JP2022132921A - Microneedle and microneedle array - Google Patents

Abstract

To provide a microneedle array for reducing mechanical irritation on a skin front layer or a skin horny layer of a user.SOLUTION: A microneedle array 1 is configured so that, on a substrate sheet 10, a plurality of microneedles 20 is arranged in a dispersed state (erected in a set arrangement pattern). The microneedle 20 is formed of a dissolvable material, and on a side face of the microneedle, a groove is formed. When the microneedle is pierced to a skin, a surface area of the microneedle contacting a front layer and a horny layer of the skin is reduced, so that mechanical irritation is reduced, thereby reducing pain which occurs when the microneedle is pierced to the skin.SELECTED DRAWING: Figure 14

Description

TECHNICAL FIELD The present invention relates to microneedles and microneedle arrays that reduce mechanical irritation on the user's skin superficial layer or skin stratum corneum upon insertion.

As a method for transdermally administering useful ingredients such as drugs, vaccines, and skin-beautifying ingredients into the body, a method using a microneedle array in which fine microneedles are dispersed on a substrate sheet has been widely used in recent years (for example, Patent Document 1. , 2). In transdermal administration, it is known that the stratum corneum functions as a barrier layer, and by penetrating the stratum corneum with microneedles, it is possible to efficiently administer useful ingredients into the body. As a method of imparting a useful ingredient for administration purposes to microneedles, a method of supporting a useful ingredient on the surface of a microneedle, a method of incorporating a useful ingredient into a material constituting a microneedle, and the like are known. Dissolving microneedles using biodegradable polymers such as hyaluronic acid, which themselves can be useful components, are also spreading (for example, Patent Document 3).

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

However, when the microneedle is inserted into the surface layer of the skin or the stratum corneum, mechanical stimulation occurs due to friction between the side surface of the microneedle and body tissue, which causes discomfort and pain.
In order to further reduce the mechanical irritation of the microneedles, there is a method of making the microneedles thinner, but when the microneedles are made thinner, the mechanical strength of the microneedles is insufficient, and the microneedles break at the epidermis when they are pierced into the skin. There is In addition, when the microneedles are thinned, the microneedles that contain useful ingredients in the constituent materials and the dissolution type microneedles in which the constituent materials themselves also act as useful ingredients are disadvantageous in that the amount of useful ingredients decreases as the microneedles become thinner. There was also
There is also a method of coating the surface of the microneedles with a lubricating component to suppress mechanical stimulation (eg, Patent Document 4), but this method was not a complete solution either.

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

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

As a result of intensive research to solve the above problems, the present inventor found that providing a groove (recess) on the side surface of the microneedle reduces the contact area in the body and reduces mechanical stimulation. I came up with the invention.

That is, the present invention relates to the following inventions.
<1> A dissolving microneedle for piercing the skin and absorbing a useful ingredient into the body, wherein 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 two or more.
<4> The microneedle according to <3>, wherein the grooves have the same shape and are formed at regular intervals.
<5> The microneedle according to any one of <1> to <4>, wherein the shape of the microneedle is a cone or a pyramidal column.
<6> The microneedle according to <5>, wherein the groove is formed such that a part of the side surface of the pyramid or the pyramidal column is recessed in the axial direction of the pyramid or the pyramidal column.
<7> The microneedle according to <6>, wherein the shape of the microneedle is conical.
<8> The microneedle according to <7>, wherein the grooves are radially formed from the middle of the side surface of the cone to the bottom of the cone with the tip as the center.
<9> The microneedle according to <6>, wherein the shape of the microneedle is a conical columnar body, and the grooves are radially formed from the middle of the side surface of the conical columnar body to the bottom part with the tip as the center.
<10> A microneedle array in which the microneedles according to any one of <1> to <9> are dispersed on a substrate sheet.
<11> The microneedle array according to <10>, wherein the microneedles and the base sheet are integrally formed.
<12> A microneedle patch comprising the microneedle array according to <10> or <11>.

ADVANTAGE OF THE INVENTION According to this invention, the microneedle and microneedle array which reduced the mechanical stimulation at the time of sticking in the body, and suppressed the pain are provided.

