Injection kit and holder

Abstract

An injection kit (100) comprises an injection device (40) and a holder (1) for holding the injection device (40). The injection device (40) includes an injection needle (41) having fine protrusions (44) and a drug solution container part (52) containing a drug solution. The fine protrusions (44) each have an opening. The holder (1) has a biasing member (30) that biases the injection device (40) in the puncturing direction of the injection needle (41). The mass of the injection device (40) and the kinetic energy generated when the fine protrusions (44) of the injection device (40) biased by the biasing member (30) puncture the skin satisfy formula (1).　(1): E ≥ 0.0077 ln (x) + 0.0057 (In the formula, E represents the kinetic energy, and x represents the mass of the injection device.)

Description

Injection kits and holders

[0001] The present invention relates to an injection kit and holder.

[0002] In recent years, intradermal administration of liquids such as medicines using injection needles equipped with fine needle-like protrusions, also known as microneedles, has been attracting attention in the medical and cosmetic fields. These injection needles enable liquids to be injected into the body by inserting the microneedles into a relatively shallow layer of the skin, such as the stratum corneum, and because the pain felt by the subject is significantly reduced compared to ordinary injection devices, they have attracted attention as a minimally invasive means of administering liquids.

[0003] It has been known to puncture the skin with a microneedle using a holder that moves the microneedle toward the skin. For example, Patent Document 1 describes using an operation assisting device for puncture and injection to puncture a hollow needle-shaped object having multiple protrusions at a puncture speed of 0.2 m / s.

[0004] Patent Document 2 describes that a microneedle array having a plurality of microneedles is attached to the skin using an external applicator, and that the applicator is designed to use a spring mechanism to obtain the desired speed so that the microneedles penetrate the skin.

[0005] Patent Literature 3 describes a microneedle delivery device that allows a microneedle device equipped with microneedles to reach a desired speed and presses it against the stratum corneum of the skin. The document also describes that after the microneedles that have penetrated the stratum corneum are removed from the skin, a drug is applied to the skin and passes through the through-holes formed in the skin. The document also describes that a piston provides sufficient acceleration to reach the desired speed, that the maximum speed obtained by the piston is preferably 20 m / s or less, and that the minimum speed obtained by the piston is preferably 2 m / s or more per second.

[0006] US2017 / 021112A1US2011 / 0213335A1US2005 / 0261631A1

[0007] The present invention provides an injection kit including an injection device and a holder for holding the injection device. In one embodiment, the injection device preferably includes an injection needle having fine protrusions and a medicinal solution container in which a medicinal solution is contained. In one embodiment, the fine protrusions preferably have openings. In one embodiment, the container preferably includes a biasing member that biases the injection device in the puncture direction of the injection needle. In one embodiment, the mass of the injection device and the kinetic energy when the fine protrusions of the injection device biased by the biasing member puncture the skin preferably satisfy the following formula (1): E≧0.0077ln(x)+0.0057 (1) (where E represents the kinetic energy, and x represents the mass of the injection device.)

[0008] The present invention provides a holder for holding a syringe. In one embodiment, the syringe preferably includes a syringe needle having fine protrusions and a drug solution storage section capable of storing a drug solution. In one embodiment, the fine protrusions preferably have openings. In one embodiment, the holder preferably includes a biasing member that biases the syringe in the puncture direction of the syringe needle. In one embodiment, the mass of the syringe and the kinetic energy when the fine protrusions of the syringe biased by the biasing member puncture the skin preferably satisfy the following formula (1): E≧0.0077ln(x)+0.0057 (1) (where E represents the kinetic energy, and x represents the mass of the syringe.)

[0009] FIG. 1 is a perspective view of a holder according to a preferred embodiment of the present invention. FIG. 2 is a cross-sectional view taken along line II-II in FIG. 1. FIG. 3 is a schematic enlarged cross-sectional view of an injection needle provided in an injection device attached to the holder shown in FIG. 1. FIGS. 4(a) to 4(c) are schematic enlarged cross-sectional views of protrusions of the injection needle shown in FIG. 3, with FIG. 4(a) being a schematic enlarged cross-sectional view of a micro-protrusion, FIG. 4(b) being a schematic enlarged cross-sectional view of a stimulating protrusion, and FIG. 4(c) being a schematic enlarged cross-sectional view of a control protrusion. FIG. 5 is a diagram showing a state in which a micro-protrusion has been punctured into skin using the holder shown in FIG. 1, and is a cross-sectional view schematically showing a cross section along the thickness direction of the skin. FIG. 6 is a schematic cross-sectional view for explaining a method for measuring the puncture speed. FIG. 7 is a schematic diagram for explaining the amount of compression of a spring. FIG. 8 is a diagram for explaining the lengths of the major and minor axes of a wheal. FIG. 9 is a graph plotting the kinetic energy at the time of puncture on the vertical axis and the mass of the injection device on the horizontal axis for each example and each comparative example. FIG. 10 is a graph showing an enlarged portion of FIG. 9 . FIG. 11 is a graph plotting the kinetic energy at the time of puncturing on the vertical axis and the mass of the injection device on the horizontal axis for each test example. FIG. 12 is a graph showing an enlarged portion of FIG. 11 . FIG. 13 is a perspective view showing the injection device attached to the holder shown in FIG. 1 . FIG. 14 is a perspective view showing the injection needle of the injection device shown in FIG. 13 in an unconnected state. FIG. 15 is an enlarged view of the microprotrusions as viewed from the side where the apertures are formed. FIG. 16 is a perspective view schematically showing another embodiment of the injection kit of the present invention. FIG. 17 is a perspective view showing the main body of the holder shown in FIG. 16 with the slider advanced. FIG. 18 is a perspective view showing the main body of the holder shown in FIG. 17 with the slider retracted. FIG. 19 is a cross-sectional view taken along CC in FIG. 17 . FIG. 20 is a cross-sectional view taken along DD in FIG. 17 . FIG. 21 is an explanatory diagram of the locked state using the locking mechanism. FIG. 22 is a perspective view showing the holder shown in FIG. 16 with the slider retracted. Detailed Description of the Invention

[0010] As described above, in order to administer a drug such as a drug solution intradermally using a microneedle, it is necessary to insert the microneedle into a relatively shallow layer of the skin. In other words, it is necessary to insert the microneedle to an appropriate depth that is neither too shallow nor too deep, but it has been difficult to insert the microneedle to such an appropriate depth. After extensive research, the inventors have found that simply specifying the microneedle puncture speed, as in Patent Documents 1 to 3, is insufficient to insert the microneedle to an appropriate depth that allows intradermal administration. Furthermore, as described above, the technology of Patent Document 3 involves forming a through-hole in the skin with the microneedle and then passing the drug through the through-hole, and this document does not consider intradermal administration using a hollow microneedle.

[0011] Therefore, the present invention relates to an injection kit and holder that allows the microprotrusions for injection to be easily inserted to an appropriate depth, thereby enabling efficient intradermal administration.

[0012] The present invention will be described below based on preferred embodiments with reference to the drawings. In the following description of the drawings, the same or similar parts are designated by the same or similar reference numerals. The drawings are basically schematic, and the ratios of the dimensions may differ from those of the actual ones.

[0013] 1 and 2 show a holder 1 according to a preferred embodiment of the present invention. An injection kit 100, which is a preferred embodiment of the present invention, includes an injection device 40 and a holder 1 that holds the injection device 40. The holder 1 has a biasing member that biases the injection device 40 in the puncture direction of the injection needle 41, and is used to puncture the skin with hollow microprotrusions 44 that the injection device 40 has. In this embodiment, the biasing member is a spring 30. The holder 1 also has an injection device holder 20 that holds the injection device 40, and a guide mechanism that regulates the movement direction of the injection device 40. The spring 30 biases the injection device holder 20 in the puncture direction.

[0014] The guide mechanism includes a guide hole 11 provided in the side wall of a cylindrical main body 10 that forms the main body of the holder 1, and a guide protrusion 22 provided to protrude from the side surface of a cylindrical main body 21 that forms the main body of the injection device holder 20. The guide hole 11 has an opening shape that extends along the axial direction X of the main body 10. By inserting the guide protrusion 22 of the injection device holder 20 into the guide hole 11, the movement direction of the injection device holder 20 is restricted to the axial direction X of the main body 10 of the holder 1. The injection device holder 20 is disposed inside the main body 10 of the holder 1.

[0015] The holder 1 also has a stopper mechanism for maintaining the spring 30, which is a biasing member, in a contracted state. The stopper mechanism maintains the spring 30 in a contracted state by fixing the position of the guide protrusion 22. In this embodiment, the stopper mechanism includes a step portion 11a provided in the guide hole 11. The position of the guide protrusion 22 can be fixed by engaging the guide protrusion 22 with the step portion 11a.

[0016] As described above, the syringe holder 20 holds the syringe 40. The syringe 40 includes a syringe needle 41 having fine protrusions 44 and a drug solution storage section 52 capable of storing a drug solution. The syringe 40 preferably includes the syringe needle 41 connected to a drug solution supplier 50 capable of supplying the drug solution to the fine protrusions 44. The syringe needle 41 and the drug solution supplier 50 are preferably detachably connected. When calculating kinetic energy, as described below, the drug solution is stored in the drug solution storage section of the syringe 40. The syringe 40 of the injection kit 100 includes a drug solution storage section 52 in which the drug solution is stored. The syringe 40 typically includes a base component 47 between the fine protrusions 44 and the drug solution supplier 50. The base component 47 typically supports the fine protrusions 44 directly or indirectly. The outer surface of the base component typically has a luer lock. A specific example of the syringe 40 in which the syringe needle 41 and the drug solution supplier 50 are connected is shown in FIG. 13 .

