JP6880940B2 - 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 are factors that prevent the drug from smoothly flowing into the skin through the through hole. When the smooth administration of the drug into the skin is hindered in this way, the force required for pressing the drug and the time required for the administration of the drug increase, which imposes a heavy burden on the drug admin and the recipient. Or, the drug may leak to the surface or subcutaneously of the skin, reducing the amount of drug administered intradermally.
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 one main flow path extending toward the main flow path and a plurality of sub-flow paths extending from the main flow path toward the peripheral surface of the protrusion and opening to the peripheral surface, and the extending direction of the main flow path in the main flow path. Of both ends of the protrusion, 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.

According to the above configuration, since the protrusion has a plurality of auxiliary flow paths that open on the peripheral surface of the protrusion, the drug supplied to the protrusion is dispersed and released to a plurality of places in the skin. The drug released into the skin from the protrusions spreads into the tightly packed tissue, so it is better to disperse and release it in multiple locations than to concentrate it in one location. , The drug easily spreads in the skin, and the resistance when the drug comes out from the protrusion into the skin is also reduced. Therefore, smooth administration of the drug is possible.

In the above configuration, the length along the direction orthogonal to the support surface from the center of gravity of the region defined by the opening of the sub-channel to the support surface is the height of the sub-channel, and each side flow. The height in the road may be different from the height in the other subchannels.

According to the above configuration, it is possible to prevent the openings of the plurality of subchannels from lining up on a plane parallel to the support surface. Therefore, it is possible to prevent the strength of the protrusion from becoming extremely low at a specific position in the length direction of the protrusion, so that the protrusion is less likely to be deformed when the skin is perforated. As a result, the protrusions are likely to pierce the skin to a depth corresponding to the length of the protrusions.

In the above configuration, each sub-flow path may extend from the main flow path in a direction different from the direction in which the other sub-flow path extends from the main flow path when viewed from the direction facing the support surface.

According to the above configuration, it is possible to prevent the plurality of subchannels from lining up in the length direction of the protrusions. Therefore, it is possible to prevent the strength of the protrusions from becoming extremely low at a specific position in the direction along the support surface, so that the protrusions are less likely to be deformed when the skin is perforated. As a result, the protrusions are likely to pierce the skin to a depth corresponding to the length of the protrusions.

In the above configuration, the peripheral surface of the protrusion includes a tip surface inclined with respect to the support surface and a plurality of side surfaces connected to the tip surface, and each sub-flow path is different from the other sub-flow paths. It may be opened to the side.

According to the above configuration, it is possible to prevent the positions of the plurality of sub-channels from being biased and the number of sub-channels from becoming too large. Therefore, since the strength of the protrusion is suppressed from being excessively lowered, the protrusion is less likely to be deformed when the skin is perforated. As a result, the protrusions are likely to pierce the skin to a depth corresponding to the length of the protrusions.

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.

In the above configuration, the resistance that the fluid flowing in the main flow path receives per unit length is the main flow path resistance, and the resistance that the fluid flowing in the sub flow path receives per unit length is the sub flow path resistance. The sum of the subchannel resistances for all the subchannels may be equal to the main channel resistance.

According to the above configuration, it is possible to prevent the energy of the drug flowing through the main flow path from being significantly lost when passing through the sub flow path. Therefore, the drug can be efficiently flowed from the main flow path to the sub flow path.

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. 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. Regarding other forms 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. The figure which shows the perspective structure of the main flow path and the sub-flow path about the microneedle of another form. Top view showing the planar structure of other forms of microneedles. Regarding other forms 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. The figure which shows the perspective structure of the main flow path and the sub-flow path about the microneedle of another form. Top view showing the planar structure of other forms of microneedles. Top view showing another example of the planar structure of other forms of microneedles. The perspective view which shows the perspective structure of the microneedle of a modification. The figure which shows the evaluation result of the strength of the protrusion with respect to the microneedle of Examples 1-5 and Comparative Example 1. FIG.

An embodiment of the microneedle will be described with reference to FIGS. 1 to 11.
[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 may have a structure such as a groove or a protrusion for connecting an instrument for supplying a liquid drug to the microneedle 10 and the microneedle 10 on the outer peripheral portion of the base portion 11. ..

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 a plurality of sub-flow paths 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. FIG. 1 shows an example in which the protrusion 12 has two subchannels 15s.

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]
The detailed configuration of the main flow path 15m and the sub flow path 15s will be described with reference to FIGS. 2 and 3. 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 extending direction of each sub-channel 15s with a straight line passing through as a boundary.

