JP2024080420A - Needle - Google Patents

Abstract

The present invention provides an injection needle that can achieve both the ease of injecting liquid and the effect of inducing immunity.
[Solution] An injection needle having protrusions protruding from a sheet base 2, the protrusions including a first protrusion 31 having a hollow cone shape with an opening 31a at its tip, and a second protrusion 32 having a cone shape and no opening at its tip, the injection needle including one to six first protrusions 31, a first region R1 located in the center of the sheet base 2 in a planar view, and a second region R2 which does not overlap with the first region R1 and includes two or more second protrusions 32, and a distance D1, which is the shortest distance between the first protrusion 31 in the first region R1 and the second protrusions 32 in the second region R2, is 0.3 mm to 2 mm.
[Selected Figure] Figure 1

Description

The present invention relates to an injection needle.

In recent years, in the medical and cosmetic fields, attention has been focused on intradermal administration of liquids such as medicines using injection needles equipped with fine needle-like protrusions, also known as microneedles. With these injection needles, it is possible to inject liquids into the body by inserting the microneedles into a relatively shallow layer of the skin, such as the epidermis or dermis, and as the pain felt by the subject is significantly reduced compared to using a normal syringe, they have attracted attention as a minimally invasive means of administering liquids.

Patent Document 1 describes a fine protrusion device having a needle-like hollow first protrusion formed to protrude from the top surface, which is one surface of a base sheet having a circular shape in a plan view, and a hollow second protrusion formed to protrude from the vicinity of the first protrusion on the top surface of the base sheet and to a lower protrusion height than the first protrusion. The document describes that when the first protrusion is inserted into the skin from the tip side, the first protrusion stops inserting when the tip of the nearby second protrusion comes into contact with the surface of the skin, preventing the first protrusion from penetrating deeper into the skin. An opening is formed at the tip of the first protrusion, and the hollow part of the first protrusion is connected to the outside through the opening. The document also describes that the tip of the first protrusion is inserted into the skin, and a liquid medicine stored in the hollow part of the first protrusion is injected into the skin through the opening of the tip.

Patent Document 2 describes a microneedle sheet on which multiple microscopic needle peaks are formed and protrude from the surface. The document describes that the needle peaks include penetrating needle peaks with through holes formed from the front surface side to the back surface side, and dummy needle peaks with no through holes formed.

JP 2017-038781 A International Publication No. 2021/177317

When microneedles are inserted into the skin to inject liquid, it is known that the greater the number of microneedles inserted into the skin, the greater the immune induction effect. In order to improve the immune induction effect, it is possible to increase the number of microneedles. However, in the case of microneedles that are hollow inside and have an opening at the tip, as in Patent Documents 1 and 2, if the number of microneedles is increased, it becomes difficult to properly insert all of the microneedles into the skin. Therefore, there is room for improvement in terms of the puncture ability of the microneedles. Patent Documents 1 and 2 do not consider achieving both puncture ability and immune induction effect.

The present invention relates to an injection needle that can achieve both puncture ease and immune induction effects.

The present invention provides an injection needle.
In one embodiment, the injection needle preferably has a protrusion protruding from the seat base.
In one embodiment, the primary projections are preferably cone-shaped and have apertures at their tips.
In one embodiment, the projection preferably has a first projection having a hollow cone shape and an aperture at its tip.
In one embodiment, the projections preferably include a second projection that is cone-shaped and has no aperture at its tip.
In one embodiment, the injection needle preferably has a first region and a second region.
In one embodiment, the first region includes one to six first projections, and is preferably located at the center of the seat base in a plan view.
In one embodiment, the second region is a region that does not overlap with the first region and preferably includes two or more second projections.
In one embodiment, it is preferable that a distance D1, which is the shortest distance between the first projections in the first region and the second projections in the second region, is 0.3 mm or more and 2 mm or less.

The present invention also provides an injection device having the above-mentioned injection needle and a medicine supplying device connected to the injection needle.
In one embodiment, it is preferable that the drug supplying device is capable of ejecting the drug filled in the drug supplying device through the opening via the inside of the first protrusion when connected to the injection needle.

The present invention also provides an injection kit including the above-mentioned injection needle, a medicine supplier connectable to the injection needle, and a medicine.
In one embodiment, it is preferable that the drug supplying device is capable of ejecting the drug filled in the drug supplying device from the opening through the inside of the first protrusion when connected to the injection needle.

The present invention makes it possible to achieve both puncture properties and immune induction effects.

FIG. 1 is a perspective view of an injection needle according to a preferred embodiment of the present invention. FIG. 2 is a schematic plan view of the projection arrangement region of the injection needle shown in FIG. FIG. 3 is a cross-sectional view taken along line III-III in FIG. FIG. 4 is a cross-sectional view taken along line IV-IV in FIG. FIG. 5 is a schematic diagram showing a state in which the injection needle shown in FIG. 1 is used. FIG. 6 is a plan view showing another preferred embodiment of the present invention, and corresponds to FIG. 7(a) to 7(c) are plan views showing the arrangement pattern of protrusions according to still another preferred embodiment of the present invention, and correspond to FIG. FIG. 8 is a plan view showing an arrangement pattern of protrusions according to still another preferred embodiment of the present invention, and corresponds to FIG. FIG. 9 is a cross-sectional view showing still another preferred embodiment of the present invention, and corresponds to FIG. FIG. 10(a) is a perspective view of the injection needle of Example 1, and FIG. 10(b) is a plan view that typically illustrates an arrangement pattern of protrusions of Example 1. FIG. 11 is a plan view that illustrates a schematic arrangement pattern of the projections of the injection needle of Comparative Example 1. FIG. 12 is a plan view that illustrates a schematic arrangement pattern of the projections of the injection needle of Comparative Example 2. FIG. 13 is a plan view illustrating a schematic arrangement pattern of the projections of the injection needle of Comparative Example 3. FIG. 14 is a plan view illustrating a schematic arrangement pattern of the projections of the injection needle of Comparative Example 4. FIG. 15 is a graph showing the evaluation results of the immunity-inducing effect of the injection needles of Examples 1 and 2 and Comparative Examples 1 to 4. FIG. 16 is a plan view showing a schematic arrangement of the needle protrusions used in the evaluation of the relationship between the liquid volume and the radius of the wheal. FIG. 17 is a plan view showing a schematic diagram of the major and minor axes of a wheal measured in the evaluation of the relationship between fluid volume and wheal radius. FIG. 18 is a graph showing the evaluation results of the relationship between fluid volume and wheal radius.

The present invention will now be described with reference to preferred embodiments thereof.
The injection needle 1 of the present invention typically has a protrusion protruding from the sheet base 2 .
The injection needle 1 typically has a flat sheet-like shape as a whole, and has a sheet base 2 and a plurality of protrusions protruding from one surface of the sheet base 2.
The injection needle 1 typically has a projection arrangement region in which projections are arranged in a dispersed manner in a planar direction. The projection arrangement region typically includes a first region R1 and a second region R2, which will be described later.
The injection needle 1 has a first direction X that is a direction along the surface of the sheet base 2 and a second direction Y that is perpendicular to the first direction X when viewed in a plan view.