[0017] In this embodiment, the drug solution supplier 50 is a syringe 51. More specifically, the drug solution supplier 50 is typically a syringe 51 having a syringe barrel 51a and a plunger 58. The syringe 51 typically includes a drug solution storage section 52 capable of storing a drug solution therein. The syringe barrel 51a preferably includes, at one longitudinal end thereof, a liquid inlet 53 for supplying the drug solution to the fine protrusions 44 and a connection section 54 with the base component 47 that supports the injection needle 41. The syringe 51 typically includes a cylindrical syringe barrel 51a. The syringe barrel 51a preferably includes, at one longitudinal end thereof, a tip section 51b having the connection section 54. The syringe barrel 51a preferably includes, at the other longitudinal end thereof, a flange section 56. The liquid inlet 53 is typically disposed at the tip section 51b. The injection port 53 is typically cylindrical and has a diameter smaller than that of the syringe barrel 51a, which contains the drug solution storage portion 52, and is open at its tip. The connection portion 54 preferably has a female thread ridge 54a on its inner surface. The thread ridge 54a is preferably threadably engageable with the protruding portion 49 of the base component 47. The syringe barrel 51a is made of, for example, glass or synthetic resin, but is not limited thereto. The plunger 58 typically includes an operating rod 59 and a gasket 59a. The gasket 59a is typically provided at the tip of the operating rod 59 and disposed inside the syringe barrel 51a. The gasket 59a is preferably capable of being pushed into the syringe barrel 51a. The operating rod 59 preferably has a pressing operation portion 59b at its rear end that is pressed with a finger during the drug solution injection operation. The operating rod 59 is preferably made of synthetic resin and is rod-shaped.

[0018] Gasket 59a is typically made of an elastic material such as synthetic rubber and has a cylindrical shape with a triangular pyramidal tip, and is capable of sliding on the inner circumferential surface of syringe barrel 51a. Gasket 59a forms drug solution storage section 52, which is filled with drug solution, inside syringe barrel 51a. When drug solution is stored in drug solution storage section 52, gasket 59a is pushed toward tip end 51b of syringe barrel 51a together with operating rod 59, whereby drug solution is supplied from injection port 53 provided at tip end 51b to fine protrusion 44 of injection needle 41.

[0019] The injection needle 41 is configured to include a micro-projection device 42 and a base component 47. The injection device 40 is used for intradermal administration of a medicinal solution. Here, intradermal administration refers to administering the medicinal solution into the epidermis or dermis. In the present invention, administering the medicinal solution into the epidermis is preferable. When the injection device 40 is used for intradermal administration of a medicinal solution, it means that the micro-projections 44 of the injection device 40 have openings 44a that can supply the medicinal solution to a position suitable for intradermal administration. The openings 44a of the micro-projections 44 will be described later.

[0020] The main body 21 of the injection device holder 20 is configured so that the tip end of the syringe 51 is inserted from one side in the axial direction X of the main body 21, and the base part 47 of the injection needle 41 is inserted from the other side. The injection device 40 is attached to the injection device holder 20 by inserting the tip end of the syringe 51 and the base part 47 of the injection needle 41 into the main body 21 of the injection device holder 20 and connecting the tip end of the syringe 51 and the base part 47 of the injection needle 41.

[0021] 3 and 4, the micro-protrusion device 42 of the injection needle 41 has protrusions. The protrusions of the micro-protrusion device 42 include a micro-protrusion 44, a stimulation protrusion 45, and a control protrusion 46. The micro-protrusion device 42 also has a puncture depth control section 46a disposed at an intermediate position that is lower than the tip position of the micro-protrusion 44 and higher than the base surface 43.

[0022] The microprotrusions 44 of the injection needle 41 have openings 44a through which liquid can be ejected. The microprotrusions 44 are hollow. The microprotrusions 44 are preferably conical in shape and have openings 44a at their tips. The tip of the microprotrusions 44 refers to the region toward the tip of the microprotrusions 44 from the midpoint of the protrusion height H1 from the base surface 43 to the tip of the microprotrusions 44 (see FIG. 4(a)). The openings 44a may be formed at the tip of the microprotrusions 44 or on the side surface. The hollow portions 44b of the microprotrusions 44 communicate with the outside through the openings 44a of the microprotrusions 44. The openings 44a are through-holes that penetrate the microprotrusions 44 in the thickness direction and are preferably located on the side surface of the conical microprotrusions 44. The hollow portions 44b of the microprotrusions 44 function as passages for liquid to be ejected from the openings 44a to the outside. The microprotrusions 44 are so-called microneedles and have openings. Here, the microneedle refers to a protrusion having an opening and preferably having a protruding height of 5000 μm or less from the base surface from which the microneedle protrudes.

[0023] The stimulation protrusion 45 is a protrusion without an opening. The stimulation protrusion 45 has a pyramidal shape. The pyramidal shape of the stimulation protrusion 45 may be an approximately conical shape or an approximately polygonal pyramidal shape. The tip surface of the control protrusion 46 is flat, i.e., a linear shape extending horizontally. As described above, the fine-protrusion device 42 has a puncture depth control section 46a, and in this embodiment, the tip surface of the control protrusion 46 serves as the puncture depth control section 46a. The tip surface of the control protrusion 46 may be a curved line that is convex toward the protruding direction of the control protrusion 46. The control protrusion 46 has a columnar shape. The columnar shape of the control protrusion 46 may be an approximately cylindrical shape or an approximately polygonal column shape such as a square column.

[0024] The stimulation protrusions 45 and the control protrusions 46 may be hollow or solid. In this embodiment, the stimulation protrusions 45 and the control protrusions 46 are solid. By having the stimulation protrusions 45 and the control protrusions 46 be solid, it is possible to reduce the amount of medicinal solution remaining in the fine-protrusion device 42 when injecting the medicinal solution from the fine-protrusion device 42. Note that the fine-protrusion device 42 does not necessarily have the stimulation protrusions 45 and the control protrusions 46.

[0025] The base component 47 has a cylindrical shape as a whole, and a hollow portion 47b is defined inside the base component 47. Openings are formed on both sides of the hollow portion 47b in the base component 47, and the hollow portion 47b communicates with the outside via the openings. One opening functions, for example, as a supply port when a chemical solution is supplied to the hollow portion 47b using a syringe 51. The other opening functions, for example, as a supply port when the chemical solution supplied from the syringe 51 is supplied to the fine-protrusion device 42.

[0026] A method for injecting a medicinal solution into the skin using the injection kit 100 will be described. First, the syringe 51 is filled with the medicinal solution. Specifically, with the tip opening of the syringe 51 immersed in the medicinal solution, the plunger 58 inserted into the syringe 51 is pulled up to draw the medicinal solution into the syringe 51. An injection needle 41 is attached to the syringe 51 filled with the medicinal solution to form the injection device 40. The plunger 58 of the syringe 51 is pressed down to fill the medicinal solution into the fine protrusions 44 of the injection needle 41. The injection device 40 is held by the injection device holder 20, and the injection device 40 is attached to the holder 1. The injection device holder 20 is pushed up to contract the spring 30 biasing the injection device holder. The guide protrusions 22 of the injection device holder 20 are fixed by a stopper mechanism, and the spring 30 is maintained in a contracted state (hereinafter, this state is also referred to as the "standby state"). The fine protrusions 44 of the injection needle 41 in the holder 1 in the standby state are brought close to the skin to which the medicinal liquid is to be administered. At this time, it is preferable that the axial direction X of the holder 1 is perpendicular to the skin. Then, the guide protrusions 22 of the injection device holder 20 are released from fixation. Then, the injection device holder 20 holding the injection device 40 is urged toward the skin, and the fine protrusions 44 of the injection device 40 puncture the skin (see FIG. 5 ). Then, the plunger 58 of the syringe 51 is pressed down to inject the medicinal liquid into the skin.

[0027] To efficiently perform intradermal administration, it is necessary not only to simply puncture the skin with the microprotrusions 44 of the injection device 40, but also to puncture the skin to an appropriate depth that allows intradermal administration. Specifically, when the microprotrusions 44 puncture the skin, it is preferable that the openings 44a of the microprotrusions 44 reach the layer S12 in the epidermis S1, which is deeper than the stratum corneum S11 (see FIG. 5). Note that the openings 44a of the microprotrusions 44 may extend beyond the epidermis S1 and reach the dermis S2. Even when the openings 44a of the microprotrusions 44 reach the dermis S2, the drug solution ejected from the openings 44a penetrates not only the dermis S2 but also the epidermis S1, allowing the drug solution to be injected into the epidermis S1. When the openings 44a of the micro-protrusions 44 reach the dermis S2, it is preferable that the openings 44a be located at a position in the dermis S2 closer to the epidermis S1, in order to ensure that the medicinal solution ejected from the openings 44a penetrates into the epidermis S1.

[0028] As a result of careful investigation by the inventors, it was found that by satisfying a certain relationship between the kinetic energy when the micro-protrusions 44 puncture (hereinafter also referred to as "kinetic energy at puncture") and the mass of the injection device 40, the micro-protrusions 44 can be punctured to an appropriate depth, and intradermal administration can be carried out efficiently.

[0029] Specifically, it is preferable that the kinetic energy at the time of puncturing and the mass of the injection tool 40 satisfy the above-mentioned formula (1).

[0030] If the kinetic energy at the time of puncturing and the mass of the injection device 40 satisfy the above-mentioned formula (1), the microprotrusions 44 will be more likely to penetrate the stratum corneum of the skin and reach the epidermis when the microprotrusions 44 of the injection device 40 are punctured into the skin by the holder 1. Therefore, the microprotrusions 44 will be more likely to puncture to an appropriate depth, and intradermal administration can be performed efficiently.

[0031] Furthermore, from the viewpoint of enabling the microprojections 44 to reach the epidermis more easily and enabling more efficient intradermal administration, it is preferable that the kinetic energy at the time of puncturing and the mass of the injection device 40 satisfy the following formula (2): E≧0.0077ln(x)+0.01 (2) (where E represents the kinetic energy at the time of puncturing, and x represents the mass of the injection device).

[0032] Furthermore, it is preferable that the kinetic energy at the time of puncturing and the mass of the injection device 40 satisfy the following formula (3): E≦0.05ln(x)+0.075 (3) (where E represents the kinetic energy at the time of puncturing, and x represents the mass of the injection device.) When the kinetic energy at the time of puncturing and the mass of the injection device 40 satisfy formula (3), the injection device 40 is biased by the holder 1, and excessive pain when the injection needle 41 hits the skin can be prevented.

