JP6880941B2 - Microneedle - Google Patents

Description

The present invention relates to microneedles used for administration of drugs.

As a method of administering a drug such as a vaccine into the body, a method using a microneedle is known. The microneedle is provided with a protrusion having a needle shape pointed toward the tip on the surface of the substrate portion. The administration method using a microneedle is a method in which a hole is formed in the skin by piercing a protrusion into the skin, and the drug is administered by sending the drug into the skin through the hole. Since the length of the protrusion is a length that does not reach the nerve cells of the dermis layer in the skin, the administration method using a microneedle has a hole in the skin as compared with the method of administering a drug subcutaneously using an injection needle. Pain when is formed is suppressed.

In one method of administering a drug using a microneedle, a microneedle having a through hole formed through the substrate and the protrusion in the extending direction of the protrusion is used, and the liquid drug is intradermally discharged through the through hole. (See, for example, Patent Document 1). Such microneedles are used, for example, attached to a syringe barrel like an injection needle. When administering the drug, the pusher provided in the injection tube is pushed, so that the drug filled in the outer cylinder of the injection tube is pressed toward the protrusion, and as a result, the drug is projected through the through hole. It comes out from the tip of the part and enters the skin.

Japanese Unexamined Patent Publication No. 2015-70869

By the way, unlike the subcutaneous injection in which the tip of the needle reaches the skin subcutaneously, the tip of the protrusion of the microneedle is located in the skin while the drug is being administered. The tissue is tightly packed in the skin compared to the subcutaneous one, the diameter of the through hole of the protrusion is smaller than the diameter of the through hole of a general injection needle, and the skin tissue inside the through hole. In some cases, these factors may prevent the drug from flowing smoothly through the through-hole into the skin. Therefore, from the viewpoint of smooth administration of the drug into the skin, there is still room for improvement in the structure of the drug flow path of the protrusion.
An object of the present invention is to provide a microneedle that enables smooth administration of a drug.

The microneedle for solving the above problems includes a base portion having a support surface and a protrusion protruding from the support surface, and the protrusion is formed inside the protrusion from the base end to the tip of the protrusion. It has a main flow path extending toward the main flow path and a sub-flow path extending from the main flow path toward the peripheral surface of the protrusion and opening to the peripheral surface, and both ends of the main flow path in the extending direction of the main flow path. Of these, the end on the base end side of the protrusion is an open end penetrating the support surface, and the end on the tip end side of the protrusion is closed and has a cross section orthogonal to the extending direction of the subchannel. The area of the region defined by the sub-channel is 300 μm ² or more.

According to the above configuration, the opening of the sub-channel is located on the peripheral surface of the protrusion, and the drug is discharged into the skin through this opening. When the protrusion is stuck in the skin, the tissue in the skin spreads wider in the width direction than in the length direction of the protrusion, so that the end of the through hole along the length direction of the protrusion is conventionally used. The above-mentioned structure is easier to suppress the leakage of the drug under the skin and diffuse the drug into the skin than the structure in which the portion is open near the tip of the protrusion. When the area ^{of the sub-channel is 300 μm 2} or more, the drug can be smoothly discharged from the sub-channel into the skin.
In the above configuration, the area of the region defined by the sub-channel in the cross section orthogonal to the extending direction of the sub-channel ^{is preferably 700 μm 2} or more.
According to the above configuration, the size of the sub-channel is sufficiently secured, and the drug can be more smoothly discharged from the sub-channel into the skin.

In the above configuration, the area of the region defined by the sub-channel in the cross section orthogonal to the extending direction of the sub-channel ^{may be 8000 μm 2} or less.
According to the above configuration, not only humans but also small animals can be administered, and since the size of the opening of the secondary channel is not too large with respect to the thickness of the skin, it is possible to accurately administer the drug into the skin. is there.

In the above configuration, the peripheral surface of the protrusion includes a tip surface that includes the tip point of the protrusion in the edge portion and is inclined with respect to the support surface, and the edge portion of the edge portion that includes the tip point. The sub-flow path includes a side surface shared with the surface and a side surface in the edge portion that does not include the apex point and shares the apex point-free side with the apical surface. It may be open to the shared side surface.

In a configuration in which the tip point is located at the edge of the tip face when viewed from the direction facing the support surface, when the protrusion pierces the skin, the protrusion is located at the force pressing the tip surface, that is, at the center of the protrusion. On the other hand, it receives a large force to tilt the protrusion on the side where the tip point is located. If the sub-channel is open to the side surface that does not include the tip point, the force that tries to tilt the protrusion is compared with the configuration that the sub-channel is open to the side surface that includes the tip point. The strength of the protrusion is increased.