1 is a schematic perspective view of a microneedle array according to an embodiment of the invention; FIG. BRIEF DESCRIPTION OF THE DRAWINGS It is explanatory drawing of the microneedle which comprises the microneedle array which concerns on embodiment of this invention, (a) is a top view, (b) is a schematic perspective view. It is a modification of the microneedle which concerns on this embodiment, (a) is a top view, (b) is a schematic perspective view. It is another modification of the microneedle which concerns on this embodiment, (a) is a top view, (b) is a schematic perspective view. It is another modification of the microneedle which concerns on this embodiment, (a) is a top view, (b) is a schematic perspective view. It is another modification of the microneedle which concerns on this embodiment, (a) is a top view, (b) is a front view, (c) is a schematic perspective view. It is another modification of the microneedle which concerns on this embodiment, (a) is a top view, (b) is a schematic perspective view. It is another modification of the microneedle which concerns on this embodiment, (a) is a top view, (b) is a schematic perspective view. It is a schematic perspective view of the other modification of the microneedle which concerns on this embodiment. It is another modification of the microneedle which concerns on this embodiment, (a) is a top view, (b) is a front view, (c) is a schematic perspective view. It is a schematic perspective view of the other modification of the microneedle which concerns on this embodiment. 1 is an optical microscope photograph of a master mold according to Example 1, where (a) is a plan view (magnification of 80 times) and (b) is a perspective view (magnification of 30 times). 2 is an optical microscope photograph (magnification: 80) of the projections (needles) of the master mold according to Example 1. It is an optical microscope photograph of the microneedle array of Example 1, (a) is a plan view (magnification of 80 times), (b) is a perspective view (magnification of 30 times). 1 is an optical microscope photograph (magnification: 80) of microneedles formed in the microneedle array of Example 1. FIG. It is an optical micrograph of the microneedle patch which stuck the microneedle array of Example 1, (a) is a top view, (b) is an enlarged view (magnification of 15 times) of a microneedle array. 2 is an optical microscope photograph of a master mold according to Example 2, where (a) is a plan view (magnification of 80 times) and (b) is a perspective view (magnification of 30 times). 10 is an optical microscope photograph (magnification of 80 times) of the projections (needles) of the master mold according to Example 2. It is an optical microscope photograph of the microneedle array of Example 2, (a) is a plan view (magnification of 80 times), (b) is a perspective view (magnification of 30 times). 3 is an optical micrograph (magnification: 80) of microneedles formed in the microneedle array of Example 2. FIG. It is an optical micrograph of the microneedle patch which stuck the microneedle array of Example 2, (a) is a top view, (b) is an enlarged view (magnification of 15 times) of a microneedle array.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail by showing examples and the like. In this specification, when the expression "~" is used, it is used as an expression including the numerical values before and after it.

The present invention is a dissolving microneedle for piercing the skin to absorb useful ingredients into the body, wherein a groove is formed on the side surface of the microneedle to reduce the contact area (hereinafter referred to as microneedle referred to as "microneedles of the present invention").

The microneedle of the present invention is used to pierce the skin and allow useful ingredients to reach the surface layer and stratum corneum of the skin (and the lower layer of the stratum corneum). The microneedle of the present invention is characterized in that grooves are formed on its side surface to reduce the area. Due to this groove, when the microneedle is pierced into the skin, the non-removable portion of the microneedle (portion other than the groove on the side surface, detailed in the embodiment) that comes into contact with the surface layer and stratum corneum of the skin (and the lower layer of the stratum corneum). area is reduced, and mechanical stimulation is reduced, so pain when the skin is pricked 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, with the area of the side surface of the basic shape of the microneedle being 100%. It tends to reduce the pain when the skin is punctured. In addition, 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. , 30% or more, 40% or more, 50% or more.

In the present invention, the "useful ingredient" may be any ingredient that can be transdermally administered and is useful, and includes all chemical substances that can be used for transdermal absorption (raw materials for drugs and cosmetics, etc.). can be selected as appropriate.