As shown in FIG. 2, the main flow path 15 m is located at the central portion 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. 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. Each of the plurality of subchannels 15s is open to different surfaces of the four side surfaces 14D. In other words, the number of subchannels 15s that open on one side surface 14D is 1 or less. 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. For each 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 the sub-channel area in one sub-channel 15s. Ss is constant. Further, it is preferable that the sub-channel areas Ss of each sub-channel 15s are equal.

When the resistance that the fluid flowing in the main flow path 15 m receives per unit length is the main flow path resistance Mr, and the resistance that the fluid flowing in the sub flow path 15s receives per unit length is the sub flow path resistance Sr. It is preferable that the total of the sub-flow path resistances Sr for the sub-flow path resistances 15s is equal to the main flow path resistance Mr. Specifically, the total of the sub-channel areas Ss for all the sub-channels 15s is equal to the main channel area Ms, or the total of the sub-channel resistors Sr and the main channel resistance Mr can be regarded as equal. It is preferable that they are in close proximity.

In order to smoothly release the drug from the subchannel 15s into the skin, the subchannel area Ss is ^{preferably 300 μm 2} or more, and more 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. When 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 skin thickness, not only in humans but also in small animals as a test, so that it is intradermal. Accurate administration of the drug to the skin is possible.

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 heights Hs of the plurality of subchannels 15s are different from each other. Among the height Hs of the plurality of sub-channels 15s, the smallest height Hs, that is, the height Hs of the sub-channels 15s located closest to the support surface 11S is preferably 100 μm or more. In other words, it is preferable that the center C of the auxiliary flow path 15s closest to the support surface 11S and the support surface 11S are separated by 100 μm or more. When the minimum height Hs 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. Among the height Hs of the plurality of sub-channels 15s, the smallest height Hs, that is, the height Hs of the sub-channels 15s located closest to the support surface 11S is preferably 700 μm or less. ..

It should be noted that the region occupied by each sub-channel 15s does not include a portion where the position of the protrusion 12 in the length direction coincides with the region occupied by the other sub-channel 15s, in other words, each sub-channel 15s. It is preferable that the entire region occupied by the protrusion 12 is different from the entire region occupied by the other subchannel 15s in the length direction of the protrusion 12.

Among the height Hs in the plurality of subchannels 15s, the largest height Hs, that is, the height Hs of the subchannel 15s farthest from the support surface 11S is smaller than the height Hm of the main channel 15m. Then, the sub-flow path 15s farthest from the support surface 11S is located at the end connected to the main flow path 15m, closer to the base end side of the protrusion 12 than the tip end side of the protrusion 12 in the main flow path 15m. It is preferable to be located. In other words, in the length direction of the protrusion 12, the main flow path 15m extends beyond the sub-flow path 15s farthest from the support surface 11S toward the tip end side of the protrusion 12, and the sub-flow path 15s and the main flow path 15m. It is preferable that a step portion 16 is formed at the connecting portion with the above.

In such a configuration, the sub-flow path 15s is formed after the main flow path 15m as compared with the configuration in which the sub-flow path 15s extends from the same height as the tip end side of the protrusion 12 in the main flow path 15m. When manufacturing the microneedle 10, high accuracy is not required for the alignment between the main flow path 15m and the sub flow path 15s.

As shown in FIG. 3, 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. When viewed from the direction facing the support surface 11S, the plurality of sub-flow paths 15s extend from the main flow path 15m in different directions. That is, the plurality of subchannels 15s do not overlap in the length direction of the protrusion 12. The extending direction of the sub-flow path 15s is a direction from the center E of the main flow path 15m toward the center C of the opening of the sub-flow path 15s. Further, the positions of the openings of the plurality of subchannels 15s are different from each other when viewed from the direction facing the support surface 11S, in other words, the positions of the centers C of the openings in the plurality of subchannels 15s are different from each other. It's different.

In the example shown in FIGS. 1 to 3, the two sub-channels 15s included in the protrusion 12 are open to different surfaces of the four side surfaces 14D, and the two sub-channels 15s are open. The side surfaces 14D are adjacent to each other. The side surface 14D in which the sub-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 face 14T, that is, It is a side surface 14D that shares a side of the protrusion 12 near the base end with the tip surface 14T. In other words, the subchannel 15s opens to the side surface 14D far from the tip point P when the four side surfaces 14D are divided into two side surfaces 14D near the tip point P and two side surfaces 14D far from the tip point P. doing. 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.