The protrusions protruding from the sheet base 2 of the injection needle 1 preferably include a first protrusion 31 having a hollow cone shape and an opening 31a at the tip. The protrusions preferably include a second protrusion 32 having a cone shape and no opening at the tip. The protrusions preferably include a third protrusion 33 having an approximately truncated cone shape with a tip surface 33a that is flat or curved. An example of this is shown in Figure 1.

The primary projections 31 are preferably minute projections having hollow portions 31b, so-called microneedles (see Figs. 3 and 4).
The second protrusion 32 and the third protrusion 33 may be hollow or solid. In the example shown in Fig. 1 and Fig. 3, the second protrusion 32 and the third protrusion 33 are solid. By making the second protrusion 32 and the third protrusion 33 solid, it is possible to reduce the amount of medicine remaining in the injection needle 1 when injecting a liquid such as a medicine from the injection needle 1.
It is preferable that the tip surface of the third protrusion 33 serves as the puncture depth control unit 40. In the example shown in Fig. 1 and Fig. 3, the tip surface of the third protrusion 33 is flat, that is, linearly extending in the horizontal direction. The tip surface of the third protrusion 33 may be curved, for example, curved linearly convex toward the protruding direction of the third protrusion 33.

The injection needle 1 preferably has a first region R1, which is typically located in the center of the sheet base 2 in a plan view. The first region R1 preferably includes one to six first protrusions 31. An example of this is shown in FIG.
The center of the seat base 2 is, for example, the central three regions when the seat base 2 is divided into five equal parts in the first direction X, preferably the central region when the seat base 2 is divided into thirds. The central region may also be the central three regions when the seat base 2 is divided into five equal parts in the second direction Y, or the central region when the seat base 2 is divided into thirds in the second direction Y.

The center of the seat base 2 may be the central three regions when the seat base 2 is divided into five equal parts in the first direction X and the central three regions when the seat base 2 is divided into five equal parts in the second direction Y, or it may be the central region when the seat base 2 is divided into five equal parts in the first direction X and the central three regions when the seat base 2 is divided into thirds in the second direction Y.
In addition, the center of the seat base 2 may be the central three regions when the central region of the seat base 2 is divided into thirds in the first direction X and then divided into five equal parts in the second direction Y, or the central region of the seat base 2 is divided into thirds in the first direction X and then divided into thirds in the second direction Y.

When the sheet base 2 of the injection needle 1 is circular, the center of the sheet base 2 may be a circular region having a diameter one-third, preferably one-half, of the diameter of the sheet base 2. A specific example of this is shown in Fig. 6. For convenience of explanation, the opening 31a of the first protrusion 31, the tips of the first protrusion 31 and the second protrusion 32, and the tip surface of the third protrusion are omitted in Fig. 6, Fig. 7(a)-(c), Fig. 8, Fig. 10(b), Fig. 11-14, and Fig. 16. In Fig. 6, Fig. 7(a)-(c), Fig. 8, Fig. 10(b), Fig. 11-14, and Fig. 16, the first protrusion 31 is indicated by hatching slanting upward to the right, the second protrusion 32 is indicated by hatching slanting downward to the right, and the third protrusion 33 is indicated by hatching with dots.
The center of the seat base 2 and the center of the first region R1 may be aligned or deviated from each other.

The injection needle 1 preferably has a second region R2 including two or more second projections 32. The second region R2 is a region that does not overlap with the first region R1. In the example shown in Fig. 2, the second region R2 surrounds the first region R1.
The second protrusions 32 arranged in the second region R2 are preferably arranged such that, in a plan view, a virtual line C2 connecting the centers of the second protrusions 32 forms a ring shape. For example, the virtual line C2 connecting the centers of the second protrusions 32 may be a rectangular ring shape (see FIGS. 2 and 7(b)), a triangular ring shape (see FIG. 7(c)), or a circular ring shape (see FIGS. 6 and 7(a)).
The second region R2 may sandwich the first region R1 (see FIG. 8).

Since the injection needle 1 has the opening 31a in the first projection 31, it becomes a liquid injection tool that can be used for intradermal administration of liquid such as medicine.
Typically, an opening 31a is formed at the tip of the first projection 31 (see Figs. 2 to 4), and the hollow portion 31b of the first projection 31 communicates with the outside via the opening 31a. Note that in Fig. 3, the opening 31a is greatly exaggerated for the sake of convenience of explanation.
The opening 31 a is a through hole that passes through the sheet base 2 forming the first projection 31 in the thickness direction, and is preferably located at the tip of the conical first projection 31 .
The hollow portion 31b of the first projection 31 functions as a reservoir or a passage for the liquid discharged to the outside from the opening 31a.
Here, the tip of the first projection 31 refers to a region on the tip side of the intermediate position M of the projection height H1 (see FIG. 3) from the surface of the seat base 2 to the tip of the first projection 31.

When the injection needle 1 is used for intradermal administration of a drug, the tip of the first projection 31 is inserted into the skin S, and the liquid drug L stored in the hollow portion 31b of the first projection 31 is injected into the skin S through the opening 31a at the tip (see FIG. 5). In this way, the hollow portion 31b of the first projection 31 functions as a drug storage portion, typically when no drug is supplied from the outside.
When a drug is supplied from the outside, for example, when a drug supply device (not shown) such as a syringe is used together with the injection needle 1, the hollow portion 31b functions as a passage for the drug. The drug supply device may be configured such that a sheet-like member is disposed on the back side of the injection needle 1, and a drug storage space is formed between the back side of the injection needle 1 and the sheet-like member, and the drug is supplied to the first protrusion 31 by pressing the sheet-like member (see JP 2020-096790 A [0011]).

In the injection needle 1, it is preferable that the distance D1 (see FIG. 2), which is the shortest distance between the first protrusion 31 and the second protrusion 32, is 0.3 mm or more and 2 mm or less. The advantages of the distance D1 being within the above-mentioned range are as follows.
When the tip of the first protrusion 31 is inserted into the skin S and the drug L is injected into the skin S, the injected drug L causes the skin to swell and a wheal 9 is formed (see FIG. 5). At this time, since the distance D1 is within the above-mentioned range, the second protrusion 32 punctures the skin S within the range of the wheal 9 in a planar view. In other words, when the drug L is injected by the first protrusion 31, the second protrusion 32 punctures the wheal, and the second protrusion 32 stimulates the skin S to enhance the immune induction effect.
As a result of careful investigation, the inventors have found that the immune induction effect can be more effectively enhanced when the second protrusion 32 is actively punctured into the wheal than when the distance D1 is large and the second protrusion 32 is not inserted into the wheal.