The shape, size, and material of the microneedle of the present invention may satisfy the purpose of use (for example, the amount of the intended useful ingredient) without impairing the effect of the present invention (reduction of pain when pricking the skin). The details of the microneedle of the present invention will be described later together with the embodiments.

The microneedle of the present invention is preferably of a dissolution type and made of a biodegradable polymer. Moreover, the microneedle of the present invention may contain other useful components in addition to the biodegradable polymer within a range that does not impair the object and effect of the present invention. 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 two or more (plurality) grooves are preferably formed, more preferably three or more, four or more. The upper limit of the number of grooves is not particularly limited as long as the mechanical strength can be maintained and the grooves can be stably formed.

In the microneedle of the present invention, the shape of the groove may be the same or different, but preferably the same. Also, the intervals between the grooves may be the same or different, but they are preferably the same (equal intervals).

The microneedles of the present invention are usually used as a microneedle array dispersed on a substrate sheet (hereinafter referred to as "microneedle array of the present invention").
In the microneedle array of the present invention, the shape, size, and number of the microneedles to be arranged, and the conditions for the manner and range of arrangement of the microneedles on the base sheet are the effects of the present invention (on the skin It is not particularly limited as long as it satisfies the purpose of use (for example, the amount of the intended useful ingredient) without impairing the reduction of pain when stabbed.
In addition, the microneedle array of the present invention is preferably integrally formed by using the same material for the microneedles and the base sheet. An example using hyaluronic acid as the 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 without departing from the gist of the present invention. .

<Microneedle array>
FIG. 1 shows a schematic diagram of a microneedle array according to a representative 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 (arranged in a predetermined arrangement pattern) on a base sheet 10 . In FIG. 1, in order to facilitate understanding of the structure of the microneedle array 1, as a schematic diagram, the microneedles 20 with respect to the base sheet 10 are shown larger than they actually are, and the number (density) thereof is small.

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 is selected appropriately 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, a 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 which is manufactured so that the surface on which the microneedle array is attached can be attached to the skin. The patch that fixes the microneedle array is made of flexible material, and there is also an adhesive sheet for attaching to the skin, and a protection to protect the adhesive sheet and support the microneedle array when it is attached to the skin. A release sheet or the like may be added for use. Any material can be used for the patch as long as it does not impair the purpose of the present invention. 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 arrangement density of the microneedles in the microneedle array, and the site where the microneedle patch is used (skin attachment site). It can be adjusted as appropriate. In addition, various shapes such as circular, elliptical, magatama, and face masks are possible.

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

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

The number (density) of the microneedles 20 arranged on the base sheet 10 is appropriately selected according to the intended use of the microneedle array 1 and the like. For example, it is 10 to 5000 in the range of 1 cm ² of the base sheet 10 .

The arrangement region 30 is a region of the base sheet 10 where a microneedle group 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 in a matrix on the substrate sheet 10 so as to form a rectangular shape in plan view, but the invention is not limited thereto, and the microneedle array 1 Depending on the purpose of use, they may be arranged in another regular manner (arranged in a circular or elliptical shape when viewed from above), or may be arranged in a randomly dispersed arrangement. A different arrangement may be used in each arrangement region 30 .

In addition, the shape and size of the non-placement region 40 , which is a region where the microneedles 20 are not present, on the base sheet 10 are appropriately determined according to the purpose of use of the microneedle array 1 .

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

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 is provided on the side surface thereof to reduce the area of the side surface of the microneedle.

In the present specification, the “basic shape (of microneedles)” means the three-dimensional shape of microneedles without grooves.

The basic shape of the microneedle of the present invention is a pyramidal shape or a pyramidal columnar shape. As used herein, the term “pyramidal shape” means a shape that gathers from the base to the apex, and includes conical shapes and polypyramidal shapes. In addition, the term “pyramidal columnar shape” means a three-dimensional shape in which one bottom surface of a columnar body and a bottom surface of a pyramidal body are shared. includes shapes with polygonal pyramids.

When the basic shape of the microneedle of the present invention is a cone shape or a cone-shaped columnar shape, the axis of the cone or the cone-shaped columnar A vertical line) passing through the center of the base of the pyramid or pyramidal column is preferable, but not limited to this.