[0033] From the viewpoint of further reducing the pain when the injection needle 41 hits the skin, it is preferable that the kinetic energy at the time of puncturing and the mass of the injection device 40 satisfy the following formula (4): E≦0.05ln(x)+0.055 (4) (where E represents the kinetic energy at the time of puncturing, and x represents the mass of the injection device).

[0034] Furthermore, from the viewpoint of further reducing the pain when the injection needle 41 hits the skin, it is preferable that the kinetic energy at the time of puncturing and the mass of the injection device 40 satisfy the following formula (5): E≦0.05ln(x)+0.015 (5) (where E represents the kinetic energy at the time of puncturing, and x represents the mass of the injection device).

[0035] From the viewpoint of making it easier for the micro-protrusions 44 to reach the epidermis and enabling more efficient intradermal administration, and from the viewpoint of further reducing the pain when the injection needle 41 hits the skin, it is preferable that the kinetic energy at the time of puncture and the mass of the injection device 40 satisfy the formula (1) and the formula (3), more preferably satisfying the formula (1) and the formula (4), even more preferably satisfying the formula (1) and the formula (5), even more preferably satisfying the formula (2) and the formula (3), even more preferably satisfying the formula (2) and the formula (4), and even more preferably satisfying the formula (2) and the formula (5).

[0036] The mass of the injection device 40 is preferably 1.9 g or more, more preferably 2.5 g or more, and even more preferably 3.0 g or more, from the viewpoint of providing sufficient kinetic energy during puncturing to enable the microprotrusions 44 to puncture to an appropriate depth and ensuring reliable puncturing. Furthermore, the mass of the injection device 40 is preferably 40.0 g or less, more preferably 30.0 g or less, and even more preferably 21.0 g or less, from the viewpoint of ensuring that the biasing member of the holder 1 operates appropriately and provides a constant speed. Furthermore, from the viewpoint of achieving both of these, the mass of the injection device 40 is preferably 1.9 g or more and 40.0 g or less, more preferably 2.5 g or more and 30.0 g or less, and even more preferably 3.0 g or more and 21.0 g or less.

[0037] Here, the mass of the injection device 40 includes not only the mass of the syringe 51 and the injection needle 41, but also the mass of the medicinal liquid filled in the syringe 51. If the syringe 51 is not filled with medicinal liquid, the mass of the medicinal liquid filled in the syringe 51 is 0. The mass of the injection device 40 can be measured, for example, by the following method. <Method for Measuring the Mass of an Injection Device> First, the syringe 51 is filled with the medicinal liquid. Then, the injection needle 41 is attached to the syringe 51 filled with the medicinal liquid to form the injection device 40. Thereafter, the plunger 58 is pressed down to remove air from the syringe 51. Specifically, the plunger is pressed down until the amount of medicinal liquid filled in the syringe 51 reaches a predetermined amount (e.g., 100 μL). Then, excess medicinal liquid adhering to the tip of the fine protrusions 44 of the injection needle 41 is removed by absorbing it with a Kimwipe. Then, the mass of the syringe 40 after the air removal is measured using an electronic balance (AG135, Mettler Trade Co., Ltd.). The mass is measured five times, and the average value is taken as the mass of the syringe.

[0038] The kinetic energy during puncturing is preferably 0.014 J or more, and more preferably 0.018 J or more, from the viewpoint of making it easier for the fine projections 44 to reach the epidermis.

[0039] If the kinetic energy during puncturing is excessively high, there is a risk that the fine protrusions 44 will puncture too deeply. If the fine protrusions 44 puncture too deeply, the medicinal solution ejected from the openings 44a will penetrate subcutaneously without penetrating the epidermis, making it impossible to administer the medicinal solution intradermally. Furthermore, if the kinetic energy during puncturing is excessively high, the injection needle 41 biased by the holder 1 may collide strongly with the skin, causing pain during puncturing. From the viewpoint of preventing the fine protrusions 44 from puncturing too deeply and preventing pain during puncturing, the kinetic energy during puncturing is preferably 0.23 J or less, more preferably 0.21 J or less, and even more preferably 0.17 J or less.

[0040] The kinetic energy at the time of puncturing is preferably 0.014 J or more and 0.23 J or less, more preferably 0.018 J or more and 0.21 J or less, and even more preferably 0.018 J or more and 0.17 J or less, from the viewpoint of making it easier for the micro-protrusions 44 to reach into the epidermis, preventing the micro-protrusions 44 from puncturing too deeply, and preventing pain during puncturing.

[0041] The kinetic energy at the time of puncturing can be calculated by multiplying the square of the speed at which the microprotrusions 44 puncture (hereinafter also referred to as the "puncturing speed") by the mass of the injection device 40 and dividing the result by 2. It is also preferable that the puncturing speed and the mass of the injection device 40 satisfy a certain relationship from the viewpoint of puncturing the microprotrusions 44 to an appropriate depth and efficiently administering intradermally.

[0042] Specifically, it is preferable that the puncture speed and the mass of the injection device 40 satisfy the following formula (6): S≧−750ln(x)+3850 (6) (where S represents the puncture speed, and x represents the mass of the injection device 40).

[0043] When the puncture speed and the mass of the injection device 40 satisfy formula (6), the microprotrusions 44 easily penetrate the stratum corneum of the skin and reach the epidermis when the microprotrusions 44 of the injection device 40 are punctured into the skin by the holder 1. Therefore, the microprotrusions 44 are more likely to puncture to an appropriate depth, and intradermal administration can be performed efficiently.

[0044] Furthermore, from the viewpoint of making it easier for the microprojections 44 to reach the epidermis and enabling more efficient intradermal administration, it is preferable that the puncture speed and the mass of the injection device 40 satisfy the following formula (7): S≧−750ln(x)+4070 (7) (where S represents the puncture speed, and x represents the mass of the injection device).

[0045] The puncture speed is preferably 1700 mm / s or more, and more preferably 1800 mm / s or more, from the viewpoint of making it easier for the fine projections 44 to reach the epidermis.

[0046] If the puncture speed is excessively high, the fine protrusions 44 may puncture too deeply, which may prevent the medicinal solution from being administered intradermally or cause pain during puncture. From the viewpoint of preventing the fine protrusions 44 from puncturing too deeply and causing pain during puncture, the puncture speed is preferably 9300 mm / s or less, more preferably 8600 mm / s or less, and even more preferably 7000 mm / s or less.

[0047] The puncture speed is preferably 1700 mm / s or more and 9300 mm / s or less, more preferably 1800 mm / s or more and 8600 mm / s or less, and even more preferably 1800 mm / s or more and 7000 mm / s or less, from the viewpoint of achieving both making it easier for the micro-protrusions 44 to reach into the epidermis, preventing the micro-protrusions 44 from puncturing too deeply, and preventing pain during puncture.

[0048] The puncture speed can be measured, for example, by the following method. <Method for measuring puncture speed> First, the syringe 51 is filled with the drug solution. Then, the injection needle 41 is attached to the syringe 51 filled with the drug solution, thereby forming the injection device 40. After that, the plunger 58 is pressed down to remove air from the syringe 51. Specifically, the plunger is pressed down until the amount of drug solution filled in the syringe 51 reaches a predetermined amount (e.g., 100 μL). Then, excess drug solution adhering to the tip of the fine protrusions 44 of the injection needle 41 is removed by absorbing it with a Kimwipe.

[0049] Next, the syringe 40 after air removal is attached to the holder 1. Then, a sponge 7 (chloroprene rubber sponge, thickness: 5 mm, hardness: Asker C25) is attached to the tip of the holder 1 with the syringe 40 attached. The sponge 7 is attached so that the fine protrusions of the syringe needle will puncture the sponge 7 when the holder 1 is released from the standby state.

[0050] Then, after the holder 1 with the sponge 7 attached is placed in a standby state, the syringe holder 20 is released and the puncturing operation is performed. The amount of movement and the time of movement of the end 59b of the plunger 58 opposite the injection needle 41 at this time are measured using a laser displacement meter (manufactured by Keyence Corporation, model number LK-H080) and a controller (manufactured by Keyence Corporation, model number LK-HD500). Specifically, the amount of movement and the time of movement of the position of the end of the plunger are measured from the standby state until the syringe holder 20 is released and the microprotrusions 44 puncture the sponge 7. The sampling period of the laser displacement meter is, for example, 20 μs.

[0051] The speed is then calculated from the measured movement amount and movement time. Specifically, the position of the end 59b of the plunger 58 when the fine protrusions 44 puncture the sponge 7 is set to a reference position K (see FIG. 6), and the speed is calculated when the distance D (see FIG. 6) between the end 59b of the plunger 58 and the reference position changes from 2 mm to 1 mm. The measurement of the movement amount and movement time and the calculation of the speed are performed three times, and the average of the calculated speeds is used as the puncture speed.

[0052] The puncture speed can be adjusted by adjusting the biasing force of the biasing member of the holder 1. When the biasing member is a spring 30, as in this embodiment, the biasing force is, for example, the elastic energy of the spring 30 in the standby state. The elastic energy of the spring 30 can be calculated by multiplying the square of the compression amount of the spring 30 by the spring constant and dividing the result by 2. Here, the compression amount of the spring 30 is the absolute value of the difference between the free length L0 of the spring 30 and the length L1 of the spring 30 in the standby state (see FIG. 7 ).

[0053] The elastic energy of the spring 30 in the standby state is preferably 0.03 J or more, more preferably 0.05 J or more, and even more preferably 0.07 J or more, from the viewpoint of making it easier for the fine protrusions 44 to reach the epidermis. Furthermore, with regard to the elastic energy of the spring 30 in the standby state, from the viewpoint of preventing the fine protrusions 44 from puncturing excessively deeply and from the viewpoint of preventing pain during puncturing, the kinetic energy at puncturing is preferably 0.30 J or less, more preferably 0.25 J or less, and even more preferably 0.22 J or less. Furthermore, with regard to the elastic energy of the spring 30 in the standby state, from the viewpoint of achieving both of these, the kinetic energy at puncturing is preferably 0.04 J or more and 0.30 J or less, more preferably 0.05 J or more and 0.25 J or less, and even more preferably 0.07 J or more and 0.22 J or less.