The presence or absence of an immune induction effect can be determined by various known methods. For example, the immune induction effect of the second projection 32 can be determined by injecting a liquid used as a vaccine intradermally and measuring the vaccine effect. The vaccine effect can be determined by comparing the antibody titers in the blood against antigen proteins used in the vaccine preparation and antigen proteins produced in the body by mRNA or DNA containing genetic information when each injection needle is used.
Here, the distance between the first protrusion 31 and the second protrusion 32 means the distance between the apex of the first protrusion 31 and the apex of the second protrusion 32 .

In the injection needle 1, the number of the first projections 31 included in the first region R1 is preferably 1 to 6. This allows all of the first projections 31 included in the first region R1 to be properly inserted into the skin S, improving the puncture performance, particularly the puncture performance of the first projections 31.
In this way, the injection needle 1 of the present invention can achieve both puncture ease and an immunity induction effect.

The injection needle 1 can be used, for example, as follows. First, with the first projection 31 inserted into the skin S, the liquid drug L stored in the hollow portion 31b of the first projection 31 is discharged from the opening 31a. At the same time, the second projection 32 punctures the skin S within the area where the wheal 9 will be formed by the injection of the drug L. By puncturing the skin S, an immune induction effect occurs, and the immunogenicity of the person into whom the drug L is injected can be improved.
In this way, the injection needle 1 can inject liquid and induce immunity at the same time.

The number of first protrusions 31 included in the first region R1 is preferably five or less, and more preferably four or less, from the viewpoint of making it easy to properly insert all of the first protrusions 31 included in the first region R1 into the skin S.
In addition, the number of first protrusions 31 included in the first region R1 is preferably two or more, and more preferably three or more, from the viewpoint of increasing the amount of liquid ejected from the opening 31a of the first protrusion 31 and enabling efficient injection of the drug L into the skin S.

The distance D1 is preferably 1.9 mm or less, more preferably 1.7 mm or less, and even more preferably 1.5 mm or less, from the viewpoint of ensuring that the second projection 32 reliably punctures the skin S within the range of the wheal 9 in a planar view.
In addition, the distance D1 is preferably 0.4 mm or more, more preferably 0.6 mm or more, and even more preferably 0.9 mm or more, from the viewpoint of forming a blister caused by the liquid L without suppressing it and enabling the liquid L to be smoothly ejected from the opening 31a.

The position of the second protrusion 32 can also be determined according to the amount of liquid injected into the skin S by the injection needle 1. The size of the wheal 9 that is formed varies somewhat depending on the amount of liquid injected into the skin S by the injection needle 1. Before using the injection needle 1, it is possible to check in advance how large a wheal 9 will be formed depending on the amount of liquid to be injected, and to position the second protrusion 32 within the range in which the wheal 9 will be formed. The inventors have thoroughly investigated the relationship between the amount of liquid V injected into the skin S and the radius R of the wheal that is formed using the following method.

Evaluation of the relationship between fluid volume and wheal radius
The skin of a Gottingen miniature pig (male, 6 weeks old, ventral part; Oriental Yeast Co., Ltd.) stored at -20°C was transferred to a refrigerator (4°C) the day before the test and thawed. The skin was placed on 5 to 7 Kimtowels, shaved with a shaver, and the surface was wiped with alcohol cotton before administration.
Powdered rhodamine B (Sigma-Aldrich) was adjusted to 0.5 mg/mL with ultrapure water and filled into a microsyringe (Agilent). A puncture device and an injection needle were attached to the microsyringe, and air was removed. The liquid volume in the microsyringe was set to 10, 25, 50, 100, or 250 μL, and excess liquid attached to the injection needle was removed by absorbing it with Kimwipes. The arrangement of the projections of the injection needle is shown in FIG. 16. The height H1 of the first projection 31 of the injection needle was 2 mm, the height H2 of the second projection 32 was 1.4 mm, and the height H3 of the third projection 33 was 0.9 mm. The distance D1, which is the shortest distance between the first projection 31 and the second projection 32, was 2.2 mm. The radius D2 of the imaginary circle formed by the imaginary line C1 connecting the centers of the first projection 31 was 0.75 mm.

The injection needle was inserted perpendicularly into the skin, and an appropriate amount of the rhodamine B aqueous solution was administered intradermally. After administration, the injection needle was removed, and the outline of the wheal (an area that appears whiter and raised than the surrounding area) was immediately marked with a marker pen, and the length A of the long axis and the length B of the short axis of the wheal were measured using a vernier caliper. Figure 17 shows a schematic plan view of the wheal. In Figure 17, reference numeral 91 indicates the outline of the wheal, and reference numeral 92 indicates the fluid in the wheal. Each dose was administered three times. The average value of the length A of the long axis and the length B of the short axis divided by 2 was used as the radius R of the wheal, and a logarithmic approximation curve was calculated using Microsoft Excel spreadsheet software. The results are shown in Figure 18.
As shown in FIG. 18, it was found that the amount of liquid V injected into the skin S and the radius R of the formed wheal have the relationship expressed by the following formula (1).
R = 0.5406 ln (V) + 0.9483 ... (1)

From the viewpoint of ensuring that the second protrusion 32 reliably punctures the skin S within the area where the wheal 9 is formed, it is preferable that the amount of liquid V injected into the skin S by the injection needle 1 and the shortest distance D5 from the center P of the first region R1 to the second protrusion 32 (see Figures 2 and 6) satisfy the relationship of the following formula (2).
D5≦0.5406ln(V)+0.9483 ... (2)

In the injection needle 1, the first protrusion 31 is preferably higher than the second protrusion 32. This ensures that the first protrusion 31 is reliably punctured, and the first protrusion 31 can be inserted sufficiently, allowing the drug to be injected without leakage. In addition, when the first protrusion 31 is inserted into the skin S, the insertion depth of the second protrusion 32 can be adjusted to a required extent, and the pain caused by the insertion of the second protrusion 32 can be reduced. From the viewpoint of achieving these effects more significantly, the height H2 of the second protrusion 32 (see FIG. 3) is preferably 99% or less, more preferably 97% or less, and even more preferably 95% or less of the height H1 of the first protrusion 31.
Furthermore, from the viewpoint of ensuring that the second protrusion 32 is inserted reliably and that the immune induction effect is reliably achieved, the height H2 of the second protrusion 32 is preferably 55% or more, more preferably 60% or more, and even more preferably 65% or more of the height H1 of the first protrusion 31 (see Figure 3).

The difference in height H1-H2 between the first protrusion 31 and the second protrusion 32 is 10 μm or more, preferably 50 μm or more, and more preferably 100 μm or more, from the viewpoint of reliably inserting the first protrusion 31 and reducing the pain associated with the insertion of the second protrusion 32.
In addition, the height difference H1-H2 between the first protrusion 31 and the second protrusion 32 is 4900 μm or less, preferably 3000 μm or less, and more preferably 2000 μm or less, from the viewpoint of ensuring that the second protrusion 32 is inserted reliably and that the immune induction effect is reliably achieved.