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

The diameter of the bottom surface of the microneedle (the contact surface between the base sheet and the microneedle) is appropriately determined depending on the application of the microneedle, 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 circular, the major axis when the bottom surface of the microneedle is elliptical, and the diameter of the circumscribed circle when the bottom surface of the microneedle is polygonal.

In addition, the shape of the tip of the microneedle in this embodiment may be any shape as long as it can pierce the skin and form a through hole in the surface layer or stratum corneum of the skin. That is, it may have a curved surface or a flat surface that can pierce the tip-shaped skin.

As used herein, the term “groove” refers to a recess (recess) in the side surface of the microneedle (the basic shape of the microneedle if it does not have a groove), and the surface that constitutes the recess is a curved surface or two surfaces. shall mean one that is at least one plane.

Having a groove reduces the surface area of the microneedle that contacts the surface layer and stratum corneum of the skin (and the lower layer of the stratum corneum) when the microneedle is pierced into the skin, and reduces mechanical irritation. It can reduce pain.

In the present invention, the number and arrangement of grooves in the microneedles 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, 3 or more, or 4 or more. The upper limit of the number of grooves is not particularly limited as long as the mechanical strength can be maintained and the grooves can be stably formed. Also, the intervals between 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, the groove is preferably formed such that a part of the side surface of the cone or cone-shaped column constituting the microneedle is recessed in the axial direction of the cone or cone-shaped column. Here, "the axial direction of the cone or cone-shaped column" is the direction drawn from the tip of the cone or cone-shaped column to the bottom surface (perpendicular direction).
Moreover, the cross-sectional shape of the groove parallel to the base sheet 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 the corner is curved. The width of the groove is appropriately determined according to the size and application of the microneedle, and is, for example, approximately 0.05 to 100 μm, typically 5 to 50 μm. The shape of the grooves may be the same or different, but preferably the same.

One preferred form of the shape of the groove is a substantially triangular shape. FIG. 2 shows a plan view and a perspective view of a microneedle 20 having a substantially triangular groove. In FIG. 2, the basic shape of the microneedle is conical. In addition, in FIG. 2, in the microneedle 20, five grooves 21 are provided at equal intervals, but the number of grooves 21 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 grooves 21 provided radially from the tip to the bottom of the cone on the side surface of the cone. (five in FIG. 2). As shown in FIG. 2, the groove portion 21 is formed such that a portion of the side surface of the cone is recessed in the axial direction of the cone, and the width decreases from the root side to the tip side of the cone.

The grooves 21 illustrated in FIG. 2 are formed by removing the side surfaces of the microneedles 20 so as to be recessed in the axial direction of the cone, and are formed at approximately equal intervals. A non-removed portion 22 exists between each groove portion 21 and the side portion of the cone has not been removed.

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 modified examples (basic shape: conical shape) of the groove of the microneedle of the present invention. These modified examples also have a plurality of grooves 21 radially provided on the side surface from the tip 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 (that is, the bottom surface of the microneedle) parallel to the base sheet, it can be curved (semicircular, (including a semi-elliptical shape), a substantially polygonal shape (not shown), and the like. In each microneedle, a part of the side surface is removed in the axial direction of the cone to form a groove 21, and between the grooves 21, the side of the cone is not removed and remains unremoved Part 22 is present.
The substantially polygonal shape includes not only a polygonal shape but also a case where a part of the corners are formed in a curved shape as illustrated in FIG. 4 . In addition, in FIGS. 3 and 4, the grooves 21 on the side surface of the microneedle 20 are provided at five equal intervals, but the number is not limited to this.