[0054] As described above, the injection device 40 is used for intradermal administration of a medicinal solution. Here, the injection device 40 being used for intradermal administration of a medicinal solution means that the openings 44a of the microprojections 44 of the injection device 40 are positioned in a location suitable for intradermal administration. To position the openings 44a in a location suitable for intradermal administration, the center of the openings 44a is preferably located in the upper half of the microprojections 44 when the height of the microprojections 44 is divided into two equal halves, and the center of the openings 44a is preferably located 200 μm or more and 1000 μm or less below the tip of the microprojections 44. That is, the distance H4 from the tip of the microprojections 44 to the center position of the openings 44a (see FIG. 4(a)) (hereinafter also referred to as the "center position of the openings") is preferably 1000 μm or less, and more preferably 500 μm or less. From the same viewpoint, the distance H4 is preferably 100 μm or more, and more preferably 200 μm or more, and also preferably 100 μm or more and 1000 μm or less, and more preferably 200 μm or more and 500 μm or less. Here, the center position of the aperture 44a refers to the position that divides the distance between the distal end 44x and the proximal end 44y of the aperture 44a into two equal parts in the height direction. Furthermore, the distal end 44x of the aperture 44a refers to the end of the opening of the aperture 44a that opens onto the outer surface of the micro-protrusion 44 in the height direction that is farther from the tip of the micro-protrusion 44, and the proximal end 44y of the aperture 44a refers to the end of the opening of the aperture 44a that opens onto the outer surface of the micro-protrusion 44 in the protruding direction that is closer to the tip of the micro-protrusion 44.

[0055] From the viewpoint of facilitating the discharge of the liquid medicine contained in the liquid medicine container 52 from the opening 44a, the opening 44a of the fine projection 44 has an area X of the opening calculated from the width L4 and the length L3 (hereinafter also referred to as the hole area X) of preferably 500 μm ２ More preferably, 1250 μm or more ２ From the viewpoint of preventing leakage of liquid onto the skin surface after puncturing, it is preferable that the thickness is 6100 μm or more. ２ Less than or equal to 4800 μm, more preferably ２ From the viewpoint of achieving both, it is preferably 500 μm or more and 6100 μm or less. ２Less than or equal to 1250 μm, more preferably ２ 4800 μm or more ２ Here, the horizontal width L4 and vertical width L3 for calculating the area X of the aperture are calculated based on the minimum length of the cross section of the aperture 44a in the axial direction.

[0056] From the viewpoint of making it easier to eject the medicinal liquid contained in the medicinal liquid storage section 52 from the opening 44a, the width L4 of the opening 44a of the fine protrusion 44 is preferably 25 μm or more, more preferably 40 μm or more, and from the viewpoint of preventing leakage of the liquid onto the skin surface after puncture, it is preferably 100 μm or less, more preferably 60 μm or less, and from the viewpoint of achieving both, it is preferably 25 μm or more and 100 μm or less, more preferably 40 μm or more and 60 μm or less.

[0057] From the viewpoint of making it easier to eject the medicinal liquid contained in the medicinal liquid storage section 52 from the opening 44a, the vertical width L3 of the opening 44a of the fine protrusion 44 is preferably 25 μm or more, more preferably 40 μm or more, and even more preferably 80 μm or more. From the viewpoint of preventing leakage of the liquid onto the skin surface after puncture, it is preferably 200 μm or less, more preferably 130 μm or less, and even more preferably 100 μm or less. From the viewpoint of achieving both of these, it is preferably 25 μm or more and 200 μm or less, more preferably 40 μm or more and 200 μm or less, even more preferably 25 μm or more and 130 μm or less, even more preferably 40 μm or more and 130 μm or less, particularly preferably 80 μm or more and 130 μm or less, even more particularly preferably 40 μm or more and 100 μm or less, and even more particularly preferably 80 μm or more and 100 μm or less.

[0058] The opening 44a preferably has a width L4 of 25 μm or more and 100 μm or less and a vertical width L3 of 25 μm or more and 200 μm or less, more preferably a width L4 of 40 μm or more and 60 μm or less and a vertical width L3 of 40 μm or more and 200 μm or less, and even more preferably a width L4 of 40 μm or more and 60 μm or less and a vertical width L3 of 80 μm or more and 100 μm or less. The width L4 and vertical width L3 of the opening 44a are measured as follows. The opening area X is calculated as follows.

[0059] <Method for measuring the width and length of the opening 44a> All injection devices 40 to be manufactured are inspected with a camera during production, and the dimensions of the opening 44a (dimensions along the opening surface) on the outer surface of the fine protrusion 44 are measured from the inspection image.

[0060] <Method of calculating hole area X> The hole 44a is considered to be an ellipse (including a perfect circle), and the hole area X (μm 2 )=π×(L4 / 2)×(L3 / 2) (13) It is preferable that the shape of the opening 44a in front view is circular or elliptical.

[0061] In this embodiment, when the microprotrusions 44 of the microprotrusion device 42 pierce the skin, the stimulation protrusions 45 also pierce the skin. By piercing the skin with the stimulation protrusions 45, it is possible to prevent the skin from stretching, thereby improving puncture performance. Furthermore, by piercing the skin with the stimulation protrusions 45, the stimulation protrusions 45 stimulate the skin and promote blood flow, thereby promoting the immune induction effect. Therefore, with the microprotrusion device 42 of this embodiment, the microprotrusions 44 can easily inject liquid into the skin, and the stimulation protrusions 45 can promote blood flow and promote the immune induction effect. The presence or absence of a blood flow promotion effect can be determined by various known methods, such as by determining whether a flare reaction occurs in the skin or by visualizing the blood flow distribution with a laser blood flowmeter.

[0062] Furthermore, in this embodiment, when the fine protrusions 44 and the stimulation protrusions 45 are inserted into the skin from the tip side, the puncture depth control section 46a of the control protrusions 46 comes into contact with the surface of the skin. This stops the insertion of the fine protrusions 44 and the stimulation protrusions 45, preventing the fine protrusions 44 and the stimulation protrusions 45 from penetrating deeper into the skin. In other words, the puncture depth control section 46a functions as a stopper that limits the insertion depth of the fine protrusions 44 and the stimulation protrusions 45. In other words, the fine protrusion device 42 of this embodiment is capable of controlling the penetration depth of the fine protrusions 44 and the stimulation protrusions 45 into the skin.

[0063] From the viewpoint of significantly reducing the pain associated with transdermal absorption or reliably injecting the drug solution into the skin from the microprotrusions 44, the height difference between the tip position of the microprotrusions 44 and the position of the puncture depth control unit 46a is preferably 1 μm or more, more preferably 5 μm or more, even more preferably 100 μm or more, and even more preferably 300 μm or more. This height difference is the difference H1-H3 between the protrusion height H1 of the microprotrusions 44 (see FIG. 4(a)) and the distance H3 from the base surface 43 to the puncture depth control unit 46a (see FIG. 4(c)). Furthermore, from the viewpoint of not damaging the dermis more than necessary, this difference H1-H3 is preferably 5000 μm or less, and more preferably 4000 μm or less. Furthermore, the difference H1-H3 is preferably 1 μm or more and 5000 μm or less, more preferably 5 μm or more and 4000 μm or less, even more preferably 100 μm or more and 4000 μm or less, and even more preferably 300 μm or more and 4000 μm or less. From the viewpoint of significantly reducing the pain associated with the blood flow promoting effect of the stimulation protrusions 45, suppressing poor puncturing of the second protrusions due to the elasticity of the skin, and enabling the second protrusions to fully penetrate the skin, the protrusion height H2 of the stimulation protrusions 45 (see FIG. 4(b)) is preferably equal to or greater than the distance H3 from the base surface 43 to the puncture depth control unit 46a, i.e., H2≧H3, and more preferably H2>H3. From the same viewpoint, the difference H2-H3 is preferably equal to or greater than 0, more preferably equal to or greater than 100 μm, and even more preferably equal to or greater than 400 μm. Furthermore, from the viewpoint of not unnecessarily damaging the skin, the difference H2-H3 is preferably equal to or less than 5000 μm, and even more preferably equal to or less than 4000 μm. The difference H2-H3 is preferably 0 to 5000 μm, more preferably 100 to 5000 μm, and even more preferably 400 to 4000 μm.

[0064] From the viewpoint of ensuring a more reliable blood flow promoting effect, ensuring reliable puncture by the microprotrusions 44, and suppressing leakage of medicinal solution due to insufficient penetration, it is preferable that the microprotrusions 44 be taller than the stimulation protrusions 45. More specifically, the difference H1-H2 between the protrusion height H1 of the microprotrusions 44 and the protrusion height H2 of the stimulation protrusions 45 is preferably 1 μm or more, and more preferably 5 μm or more. Furthermore, from the viewpoint of easily achieving both ease of injection of the liquid and a blood flow promoting effect, the difference H1-H2 is preferably 5,000 μm or less, and more preferably 4,000 μm or less. Furthermore, the difference H1-H2 is preferably 1 μm or more and 5,000 μm or less, and more preferably 5 μm or more and 4,000 μm or less.

[0065] The protrusion height H1 of the fine protrusions 44 is preferably 10 μm or more, and more preferably 20 μm or more, from the viewpoints of preventing puncture from being hindered due to deformation of the skin when the fine protrusions 44 are pressed against the skin, improving puncture performance, and reliably injecting the medicinal solution into the skin S. Furthermore, from the viewpoint of minimal invasiveness, the protrusion height H1 of the fine protrusions 44 is preferably 5000 μm or less, and more preferably 4000 μm or less. Furthermore, from the viewpoint of achieving both improved puncture performance and minimal invasiveness, the protrusion height H1 of the fine protrusions 44 is preferably 10 μm or more and 5000 μm or less, and more preferably 20 μm or more and 4000 μm or less.