The height H1 of the first protrusion 31 is 100 μm or more, preferably 150 μm or more, and more preferably 500 μm or more, from the viewpoint of ensuring reliable puncture even if the skin is deformed when the first protrusion 31 is pressed against the skin, improving puncture performance, and ensuring reliable injection of the drug into the skin S.
From the viewpoint of minimal invasiveness, the height H1 of the primary projections 31 is 5000 μm or less, preferably 4000 μm or less, and more preferably 3000 μm or less.

The height H2 of the secondary projections 32 is 5 μm or more, preferably 20 μm or more, and more preferably 50 μm or more, from the viewpoint of stimulating the skin when pressed against it and promoting the immune induction effect.
From the viewpoint of minimally invasive injection, the height H2 of the second projection 32 is 4900 μm or less, preferably 4000 μm or less, and more preferably 3000 μm or less.

It is preferable that the number N1 of the first projections 31 included in the first region R1 is smaller than the number N2 of the second projections 32 included in the second region R2. By doing so, it is possible to ensure that the immune induction effect is exerted. From the viewpoint of exerting this effect more significantly, the ratio N2/N1 of the number N2 of the second projections 32 included in the second region R2 to the number N1 of the first projections 31 included in the first region R1 is 2.4 or more, preferably 2.5 or more, and more preferably 2.6 or more.
In addition, the ratio N2/N1 of the number N2 of the second protrusions 32 included in the second region R2 to the number N1 of the first protrusions 31 included in the first region R1 is 10 or less, preferably 9 or less, and more preferably 8 or less, from the viewpoint of reducing the pain associated with the second protrusions 32 being inserted.

Since the injection needle 1 has the third protrusion 33, when the first protrusion 31 and the second protrusion 32 are inserted into the skin S from the tip side, the puncture depth control unit 40 of the third protrusion 33 comes into contact with the surface of the skin. This stops the first protrusion 31 and the second protrusion 32 from penetrating, and prevents the first protrusion 31 and the second protrusion 32 from penetrating deeper into the skin. In other words, the puncture depth control unit 40 functions as a stopper that limits the insertion depth of the first protrusion 31 and the second protrusion 32.

The injection needle 1 allows the insertion depth of the first protrusion 31 and the second protrusion 32 into the skin to be controllable, so that the drug can be administered intradermally to any depth in the skin and the immune induction effect can be effectively promoted. Therefore, according to the injection needle 1 of the present invention, the effect of the drug can be maximized by adjusting the insertion depth of the first protrusion 31 according to the type of drug, etc. Also, the immune induction effect can be effectively produced by adjusting the insertion depth of the second protrusion 32 according to the degree of the desired immune induction effect.

It is preferable that the third protrusion 33 is lower in height than both the first protrusion 31 and the second protrusion 32. This makes it possible to easily control the penetration depth of the first protrusion 31 and the second protrusion 32 into the skin. This point will be described below.
First, the relationship between the height H2 of the second projections 32 and the height H3 of the third projections 33 will be described. The second projections 32 are preferably taller than the third projections 33. This allows the second projections 32 to be inserted reliably, inhibits the stretching of the skin, and makes it easier to insert the first projections 31, while effectively obtaining an immune induction effect. From the viewpoint of achieving this effect more significantly, the height H3 of the third projections 33 is preferably 75% or less, more preferably 70% or less, and even more preferably 65% or less of the height H2 of the second projections 32.
Furthermore, from the viewpoint of being as non-invasive as possible to the skin, the height H3 of the third projections 33 is preferably 50% or more, more preferably 55% or more, and even more preferably 60% or more of the height H2 of the second projections 32.

The height difference H2-H3 between the second protrusion 32 and the third protrusion 33 is 100 μm or more, preferably 200 μm or more, and more preferably 300 μm or more, from the viewpoints of reliably inserting the second protrusion 32, suppressing stretching of the skin to make it easier to insert the first protrusion 31, and effectively obtaining an immune induction effect.
From the viewpoint of being as non-invasive as possible to the skin, the height difference H2-H3 between the second projections 32 and the third projections 33 is 2400 μm or less, preferably 2000 μm or less, and more preferably 1000 μm or less.

Next, the relationship between the height H1 of the first projection 31 and the height H3 of the third projection 33 will be described. The first projection 31 is preferably taller than the third projection 33. This allows the first projection 31 to be reliably inserted and the drug to be reliably injected into the skin S from the first projection 31. From the viewpoint of making this effect more pronounced, the height H3 of the third projection 33 is preferably 75% or less, more preferably 70% or less, and even more preferably 65% or less of the height H1 of the first projection 31.
Furthermore, from the viewpoint of being as non-invasive as possible to the dermis, the height H3 of the third projections 33 is preferably 30% or more, more preferably 35% or more, and even more preferably 40% or more of the height H1 of the first projections 31.

The height difference H1-H3 between the first protrusion 31 and the third protrusion 33 is 100 μm or more, preferably 300 μm or more, and more preferably 500 μm or more, from the viewpoint of reliably inserting the first protrusion 31 and reliably injecting the drug into the skin S from the first protrusion 31.
From the viewpoint of being as non-invasive as possible to the dermis, the height difference H1-H3 between the first projections 31 and the third projections 33 is 4900 μm or less, preferably 4000 μm or less, and more preferably 3000 μm or less.

The height H3 of the third protrusion 33 is 3 μm or more, preferably 10 μm or more, and more preferably 50 μm or more, from the viewpoint of easily controlling the penetration depth of the first protrusion 31 and the second protrusion 32 into the skin.
From the viewpoint of improving the puncture ability of the first projections 31 and the second projections 32, the height H3 of the third projections 33 is 3600 μm or less, preferably 3000 μm or less, and more preferably 2000 μm or less.

In the injection needle 1, the first region R1 may include only one first projection 31, or may include two or more first projections, i.e., a plurality of first projections.
When the first region R1 includes a plurality of first protrusions 31, the plurality of first protrusions 31 are preferably arranged to form an arbitrary shape as a whole. The plurality of first protrusions 31 may be arranged, for example, in a triangular shape (see FIG. 6 and FIG. 7(c)), a circular shape (see FIG. 7(a)), a rectangular shape (see FIG. 7(b)), or a linear shape (see FIG. 8(a) and (b)). The plurality of first protrusions 31 are preferably arranged such that a virtual line C1 connecting the centers of the first protrusions 31 forms a ring shape (see FIG. 6 and FIG. 7(a) to (c)).
When the first protrusions 31 are arranged so that a virtual line C1 connecting the centers of the first protrusions 31 forms a ring, it is preferable that the first protrusions 31 are not arranged within the area surrounded by the virtual line C1.