In addition, the groove is not limited to a cone (or one formed up to the vertex, which will be described later), and the groove may be formed from the middle of the side surface of the microneedle as illustrated in FIG. 5. In FIG. Although the shape of the groove portion is shown in which the width decreases from the tip side of the cone, it may be formed in a straight line shape with a constant width (not shown).In each microneedle, the groove portion 21 and the groove portion 21 There is a non-removed portion 22 where the side of the cone is not removed and remains between .In addition, in FIG. is not limited to

Moreover, the shape of the microneedle of the present invention may be a conical shape having a conical top portion 20A and a conical trunk portion 20B as shown in FIG. The “conical apex” in the microneedle of the present invention is a portion including the conical apex of the microneedle, and the “conical body” is a portion that constitutes the microneedle continuously with the conical apex and is a base (base material sheet) and the contact part. The microneedle shown in FIG. 6 has a smooth connecting portion between the conical apex and the conical body, so that the resistance when the skin is pierced is small, and pain is less likely to occur.
In addition, in the microneedle shown in FIG. 6, the groove 21 is formed so as to be recessed in the axial direction of the cone from the middle of the side surface of the conical top 20A to the bottom (root) of the conical barrel 20B. is not limited to this, and may be formed only on the conical body. Moreover, in FIG. 5, four grooves 21 on the side surface of the microneedle 20 are provided at regular intervals, but the present invention is not limited to this.

Moreover, the basic shape of the microneedle may be a polygonal pyramid. Polygonal pyramids are typically triangular pyramids, square pyramids, pentagonal pyramids, hexagonal pyramids, and octagonal pyramids, but are not limited to these. 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, grooves are formed on each side surface of the quadrangular pyramid so that the width decreases from the root side to the tip side of the quadrangular pyramid. Also, as illustrated in FIG. 8, a plurality of grooves may be provided on each side surface of the quadrangular pyramid parallel to the bottom surface. In each microneedle, there is a non-removed portion 22 in which the side portion of the pyramid is not removed and remains between the groove portions 21 .

Also, the basic shape of the microneedle may be a conical columnar body. Specific examples of the conical columnar body include a shape composed of a cone and a cylinder, and a shape composed of a polygonal pyramid and a corresponding polygonal column. When the shape of the microneedle is a pyramidal column, grooves are formed radially from the middle of the side surface to the bottom of the pyramidal column with the tip as the center, as shown in FIGS. 9 to 11 described below.

FIG. 9 shows an example of a cone-shaped column body 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 columnar body, the groove portion 21 is formed by removing it from the side portion of the columnar body portion 20b so as to be recessed in the axial direction of the conical columnar body. preferably. Further, as shown in FIG. 10, the groove portion 21 may be formed by removing not only the column portion 20b but also the conical portion 20a so as to be recessed in the axial direction. In addition, in each microneedle, there is a non-removed portion 22 between the grooves 21 and 21 where the side portion of the columnar portion remains without being removed.
In addition, in FIGS. 9 and 10, four grooves 21 on the side surface of the microneedle 20 are provided at regular intervals, but the number of grooves 21 is not limited to this.

Further, FIG. 11 shows an example of a pyramidal columnar body composed of a pyramidal portion 20a (quadrangular pyramid) and a columnar portion 20b (quadrangular prism). As shown in FIG. 11, when the basic shape of the microneedle is a conical columnar body, it is preferable that the groove is formed in the columnar body portion 20b. Also, although not shown, the groove may be formed not only in the columnar body 20b but also in the middle of the conical body 20a.
In addition, in FIG. 11, four grooves 21 on the side surface of the microneedle 20 are provided at regular intervals, but the number of grooves 21 is not limited to this.

The shape of the groove for the microneedle may be the same shape or a different shape, but preferably 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 the mechanical strength of the microneedle can be maintained and the microneedle can be stably formed.

The number of grooves is not particularly limited as long as the mechanical strength of the microneedles is maintained 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 two or more (plural) are preferably formed, more preferably four grooves. That's it. The upper limit of the number of grooves is not particularly limited as long as the mechanical strength can be maintained and the grooves can be stably formed.

Further, when a plurality of grooves are formed, when the basic shape of the microneedle is conical, it is preferable to form grooves of the same shape radially around the tip at equal intervals. If the grooves are radially equidistant and have the same shape, the strength of the microneedles is less likely to decrease due to the formation of the grooves. The groove may be formed radially from the middle of the side surface of the cone to the bottom of the cone with the tip as the center.