In the above configuration, the protrusion has a columnar portion having a columnar shape extending from the support surface and a cone-shaped portion extending from the top of the columnar portion and pointed toward the tip of the protrusion, and the secondary portion. The flow path may be open to the peripheral surface of the cone-shaped portion.

According to the above configuration, since the protrusion has a conical portion that is pointed toward the tip, the protrusion is likely to pierce the skin. On the other hand, since the protrusion has a columnar portion, it is possible to prevent the diameter of the hole formed by the protrusion from expanding near the surface of the skin. As a result, the drug administered intradermally is less likely to leak to the surface of the skin. Since the sub-channel is open on the peripheral surface of the cone-shaped portion, the effect of preventing the drug from leaking to the surface of the skin is enhanced.

According to the present invention, it is possible to enable smooth administration of a drug.

Regarding one embodiment of the microneedle, (a) is a perspective view showing a perspective structure of the microneedle seen from the front side, and (b) is a perspective view showing the perspective structure of the microneedle seen from the back side. Regarding the microneedles of one embodiment, (a) is a diagram showing a perspective structure of a main flow path and a sub flow path, and (b) is a diagram showing a cross-sectional structure in a cross section along the extending direction of the sub flow path. FIG. 5 is a cross-sectional view showing another example of the cross-sectional structure of the microneedle of one embodiment. The plan view which shows the planar structure of the microneedle of one Embodiment. The figure which shows the form in which the microneedle of one Embodiment was attached to an injection cylinder by breaking a part of the outer cylinder provided with the injection cylinder. The perspective view which shows the perspective structure of the microneedle of a modification. The perspective view which shows the perspective structure of the microneedle of a modification. A graph showing the relationship between the area of the subchannel and the time required to release pure water for Test Examples 1 to 11. The graph which shows a part of FIG. 8 enlarged.

An embodiment of the microneedle will be described with reference to FIGS. 1 to 6.
[Overall configuration of microneedle]
As shown in FIGS. 1A and 1B, the microneedle 10 includes a base portion 11 having a support surface 11S and a protrusion 12 protruding from the support surface 11S.

The support surface 11S supports the base end of the protrusion 12. The shape of the support surface 11S is not particularly limited, and the support surface 11S may have a circular shape or a polygonal shape. The base portion 11 may have a flat plate shape as in the example shown in FIG. 1, or may have a tubular shape extending from the support surface 11S in the direction opposite to the protrusion 12. The base portion 11 has a structure such as a groove or a protrusion on the outer peripheral portion of the base portion 11 for connecting an instrument for supplying a liquid agent which is a liquid agent to the microneedle 10 and the microneedle 10. You may.

The protrusion 12 is composed of a columnar portion 13 having a columnar shape extending from the support surface 11S, and a cone-shaped portion 14 having a shape in which a cone extending from the top of the columnar portion 13 is cut diagonally with respect to the extending direction. Will be done.

Specifically, the columnar portion 13 has a quadrangular prism shape and includes four side surfaces 13D extending from a square-shaped bottom surface partitioned within the support surface 11S. The side surface 13D is orthogonal to the support surface 11S. Further, the pyramid portion 14 has a shape obtained by cutting a quadrangular pyramid diagonally with respect to its extending direction, and has four side surfaces 14D and one tip that shares a side with each of these side surface 14Ds. It has a surface 14T.

The side surface 14D is inclined with respect to the support surface 11S, and one side surface 14D shares one side with one side surface 13D. The tip surface 14T is also inclined with respect to the support surface 11S, and all the sides included in the tip surface 14T are inclined with respect to the support surface 11S. In the example shown in FIG. 1, among the vertices of the apex surface 14T, the apex closest to the base portion 11, that is, the apex located closest to the proximal end side of the protruding portion 12, is the distal end side of the cone-shaped portion 14. It is located at a portion, that is, an end portion in contact with the columnar portion 13. In such a configuration, the side surface 14D that shares the apex of the tip surface 14T closest to the base portion 11 with the tip surface 14T has a triangular shape.

The tip surface 14T has a shape that is line-symmetric with respect to a straight line connecting the apex closest to the base portion 11 and the apex farthest from the base portion 11, and the apex farthest from the base portion 11 is the protrusion 12. It constitutes the apex point P, which is the point of the apex.

The peripheral surface of the protrusion 12 is composed of the four side surfaces 13D, the four side surfaces 14D, and the tip surface 14T. The length of the protrusion 12 from the support surface 11S is the largest at the tip point P.

Inside the protrusion 12, one main flow path 15 m extending from the base end of the protrusion 12 toward the tip end and one sub-flow path 15s extending from the main flow path 15 m toward the peripheral surface of the protrusion 12 are provided. Have. The main flow path 15m and the sub-flow path 15s communicate with each other, and each of the main flow path 15m and the sub-flow path 15s defines a space in which a fluid can flow inside the protrusion 12. The main flow path 15m penetrates the support surface 11S and communicates with the outside of the microneedle 10, and the sub flow path 15s opens on the peripheral surface of the protrusion 12.