[Action]
The operation of the microneedle 10 of the present embodiment will be described with reference to FIG.
As shown in FIG. 4, 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.

Here, when the protrusion has one through hole which penetrates the protrusion and opens to the tip of the protrusion as in the conventional case, or when the number of sub-flow paths 15s is one. As described above, when there is only one outlet for the drug, the drug is discharged from the protrusion in a concentrated manner in one place in the skin. On the other hand, in the present embodiment, since the protrusion 12 has a plurality of sub-channels 15s, there are a plurality of outlets for the drug from the protrusion 12, and the drug is dispersed in a plurality of locations in the skin to release the drug. Will be done. At this time, since the flow of the released drug receives a large resistance from the tissue densely packed with cells, the amount of the drug spreading from one place into the tissue per unit time is limited by this resistance. In this regard, if the drug is dispersed and released from a plurality of locations, it is possible to increase the amount of the drug that spreads in the skin per unit time.

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.

Further, in the conventional configuration in which the end of the through hole along the length direction of the protrusion is opened near the tip of the protrusion, the drug is released along the length direction of the protrusion. On the other hand, 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.

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.

Further, since the heights Hs of the plurality of sub-channels 15s are different from each other, it is possible to prevent the plurality of sub-channels 15s from lining up on a plane along the width direction of the protrusion 12. As a result, the length of the protrusion 12 is longer than that of the structure in which the plurality of subchannels 15s are lined up in the width direction of the protrusion 12, that is, the structure in which the holes formed in the protrusion 12 are lined up in the width direction of the protrusion 12. It is possible to prevent the strength of the protrusion 12 from becoming extremely low at a specific position in the longitudinal direction. Further, since the plurality of sub-channels 15s extend in different directions when viewed from the direction facing the support surface 11S, it is possible to prevent the plurality of sub-channels 15s from lining up in the length direction of the protrusion 12. .. As a result, as compared with the structure in which a plurality of sub-channels 15s are arranged in the length direction of the protrusion 12, that is, the structure in which the holes formed in the protrusion 12 are arranged in the length direction of the protrusion 12, the protrusion It is possible to prevent the strength of the protrusion 12 from becoming extremely low at a specific position in the width direction. Therefore, since the protrusion 12 is less likely to be deformed when the protrusion 12 is perforated into the skin, the protrusion 12 is likely to pierce the skin to a depth corresponding to the length of the protrusion 12. Therefore, it is possible to accurately administer the drug to a desired position in the skin.

Further, 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 pressed against the protrusion 12. It receives a large force to tilt it toward the side where the tip point P is located with respect to the center. Therefore, when the number of the sub-channels 15s is two, if the sub-channel 15s is open only to the side surface 14D far from the tip point P, the sub-channel 15s is the side surface close to the tip point P. Compared with the configuration opened in 14D, the strength of the protrusion 12 against the force of tilting the protrusion 12 toward the side where the tip point P is located is increased, and the protrusion 12 is also deformed by this. It becomes difficult.

[Other forms of microneedles]
In the above description, the protrusion 12 having two sub-channels 15s has been illustrated, but the number of sub-channels 15s is not limited as long as it is 2 or more. With reference to FIGS. 5 to 11, a mode in which the number of sub-channels 15s is three and a mode in which the number of sub-channels 15s is four will be described.

The protrusion 17 shown in FIGS. 5A and 5B has three sub-flow passages 15s. Each of the three subchannels 15s is open to different surfaces of the four side surfaces 14D.

As shown in FIG. 6, the height Hs of each of the three subchannels 15s is different from each other. In the length direction of the protrusion 17, the centers C of the openings of the three auxiliary flow paths 15s are preferably arranged at equal intervals. That is, among the height Hs of the three subchannels 15s, the median height Hs is preferably the average value of the largest height Hs and the smallest height Hs. According to such a configuration, the drug can be more evenly dispersed and released in the length direction of the protrusion 17. The total of the sub-channel resistances Sr for the three sub-channels 15s is preferably equal to the main channel resistance Mr, and the total of the sub-channel areas Ss for the three sub-channels 15s is equal to the main channel area Ms. Alternatively, it is preferable that the total of the subchannel resistance Sr and the main channel resistance Mr are close to each other so that they can be regarded as equal.