Moreover, when the basic shape of the microneedle is a polygonal pyramid, it is preferable to form the same number of grooves of the same shape on each side surface.
Moreover, when the shape of the microneedle is a conical columnar body, it is preferable that grooves of the same shape are formed radially from the middle of the side surface of the conical columnar body to the bottom part thereof, 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 capable of forming a microneedle with the desired shape. Here, the term "biocompatible material" means any material that can coexist with the body while performing its original function without adversely affecting or strongly stimulating the body for a long period of time. However, it is preferable that the material contains only biosoluble materials.

Both inorganic and organic materials can be selected as the biocompatible material.

Specific examples of biocompatible materials made of polymeric substances include polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer, polycaprolactone, polycarbonate, nylon, polyvinyl alcohol, silicone (organosiloxane), polyester, Synthetic polymers such as polyurethane, polyethylene, polyethylene terephthalate, polystyrene, polypropylene, polytetrafluoroethylene, polymethyl methacrylate, poly 2-hydroxyethyl methacrylate, various proteins such as collagen, gelatin, albumin, cellulose, amylose, dextran , chitin, chitosan, and polysaccharides such as hyaluronic acid. These may be used by mixing polymeric substances of the same type with different degrees of polymerization, or may be used singly or in combination of two or more.

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

As hyaluronic acid, both biologically-derived hyaluronic acid and culture-derived hyaluronic acid can be used.

When a biocompatible polymeric substance is used as the biocompatible material, the weight average molecular weight is usually preferably 5,000 to 2,000,000. If the weight-average molecular weight is too small, the mechanical strength will be low, and it will be easy to break during storage or when piercing the skin. Conversely, if the weight-average molecular weight is too large, the hardness will decrease, making it difficult to stick into the skin.

A useful component may be further added to the biocompatible material. Examples of the method of imparting a useful component to a biocompatible material include a method of kneading a biocompatible material and a useful component and using the raw material to form microneedles, and a method of forming microneedles using a biocompatible material. A method of adsorbing/absorbing a useful component to a biocompatible material after forming the biocompatible material.

The useful ingredient may be a useful ingredient that imparts properties to biocompatible materials and is a raw material for drugs and cosmetics conventionally used as percutaneous absorption preparations, and can be appropriately selected according to the purpose. It may be one that dissolves itself and functions as a useful component, such as the above-described biosoluble polymeric substances such as hyaluronic acid.

<Method for producing microneedles>
The microneedle of the present invention is not particularly limited as long as the manufacturing method is capable of forming the above-described microneedle on the base sheet, and the same manufacturing method as 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 reverse-transferred (transferred with the unevenness reversed). For example, a master mold is produced in which convex portions of the desired shape and arrangement of microneedles are formed, and the master mold is molded with metal plating or curable silicon resin (typically polydimethylsiloxane (PDMS)). A replica mold is produced, and a biocompatible material (e.g., hyaluronic acid) is embedded in the replica mold and removed from the mold to produce a microneedle array. are integrally molded to produce a microneedle array, 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 examples and drawings, the embodiments disclosed this time are illustrative in all respects and are not restrictive. In particular, matters not explicitly disclosed in the embodiments disclosed this time do not deviate from the scope normally practiced by those skilled in the art, and can be easily conceived by those of ordinary skill in the art. value can be adopted.

Moreover, although the microneedle and microneedle array of the present invention are generally used for humans, they can also be applied to animals other than humans.

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these.

<Example 1>
(Manufacture of microneedle array)
A resin master in which protrusions ⁽ needles) having a shape similar to that shown in FIG. A mold (convex mold) was produced. 12 and 13 show the observation results of the master mold and the projections (needles) with an optical microscope (Nikon-SMZ800N), 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 column height of 169 μm, and a base. The diameter (D) of the bottom surface of the groove was 94 μm, the width of the groove (bottom surface of the base portion) was 23 μm, and the height of the groove was 175.5 μm.