The number of protrusions 12 included in the microneedle 10 may be one or a plurality. When the microneedle 10 includes one protrusion 12, the protrusion 12 is preferably located at the center of the support surface 11S. When the microneedle 10 includes a plurality of protrusions 12, the plurality of protrusions 12 are arranged on the support surface 11S, for example, in a grid pattern, a circular shape, or a concentric circle shape.

[Detailed configuration of flow path]
A detailed configuration of the main flow path 15 m and the sub flow path 15s will be described with reference to FIGS. 2 to 4. FIG. 2A is a diagram showing the outer shape of the main flow path 15 m and the sub-flow path 15s with a solid line, and FIG. 2B is a diagram showing the outer shape of the protrusion 12 with a chain double-dashed line. It is a figure which shows the cross section of the protrusion 12 along the direction.

As shown in FIGS. 2A and 2B, the main flow path 15m is located at the center of the protrusion 12 and extends in the length direction of the protrusion 12, that is, in the direction orthogonal to the support surface 11S. ing. Of both ends in the extending direction of the main flow path 15 m, the end on the base end side of the protrusion 12 is an open end. For example, the main flow path 15m penetrates the base portion 11 and opens to the surface of the base portion 11 opposite to the support surface 11S. On the other hand, of both ends in the extending direction of the main flow path 15 m, the end on the tip end side of the protrusion 12 is closed. That is, the end portion on the tip end side of the protrusion 12 in the main flow path 15 m does not reach the tip surface 14T of the protrusion 12.

The sub-flow path 15s extends along the width direction of the protrusion 12, that is, the direction parallel to the support surface 11S. Of both ends of the auxiliary flow path 15s in the extending direction, one end is connected to the main flow path 15m, and the other end is open to the side surface 14D of the cone 14 in the protrusion 12. The tip surface 14T and the side surface 13D of the columnar portion 13 do not have an opening which is an end portion of the flow path.

The main flow path 15m and the sub-flow path 15s form a fluid flow path from the opening end of the main flow path 15m to the opening of the sub-flow path 15s inside the protrusion 12, and this flow path is the main flow. It is bent at the connecting portion between the road 15m and the auxiliary flow path 15s.

For each of the main flow path 15m and the sub flow path 15s, the region defined by each flow path in the cross section orthogonal to the extending direction of each flow path shows a circular shape. The area of the region defined by the main flow path 15m in the cross section orthogonal to the extending direction of the main flow path 15m is the main flow path area Ms, and the main flow path area Ms is constant in one main flow path 15m. With respect to the sub-channel 15s, the area of the region partitioned by the sub-channel 15s in the cross section orthogonal to the extending direction of the sub-channel 15s is the sub-channel area Ss, and in one sub-channel 15s, the sub-channel area Ss. Is constant.
The sub-channel area Ss is 300 μm ² or more, and ^{preferably 700 μm 2} or more. Further, the auxiliary flow channel area Ss is preferably at 8000Myuemu ² or less, and more preferably 2000 .mu.m ² or less.
Main channel area Ms is preferably 3000 .mu.m ² or more 70000Myuemu ² or less. The main flow path area Ms and the sub flow path area Ss may be equal or different.

The length Lt of the protrusion 12 is the length from the support surface 11S to the tip point P of the protrusion 12 in the length direction of the protrusion 12, that is, in the direction orthogonal to the support surface 11S. The length Lt of the protrusion 12 is preferably a length that penetrates the stratum corneum, which is the outermost layer of the skin, and does not reach the subcutaneous layer, and specifically, is preferably 200 μm or more and 2000 μm or less.

The length Lc of the columnar portion 13 is the length from the support surface 11S in the length direction of the protrusion 12 to the top of the columnar portion 13, and the length Lc of the columnar portion 13 is the length of the protrusion 12. It is preferably 1/20 or more and 1/2 or less of Lt.

The width Wt of the protrusion 12 is the maximum length of the protrusion 12 in the width direction of the protrusion 12, that is, in the direction parallel to the support surface 11S. That is, the width Wt of the protrusion 12 is the length of the diagonal line of the square indicated by the bottom surface of the protrusion 12 partitioned in the support surface 11S. The width Wt of the protrusion 12 is preferably 150 μm or more and 1000 μm or less.

The height Hm of the main flow path 15 m is the length of the main flow path 15 m from the support surface 11S in the length direction of the protrusion 12, that is, the end of the protrusion 12 on the main flow path 15 m from the support surface 11S on the tip end side. It is the length to the part. The height Hm of the main flow path 15 m is smaller than the length Lt of the protrusion 12.