[0066] The protrusion height H2 of the stimulation protrusions 45 is preferably 10 μm or more, more preferably 20 μm or more, from the viewpoint of stimulating the skin by pressing it against the skin and promoting blood flow. Furthermore, the protrusion height H2 of the stimulation protrusions 45 is preferably 5000 μm or less, more preferably 4000 μm or less, from the viewpoint of minimal invasiveness. Furthermore, the protrusion height H2 of the stimulation protrusions 45 is preferably 10 μm or more and 5000 μm or less, more preferably 20 μm or more and 4000 μm or less, from the viewpoint of improving blood flow promotion and minimal invasiveness. The distance H3 from the base surface 43 to the puncture depth control unit 46a is preferably 5 μm or more, more preferably 10 μm or more. Furthermore, the distance H3 is preferably 4000 μm or less, more preferably 3000 μm or less, from the viewpoint of improving the puncture ability of the microprotrusions 44. Furthermore, the distance H3 is preferably 5 μm or more and 4000 μm or less, more preferably 10 μm or more and 3000 μm or less.

[0067] Next, the constituent material of the micro-projection device 42 will be described. The micro-projection device 42 preferably contains a thermoplastic resin from the viewpoints of material handling, strength and processability of the injection needle, and ensuring hardness of the micro-projections 44 to facilitate injection of liquid. The injection needle is more preferably formed from a base sheet containing a thermoplastic resin. Examples of the thermoplastic resin include one or more selected from polyolefin, polyester, polyamide, polyamideimide, polyetheretherketone, polyetherimide, polyvinyl chloride, acrylic resin, polystyrene resin, etc. Examples of the polyolefin include one or more selected from polypropylene, polyethylene, etc. Examples of the polyester include one or more selected from polyethylene terephthalate, polyfatty acid ester, polylactic acid, polycaprolactone, polybutylene succinate, etc. Examples of the polyamide include one or more selected from nylon, etc. From the viewpoint of biodegradability, it is preferable to contain a polyfatty acid ester. Specifically, examples of the polyfatty acid ester include one or more selected from polylactic acid and polyglycolic acid.

[0068] The mass ratio of the thermoplastic resin contained in the micro-projections 42 to the total mass of the micro-projections 42 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. Furthermore, 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, functional agents. Examples of the various functional agents that can be used include antibacterial agents, disinfectants, moisturizers, flow-improving agents, antistatic agents, and colorants.

[0069] The medicinal solution injected into the skin using the micro-projection device 42 can be selected appropriately depending on the intended use of the injection needle 41. According to this embodiment, the medicinal solution can be easily administered intradermally. Therefore, the medicinal solution injected into the skin using the micro-projection device 42 is preferably an intradermal drug, and more preferably an intradermal vaccine drug. In particular, when an intradermal vaccine drug is used, not only can the drug be reliably administered intradermally, but antigen recognition by the immune system can be more efficiently strengthened compared to subcutaneous administration, which is expected to enhance the effectiveness of the vaccine. The skin has, in order from the body surface side, the epidermis, dermis, and subcutaneous tissue, and the dermis is relatively rich in immune cells. Therefore, when an intradermal vaccine drug is administered intradermally using the micro-projection device 42, it is preferably administered into the dermis from the perspective of enhancing the effectiveness of the vaccine. Note that an intradermal drug refers to a drug whose recommended administration method is intradermal administration.

[0070] The medicinal solution may include one or more selected from the group consisting of vaccines for preventing infectious diseases such as hepatitis A, hepatitis B, hepatitis C, influenza, COVID-19, respiratory syncytial virus (RSV), tuberculosis, rabies, polio, chickenpox, rubella, measles, tetanus, shingles, and malaria; vaccines for treating chronic hepatitis B, tuberculosis, rabies, malignant neoplasms, and shingles; analgesics for cancer patients; insulin; biological products; gene therapy drugs; injectables, and skin-applied preparations. Because the microprotrusions 44 of the microprotrusion device 42 puncture the skin, the microprotrusion device 42 can be used not only for pharmacologically active substances used for conventional transdermal administration, but also for pharmacologically active substances that require subcutaneous injection. The skin S into which the medicinal solution is injected by the microprotrusion device 42 may be human skin or the skin of a non-human animal.

[0071] It is preferable that the holder stores energy for moving the injection device 40 in the biasing member by, for example, contracting a spring, and holds the injection device 40 at a retracted position retracted away from the skin from the advanced position by a stopper mechanism or a holding mechanism, and then releases the held state by any operation such as pressing it against the skin or releasing the engagement state of the engaging protrusions, thereby obtaining the required kinetic energy when the microprotrusions puncture the skin. It is preferable to design the amount of energy applied to the injection device 40 by the biasing member so that the required kinetic energy can be obtained, taking into consideration the mass of the injection device, including the mass of the medicinal solution, and the distance from the retracted position to the advanced position where the microprotrusions 44 puncture.

[0072] The holder for obtaining the required kinetic energy is not limited to the holder 1 described above, and a wide variety of holders equipped with a biasing member can be used. For example, holder 1a shown in FIGS. 16 to 22 can also be used. Holder 1a preferably includes a slider 120 and a main body 130. The slider 120 is preferably capable of detachably fixing the injection device 40. The slider 120 is preferably disposed inside the main body 130. The main body 130 preferably supports the slider 120 so that it can move back and forth in one direction X. The one direction X in which the slider 120 moves back and forth is also simply referred to as the slider movement direction X. Furthermore, the same direction as the slider movement direction X in the main body 130 is also referred to as the axial direction X of the main body.

[0073] The slider 120 typically has an elongated shape extending in the advancing / retreating direction X, with the length in the axial direction X being longer than the length in the width direction Y perpendicular to the axial direction. The slider 120 preferably has an arc-shaped cross section in which a circumferential portion of the peripheral wall of the cylinder is continuously missing along the axial direction of the cylinder. The missing portion of the cylinder preferably forms a side opening 123 extending along the advancing / retreating direction X of the slider 120. The slider 120 preferably has a drug solution feeder housing 121. The drug solution feeder housing 121 typically houses a syringe 51, which is the drug solution feeder 50. A fixing protrusion 122 that restrains a portion of the base component 47 of the injection device 40 is preferably provided on the skin side of the drug solution feeder housing 121. It is preferable that the length of the drug solution feeder housing 121 along the circumferential direction of the injection device 40 be equal to or shorter than half the circumference of the injection device 40, from the viewpoint of facilitating attachment of the injection device 40. The fixing protrusion 122 preferably has an arc shape in a cross section perpendicular to the one direction. The radius of curvature of the fixing protrusion 122 is preferably smaller than that of the drug solution feeder housing portion 121. The fixing protrusion 122 preferably includes a pair of gripping protrusions 122a at both ends in the circumferential direction. The length of the fixing protrusion 122 along the circumferential direction of the injection device 40, including the pair of gripping protrusions 122a, is preferably longer than half the length of the restrained portion of the injection device 40.

[0074] The injection device 40 preferably has a constricted portion 48 between the large-diameter portion 47c of the base part 47 and the tip end 51b of the syringe 51. This constricted portion 48 preferably serves as an engagement groove that engages with the fixed protrusion 122 and / or the pair of gripping protrusions 122a. The outer diameter of this constricted portion 48 is smaller than the outer diameter of the large-diameter portion 47c and the tip end 51b. This constricted portion 48 preferably serves as a restrained portion that is restrained by the fixed protrusion 122. In this case, simply by pushing the constricted portion 48 of the injection needle 41 into the fixed protrusion 122 from the side where the side opening 123 is open, the constricted portion is restrained by the fixed protrusion 122. This makes it difficult for rattle to occur between the injection needle 41 and the fixed protrusion 122. The engagement groove that engages with the fixed protrusion 122 and / or the pair of gripping protrusions 122a is also referred to as a restraining engagement groove hereinafter. The restraining engagement groove is preferably disposed between the microprotrusion 44 and the drug solution supplier 50, such as a syringe 51. The restraining engagement groove is, for example, a constricted portion 48 formed around the female connector by connecting the male and female connectors of a small-diameter connector for liquids and gases (ISO 80369-7:2021). However, it may be formed by other methods. For example, a circular groove may be formed around the large-diameter portion 47c, and the groove may be used as the engagement groove. When connecting the base component 47 and the drug solution supplier 50, such as a syringe 51, with a luer connector, the male and female connectors are preferably luer lock connectors. Luer lock connectors are preferred because they are difficult to disconnect and the state in which the syringe 40 is held by the slider 120 is difficult to release. The restraining engagement groove is not limited to a length that is the entire circumference of the syringe 40, but may be a length that is not the entire circumference of the syringe 40, for example, a length that is half the circumference.

[0075] The fixing protrusion 122 preferably engages with an engagement groove located between the fine protrusion 44 and the drug solution supplier 50, for example, the constricted portion 48 described above. With such a fixing protrusion 122, the portion located near the skin is restrained when the syringe 40 is punctured into the skin. This makes it less likely that the syringe 40 will be affected even if it is tilted slightly within the slider 120. Therefore, individual differences in puncture conditions, such as the puncture angle, are less likely to occur. Furthermore, the syringe 40 can also be used with a syringe 51 that uses another syringe 51 with a smaller outer diameter.

[0076] The slider 120 preferably includes a rear fixing portion 124 that fits around the injection device 40 on the non-skin side of the drug solution feeder housing 121. The rear fixing portion 124 preferably has an arc-shaped cross section with a smaller radius of curvature than the drug solution feeder housing 121, and includes a pair of gripping protrusions 124a at both circumferential ends. The length of the rear fixing portion 124 along the circumferential direction of the injection device 40, including the pair of gripping protrusions 124a, is preferably longer than half the circumference of the syringe barrel 151a, which is the restrained portion of the injection device 40. Therefore, simply by pushing a portion of the injection device 40 into the rear fixing portion 124 from the side where the side opening 123 is open, the portion can be fixed without any rattle between the rear fixing portion 124 and the syringe barrel 151a.