As shown in FIG. 7, when viewed from the direction facing the support surface 11S, the three sub-flow paths 15s extend from the main flow path 15m in different directions. Two of the three auxiliary flow paths 15s are opened one by one on the side surface 14D not including the tip point P of the protrusion 12. The remaining one of the three auxiliary flow paths 15s is centered on the boundary portion of the two side surfaces 14D sharing the tip point P, that is, the two side surfaces 14D close to the tip point P among the four side surfaces 14D. As a result, it is open across these two side surfaces 14D. Even in such a configuration, the number of subchannels 15s opened in one side surface 14D is 1 or less for each of the four side surfaces 14D.

The three subchannels 15s may be opened one by one on each of the two side surfaces 14D far from the tip point P and on either of the two side surfaces 14D near the tip point P. However, as shown in FIGS. 5 to 7, the three auxiliary flow paths 15s are located in the respective planes of the two side surfaces 14D far from the tip point P and across the two side surfaces 14D close to the tip point P. The structure that is open to the surface allows the drug to be more evenly dispersed and released in the width direction of the protrusion 17.
The protrusion 18 shown in FIGS. 8A and 8B has four sub-channels 15s. Each of the four subchannels 15s is open to different faces of the four side surfaces 14D.

As shown in FIG. 9, the height Hs of each of the four subchannels 15s is different from each other. It is preferable that the centers C of the openings of the four auxiliary flow paths 15s are arranged at equal intervals in the length direction of the protrusion 18. According to such a configuration, the drug can be more evenly dispersed and released in the length direction of the protrusion 18. The total of the sub-channel resistance Sr for the four sub-channels 15s is preferably equal to the main channel resistance Mr, and the total of the sub-channel areas Ss for the four sub-channels 15s is equal to the main channel area Ms. Alternatively, it is preferable that the total of the subchannel resistance Sr and the main channel resistance Mr are close to each other so that they can be regarded as equal.

As shown in FIG. 10, when viewed from the direction facing the support surface 11S, the four sub-flow paths 15s extend from the main flow path 15m in different directions. The four subchannels 15s are open one on each of the four side surfaces 14D. That is, for each of the four side surfaces 14D, the number of subchannels 15s that open in one side surface 14D is one.

When viewed from the direction facing the support surface 11S, the directions in which the four sub-flow paths 15s extend are preferably evenly distributed around the main flow path 15m. According to such a configuration, the drug can be more evenly dispersed and released in the width direction of the protrusion 18.

In the example shown in FIG. 10, the main flow path 15m divides the center C of the opening in the sub-flow path 15s opened on the two side surfaces 14D located across the main flow path 15m when viewed from the direction facing the support surface 11S. They are lined up on a straight line K1 passing through the center E of the region.

Instead, as shown in FIG. 11, the center C of the opening of the auxiliary flow path 15s opened on the two side surfaces 14D may be arranged so as not to line up on a straight line passing through the center E. According to such a configuration, when viewed from the direction facing the support surface 11S, the holes forming the sub-flow path 15s are suppressed from being lined up along one direction, so that the protrusion 12 with respect to the force from a specific direction The decrease in strength is further suppressed.

As described above, if the auxiliary flow path 15s is open to the side surface 14D near the tip point P in addition to the side surface 14D far from the tip point P, a wider range is provided in the width direction of the protrusion 17. The drug can be dispersed and released. Therefore, the drug can be administered more smoothly.

[Manufacturing method of microneedles]
The material and manufacturing method of the microneedle 10 will be described.
The material for forming the protrusions 12, 17, 18 is not particularly limited, and the protrusions 12, 17, 18 may be made of a metal material such as silicon, stainless steel, titanium, cobalt-chromium alloy, or magnesium alloy. Good. Further, the protrusions 12, 17 and 18 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 materials exemplified as the materials of the protrusions 12, 17, and 18 described above.

The microneedle 10 may be an integrally molded product in which the base portion 11 and the protrusions 12, 17, 18 are integrally formed, or the base portion 11 and the protrusions 12, 17, 18 are formed separately. It may be formed by joining afterwards, or it may be formed by a combination of a metal material and a resin material. For example, the protrusions 12, 17 and 18 may be made of metal and the base portion 11 may be made of resin, and conversely, the protrusions 12, 17 and 18 may be made of resin and the base portion 11 may be made of metal. Good.

When the base portion 11 and the protrusions 12, 17, and 18 are formed separately, or when the microneedle 10 is formed by a combination of a metal material and a resin material, the microneedle 10 is formed as necessary. A sealant, an adhesive, a gasket, an O-ring, or the like for bringing each of the constituent parts into close contact with each other may be used in combination.