The height Hs of the sub-channel 15s is the distance from the support surface 11S in the length direction of the protrusion 12 to the center C of the opening of the sub-channel 15s. The center C of the opening is the center of gravity of the figure indicated by the region defined by the opening, and is located on a line passing through the center of gravity of the region defined by the subchannel 15s in each cross section orthogonal to the extending direction of the subchannel 15s. For example, when the sub-channel 15s is circular in each of the cross sections and the sub-channel 15s is cylindrical, a side flow is formed at the line passing through the center of the circle, that is, at the end of the central axis of the cylinder. The center C of the opening of the road 15s is located.

The height Hs of the subchannel 15s is preferably 100 μm or more. In other words, it is preferable that the center C of the subchannel 15s and the support surface 11S are separated by 100 μm or more. When the height Hs of the auxiliary flow path 15s is 100 μm or more, it is possible to prevent the drug supplied to the protrusion 12 from flowing out from the vicinity of the support surface 11S in the protrusion 12, that is, from a portion close to the surface of the skin. Therefore, it is possible to prevent the drug to be administered intradermally from leaking to the surface of the skin. The height Hs of the subchannel 15s is preferably 1500 μm or less.

As shown in FIG. 2B, the sub-flow path 15s may extend from the same height as the tip end side of the protrusion 12 in the main flow path 15m. Alternatively, as shown in FIG. 3, the sub-flow path 15s is located closer to the base end of the protrusion 12 than the end of the protrusion 12 in the main flow path 15 m at the end connected to the main flow path 15 m. May be located. In any case, the height Hs of the sub flow path 15s is smaller than the height Hm of the main flow path 15m.

In the configuration shown in FIG. 2B, at the connection portion between the sub-flow path 15s and the main flow path 15m, the position of the tip end side of the protrusion 12 in the main flow path 15m and the protrusion 12 in the sub-flow path 15s. The position of the end portion on the tip end side coincides with the position of the end portion on the tip end side in the length direction of the protrusion 12.

On the other hand, in the configuration shown in FIG. 3, in the length direction of the protrusion 12, the main flow path 15m extends beyond the sub-flow path 15s toward the tip end side of the protrusion 12, and connects the sub-flow path 15s and the main flow path 15m. A step portion 16 is formed in the portion. Compared with the configuration shown in FIG. 2B, the configuration shown in FIG. 3 shows the main flow path 15m and the sub-flow path when the microneedle 10 is manufactured by the method of forming the sub-flow path 15s after the main flow path 15m. High accuracy is not required for alignment with 15s.

As shown in FIG. 4, the tip point P of the protrusion 12 is located at the edge of the tip surface 14T when viewed from the direction facing the support surface 11S. The side surface 14D in which the auxiliary flow path 15s is open is a side surface 14D that does not include the tip point P of the protrusion 12, and is a side located on the lower side of the inclination among the sides of the tip surface 14T, that is, a protrusion. It is a side surface 14D that shares a side close to the base end of the portion 12 with the tip surface 14T. In other words, the subchannel 15s divides the four side surfaces 14D into two side surfaces 14D near the tip point P and two side surfaces 14D far from the tip point P, and the two side surfaces 14D far from the tip point P. It is open to one of. The side surface 14D close to the tip point P is a side surface 14D that shares the side including the tip point P with the tip surface 14T in the edge portion of the tip surface 14T, and the side surface 14D far from the tip point P is the edge of the tip surface 14T. It is a side surface 14D that shares a side of the portion that does not include the tip point P with the tip face 14T.

In the configuration in which the tip point P is located at the edge of the tip surface 14T, when the protrusion 12 pierces the skin, the protrusion 12 presses the tip surface 14T, that is, the protrusion 12 is centered on the protrusion 12. On the other hand, it receives a large force to tilt it toward the side where the tip point P is located. Therefore, if the sub-flow path 15s is open to the side surface 14D far from the tip point P, the protrusion is compared with the configuration in which the sub-flow path 15s is open to the side surface 14D near the tip point P. The strength of the protrusion 12 against the force of tilting the portion 12 toward the side where the tip point P is located is increased.

[Action]
The operation of the microneedle 10 of the present embodiment will be described with reference to FIG.
As shown in FIG. 5, the microneedle 10 is attached to the tip of the outer cylinder 31 included in the injection cylinder 30. When the drug is administered, the microneedle 10 is pressed against the skin to which the drug is administered, so that the protrusion 12 pierces the skin. Then, the pusher 32 is pushed toward the microneedle 10 with the protrusion 12 piercing the skin. When the pusher 32 is pushed in, the liquid chemical lm filled in the outer cylinder 31 is supplied to the main flow path 15m of the protrusion 12, and the chemical lm flows from the main flow path 15m to the sub-flow path 15s. .. Then, the drug lm exits from the opening of the side surface 14D of the protrusion 12 and enters the skin.