The injection needle 1 also preferably has a third region R3. The third region R3 includes the third protrusion 33 and is a region that sandwiches or surrounds the second region R2. In the example shown in Fig. 6, the third region R3 surrounds the second region R2.
The third protrusions 33 arranged in the third region R3 are preferably arranged such that, in a plan view, a virtual line C3 connecting the centers of the respective third protrusions 33 forms a ring shape. For example, the virtual line C3 connecting the centers of the third protrusions 33 may be a circular ring shape (see FIGS. 6 and 7(a)), a square ring shape (see FIG. 7(b)), or a triangular shape (see FIG. 7(c)).

From the viewpoint of allowing the wheal 9 to be formed without restriction and for liquid to be injected efficiently, the injection needle 1 has a distance D4, which is the shortest distance between the second protrusion 32 included in the second region R2 and the third protrusion 33 included in the third region R3, which is preferably 0.5 mm or more, more preferably 1.0 mm or more, and even more preferably 1.5 mm or more.
From the viewpoint of appropriately controlling the puncture depth of the first projection 31 and the second projection 32, the distance D4 is preferably 5.0 mm or less, more preferably 4.5 mm or less, and even more preferably 4.0 mm or less.
As in the example shown in FIG. 6, when the second region R2 includes a plurality of second protrusions 32, it is preferable that the distance D4 for each of the plurality of second protrusions 32 be within the above-mentioned range.

The injection needle 1 preferably has a projection-free region R4 between the second region R2 and the third region R3, the projection-free region R4 not including any projection.
The protrusion-free region R4 is a region in which the distance D4 is within the above-mentioned range for each of the second protrusions 32 included in the second region R2. The protrusion-free region R4 is a region having a predetermined width, and in the example shown in FIG. 6, the width of the protrusion-free region R4 is the same as the distance D4. It is preferable that the protrusion-free region R4 is a region that does not include at least the tips of the second protrusions 32 and the third protrusions 33. The second protrusions 32 and the third protrusions 33 may rise sharply or gently from the seat base 2, and the protrusion-free region R4 may include the base end of the second protrusion 32 or the third protrusion 33 when the second protrusion 32 or the third protrusion 33 rises gently from the seat base 2, for example.
When the second protrusion 32 or the third protrusion 33 rises gently from the seat base 2, the width of the protrusion non-existence region R4 may be the distance between the second protrusion 32 and the third protrusion 33 at a height position that is 80% of the height H2 of the second protrusion 32. When the second protrusion 32 or the third protrusion 33 rises sharply from the seat base 2, the distance between the base ends of the second protrusion 32 and the third protrusion 33 may be the width of the protrusion non-existence region R3.

In the example shown in FIG. 6, the protrusion-free region R4 surrounds the second region R2 when the seat base 2 is viewed in plan.
In addition, the non-protrusion region R4 has a predetermined width and continuously surrounds the periphery of the second region R2. In the example shown in Fig. 8, the non-protrusion region R3 sandwiches the first region R1 when the seat base 2 is viewed in a plan view.
Since the injection needle 1 has the non-protrusion region R4, the third protrusion 33 included in the third region R3 can be prevented from coming into contact with the wheal 9 when liquid is injected into the skin with the injection needle 1, so that the formation of the wheal 9 is less likely to be inhibited when liquid is injected and the liquid can be injected efficiently.
The shape of the protrusion-free region R4 in a plan view is not particularly limited, and may be, for example, a circular ring (see FIG. 6), a rectangular ring, a triangular ring, or the like.

The second region R2 may include the third protrusion 33, but preferably does not include the third protrusion 33. Since the second region R2 does not include the third protrusion 33, the third protrusion 33 does not come into contact with the wheal 9 when the first protrusion 31 and the second protrusion 32 are inserted into the skin S to inject liquid. This makes it easier for the wheal 9 to be formed without constraints when liquid is injected, and allows the liquid to be injected efficiently.
The second region R2 and the third region R3 may include the first protrusion 31, but preferably do not include the first protrusion 31. In this way, only the first region R1 of the injection needle 1 is a region into which liquid can be injected, making it easy to inject liquid into a desired position using the injection needle 1.
The first region R1 may include the second protrusion 32 and the third protrusion 33, but preferably does not include the second protrusion 32 and the third protrusion 33. Since the first region R1 does not include the second protrusion 32, it is possible to make the skin as non-invasive as possible. Furthermore, since the first region R1 does not include the third protrusion 33, the third protrusion 33 does not come into contact with the wheal 9 when the liquid is injected. This makes it easier for the wheal 9 to form without restrictions, and makes it possible to efficiently inject the liquid.

From the viewpoint of reliably obtaining ease of administration and immune induction, the number N1 of the first projections 31 included in the first region R1 is preferably one or more, more preferably two or more, and even more preferably three or more.
Furthermore, the number N1 of the first projections 31 included in the first region R1 is preferably 6 or less, more preferably 5 or less, and even more preferably 4 or less, from the viewpoint of ensuring ease of administration while being as non-invasive as possible.

The number N2 of the second projections 32 included in the second region R2 is preferably 2 or more, more preferably 5 or more, and even more preferably 7 or more, from the viewpoint of reliably obtaining ease of administration and immune induction.
In addition, the number N2 of the second projections 32 included in the second region R2 is preferably 25 or less, more preferably 20 or less, and even more preferably 15 or less, from the viewpoint of ensuring ease of administration while being as non-invasive as possible.

The number N3 of the third projections 33 included in the third region R3 is preferably 2 or more, and more preferably 3 or more, from the viewpoint of reliably obtaining ease of administration and immune induction.
In addition, the number N3 of the third projections 33 included in the third region R3 is preferably 23 or less, more preferably 20 or less, and even more preferably 15 or less, from the viewpoint of ensuring administerability while being as non-invasive as possible.

In the injection needle 1, the total number N2+N3 of the number N2 of the second protrusions 32 and the number N3 of the third protrusions 33 is preferably greater than the number N1 of the first protrusions. This reduces the number of needles that administer the drug solution, thereby realizing reliable administration and enhancing the immune induction effect of the second protrusions 32. From the viewpoint of making this effect more pronounced, the ratio (N2+N3)/N1 of the total number N2+N3 of the number N2 of the second protrusions and the number N3 of the third protrusions to the number N1 of the first protrusions is preferably 2 or more, more preferably 2.5 or more, and even more preferably 3 or more.
From the viewpoint of being as non-invasive as possible, the ratio (N2+N3)/N1 is preferably 25 or less, more preferably 20 or less, and even more preferably 15 or less.

In order to ensure ease of administration and immune induction, it is preferable to arrange one or more first protrusions 31, two or more second protrusions 32, and two or more third protrusions 33 on the injection needle 1, and the total number of protrusions on the injection needle 1 is five or more, preferably seven or more, and more preferably ten or more.
The total number of protrusions on the injection needle 1 is 26 or less, preferably 20 or less, and more preferably 16 or less, from the viewpoint of ensuring ease of administration while being as non-invasive as possible.