As a method of forming the microneedle 10, for example, after forming the outer shape of the base portion 11 and the protrusions 12, 17, 18 by machining, a hole to be a main flow path 15 m and a hole to be a sub flow path 15s are formed. Method is used. 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 protrusions 12, 17, and 18 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 protrusions 12, 17, and 18 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 has one main flow path 15 m and a plurality of sub-flow paths 15s, the drug is dispersed from the protrusion to a plurality of locations in the skin and the drug is released. Therefore, the drug is more likely to spread in the skin than the drug is released in one place. Further, since the sub-channel 15s extends in a direction different from the length direction of the protrusion and opens on the peripheral surface of the protrusion, it is difficult for skin tissue to enter the sub-channel 15s in the process of perforation. Therefore, smooth administration of the drug is possible.

(2) Since the height Hs of each sub-channel 15s is different from the height Hs of the other sub-channels 15s, a plurality of sub-channels 15s may be lined up on a plane along the width direction of the protrusion. It can be suppressed. As a result, it is possible to prevent the strength of the protrusion from becoming extremely low at a specific position in the length direction of the protrusion, so that the protrusion is less likely to be deformed when the skin is perforated. In particular, the above effect is enhanced if the region occupied by each sub-channel 15s does not include a portion where the position of the protrusion 12 in the length direction coincides with the region occupied by the other sub-channels 15s.

(3) When viewed from the direction facing the support surface 11S, each sub-flow path 15s extends from the main flow path 15m in a direction different from the direction in which the other sub-flow paths 15s extend from the main flow path 15m. It is suppressed that the sub-flow paths 15s of the above are arranged in the length direction of the protrusion. As a result, it is possible to prevent the strength of the protrusion from becoming extremely low at a specific position in the width direction of the protrusion, so that the protrusion is less likely to be deformed when the skin is perforated. In particular, the above effect is enhanced if the region occupied by each sub-flow path 15s does not include a portion overlapping the region occupied by the other sub-channels 15s when viewed from the direction facing the support surface 11S.

(4) Since each sub-channel 15s opens on the side surface 14D different from the other sub-channels 15s, it is possible to prevent the positions of the plurality of sub-channels 15s from being biased and the number of sub-channels 15s from becoming too large. Therefore, since the strength of the protrusion is suppressed from being excessively lowered, the protrusion is less likely to be deformed when the skin is perforated.

(5) Since the protrusion has a cone-shaped portion 14 that is pointed toward the tip, the protrusion is likely to pierce the skin. On the other hand, since the protrusion has the columnar portion 13, 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 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.

(6) The total of the subchannel resistance Sr for all the subchannels 15s is equal to the main channel resistance Mr. Therefore, it is possible to prevent the energy of the drug flowing through the main flow path 15 m from being significantly lost when flowing through the sub flow path 15s. Therefore, the drug can be efficiently flowed from the main flow path 15m to the sub-flow path 15s.

[Modification example]
The above embodiment can be modified and implemented as follows.
-The shape of the protrusion 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 19 illustrated in FIG. 12 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 19 is four side surfaces 19D extending from the support surface 11S in a direction inclined with respect to the support surface 11S, and a pointed surface 19T connected to the four side surfaces 19D with respect to the support surface 11S. It is composed of an inclined tip surface 19T. 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.

In a configuration in which the heights Hs of the plurality of sub-channels 15s are different from each other, the region occupied by the arbitrary sub-channel 15s overlaps the region occupied by the other sub-channels 15s at the position of the protrusion 12 in the length direction. It may include a part. Further, in a configuration in which a plurality of sub-channels 15s extend in different directions when viewed from a direction facing the support surface 11S, the region occupied by the arbitrary sub-channel 15s overlaps with the region occupied by the other sub-channels 15s. It may include a portion.
-If the protrusion has a plurality of sub-channels 15s that open on the peripheral surface of the protrusion, the position of the opening of the sub-channel 15s and the extending direction of the sub-channel 15s are not limited.

For example, when the number of sub-channels 15s is two, the sub-channels 15s may be opened one by one on each of the two side surfaces 14D close to the tip point P, or close to the tip point P. One of the side surfaces 14D and one of the side surfaces 14D far from the tip point P may be opened. Further, the arrangement of the openings when the number of the sub-channels 15s is three or four may be different from the arrangement shown in the above embodiment. Further, two or more auxiliary flow paths 15s may be opened on one side surface 14D of the side surface 14D of the protrusion, or in the plane of the tip surface 14T or the side surface 13D of the columnar portion 13, or the protrusion. The sub-flow path 15s may be opened at a position straddling the surfaces adjacent to each other among the surfaces constituting the peripheral surface of the portion.