In the conventional configuration in which the end of the through hole along the length direction of the protrusion is open near the tip of the protrusion, the drug is released along the length direction of the protrusion. , The drug is released from the protrusion 12 of the present embodiment along the width direction of the protrusion 12. In the state where the protrusion 12 is stuck in the skin, the tissue in the skin spreads wider in the width direction than in the length direction of the protrusion 12, so that the configuration of this embodiment is more suitable than the conventional configuration. It suppresses the leakage of the drug under the skin and facilitates the diffusion of the drug into the skin.

Further, the protrusion 12 is inserted into the skin from the tip point P along the length direction thereof. Therefore, as in the present embodiment, the end portion of the through hole along the length direction of the protrusion portion is opened near the tip of the protrusion portion as in the length direction of the protrusion portion 12 as in the present embodiment. In a configuration in which the ends of the sub-channels 15s extending in different directions are opened on the peripheral surface of the protrusion 12, it is difficult for skin tissue to enter the drug flow path during the perforation process.

Here, if the sub-channel area Ss is small, the outlet of the drug from the protrusion 12 becomes small, so that it is difficult for the drug to smoothly flow out from the sub-channel 15s into the skin. When the sub-channel area Ss is 300 μm ² or more, the drug can be smoothly discharged from the sub-channel 15s into the skin, and especially when the sub- ^{channel area Ss is 700 μm 2 or more, the sub channel area Ss is 700 μm 2.} The release of the drug from the flow path 15s into the skin proceeds smoothly.

Furthermore, if the subchannel area Ss is 8000 μm ² or less, the size of the opening of the subchannel 15s is not too large with respect to the skin thickness, not only in humans but also in small animals as a test. Accurate administration of the drug into the skin is possible.

As described above, according to the microneedle 10 of the present embodiment, smooth administration of the drug is possible. As a result, it is possible to suppress an increase in the force required for pressing the drug and an increase in the time required for administration of the drug, so that the burden on the drug admin and the recipient can be suppressed. In addition, because the amount of the drug that can spread in the skin is limited, the drug is prevented from flowing out to the surface or subcutaneous of the skin, so that the drug leaks to a site different from the desired position. It is also possible to prevent the amount of the drug administered intradermally from being reduced.

Further, since the protrusion 12 has a cone-shaped portion 14 that is pointed toward the tip, the protrusion 12 is likely to pierce the skin. On the other hand, since the protrusion 12 has the columnar portion 13, when the protrusion is composed of only the cone-shaped portion 14, that is, the side surface inclined with respect to the support surface 11S extends to the support surface 11S. Compared with the case, the diameter of the hole formed by the protrusion is suppressed from expanding near the surface of the skin. As a result, the drug administered intradermally is less likely to leak to the surface of the skin. In particular, since the sub-channel 15s opens on the side surface 14D of the cone 14 and the side surface 13D of the columnar portion 13 does not have an opening that is the end of the sub-channel 15s, the drug can be applied to the surface of the skin. A high effect of preventing leakage can be obtained.

[Manufacturing method of microneedles]
The material and manufacturing method of the microneedle 10 will be described.
The material for forming the protrusion 12 is not particularly limited, and the protrusion 12 may be made of a metal material such as silicon, stainless steel, titanium, a cobalt-chromium alloy, or a magnesium alloy. Further, the protrusion 12 may be formed of a resin material such as a general-purpose plastic, a medical plastic, and a cosmetic plastic. Examples of the resin material include polyethylene, polypropylene, polystyrene, polyamide, polycarbonate, cyclic polyolefin, polylactic acid, polyglycolic acid, polycaprolactone, acrylic, urethane resin, aromatic polyetherketone, epoxy resin, and these resins. Examples include copolymer materials.
The material of the base portion 11 is not particularly limited, and the base portion 11 may be formed from, for example, the material exemplified as the material of the protrusion 12 described above.

The microneedle 10 may be an integrally molded product in which the base portion 11 and the protrusion 12 are integrally formed, or the microneedle 10 is formed by joining the base portion 11 and the protrusion 12 after they are formed separately. It may be formed by a combination of a metal material and a resin material. For example, the protrusion 12 may be made of metal and the base portion 11 may be made of resin, and conversely, the protrusion 12 may be made of resin and the base portion 11 may be made of metal.

When the base portion 11 and the protrusion 12 are formed separately, or when the microneedle 10 is formed by a combination of a metal material and a resin material, each of the separate parts constituting the microneedle 10 is required. A sealant, an adhesive, a gasket, an O-ring, or the like for bringing the portions in close contact with each other may be used in combination.