The injection needle 1 may include a composite second protrusion 52 in which the puncture depth control unit 40 is integrally formed around the second protrusion 32. For example, it is preferable that the composite second protrusion 52 is formed by integrally molding the puncture depth control unit 40 on the outer periphery of the base side portion of the second protrusion 32. More specifically, an enlarged diameter portion 41 is formed on the base side portion, and a step portion that protrudes outward in the radial direction of the second protrusion 32 is formed at the upper end of the enlarged diameter portion 41. The step portion serves as the puncture depth control unit 40. This example is shown in FIG.
When the first projection 31 and the composite second projection 52 are inserted into the skin from the tip side, the puncture depth control unit 40 comes into contact with the surface of the skin, stopping the first projection 31 and the composite second projection 52 from penetrating deeper into the skin, preventing the first projection 31 and the composite second projection 52 from penetrating deeper into the skin. Since the puncture depth control unit 40 is integrally formed around the second projection 32 in the composite second projection 52, it is possible to more reliably prevent the composite second projection 52 from penetrating deeper into the skin.

Next, the constituent materials of the injection needle 1 will be described.
The injection needle 1 preferably contains a thermoplastic resin from the viewpoints of material handleability, strength and processability of the injection needle, and ensuring hardness in the first projections 31, the second projections 32, and the third projections 33 to facilitate injection of liquid. The injection needle is more preferably formed from a base sheet containing a thermoplastic resin.
The thermoplastic resin may include one or more selected from polyolefin, polyester, polyamide, polyamideimide, polyetheretherketone, polyetherimide, polyvinyl chloride, acrylic resin, polystyrene resin, and the like.
The polyolefin may include one or more selected from polypropylene, polyethylene, and the like.
The polyester may include one or more selected from polyethylene terephthalate, polyfatty acid ester, polylactic acid, polycaprolactone, polybutylene succinate, and the like.
The polyamide may include one or more selected from nylon and the like.
From the viewpoint of biodegradability, it is preferable that the composition contains a polyfatty acid ester.
Specifically, the polyfatty acid ester may include one or more selected from polylactic acid and polyglycolic acid.

The ratio of the mass of the thermoplastic resin contained in the injection needle 1 to the total mass of the injection needle 1 is preferably 50% or more, more preferably 70% or more, and even more preferably 90% or more, from the viewpoint of improving the moldability and dimensional stability of the injection needle.
The mass ratio of the thermoplastic resin is preferably 100% or less, more preferably 98% or less, and even more preferably 96% or less, from the viewpoint of imparting various effects to the injection needle by adding, for example, a functional agent.
The mass proportion of the thermoplastic resin is preferably 50% or more and 100% or less, more preferably 70% or more and 98% or less, and even more preferably 90% or more and 96% or less.
Here, as various functional agents, antibacterial agents, bactericides, moisturizing agents, flow improvers, antistatic agents, colorants, etc. can be used.

The drug to be injected into the skin by the injection needle 1 can be appropriately selected depending on the intended use of the injection needle 1. The drug can include, for example, one or more selected from vaccines for preventing infectious diseases such as hepatitis A, hepatitis B, hepatitis C, influenza, COVID-19, tuberculosis, rabies, polio, chickenpox, rubella, measles, tetanus, etc., or for treating chronic hepatitis B, tuberculosis, rabies, malignant neoplasms, etc., painkillers for cancer patients, insulin, biological products, gene therapy drugs, injections, skin application preparations, etc.
Since the first protrusion 31 of the injection needle 1 punctures the skin, the injection needle 1 can be applied to pharmacologically active substances that require subcutaneous injection, intramuscular injection, or intravenous injection in addition to pharmacologically active substances used for conventional transdermal administration.

The present invention includes an injection device having an injection needle and a drug supplying device connected to the injection needle. The drug supplying device is capable of discharging a drug filled in the drug supplying device from the opening through the inside of the first projection while connected to the injection needle. The injection needle and the drug supplying device may be connected to each other when used, connected before use and separable after use, or integrated and inseparable. The drug is typically pre-filled in the drug supplying device, or transferred from an arbitrary container such as an ampoule or a small bottle to the drug supplying device when used.
The injection needle of the injection device of the present invention can be the injection needle 1 of the present invention described above. When the medicine supplying device is connected to the injection needle, the medicine filled in the medicine supplying device can be discharged from the opening 31a via the inside of the first projection 31. As the medicine supplying device, for example, a syringe, a tube, etc. can be used.
According to the injection device of the present invention, it is possible to achieve both puncture performance and an immunity induction effect when injecting a medicine.

The present invention includes an injection kit including an injection needle, a drug supplying device connectable to the injection needle, and a drug. The drug supplying device is capable of discharging the drug filled in the drug supplying device from the opening through the inside of the first projection when connected to the injection needle. The injection needle and the drug supplying device may be connected to each other when in use, connected before use and separable after use, or integrated and inseparable. The drug is typically pre-filled in the drug supplying device, or transferred from an arbitrary container such as an ampoule or a small bottle to the drug supplying device when in use.
The injection needle of the injection kit of the present invention may be the injection needle 1 of the present invention described above. The drug supplying device may be the same as the drug supplying device of the injection device of the present invention described above. The drug may be the same as the drug used in the injection needle 1 of the present invention described above.
According to the injection kit of the present invention, when injecting a drug, it is possible to achieve both puncture ease and an immunity induction effect.

Although the present invention has been described based on the preferred embodiment, the present invention is not limited to the above-described embodiment and can be modified as appropriate.
For example, in the example shown in Fig. 3, the second protrusion 32 and the third protrusion 33 are solid, but either one or both of the second protrusion 32 and the third protrusion 33 may be hollow. Also, in the example shown in Fig. 7, the composite second protrusion 52 is solid, but the composite second protrusion 52 may be hollow. In the injection needle 1, it is preferable that the protrusions other than the first protrusion 31 are solid. By doing so, it is possible to prevent the liquid to be discharged from the opening 31a of the first protrusion 31 from being accumulated inside the other protrusions, so that the liquid can be injected efficiently.

The following notes are further provided with respect to the embodiment of the present invention described above.

＜1＞
A projection protruding from the seat base,
The projections include a first projection having a hollow cone shape and an opening at a tip portion, and a second projection having a cone shape and no opening at a tip portion,
A first region and a second region are included.
the first region includes one to six first projections and is located at a center of the seat base in a plan view;
the second region is a region that does not overlap with the first region and includes two or more second projections;
The injection needle, wherein a distance D1, which is the shortest distance between a first projection in the first region and a second projection in the second region, is 0.3 mm or more and 2 mm or less.
＜2＞
The injection needle according to <1> above, wherein the number of the first projections included in the first region is 2 or more and 5 or less, preferably 3 or more and 4 or less.