[0077] The main body 130 preferably has an internal space and an internal space surrounding portion 131. The slider 120 is accommodated in the internal space. In a cross section perpendicular to the slider advance / retract direction X, the internal space surrounding portion 131 surrounds the periphery of the internal space except for a portion that forms a side opening 133. The internal space surrounding portion 131 has an inner wall 134 facing the internal space and an outer wall 135 that forms the outer surface of the main body 130. Furthermore, the side opening 123 of the slider 120 and the side opening 133 of the main body 130 typically open in the same direction in a cross section perpendicular to the slider advance / retract direction X. Furthermore, both sides of the side opening 133 in the main body 130 typically form connecting walls that connect the inner wall 134 and the outer wall 135, and the gap between these connecting walls forms the side opening 133. It is preferable that the side openings 123, 133 have a width sufficient to allow passage of the injection tool 40. In a cross section of the main body 130 perpendicular to the advancing / retreating direction X of the slider 120, the side having the side opening 133 is also referred to as the front side, and the side not having the side opening 133 is also referred to as the back side.

[0078] The holder 1a typically allows the injection device 40 to be attached to the slider 120 from the side of the main body 130 via the side openings 123, 133, facilitating the attachment operation of the injection device 40. This reduces the possibility of contact between the fine protrusions 44 and the holder 1a when attaching the injection device 40 to the slider 120 or when removing it after an injection. This prevents damage to the fine protrusions 44, which could render the injection device 40 or injection needle 41 unusable or reduce the effectiveness of the injection. Furthermore, when attaching the injection device 40 to the slider 120, it is not necessary to remove the injection needle 41 from the syringe 51. Therefore, the injection needle 41 can be attached to the syringe 51, and the amount of drug contained in the drug solution storage portion 52 can be optimized before being attached to the slider. When removing the injection device 40 from the slider 120 after an injection, it is also not necessary to remove the injection needle 41 from the syringe 51. This also reduces the possibility that the medicinal liquid coming out of the syringe 40 will adhere to the holder 1a. Therefore, after the syringe 40 is attached to the holder 1a and an injection operation is performed, the holder 1a can be reused by simply replacing the syringe 40.

[0079] The holder 1a preferably has a guide mechanism that restricts the advancement / retraction direction X of the slider 120 to one direction X. The guide mechanism preferably includes a groove formed in the inner wall 134 of the internal space surrounding portion 131 and a guide protrusion 121a provided on the slider 120. The guide protrusion 121a preferably slidably engages with the groove in the one direction X to constitute the guide mechanism. The groove typically has an opening shape extending along the advancement / retraction direction X of the slider 120. The guide protrusion 121a inserted into the groove moves along the guide hole, thereby restricting the advancement / retraction direction X of the slider 120 to the specific one direction X. The guide protrusions 121a are provided, for example, at both ends of a peripheral wall portion of the drug solution supply device accommodating portion 121 of the slider 120 that has an arc-shaped cross section, protruding outward in the width direction Y. Two or more guide protrusions 121a may be provided at intervals in the longitudinal direction of the slider 120. From the viewpoint of more accurately regulating the forward / backward direction of the slider 120, it is preferable that the gap between the groove and the guide protrusion 121a when they are engaged be greater than 0 mm and less than 1 mm. From the same viewpoint, it is preferable that the groove and guide protrusion 121a constituting the guide mechanism are each provided at two or more locations in the circumferential direction of the holder 1a. The guide may be provided with guide protrusions 121a on the inner wall 134 of the internal space surrounding portion 131 and a groove on the slider 120 into which the guide protrusions 121a are inserted. The presence of a guide suppresses slider wobble during puncture and / or drug injection. Furthermore, it becomes easier to maintain an appropriate angle of inclination of the injection needle relative to the skin during puncture and / or drug injection.

[0080] The main body 130 of the holder 1a preferably includes two biasing members that bias the slider 120 in the forward direction A. In this embodiment, the biasing members are coil springs. The coil spring 161 is typically disposed in a slightly compressed state between the rear wall 136 of the main body 130 and a spring receiving portion 125 formed on the slider 120 so as to protrude outward from the side wall portion. The forward position of the slider 120 is typically a position where the slider 120 has advanced due to the repulsive force of the coil spring 161 until it abuts against a front restriction portion 162 provided on the main body 130. An example of this is shown in FIG. 19 .

[0081] The main body 130 preferably includes a holding mechanism and a holding release mechanism. The holding mechanism holds the slider 120 in a retracted position, which is retracted away from the skin from the advanced position. The holding release mechanism releases the holding mechanism and advances the slider to the advanced position. The advanced position is the position where the injection needle penetrates the skin. The non-skin direction is the direction away from the skin, typically the same direction as the retracted direction B. The holding mechanism includes, for example, a holding protrusion 164 protruding from the slider 120 and a holding support 165 provided on the main body 130. The holding protrusion 164 and the holding support 165 are configured to engage with each other when the slider 120 is retracted beyond a predetermined position against the biasing force of the coil spring 161. Specifically, the holding protrusion 164 is preferably provided on the back surface of the slider 120. Preferably, the inner wall 134 of the main body 130 is provided with a guide hole 134a extending in the axial direction X of the main body 130 and allowing the inserted holding protrusion 164 to move in the forward / backward direction X. An example of this is shown in FIGS. 20 and 21 . The holding release mechanism preferably includes a rod-shaped release member 168 that physically interlocks with the skin holder 71 (described later). When the skin holder 171 is pressed against the skin, the release member 168 mechanically interlocks with the skin holder 171 and presses a portion of the holding support 165. This preferably disengages the holding protrusion 164 from the holding support 165. Specifically, the holding support 165 preferably has a portion fixed to the outer wall 135 and an inclined portion that is inclined away from the outer wall 135 and approaches the slider 120. The inclined portion is pressed by the release member 168 and displaced in the direction D in the figure, thereby disengaging the engagement. When the engagement between the holding protrusion 164 and the holding support 165 is released, the slider 120 moves forward to the forward position due to the repulsive force of the highly compressed coil spring 161 generated by moving the slider 120 backward. In the drawing, symbol A indicates the forward direction, and symbol B indicates the backward direction.

[0082] The configurations of the holding mechanism and the holding release mechanism that hold the slider 120 in a retracted position that is retracted from the advanced position can be changed as desired. For example, a switch that activates the holding release mechanism may be provided on the side of the holder, and after pressing a part of the holder, such as a movable or non-movable skin presser, against the skin, the switch or the like may be operated to activate the holding release mechanism without interlocking with the skin presser.

[0083] The holder 1a has an automatic advancement mechanism that uses a biasing force to advance the slider 120 to an advance position where the microprotrusions 44 pierce the skin. The automatic advancement mechanism typically includes two coil springs 161 that bias the slider 120 in the advancement direction A. The two coil springs 161 are arranged so that the injection device 40 attached to the slider 120 is located between them. This makes it easier to form side openings 123, 133 in the main body 130 and the slider 120 than when the slider 120 is arranged at the center of the coil springs. Furthermore, the movement of the slider 120 in the one direction X is more stable than when a single coil spring 161 is arranged around the slider 120. Furthermore, this configuration makes it easier to install a guide that restricts the advancement / retraction direction X of the slider 120 to the one direction X.

[0084] According to the holder 1a, typically, after the slider 120 is released from the retracted holding state, the slider 120 automatically moves forward due to the repulsive force of the compressed coil spring 161. This causes the fine protrusions 44 to puncture the skin, so that individual differences in puncture conditions such as the puncture angle and puncture speed relative to the skin are unlikely to occur.

[0085] The holder 1a of this embodiment typically has a holding mechanism that holds the slider 120 in a retracted position, retracted away from the skin side from the advanced position, by engaging the holding protrusions 164 with the holding support 165. It also typically has a holding release mechanism that disengages the holding protrusions 164 with the holding support 165 and advances the slider 120 to the advanced position using the repulsive force of the coil spring 161, rather than manually. This allows the holder 1a to be released from the held state after being brought close to the appropriate state for the skin to which the medicinal solution is to be administered. This further ensures that the microprotrusions 44 can be punctured using the holder 1. The holding release mechanism is preferably a mechanism that releases the engagement between the holding protrusions 164 and the holding support 165 using a release member 168 that operates in conjunction with the skin presser 171. This mechanism is activated by pressing a portion of the holder 1a against the skin. Therefore, the microprotrusions 44 can be punctured while the skin area in contact with the microprotrusions 44 is appropriately taut. It is also possible to reduce individual differences in the pressure applied to the skin.

[0086] The holder 1a preferably has a substantially annular skin presser 171 at its end in the skin direction, i.e., at the end closer to the skin in the advancing / retracting direction X of the slider 120. The substantially annular skin presser is preferably arranged on the circumferential outer side of the slider 120. "Arranged on the circumferential outer side of the slider" means that the holder 1a is located around the slider 120 when viewed from the end side in the skin direction. More preferably, the holder 1a of the present invention preferably has a substantially annular skin presser 171 that abuts against the periphery of the skin area with which the microprotrusions 44 come into contact. More specifically, the main body 130 preferably has, at its skin-side tip, a skin presser 171 that displaces along the advancing / retracting direction X. The displacing skin presser 171 is constantly biased in the advancing direction A by a biasing member such as a coil spring 161, and preferably retracts along the advancing / retracting direction X by pressing the skin presser 171 against the skin. The term "substantially annular" may refer to a continuous annular shape, i.e., a 360° continuous configuration, or may include a shape that is partially interrupted but can be considered annular as a whole. Annular skin presser 171 preferably has a surface that is parallel to a plane perpendicular to the advancing / retreating direction X of slider 120.

[0087] The holder 1a typically has a substantially annular skin presser 71 that abuts against the periphery of the skin area that comes into contact with the fine protrusions 44. This makes it possible to prevent height differences from occurring around the skin area that comes into contact with the fine protrusions 44. This prevents the skin from tilting when the fine protrusions 44 are applied perpendicularly to the skin, making it easier to apply the fine protrusions 44 perpendicularly.