As a method for forming the microneedle 10, for example, a method of forming a hole to be a main flow path 15 m and a hole to be a sub flow path 15s after forming the outer shape of the base portion 11 and the protrusion portion 12 by machining is used. Be done. Specifically, a structure having a shape in which a cone or a frustum is connected to the column is formed, and the structure is cut diagonally with respect to the length direction to form a columnar portion 13 and a cone shape. The outer shape of the protrusion 12 composed of the portion 14 is formed.

Alternatively, when the microneedle 10 is formed from a resin material, the microneedle 10 may be formed by a combination of injection molding and machining. For example, after the outer shape of the base portion 11 and the protrusion 12 and the hole serving as the main flow path 15m are formed by injection molding, the hole serving as the sub flow path 15s is formed by machining.
Alternatively, the microneedles 10 may be formed by combining a plurality of movable dies using only injection molding.
Examples of the machining method used for forming the main flow path 15 m and the sub flow path 15s include laser machining.

As described above, according to the present embodiment, the following effects can be obtained.
(1) Since the protrusion 12 has a sub-flow path 15s extending from the main flow path 15 m and opening to the peripheral surface of the protrusion 12, the drug is prevented from leaking subcutaneously and the drug is diffused into the skin. Cheap. When the sub-channel area Ss in the sub-channel 15s is 300 μm ² or more, the drug can be smoothly discharged from the sub-channel 15s into the skin. Further, when the sub-channel area Ss is 700 μm ² or more, the drug can be more smoothly discharged from the sub-channel 15s into the skin.

(2) Since the sub-channel area Ss is 8000 μm ² or less, the size of the opening of the sub-channel 15s is not too large with respect to the thickness of the skin as well as humans, so that the drug can be accurately administered intradermally. Is possible.

(4) The sub-flow path 15s opens to the side surface 14D that does not include the tip point P among the four side surfaces 14D. According to such a configuration, the force of the protrusion 12 against the force received by the protrusion 12 when the protrusion 12 is perforated, that is, the force of tilting the protrusion 12 toward the side where the tip point P is located with respect to the center of the protrusion 12. Strength is increased.

(5) Since the protrusion 12 has a cone-shaped portion 14 that is pointed toward the tip, the protrusion 12 easily sticks into the skin. On the other hand, since the protrusion 12 has the columnar portion 13, it is possible to prevent the diameter of the hole formed by the protrusion 12 from expanding near the surface of the skin. As a result, the drug administered intradermally is less likely to leak to the surface of the skin. Since the sub-channel 15s is open on the peripheral surface of the cone-shaped portion 14, the effect of preventing the drug from leaking to the surface of the skin can be highly obtained.

[Modification example]
The above embodiment can be modified and implemented as follows.
-For each of the main flow path 15m and the sub-flow path 15s, the shape of the region in which the flow path is partitioned by the cross section orthogonal to the extending direction of the flow path may not be circular, and may be, for example, rectangular. Further, the shape of the region defined by the main flow path 15m in the above cross section may be different from the shape of the region partitioned by the sub flow path 15s in the above cross section. Regardless of the shape of the region defined by the subchannel 15s, the subchannel area Ss may be 300 μm ² or more, and the subchannel area Ss should be 700 μm ² or more for smooth release of the drug. It is preferable to have.

The shape of the protrusion 12 is not limited to the shape of the above embodiment. For example, if the shape of the protrusion is a shape in which the bottom surface of the pyramid is connected to the upper surface of the pillar and is cut diagonally with respect to the extending direction, the apex of the tip surface 14T closest to the base portion 11 May be located on the tip end side of the protrusion with respect to the boundary between the pillar and the pyramid, or may be located on the base end side of the protrusion.

Further, for example, the protrusion may have a shape in which a cone or a pyramid is cut diagonally with respect to the extending direction thereof. The protrusion 17 illustrated in FIG. 6 has a shape in which a quadrangular pyramid is cut diagonally with respect to its extending direction. In this case, the peripheral surface of the protrusion 17 is four side surfaces 17D extending from the support surface 11S in a direction inclined with respect to the support surface 11S, and a pointed surface 17T connected to the four side surfaces 17D, with respect to the support surface 11S. It is composed of an inclined tip surface 17T. Further, when the protrusion has a shape in which the cone is cut diagonally with respect to the extending direction, the peripheral surface of the protrusion is connected to the side surface which is a curved surface extending from the support surface 11S and the side surface. It is composed of a tip surface inclined with respect to the support surface 11S.

Further, for example, the protrusion may have a shape in which a prism or a cylinder is cut diagonally with respect to the extending direction thereof, or has no inclined tip surface and is supported like a cone shape or a pyramid shape. When viewed from the direction facing the surface 11S, the tip point of the protrusion may have a shape located at the center of the protrusion. Further, the tip surface of the protrusion may be curved, or a groove or a step may be formed on the peripheral surface of the protrusion. In short, the protrusion may have a shape capable of piercing the skin.