＜5＞
The injection needle according to any one of <1> to <4>, wherein the first projection is taller than the second projection.
＜6＞
The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
The injection needle according to any one of <1> to <5>, wherein the third projection is lower in height than both the first projection and the second projection.
＜8＞
The injection needle according to any one of <1> to <6>, wherein the number of the first projections included in the first region is smaller than the number of the second projections included in the second region, and the ratio of the latter to the former is 2.4 or more and 10 or less, preferably 2.5 or more and 9 or less, and more preferably 2.6 or more and 8 or less.

＜9＞
The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
the total number N2+N3 of the number N2 of the second protrusions and the number N3 of the third protrusions is greater than the number N1 of the first protrusions,
The injection needle according to any one of <1> to <8>, wherein a ratio (N2+N3)/N1 of the total number N2+N3 of the number N2 of the second projections and the number N3 of the tertiary projections to the number N1 of the first projections is preferably 2 or more and 25 or less, more preferably 2.5 or more and 20 or less, and even more preferably 3 or more and 15 or less.
＜10＞
The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
The second protrusion is taller than the third protrusion,
The injection needle according to any one of <1> to <9>, wherein the height of the third projections is preferably 50% or more and 75% or less, more preferably 55% or more and 70% or less, and even more preferably 60% or more and 65% or less, of the height of the second projections.
<11>
The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
The second protrusion is taller than the third protrusion,
The injection needle according to any one of <1> to <10>, wherein a difference in height between the second projections and the third projections is 100 μm or more and 2400 μm or less, preferably 200 μm or more and 2000 μm or less, and more preferably 300 μm or more and 1000 μm or less.

＜12＞
The first protrusion is taller than the second protrusion,
The injection needle according to any one of <1> to <11>, wherein the height of the second projections is preferably 55% or more and 99% or less, more preferably 60% or more and 97% or less, and even more preferably 65% or more and 95% or less, of the height of the first projections.
＜13＞
The first protrusion is taller than the second protrusion,
The injection needle according to any one of <1> to <12>, wherein a difference in height between the first projections and the second projections is 10 μm or more and 4,900 μm or less, preferably 50 μm or more and 3,000 μm or less, and more preferably 100 μm or more and 2,000 μm or less.
＜14＞
The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
The first protrusion is taller than the third protrusion,
The injection needle according to any one of <1> to <13>, wherein the height of the third projections is preferably 30% or more and 75% or less, more preferably 35% or more and 70% or less, and even more preferably 40% or more and 65% or less, of the height of the first projections.
＜15＞
The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
The first protrusion is taller than the third protrusion,
The injection needle according to any one of <1> to <14>, wherein a difference in height between the first projections and the third projections is 100 μm or more and 4900 μm or less, preferably 300 μm or more and 4000 μm or less, and more preferably 500 μm or more and 3000 μm or less.

＜16＞
The injection needle according to any one of <1> to <15>, wherein the height of the primary projections is 100 μm or more and 5000 μm or less, preferably 150 μm or more and 4000 μm or less, and more preferably 500 μm or more and 3000 μm or less.
＜１７＞
The injection needle according to any one of <1> to <16>, wherein the height of the secondary projections is 5 μm or more and 4,900 μm or less, preferably 20 μm or more and 4,000 μm or less, and more preferably 50 μm or more and 3,000 μm or less.
＜18＞
The injection needle according to any one of <1> to <17>, wherein the height of the third projections is 3 μm or more and 3600 μm or less, preferably 10 μm or more and 3000 μm or less, and more preferably 50 μm or more and 2000 μm or less.
＜19＞
The injection needle according to any one of <1> to <18>, wherein the total number of protrusions of the injection needle is 5 to 26, preferably 7 to 20, more preferably 10 to 16.

＜20＞
The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
The injection needle according to any one of <1> to <19>, having a third region that includes a third projection and sandwiches or surrounds the second region.
＜21＞
a protrusion-free region that does not include a protrusion is disposed between the second region and the third region;
The injection needle according to <20> above, wherein the shortest distance between the second projections included in the second region and the third projections included in the third region is preferably 0.5 mm or more and 5.0 mm or less, more preferably 1.0 mm or more and 4.5 mm or less, and even more preferably 1.5 mm or more and 4.0 mm or less.
＜22＞
The injection needle according to any one of <20> or <21>, wherein the second region does not include a third projection.
＜23＞
The injection needle according to any one of <20> to <22>, wherein the second region and the third region do not include the first projection.
＜24＞
The injection needle according to any one of <20> to <23>, wherein the first region does not include the second projection and the third projection.
＜25＞
The injection needle according to any one of <1> to <24>, wherein the injection needle contains a thermoplastic resin.

＜26＞
The number of the first projections is 3 or more and 4 or less,
The distance D1 is equal to or greater than 0.9 mm and equal to or less than 1.5 mm,
The first projection is taller than the second projection,
The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
The third projection is lower in height than the first projection and the second projection,
a ratio of the number of the secondary projections to the number of the primary projections is 2.6 or more and 8 or less;
a ratio of the total number of the secondary projections and the tertiary projections to the number of the primary projections is 3 or more and 15 or less;
The height of the primary projections is 500 μm or more and 3000 μm or less,
the difference in height between the primary projections and the secondary projections is 100 μm or more and 2000 μm or less;
The injection needle according to any one of <1> to <25>, wherein a difference in height between the first projections and the third projections is 500 μm or more and 3000 μm or less.

＜27＞
The amount of liquid discharged from the opening of the first projection is denoted by V,
When the shortest distance from the center of the first region to the second protrusion in a plan view is D5,
The injection needle according to any one of <1> to <26>, wherein a liquid volume V (μL) and a shortest distance D5 (mm) satisfy the following formula (1):
D5≦0.5406ln(V)+0.9483... (1)
＜28＞
The injection needle according to any one of <1> to <27> and a drug supply device connected to the injection needle,
The medicine supply device is configured to eject medicine filled in the medicine supply device through the inside of the first projection and from the opening when connected to the injection needle.
＜29＞
The injection needle according to any one of <1> to <28>, a drug supplier connectable to the injection needle, and a drug;
The medicine supply device is configured to eject a medicine filled in the medicine supply device through the inside of the first projection and from the opening when the medicine supply device is connected to the injection needle.