Further, the plurality of subchannels 15s may be arranged in the length direction and the width direction of the protrusions. That is, the plurality of sub-channels 15s include the plurality of sub-channels 15s having the same height Hs and the plurality of sub-channels extending in the same direction from the main channel 15 m when viewed from the direction facing the support surface 11S. 15s may be included.

Further, the subchannel 15s may extend in a direction different from the width direction of the protrusion, in other words, may extend in a direction inclined with respect to the support surface 11S. Further, the sub-flow path 15s farthest from the support surface 11S may extend from the same height as the tip end side of the protrusion 12 in the main flow path 15 m. Alternatively, in the portion where the sub-flow path 15s farthest from the support surface 11S is connected to the main flow path 15m, the end portion on the tip end side of the protrusion 12 in the sub-flow path 15s is the tip end of the protrusion 12 in the main flow path 15m. It may be located on the tip end side of the protrusion 12 rather than the side end portion.
The effect of (1) above can be obtained if the protrusion has a plurality of auxiliary flow paths 15s that open on the peripheral surface of the protrusion.

-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. Further, the sub-channel area Ss may be different for each sub-channel 15s, and the total of the sub-channel areas Ss for all the sub-channels 15s may be different from the main channel area Ms. Then, the total of the subchannel resistance Sr for all the subchannels 15s may be different from the main channel resistance Mr.

-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 by an instrument different from the injection tube 30. Further, after administration of the drug, the protrusion may be separated from the substrate portion 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 and comparative examples.
<Example 1>
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 two holes serving as a secondary flow path in the structure by laser processing. As a result, the microneedles of Example 1 were obtained.

The protrusion in the microneedle of Example 1 has the shape shown in FIGS. 1 to 3, the length Lt of the protrusion is 750 μm, and the length Lc of the columnar portion is 100 μm. Further, the inclination of the side surface of the cone-shaped portion with respect to the support surface is 80 °. The height Hm of the main flow path is 600 μm, and the height Hs of the two sub-channels is 460 μm and 510 μm in ascending order. 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, and the diameter thereof is 100 μm. In each of the two sub-channels, the shape of the region in which the sub-channels are partitioned by the cross section orthogonal to the extending direction of the sub-channels is circular, and the diameter thereof is 70 μm.

<Example 2>
By the same process as in Example 1, a microneedle of Example 2 having the same shape as that of Example 1 except for the configuration of the subchannel was obtained.
The protrusion of the microneedle of Example 2 has three sub-channels, and the protrusion of Example 2 has the shape shown in FIGS. 5 to 7. The heights Hs of the three subchannels are 350 μm, 430 μm, and 510 μm in ascending order. A sub-channel having the largest height Hs is opened at a position straddling the two side surfaces near the tip point P of the protrusion, and the three sub-channels are viewed from the direction facing the support surface. It is arranged so that the height Hs increases clockwise from one of the side surfaces far from the tip point P of the protrusion. In each of the three sub-channels, the shape of the region in which the sub-channels are partitioned by the cross section orthogonal to the extending direction of the sub-channels is circular, and the diameter thereof is 58 μm.

<Example 3>
By the same process as in Example 1, a microneedle of Example 3 having the same shape as that of Example 1 except for the configuration of the subchannel was obtained.
The protrusion of the microneedle of Example 3 has four sub-channels, and the protrusion of Example 2 has the shape shown in FIGS. 8 to 10. The heights Hs of the four subchannels are 350 μm, 400 μm, 450 μm, and 510 μm in ascending order. A sub-channel having the smallest height Hs and a sub-channel having the second smallest height Hs are open on the two side surfaces far from the tip point P of the protrusion, and the tip point of the protrusion A sub-channel having the largest height Hs and a sub-channel having the second largest height Hs are open on the two side surfaces close to P. When viewed from the direction facing the support surface, the four subchannels are arranged so that the height Hs increases clockwise from one of the side surfaces far from the tip point P of the protrusion. In each of the four sub-channels, the shape of the region in which the sub-channels are partitioned by the cross section orthogonal to the extending direction of the sub-channels is circular, and the diameter thereof is 50 μm.

<Comparative example 1>
By the same process as in Example 1, a microneedle of Comparative Example 1 having the same shape as that of Example 1 except for the configuration of the subchannel was obtained.
One sub-channel is formed in the protrusion of the microneedle of Comparative Example 1, and the height Hs of this sub-channel is 450 μm. The auxiliary flow path is open at a position straddling two side surfaces near the tip point P of the protrusion. The shape of the region defined by the sub-channel in a cross section orthogonal to the extending direction of the sub-channel is circular, and the diameter thereof is 100 μm.