When the protrusion has a shape in which the size of the protrusion in the width direction gradually increases from the tip of the protrusion to the support surface 11S toward the base end, the strength in the vicinity of the base end of the protrusion is increased. On the other hand, when the protrusion has a portion at the base end where the size of the protrusion is constant in the width direction, the resistance when the protrusion is pierced into the skin is compared with the case where the size in the width direction changes. Can be kept small.

-If the protrusion 12 has a sub-flow path 15s that extends from the main flow path 15 m and opens on the peripheral surface of the protrusion 12, the position of the opening of the sub-flow path 15s and the extension direction of the sub-flow path 15s are limited. Not done. For example, the sub-flow path 15s may be opened on the side surface 14D near the tip point P, in-plane of the tip surface 14T or the side surface 13D of the columnar portion 13, or a surface forming the peripheral surface of the protrusion 12. It may be opened at a position straddling the surfaces adjacent to each other. Further, the sub-flow path 15s may extend in a direction different from the width direction of the protrusion 12, in other words, may extend in a direction inclined with respect to the support surface 11S. Further, in the portion where the main flow path 15m and the sub-flow path 15s are connected, the end portion on the tip end side of the protrusion 12 in the sub-flow path 15s is larger than the end portion on the tip end side of the protrusion 12 in the main flow path 15m. It may be located on the tip end side of the protrusion 12.

The protrusion 12 may have a plurality of sub-flow passages 15s extending from the main flow path 15 m and opening on the peripheral surface of the protrusion 12. FIG. 7 shows an example in which the protrusion 12 has two subchannels 15s. In order to prevent the strength of the protrusion 12 from being excessively lowered at a specific position, it is preferable that the heights Hs of the plurality of auxiliary flow paths 15s are different from each other, and from the direction facing the support surface 11S. As seen, it is preferable that the plurality of sub-flow paths 15s extend from the main flow path 15 m in different directions. For example, it is preferable that the open side surface 14D of each sub-channel 15s is different from the open side surface 14D of the other sub-channel 15s.

When the protrusion 12 has a plurality of sub-channels 15s, the sub-channel area Ss of each of the sub-channels 15s ^{may be 300 μm 2} or more in order to smoothly release the drug. Further, the subchannel area Ss is ^{preferably 700 μm 2} or more.

-The form of use of the microneedle 10 is not limited to the form of being attached to the injection tube 30. The drug may be supplied to the main flow path 15 m of the protrusion 12 by an instrument different from the injection tube 30. Further, after administration of the drug, the protrusion 12 may be separated from the substrate 11 and left in the skin to be administered.

-The target to which the drug is administered by the microneedle 10 is not limited to humans, but may be other animals. In addition, each of the above-described configuration of the embodiment and the configuration of the modified example can be implemented in an appropriate combination.

[Example]
The above-mentioned microneedles will be described with reference to specific examples.
<Making microneedles>
A structure in which polycarbonate is used as the material for the microneedles, and a quadrangular pyramid connected to the upper surface of a quadrangular prism having a square bottom is cut diagonally in the extending direction together with a plate-shaped base portion by injection molding. Therefore, a structure having a hole serving as a main flow path was formed inside. Further, a protrusion was formed by forming a hole serving as a secondary flow path in the structure by laser processing. By changing the shape of the holes formed by laser machining, microneedles of Test Examples 1 to 11 having different subchannel areas Ss were obtained.

In each of the microneedles of Test Examples 1 to 11, the outer shape of the protrusion is the shape shown in FIG. 1, the inclination of the side surface of the cone with respect to the support surface is 80 °, and the length Lt of the protrusion is It is 750 μm, and the length Lc of the columnar portion is 100 μm. Further, in each of the microneedles of Test Examples 1 to 11, the height Hm of the main flow path is 600 μm, and the shape of the region defined by the main flow path in the cross section orthogonal to the extending direction of the main flow path is circular. Its diameter is 100 μm. Further, in all of the microneedles of Test Examples 1 to 11, the height Hs of the sub-channel is 450 μm, and the sub-channel is the side surface of the cone-shaped portion far from the tip point P of the protrusion. It is open to.

In the microneedles of Test Examples 1 to 6, the shape of the region in which the sub-channel is partitioned by the cross section orthogonal to the extending direction of the sub-channel is circular, and the diameter thereof differs for each test example.

In the microneedles of Test Examples 7 to 11, the shape of the region defined by the subchannel in the cross section orthogonal to the extending direction of the subchannel is rectangular, and the combination of the length of the long side and the length of the short side is , Different for each test example.