Liquid PDMS (Polydimethylsiloxane) was poured into the manufactured convex master mold, dried and cured sufficiently, and then the cured PDMS was peeled off to obtain a PDMS mold (concave mold).
A 4% by weight sodium hyaluronate aqueous solution, which is the material of the microneedles, is supplied to the PDMS mold, left to stand at a predetermined temperature to sufficiently dry and harden, and then the PDMS mold is removed to form a hyaluronic acid. A microneedle array of Example 1 was obtained.
The results of observation of the microneedle array and the microneedle portion with an optical microscope (Nikon-SMZ800N) are shown in FIGS. 14 and 15, respectively.
As shown in FIGS. 14 and 15, in the microneedle array of Example 1, it was confirmed that the formed microneedles were neither broken nor deformed, and the shape of the master mold was accurately transferred.

(Manufacturing of microneedle patch)
The microneedle array of Example 1 was fixed to the inner diameter of a hydrocolloid band (outer diameter: 14 cm, inner diameter: 8 cm) to prepare the microneedle patch of Example 1 that can be attached to the skin. An optical micrograph of the microneedle patch of Example 1 is shown in FIG.

<Example 2>
(Manufacture of microneedle array)
A resin master in which protrusions ⁽ needles) having a shape similar to that shown in FIG. A mold (convex mold) was produced. 17 and 18 show the observation results of the master mold and the projections (needles) with an optical microscope (Nikon-SMZ800N), 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 conical top height of 99 μm, 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 of the pedestal) was 24 μm, the width of the groove (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 manufactured convex master mold, dried and cured sufficiently, and then the cured PDMS was peeled off to obtain a PDMS mold (concave mold).
A 4% by weight sodium hyaluronate aqueous solution, which is the material of the microneedles, is supplied to the PDMS mold, left to stand at a predetermined temperature to sufficiently dry and harden, and then the PDMS mold is removed to form a hyaluronic acid. A microneedle array of Example 2 was obtained.
The results of observation of the microneedle array and the microneedle portion with an optical microscope (Nikon-SMZ800N) are shown in FIGS. 19 and 20, respectively.
As shown in FIGS. 19 and 20, in the microneedle array of Example 2, it was confirmed that the formed microneedles were neither broken nor deformed, and the shape of the master mold was accurately transferred.

(Manufacturing of microneedle patch)
The microneedle array of Example 2 was fixed to the inner diameter of a hydrocolloid band (outer diameter: 14 cm, inner diameter: 8 cm) to prepare the microneedle patch of Example 1 that can adhere 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 is provided that reduces mechanical irritation in the user's skin superficial layer and/or skin stratum corneum, and thus is industrially useful.

1 Microneedle Array 10 Substrate Sheet 20 Microneedle 21 Groove 22 Non-Removed Part 20A Conical Top 20B Conical Body 20a Conical Part (Conical or Pyramidal)
20b Column body part (cylinder or square column)
30 Placement region (of microneedles) 40 Non-placement region (of microneedles) L Boundary (between cone top and cone body)

Claims (12)

A dissolving microneedle for piercing the skin to absorb a useful ingredient into the body, characterized in that grooves are formed on the side surface of the microneedle to reduce the contact area. The microneedle according to claim 1, wherein the material is a biodegradable polymer. The microneedle according to claim 1 or 2, wherein the number of said grooves is two or more. The microneedle according to claim 3, wherein the grooves have the same shape and are formed at regular intervals. 5. The microneedle according to any one of claims 1 to 4, wherein the shape of the microneedle is a cone or a pyramidal column. 6. The microneedle according to claim 5, wherein the groove is formed such that a part of the side surface of the pyramid or the pyramidal column is recessed in the axial direction of the pyramid or the pyramidal column. The microneedle according to claim 6, wherein the shape of the microneedle is conical. 8. The microneedle according to claim 7, wherein the grooves are formed radially from the middle of the side surface of the cone to the bottom of the cone with the tip as the center. 7. The microneedle according to claim 6, wherein the shape of the microneedle is a conical columnar body, and the grooves are formed radially from the middle of the side surface of the conical columnar body to the bottom part, with the tip as the center. A microneedle array in which the microneedles according to any one of claims 1 to 9 are dispersed on a substrate sheet. The microneedle array according to claim 10, wherein the microneedles and the base sheet are integrally formed. A microneedle patch comprising the microneedle array according to claim 10 or 11.

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