<Comparative example 2>
By the same steps as in Example 1, microneedles of Comparative Example 2 having the same shape as that of Example 1 except for the structure of the flow path were obtained.
The microneedle of Comparative Example 2 is not formed with a sub-flow path, and instead of the main flow path in which the end on the tip side is closed, the protrusion and the substrate are formed from the base end to the tip of the protrusion. A through hole is formed to penetrate the portion. Such through holes are formed in the manufacturing process of Example 1 by adjusting the length of the holes inside the structure formed by injection molding. The shape of the region defined by the through hole in the cross section orthogonal to the extending direction of the through hole is circular, and the diameter thereof is 100 μm.

[Evaluation of liquid release capacity]
The liquid discharge ability of the microneedles of Examples 1 to 3 and Comparative Example 1 in which the auxiliary flow path was formed 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 measurement was performed three times for each Example and Comparative Example. 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 number of sub-channels, the measurement results of the time required to release the pure water, and the average value thereof for the microneedles of Examples 1 to 3 and Comparative Example 1. The average value is rounded off to the second place in the minority.

As shown in Table 1, in Examples 1 to 3 and Comparative Example 1, the time required to release 1000 μL of pure water under a pressure of 0.2 MPa is about 22 seconds, and there is a big difference. Absent. That is, the main flow path and the sub flow path in the microneedles of Examples 1 to 3 and Comparative Example 1 are all capable of discharging the same amount of liquid under the same pressure at the same time. It is suggested that it is composed of. The configuration of the flow path between Comparative Example 1 and Comparative Example 2 differs in that the flow path is bent in Comparative Example 1 and the flow path extends in one direction in Comparative Example 2, but that of Comparative Example 1 Since the diameter of the flow path is equal to the diameter of the flow path of Comparative Example 2, it is presumed that Comparative Example 2 also gives the same result as that of Comparative Example 1 in terms of the time required to release pure water into the atmosphere. To.

[Evaluation of drug dose]
The dose of the drug was evaluated using the microneedles of Examples 1 to 3 and Comparative Examples 1 and 2.
Each microneedle is attached to an injection tube filled with saline as a drug, and after piercing the protrusion into the skin removed from a 12-week-old Wistar rat, the drug is directed toward the protrusion with a force of 0.2 MPa. Pressed. The pressing of the drug was performed by inserting a tube to which the pressure gauge was connected into the outer cylinder of the injection tube instead of the pusher, and supplying gas into the tube so that the inside of the tube became 0.2 MPa. While observing the skin of the Wistar rat, the pressure of the drug was continued for 300 seconds, and the dose of the drug into the skin, that is, the maximum amount of the drug that could be injected without leaking to the surface or subcutaneous of the skin was measured. However, the upper limit of the dose of the drug was set to 600 μL, and when the dose exceeded 600 μL, the administration was terminated at that time.
Table 2 shows the number of sub-channels and the measurement results of the dose of the drug into the skin for the microneedles of each Example and Comparative Example. In the test using the microneedles of Comparative Example 2, leakage of the drug from the surface of the excised skin opposite to the surface to which the drug was administered was confirmed. In Comparative Example 2, the total dose of the drug was 600 μL, and the dose of the drug intradermally was calculated to be 100 μL by estimating the amount of the drug leaked subcutaneously.

As shown in Table 2, in any of Examples 1 to 3, it is possible to administer a larger amount of the drug than in Comparative Examples 1 and 2. That is, in the example having a plurality of subchannels, the drug is more likely to spread into the skin than in the comparative example, and the pressure is insufficient depending on the force of 0.2 MPa, which makes it impossible to inject the drug. It is suggested that the drug is suppressed from flowing out to the surface of the skin or subcutaneously, and as a result, a large amount of the drug can be injected into the skin. From this, it was shown that in the example having a plurality of subchannels, the drug can be smoothly administered as compared with the comparative example.

In addition, it is possible to administer a larger amount of the drug in Examples 2 and 3 than in Example 1. Therefore, the number of sub-channels is 3 or more, and the number of sub-channels is larger in the configuration in which the sub-channels are open on the side surface close to the tip point P in addition to the side surface far from the tip point P. It was shown that smooth administration of the drug is possible as compared with the configuration in which the secondary flow path is open only on the side surface far from the tip point P, which is two.