<Evaluation of liquid release capacity>
The liquid release ability of the microneedles of Test Examples 1 to 11 was evaluated. Each microneedle is attached to an injection tube filled with pure water, and this pure water is continuously pressed with a force of 0.2 MPa to release pure water into the atmosphere from the sub-channel of the protrusion, and 1000 μL of pure water is released. The time required to complete the release of was measured. The pressing of pure water was performed by inserting a tube to which a pressure gauge was connected into the outer cylinder of the syringe cylinder instead of the pusher, and supplying gas into the tube so that the inside of the tube became 0.2 MPa.

Table 1 shows the measurement results of the shape of the subchannel, the subchannel area Ss, and the time required to release the pure water for the microneedles of Test Examples 1 to 11. The sub-channel area Ss is rounded off to the first minority.

FIG. 8 is a graph showing the results of Table 1 with the horizontal axis representing the subchannel area Ss and the vertical axis representing the time required for the discharge of pure water. FIG. 9 is a graph showing the sidestream of FIG. It is a figure which enlarges and shows the region where the road area Ss is 3000 μm ^{2 or less.} That is, FIG. 9 shows the results obtained for Test Examples 1 to 5.

As shown in FIGS. 8 and 9 ^{, in Test Example 1 in which the subchannel area Ss is about 100 μm 2} , the release time is extremely long as compared with other test examples, and the subchannel area Ss is less than ^{300 μm 2.} In the range, the release time sharply decreases as the subchannel area Ss increases. Then, in the range where the sub-channel area Ss is 300 μm ² or more, the release time is kept smaller than the level where the sub-channel area Ss is ^{less than 300 μm 2} , and the change in the release time due to the increase in the sub-channel area Ss is It is gradual. In particular, in the range where the subchannel area Ss is 700 μm ² or more, the change in the release time due to the increase in the subchannel area Ss is small. Even when the magnitude of the force for pressing pure water was changed in the range of 0.1 MPa or more and 0.3 MPa or less, the same tendency was observed between the subchannel area Ss and the discharge time.

Based on the above results, when the subchannel area Ss is 300 μm ² or more, the discharge time is remarkably shorter than when the subchannel area Ss is ^{less than 300 μm 2, and the subchannel area is smooth.} It was shown that the drug can be discharged. Furthermore, it was shown that when the sub-channel area Ss is 700 μm ² or more, the release time is near the minimum, and smoother discharge of the drug from the sub-channel is possible.

10 ... Microneedle, 11 ... Base part, 11S ... Support surface, 12, 17 ... Protrusions, 13 ... Columnar part, 13D ... Side surface, 14 ... Cone-shaped part, 14D ... Side surface, 14T ... Tip surface, 15m ... Main flow path , 15s ... sub-channel, 16 ... stepped portion, 30 ... injection tube, 31 ... outer tube, 32 ... pusher, P ... tip point.

Claims (6)

A base part having a support surface and
With a protrusion protruding from the support surface,
The protrusions are a main flow path extending from the base end to the tip of the protrusion inside the protrusion, and a side flow extending from the main flow path toward the peripheral surface of the protrusion and opening to the peripheral surface. Have a road and
The protrusion has a conical portion, and the peripheral surface of the conical portion includes a tip surface inclined with respect to the support surface and a plurality of side surfaces connected to the tip surface.
Of both ends of the main flow path in the extending direction of the main flow path, the end on the base end side of the protrusion is an open end penetrating the support surface, and the end on the tip end side of the protrusion is closed. ,
The area of the region defined by the main flow path in the cross section orthogonal to the extending direction of the main flow path is constant and is 3000 μm ² or more.
The sub-channel does not open at the tip surface, the sub-channel opens at the side surface of the cone, and the area of the region defined by the sub-channel in a cross section orthogonal to the extending direction of the sub-channel. Is a ^{microneedle of 300 μm 2} or more. The microneedle according to claim 1, wherein the area of the region defined by the sub-channel in a cross section orthogonal to the extending direction of the sub-channel is 700 μm ^{2 or more.} The microneedle according to claim 1 or 2, wherein the area of the region defined by the sub-channel in a cross section orthogonal to the extending direction of the sub-channel is 8000 μm ^{2 or less.} The protrusion has a columnar portion having a columnar shape extending from the support surface and a conical portion extending from the top of the columnar portion and pointed toward the tip of the protrusion.
The microneedle according to any one of claims 1 to 3 , wherein the sub-channel opens on the peripheral surface of the cone-shaped portion and does not open on the side surface of the columnar portion. The area of the region defined by the main flow path in the cross section orthogonal to the extending direction of the main flow path is equal to the area of the region partitioned by the sub flow path in the cross section orthogonal to the extending direction of the sub flow path.
The microneedle according to any one of claims 1 to 4. The area of the region defined by the main flow path in the cross section orthogonal to the extending direction of the main flow path and the area of the region partitioned by the sub flow path in the cross section orthogonal to the extending direction of the sub flow path are different.
The microneedle according to any one of claims 1 to 4.

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