＜30＞
The seat has first and second projections protruding from a base portion of the seat;
The first projection has a hollow cone shape and has an opening at a tip portion,
The second projections are cone-shaped and have no openings at their tips,
A method for injecting a drug into the skin using an injection needle having a first region including one to six first projections and located at the center of the sheet base in a plan view, and a second region not overlapping with the first region and including two or more second projections,
With the first projections inserted into the skin, the drug is discharged from the openings of the first projections, thereby injecting the drug into the skin; and
A method for improving the immunogenicity of a person into whom the drug is injected, by puncturing with a second projection the skin within the area in which a wheal forms upon injection of the drug.
＜31＞
The amount of liquid discharged from the opening of the first projection is denoted by V,
When the shortest distance from the center of the first region to the second protrusion in a plan view is D5,
The method according to <31> above, wherein the liquid volume V (μL) and the shortest distance D5 (mm) satisfy the following formula (1).
D5≦0.5406ln(V)+0.9483... (1)

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

Example 1
An injection needle having the same configuration as the injection needle 1 shown in Fig. 10(a) and the same projection arrangement as that in Fig. 10(b) was manufactured. The injection needle of Example 1 has the same configuration as the injection needle shown in Fig. 1 except for the projection arrangement pattern. The dimensions of each projection of the injection needle, the dimensions of the sheet base, the distance D1 which is the shortest distance between the first projection 31 and the second projection 32, the radius D2 of the imaginary circle formed by the imaginary line C1 connecting the centers of the first projections 31, and the shortest distance D3 between the first projections 31 in the first region R1 are as shown in Table 1. The injection needle was formed by applying ultrasonic vibration to a base sheet made of 100% polylactic acid, a thermoplastic resin, and performing projection formation processing using a processed needle.
[Comparative Examples 1 to 4]
Except for changing the number and arrangement of the projections, the injection needles were manufactured in the same manner as in Example 1. The projection arrangements of Comparative Examples 1 to 4 are shown in Figures 11 to 14, respectively.

[Puncture]
The injection needles of Example 1 and Comparative Examples 1 to 4 were evaluated for their puncture resistance with liquid by the following method.
The skin excised from a Gottingen miniature pig (male, 6 weeks old, ventral part; Oriental Yeast Co., Ltd.) stored at -20°C was transferred to a refrigerator (4°C) the day before the test and thawed. The excised skin was placed on 5 to 7 Kimtowels, shaved with a shaver, and the surface was wiped with alcohol cotton before administration.

Powdered rhodamine B (Sigma-Aldrich) was adjusted to 0.5 mg/mL with ultrapure water and filled into a microsyringe (Agilent). The injection needles of Example 1 and Comparative Examples 1 to 4 were attached to the microsyringes, and air was removed. The liquid volume in the microsyringe was set to 100 μL, and excess liquid adhering to the injection needle was removed by absorbing it with Kimwipes. The projection of the injection needle was punctured vertically into the target, and an aqueous solution of rhodamine B was injected, and it was visually confirmed whether or not there was a problem with the injection of the liquid.
[Evaluation criteria for puncture resistance]
○: Meets both (1) and (2) below.
(1) When the first projection is punctured, it can be punctured to a depth sufficient to allow injection.
(2) When the first projection is inserted, it does not penetrate too deeply, but can be inserted to a depth that causes a wheal to form when the medicinal solution is injected.
×: Either or both of (1) and (2) above are not satisfied.

[Immunity induction effect]
The injection needles of Example 1 and Comparative Examples 1 to 3 were evaluated for their immunity-inducing effects by the following method.
Guinea pigs (Hartley, female, 6 weeks old; Japan SLC Co., Ltd.) were pre-bred for 7 days with free access to food and water, and then divided into groups taking into consideration the variation in body weight. The guinea pigs were put to sleep with isoflurane anesthesia, and the administration site (flank) was depilated using clippers and a shaver, and disinfected with alcohol. The injection needles of Example 1 and Comparative Examples 1 to 3 were attached to 100 μL Luer-lock microsyringes (Agilent), and the protein solution (hepatitis B surface antigen protein preparation: manufactured by Vehicle Co., Ltd.) was filled and air was removed. The skin of the guinea pig's flank was pinched and stretched with fingers, and the syringe with the injection needle was swung down vertically to puncture the skin, and 1.0 μg/25 μL of protein solution was administered. The protein solution was administered to the guinea pigs in the separate groups divided according to the above-mentioned grouping for each of the injection needles of Example 1 and Comparative Examples 1 to 3.
After a 2-week interval, the second administration was performed in the same manner, and 42 days after the first administration, blood samples were taken from the dorsalis pedis vein. The collected blood was immediately transferred from the syringe to a Capiject II (Terumo Corporation), left at room temperature for 30 minutes, stored on ice, and centrifuged at 3,000 xg and 4°C for 10 minutes. The supernatant was collected in a 1.5 mL Eppendorf tube and stored at 4°C until the day of analysis.
The antibody titer against the protein solution was measured by the ELISA method.
The results are shown in Figure 15. In Figure 15, the absorbance on the vertical axis is an index of the antibody titer against the administered protein, and a higher absorbance indicates a higher immunity induction.

The injection needle of Example 1 exhibits good puncture properties as shown in Table 1. In addition, the injection needle of Example 1 has a higher immunity induction effect than the injection needles of Comparative Examples 1 to 3 as shown in Figure 15.
As shown in Table 1, the injection needles of Example 1 and Comparative Examples 1 to 3 have better puncture properties than the injection needle of Comparative Example 4. Moreover, as shown in Figure 15, the injection needle of Example 1 has a superior immunity induction effect to the injection needles of Comparative Examples 1 to 3.
Since the injection needle of Example 1 is capable of both injecting liquid and inducing immunity, it is clear that the injection needle of the present invention is capable of both injecting liquid and inducing immunity.

1: injection needle 2: sheet base 31: first projection 32: second projection R1: first region R2: second region

Claims (8)

A projection protruding from the seat base,
The projections include a first projection having a hollow cone shape and an opening at a tip portion, and a second projection having a cone shape and no opening at a tip portion,
A first region and a second region are included.
the first region includes one to six first projections and is located at a center of the seat base in a plan view;
the second region is a region that does not overlap with the first region and includes two or more second projections;
The injection needle, wherein a distance D1, which is the shortest distance between a first projection in the first region and a second projection in the second region, is 0.3 mm or more and 2 mm or less. The injection needle according to claim 1, wherein the number of first projections included in the first region is 2 or more and 5 or less. The injection needle according to claim 1 or 2, wherein the first protrusion is taller than the second protrusion. The injection needle according to any one of claims 1 to 3, wherein the number of first projections included in the first region is less than the number of second projections included in the second region. The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
The injection needle according to any one of claims 1 to 4, wherein the second projection is taller than the third projection. The protrusion protruding from the seat base includes a third protrusion having a generally truncated cone shape with a tip surface that is flat or curved,
The injection needle according to any one of claims 1 to 5, wherein the first projection is taller than the third projection. A syringe comprising the injection needle according to any one of claims 1 to 6 and a drug supply device connected to the injection needle,
The medicine supply device is configured to eject medicine filled in the medicine supply device through the inside of the first projection and from the opening when connected to the injection needle. The injection needle according to any one of claims 1 to 6, a drug supplier connectable to the injection needle, and a drug;
The medicine supply device is configured to eject a medicine filled in the medicine supply device through the inside of the first projection and from the opening when the medicine supply device is connected to the injection needle.