<Example 4>
By the same process as in Example 1, a microneedle of Example 4 having the same shape as that of Example 1 except for the configuration of the subchannel was obtained.
The protrusions of the microneedles of Example 4 are formed so that two subchannels are arranged in the length direction of the protrusions. That is, the two sub-flow paths extend in the same direction from the main flow path when viewed from the direction facing the support surface. The heights Hs of the two subchannels are 360 μm and 510 μm in ascending order. The two sub-channels are open at positions straddling the two side surfaces near the tip point P of the protrusion. In each of the two sub-channels, the shape of the region in which the sub-channels are partitioned by the cross section orthogonal to the extending direction of the sub-channels is circular, and the diameter thereof is 70 μm.

<Example 5>
By the same process as in Example 1, a microneedle of Example 5 having the same shape as that of Example 1 except for the configuration of the sub-channel was obtained.
Three sub-channels are formed in the protrusions of the microneedles of Example 5 so as to have the same height Hs. That is, the three subchannels are arranged on a plane along the width direction of the protrusion. The height Hs of all three subchannels is 400 μm. The three sub-channels are opened one by one at each of the two side surfaces far from the tip point P of the protrusion and at a position straddling the two side surfaces near the tip point P of the protrusion. In each of the three sub-channels, the shape of the region in which the sub-channels are partitioned by the cross section orthogonal to the extending direction of the sub-channels is circular, and the diameter thereof is 70 μm.

[Evaluation of protrusion strength]
The strength of the protrusions was evaluated for the microneedles of Examples 1 to 5 and Comparative Example 1 in which the secondary flow path was formed.
Each microneedle was attached to an injection tube, a protrusion was pierced into the skin removed from a 12-week-old Wistar rat, and then the microneedle was withdrawn from the skin. Before and after perforation into the skin, each microneedle was observed with a stereomicroscope to confirm the presence or absence of a change in shape.

FIG. 13 shows the number of sub-channels, images of protrusions before and after drilling for the microneedles of Examples 1 to 5 and Comparative Example 1, and evaluation results of the presence or absence of deformation of the protrusions. Is shown.

As shown in FIG. 13, in the comparative example, the deformation of the protrusion is larger than that in the embodiment. That is, when the total of all the sub-channel areas Ss is the same, the strength of the protrusion is stronger in the configuration with a plurality of sub-channels than in the configuration with one sub-channel. It is suggested that it can be enhanced.

Further, in Examples, deformation of the protrusions was not observed in Examples 1 to 3, whereas deformation of the protrusions was confirmed in Examples 4 and 5. That is, it was shown that the strength of the protrusions is higher and the protrusions are less likely to be deformed at the time of drilling when the plurality of subchannels are not arranged in the length direction or the width direction of the protrusions.

10 ... microneedle, 11 ... base part, 11S ... support surface, 12, 17, 18, 19 ... protrusion, 13 ... columnar part, 13D ... side surface, 14 ... cone-shaped part, 14D ... side surface, 14T ... tip surface, 15m ... main flow path, 15s ... sub-flow path, 16 ... stepped portion, 30 ... injection tube, 31 ... outer tube, 32 ... pusher, P ... tip point.

Claims (4)

A base part having a support surface and
With a protrusion protruding from the support surface,
The protrusions have one main flow path extending from the base end of the protrusion toward the tip inside the protrusion, and extending from the main flow path toward the peripheral surface of the protrusion and opening to the peripheral surface. It has multiple sub-channels 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. ,
Each of the sub-channels does not open at the tip surface, but opens at the side surfaces different from each other, and the direction orthogonal to the support surface from the center of gravity of the region where the opening of the sub-channel divides to the support surface. Microneedles whose heights are different from each other when the length along the above is taken as the height of the sub-channel . The micro according to claim 1, wherein each sub-flow path extends from the main flow path in a direction different from the direction in which the other sub-flow path extends from the main flow path when viewed from a direction facing the support surface. needle. The protrusion, the pillar-like shape extending from the support surface possess a columnar portion to be connected to the conical portion, the side surface of the columnar portion claim 1 without the opening of the secondary flow channel or The microneedle described in. The resistance that the fluid flowing in the main flow path receives per unit length is the main flow path resistance.
The resistance that the fluid flowing in the sub-channel receives per unit length is the sub-channel resistance.
The microneedle according to any one of claims 1 to 3 , wherein the total of the subchannel resistances for all the subchannels is equal to the main channel resistance.

Images