[0088] To facilitate the operation of retracting the slider 120 with the syringe 40 attached thereto, it is preferable to provide a knob 126 having an arc-shaped cross section at the end of the slider 120 on the retraction direction B side. The provision of the knob 126 makes it easy to pinch or grip the slider 120 with fingers and move it in the retraction direction B. The shape and size of the knob 126 can be changed as desired. Note that a shape and size that do not interfere with the attachment of the syringe 40 to the slider 120 are preferred. It is also possible not to provide the knob 126.

[0089] The present invention includes an injection kit including a holder, an injection device, and a medicinal solution to be filled in a medicinal solution supply device. The holder included in the injection kit of the present invention can be the holder 1 or 1a described above. The holder and injection kit of the present invention make it easy to insert the microprotrusions for injection to an appropriate depth, allowing for efficient intradermal administration.

[0090] While the present invention has been described above based on preferred embodiments, it is not limited to the above-described embodiments and can be modified as appropriate. For example, in this embodiment, the biasing member of the holder 1 is the spring 30, but the biasing member of the holder 1 may be something other than the spring 30, such as compressed air, gunpowder, an elastic body, or a rotating body. Furthermore, the injection needle 41 may have a non-perforated protrusion in addition to the perforated micro-protrusion 44. The non-perforated protrusion may be solid or soluble.

[0091] In the present embodiment, the liquid medicine container is the syringe 51, but the liquid medicine container is not limited to the syringe 51 and may be, for example, a tube, an electric injector, or the like.

[0092] The following supplementary notes are further disclosed regarding the above-described embodiments of the present invention. <1> An injection kit having an injection device and a holder for holding the injection device, wherein the injection device comprises an injection needle with fine protrusions and a medicinal solution container in which a medicinal solution is contained, the fine protrusions having openings, and the holder has a biasing member for biasing the injection device in the puncture direction of the injection needle, and wherein the mass of the injection device and the kinetic energy when the fine protrusions of the injection device biased by the biasing member puncture the skin satisfy the following formula (1), preferably the following formula (2): E ≥ 0.0077ln(x) + 0.0057 (1) E ≥ 0.0077ln(x) + 0.01 (2) (where E represents the kinetic energy, and x represents the mass of the injection device.)

[0093] <2> The injection kit according to <1>, wherein the mass of the injection device and the kinetic energy when the fine protrusions of the injection device, biased by the biasing member, puncture the skin further satisfy the following formula (3), preferably the following formula (4), preferably the following formula (5): E≦0.05ln(x)+0.075... (3) E≦0.05ln(x)+0.055... (4) E≦0.05ln(x)+0.015... (5) <3> An injection kit comprising an injection device and a holder for holding the injection device, wherein the injection device comprises an injection needle having fine protrusions and a drug solution containing section in which a drug solution is contained, the fine protrusions have openings, and the holder has a biasing member for biasing the injection device in the puncture direction of the injection needle, An injection kit in which the mass of the injection device and the kinetic energy when the microprotrusions of the injection device biased by the biasing member puncture the skin preferably satisfy the following formula (1) and formula (3), more preferably the following formula (1) and formula (4), even more preferably the following formula (1) and formula (5), still more preferably the following formula (2) and formula (3), even more preferably the following formula (2) and formula (4), and still more preferably the following formula (2) and formula (5). E≧0.0077 ln(x)+0.0057 (1) E≧0.0077 ln(x)+0.01 (2) E≦0.05 ln(x)+0.075 (3) E≦0.05 ln(x)+0.055 (4) E≦0.05 ln(x)+0.015 (5) (where E represents the kinetic energy, and x represents the mass of the syringe.) <4> The injection kit according to any one of <1> to <3>, wherein the microprotrusions have a protrusion height from a base surface from which the protrusions protrude is preferably 1 μm or more, more preferably 5 μm or more, even more preferably 100 μm or more, and still more preferably 300 μm or more, and is preferably 5000 μm or less, more preferably 4000 μm or less, and is 1 μm or more and 5000 μm or less, preferably 5 μm or more and 4000 μm or less, more preferably 100 μm or more and 4000 μm or less, and still more preferably 300 μm or more and 4000 μm or less.<5> The injection kit according to any one of <1> to <4>, wherein the injection needle has a stimulation protrusion that does not have an opening, and a puncture depth control unit that is arranged at an intermediate position that is lower than the tip position of the fine protrusion and higher than the base surface.

[0094] <6> The injection kit according to any one of <1> to <5> above, wherein the kinetic energy is 0.014 J or more, preferably 0.018 J or more, and 0.230 J or less, preferably 0.210 J or less, more preferably 0.170 J or less, and is 0.014 J or more and 0.23 J or less, preferably 0.018 J or more and 0.21 J or less, more preferably 0.018 J or more and 0.17 J or less. <7> The injection kit according to any one of <1> to <6> above, wherein the puncture speed when the microprotrusions of the injection device biased by the biasing member puncture the skin and the mass of the injection device preferably satisfy the following formula (6), more preferably the following formula (7). S≧−750ln(x)+3850 (6) S≧−750ln(x)+4070 (7) (wherein S represents the puncture speed, and x represents the mass of the injection device.) <8> The injection kit according to any one of <1> to <7> above, wherein the puncture speed when the fine protrusions of the injection device biased by the biasing member puncture the skin is preferably 1700 mm / s or more, more preferably 1800 mm / s or more, preferably 9300 mm / s or less, more preferably 8600 mm / s or less, and even more preferably 7000 mm / s or less, and is preferably 1700 mm / s or more and 9300 mm / s or less, more preferably 1800 mm / s or more and 8600 mm / s or less, and even more preferably 1800 mm / s or more and 7000 mm / s or less. <9> The injection kit according to any one of the above <1> to <8>, wherein the mass of the injection device is preferably 1.9 g or more, more preferably 2.5 g or more, even more preferably 3.0 g or more, and preferably 40.0 g or less, more preferably 30.0 g or less, still more preferably 21.0 g or less, and preferably 1.9 g or more and 40.0 g or less, more preferably 2.5 g or more and 30.0 g or less, even more preferably 3.0 g or more and 21.0 g or less. <10> The injection kit according to any one of the above <1> to <9>, wherein the center position of the opening of the microprojection is preferably 100 μm or more and 1000 μm or less, more preferably 200 μm or more and 500 μm or less, downward from the tip of the microprojection.

[0095] <11> The injection kit according to any one of <1> to <10>, wherein the injection needle has a stimulation protrusion having no aperture and a puncture depth control section arranged at an intermediate position that is lower than the tip positions of the fine protrusions and higher than the base surface, and the difference in height between the tip positions of the stimulation protrusions and the tip positions of the puncture depth control section is preferably 0 or more, more preferably 100 μm or more, even more preferably 400 μm or more, preferably 5000 μm or less, more preferably 4000 μm or less, and preferably 0 to 5000 μm, more preferably 100 μm to 5000 μm, even more preferably 400 μm to 4000 μm. <12> The injection kit according to any one of <1> to <11> above, wherein the injection needle has stimulation protrusions without apertures, and the difference in height between the tip positions of the fine protrusions and the tip positions of the stimulation protrusions is preferably 1 μm or more, more preferably 5 μm or more, preferably 5,000 μm or less, more preferably 4,000 μm or less, and preferably 1 μm to 5,000 μm, more preferably 5 μm to 4,000 μm. <13> The injection kit according to any one of <1> to <12> above, wherein the protrusion height from the base surface of the fine protrusions is preferably 10 μm or more, more preferably 20 μm or more, preferably 5,000 μm or less, more preferably 4,000 μm or less, and preferably 10 μm to 5,000 μm, more preferably 20 μm to 4,000 μm. <14> The injection kit according to any one of <1> to <13>, wherein the injection needle has a stimulation protrusion that has no hole, and the protrusion height of the stimulation protrusion from the base surface is preferably 10 μm or more, more preferably 20 μm or more, and preferably 5000 μm or less, more preferably 4000 μm or less, and preferably 10 μm or more and 5000 μm or less, more preferably 20 μm or more and 4000 μm or less.

[0096] <15> The injection kit according to any one of <1> to <14>, wherein the injection needle has a puncture depth control section disposed at an intermediate position that is lower than the tip position of the fine projection and higher than the base surface, and the protrusion height of the puncture depth control section from the base surface is preferably 5 μm or more, more preferably 10 μm or more, preferably 4000 μm or less, more preferably 3000 μm or less, and preferably 5 μm to 4000 μm or less, more preferably 10 μm to 3000 μm or less. <16> The aperture has a circular or elliptical shape in front view, a horizontal width of the aperture is preferably 25 μm to 100 μm, more preferably 40 μm to 60 μm, and a vertical width of the aperture is preferably 25 μm to 200 μm, more preferably 40 μm to 200 μm, even more preferably 40 μm to 130 μm, and even more preferably 80 μm to 100 μm. The injection kit according to any one of <1> to <15>, wherein the width of the opening is from 25 μm to 100 μm and the vertical width of the opening is from 25 μm to 200 μm, more preferably from 40 μm to 60 μm and the vertical width of the opening is from 40 μm to 200 μm, and even more preferably from 40 μm to 60 μm and the vertical width of the opening is from 80 μm to 100 μm. ２ More preferably, 1250 μm or more ２ or more, preferably 6100 μm ２ Less than or equal to 4800 μm, more preferably ２ less than 500 μm, preferably ２ 6100 μm or more ２ Less than or equal to 1250 μm, more preferably ２ 4800 μm or more ２ The injection kit according to the above <16>, which is: <18> Use of the injection kit according to any one of the above <1> to <17> for intradermal administration of a medicinal solution. <19> A method for intradermal administration of a medicinal solution using the injection kit according to any one of the above <1> to <17>.

