (needle) has a tip apex angle of 42 °, a tip diameter of 6.6 μm, an overall height (H) of 269 μm, a cone top height of 99 μm, and a cone body height of 170 μm. The diameter (D) of the bottom surface of the pedestal was 94 μm, the width of the groove (bottom surface of the pedestal) was 24 μm, the width of the groove (the boundary between the top of the cone and the body of the cone) was 14 μm, and the height of the groove was 180 μm.

Liquid PDMS (Polydimethylsiloxane) was poured into the produced convex master mold, and after sufficiently drying and curing, the cured PDMS was peeled off to obtain a PDMS mold (concave mold).
A 4 wt% sodium hyaluronate aqueous solution, which is a material for microneedles, was supplied to the PDMS mold, allowed to stand at a predetermined temperature to be sufficiently dried and cured, and then the PDMS mold was removed to form the PDMS mold with hyaluronic acid. The microneedle array of Example 2 was obtained.
The observation results of the microneedle array and the microneedle portion by an optical microscope (Nikon-SMZ800N) are shown in FIGS. 19 and 20, respectively.
As shown in FIGS. 19 and 20, it was confirmed that in the microneedle array of Example 2, the formed microneedles were not broken or deformed, and the shape of the master mold was accurately transferred.

(Manufacturing of microneedle patches)
The microneedle array of Example 2 was fixed to the inner diameter portion of a Hydrocolloid band (outer diameter 14 cm, inner diameter 8 cm) to produce a microneedle patch of Example 1 capable of adhering to the skin. An optical micrograph of the microneedle patch of Example 1 is shown in FIG.

INDUSTRIAL APPLICABILITY According to the present invention, a microneedle array that reduces mechanical irritation in the skin surface layer and / or the skin stratum corneum of a user is provided, which is industrially useful.

1 Microneedle array 10 Substrate sheet 20 Microneedle 21 Groove 22 Non-removal part 20A Cone top 20B Cone body 20a Cone (cone or pyramid)
20b Pillar part (cylinder or prism)
30 Placement area (of microneedle) 40 Non-placement area (of microneedle) L Boundary (between top and body of cone)

Claims (11)

Dissolved microneedles for piercing the skin and absorbing useful ingredients into the body
The microneedle has a basic shape of a cone, and other than the groove portion formed by removing a part of the side surface of the cone constituting the microneedle so as to be recessed in the axial direction of the cone, and the groove portion on the side surface. Has a non-removal part that is a part of
The groove, microneedles, wherein Rukoto such are formed radially around the tip from the middle side of the cone forming the microneedles on the bottom. The microneedle of claim 1 basic shape of the microneedles is circular cone. Dissolved microneedles for piercing the skin and absorbing useful ingredients into the body
The basic shape of the microneedle is a conical column composed of a cone and a column, and a part of the side surface of the cone constituting the microneedle is recessed in the axial direction of the cone. It has a groove portion formed by being removed as described above, and a non-removal portion which is a portion other than the groove portion on the side surface.
The groove portion is a microneedle formed radially from the middle of the side surface of the conical prism constituting the microneedle to the bottom with the tip as the center. The microneedle according to claim 3, wherein the groove portion is formed only in the prism body portion. The microneedle according to claim 3, wherein the groove portion is formed in the cone portion and the prism portion. The microneedle according to any one of claims 3 to 5, wherein the cone-shaped pillar body includes a cone portion formed of a cone and a pillar portion formed of a cylinder. The microneedle according to any one of claims 1 to 6 , wherein the material is a biodegradable polymer. The microneedle according to any one of claims 1 to 7, wherein the grooves have the same shape and are formed at equal intervals. A microneedle array in which the microneedles according to any one of claims 1 to 8 are dispersedly arranged on a base sheet. The microneedle array according to claim 9 , wherein the microneedle and the base sheet are integrally molded. A microneedle patch comprising the microneedle array according to claim 9 or 10.

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