[0097] <20> A holder for holding an injection device, wherein the injection device comprises an injection needle having fine protrusions and a drug solution storage section capable of storing a drug solution, the fine protrusions having openings, and the holder has a biasing member that biases the injection device in a puncture direction of the injection needle, and wherein, in a state where the drug solution is stored in the drug solution storage section, a mass of the injection device and a kinetic energy when the fine protrusions of the injection device biased by the biasing member puncture the skin preferably satisfy the following formula (1), and more preferably the following formula (2). E≧0.0077ln(x)+0.0057 (1) E≧0.0077ln(x)+0.01 (2) (wherein E represents the kinetic energy, and x represents the mass of the injection device.) <21> The holder according to <20>, wherein the biasing member is a spring, and in a standby state in which the spring is maintained in a contracted state, the elastic energy of the spring is preferably 0.03 J or more, more preferably 0.05 J or more, even more preferably 0.07 J or more, preferably 0.30 J or less, more preferably 0.25 J or less, even more preferably 0.22 J or less, and preferably 0.04 J or more and 0.30 J or less, more preferably 0.05 J or more and 0.25 J or less, even more preferably 0.07 J or more and 0.22 J or less. <22> The holder according to <20>, wherein the mass of the injection device and the kinetic energy when the fine protrusions of the injection device biased by the biasing member puncture the skin further satisfy the following formula (3), preferably the following formula (4), and more preferably the following formula (5).E≦0.05ln(x)+0.075 (3) E≦0.05ln(x)+0.055 (4) E≦0.05ln(x)+0.015 (5) <23> A holder for holding an injection device, wherein the injection device comprises an injection needle having fine protrusions and a drug solution containing portion capable of containing a drug solution, the fine protrusions have openings, and the holder has a biasing member for biasing the injection device in a puncturing direction of the injection needle, A holder in which the mass of the injection device and the kinetic energy when the fine protrusions of the injection device biased by the biasing member puncture the skin preferably satisfy the following formula (1) and formula (3), more preferably the following formula (1) and formula (4), even more preferably the following formula (1) and formula (5), still more preferably the following formula (2) and formula (3), still more preferably the following formula (2) and formula (4), and still more preferably the following formula (2) and formula (5). E≧0.0077 ln(x)+0.0057 (1) E≧0.0077 ln(x)+0.01 (2) E≦0.05 ln(x)+0.075 (3) E≦0.05 ln(x)+0.055 (4) E≦0.05 ln(x)+0.015 (5) (where E represents the kinetic energy, and x represents the mass of the syringe.) <24> The holder according to any one of <20> to <23> above, wherein the microprotrusions have a protrusion height from a base surface from which the protrusions protrude is preferably 1 μm or more, more preferably 5 μm or more, even more preferably 100 μm or more, still more preferably 300 μm or more, and preferably 5,000 μm or less, more preferably 4,000 μm or less, and is 1 μm or more and 5,000 μm or less, preferably 5 μm or more and 4,000 μm or less, more preferably 100 μm or more and 4,000 μm or less, and still more preferably 300 μm or more and 4,000 μm or less. <25> The holder according to any one of <20> to <24> above, wherein the injection needle has a stimulation protrusion having no aperture, and a puncture depth control section arranged at an intermediate position that is lower than the tip position of the microprotrusion and higher than the base surface.

[0098] <26> The holder according to any one of <20> to <25> above, wherein the kinetic energy is 0.014 J or more, preferably 0.018 J or more, and 0.230 J or less, preferably 0.210 J or less, more preferably 0.170 J or less, and is 0.014 J or more and 0.23 J or less, preferably 0.018 J or more and 0.21 J or less, more preferably 0.018 J or more and 0.17 J or less. <27> The holder according to any one of <20> to <26> above, wherein a puncture speed when the fine protrusions of the syringe biased by the biasing member puncture the skin and a mass of the syringe satisfy the following formula (6), preferably the following formula (7): S≧−750ln(x)+3850 (6) S≧−750ln(x)+4070 (7) (wherein S represents the puncture speed, and x represents the mass of the injection device.) <28> The holder according to any one of <20> to <27> above, wherein the puncture speed when the fine protrusions of the injection device biased by the biasing member puncture the skin is preferably 1700 mm / s or more, more preferably 1800 mm / s or more, preferably 9300 mm / s or less, more preferably 8600 mm / s or less, and even more preferably 7000 mm / s or less, and is preferably 1700 mm / s or more and 9300 mm / s or less, more preferably 1800 mm / s or more and 8600 mm / s or less, and even more preferably 1800 mm / s or more and 7000 mm / s or less. <29> The holder according to any one of the above <20> to <28>, wherein the mass of the injection device is preferably 1.9 g or more, more preferably 2.5 g or more, even more preferably 3.0 g or more, and preferably 40.0 g or less, more preferably 30.0 g or less, still more preferably 21.0 g or less, and preferably 1.9 g or more and 40.0 g or less, more preferably 2.5 g or more and 30.0 g or less, even more preferably 3.0 g or more and 21.0 g or less. <30> The holder according to any one of the above <20> to <29>, wherein the center position of the opening of the fine protrusion is preferably 100 μm or more and 1000 μm or less, more preferably 200 μm or more and 500 μm or less, downward from the tip of the fine protrusion.

[0099] <31> The holder according to any one of <20> to <30>, wherein the injection needle has a stimulation protrusion having no aperture and a puncture depth control section arranged at an intermediate position that is lower than the tip positions of the fine protrusions and higher than the base surface, and the difference in height between the tip positions of the stimulation protrusions and the tip positions of the puncture depth control section is preferably 0 or more, more preferably 100 μm or more, even more preferably 400 μm or more, preferably 5000 μm or less, more preferably 4000 μm or less, and preferably 0 to 5000 μm, more preferably 100 μm to 5000 μm, even more preferably 400 μm to 4000 μm. <32> The holder according to any one of <20> to <31> above, wherein the injection needle has stimulation protrusions without apertures, and the difference in height between the tip positions of the fine protrusions and the tip positions of the stimulation protrusions is preferably 1 μm or more, more preferably 5 μm or more, preferably 5,000 μm or less, more preferably 4,000 μm or less, or preferably 1 μm to 5,000 μm, more preferably 5 μm to 4,000 μm. <33> The holder according to any one of <20> to <32> above, wherein the protrusion height from the base surface of the fine protrusions is preferably 10 μm or more, more preferably 20 μm or more, preferably 5,000 μm or less, more preferably 4,000 μm or less, or preferably 10 μm to 5,000 μm, more preferably 20 μm to 4,000 μm. <34> The holder according to any one of <20> to <33>, wherein the injection needle has a stimulation protrusion having no hole, and the protrusion height of the stimulation protrusion from the base surface is preferably 10 μm or more, more preferably 20 μm or more, and preferably 5000 μm or less, more preferably 4000 μm or less, and preferably 10 μm or more and 5000 μm or less, more preferably 20 μm or more and 4000 μm or less.<35> The holder according to any one of <20> to <34>, wherein the injection needle has a puncture depth control section disposed at an intermediate position that is lower than the tip positions of the fine protrusions and higher than the base surface, and the protrusion height of the puncture depth control section from the base surface is preferably 5 μm or more, more preferably 10 μm or more, and preferably 4000 μm or less, more preferably 3000 μm or less, and is preferably 5 μm or more and 4000 μm or less, more preferably 10 μm or more and 3000 μm or less.

[0100] <36> The apertures have a circular or elliptical shape when viewed from the front, a horizontal width of preferably 25 μm or more and 100 μm or less, more preferably 40 μm or more and 60 μm or less, a vertical width of preferably 25 μm or more and 200 μm or less, more preferably 40 μm or more and 200 μm or less, even more preferably 40 μm or more and 130 μm or less, and even more preferably 80 μm or more and 100 μm or less, and preferably The holder according to any one of the above items <20> to <35>, wherein the width of the aperture is 25 μm or more and 100 μm or less and the vertical width of the aperture is 25 μm or more and 200 μm or less, more preferably the width of the aperture is 40 μm or more and 60 μm or less and the vertical width of the aperture is 40 μm or more and 200 μm or less, and even more preferably the width of the aperture is 40 μm or more and 60 μm or less and the vertical width of the aperture is 80 μm or more and 100 μm or less. <37> The area X of the aperture calculated from the width and vertical width of the aperture is preferably 500 μm ２ More preferably, 1250 μm or more ２ or more, preferably 6100 μm ２ Less than or equal to 4800 μm, more preferably ２ less than 500 μm, preferably ２ 6100 μm or more ２ Less than or equal to 1250 μm, more preferably ２ 4800 μm or more ２ The holder according to <36>, which is as follows:

[0101] The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these examples.

[0102] Example 1-1 <Chemical Solution> A solution of rhodamine B (Wako Pure Chemical Industries, Ltd.) adjusted to 0.5 mg / mL with ultrapure water was used as the chemical solution. <Injection Device> A glass syringe (Agilent Technologies, model number 5190-1513) was used as the chemical solution supply device. After filling the syringe with the chemical solution, a syringe needle was connected to form the syringe. The syringe needle had a configuration similar to that of the syringe needle 41 according to the present embodiment. After forming the syringe, air was removed so that the amount of chemical solution filled in the syringe was 100 μL. After air removal, excess liquid adhering to the syringe needle was removed with Kimwipes. <Holder> A holder with a configuration similar to that of the holder 1 shown in FIG. 1 was prepared, and the syringe was attached to the holder. A round wire coil spring with a standard inner diameter (model number: VUF12-45) manufactured by Misumi Group Holdings, Inc. was used as the spring 30. The specifications of the spring in Example 1-1 are as shown in Table 1. Note that the "spring length L2 when colliding with the skin" in Table 1 refers to the length of the spring when the holder with the syringe attached is set to the standby state, the guide protrusion is released, and the syringe needle is caused to collide with the skin to be punctured (see FIG. 6).

[0103] Examples 1-2 to 1-5 and Comparative Example 1 The same injection devices and holders as those in Example 1-1 were prepared, except that springs with different spring constants and free lengths L0 were used, and that the spring length L1 in the standby state and the spring length L2 when the injection needle hits the skin were changed. The spring constants, spring free lengths L0, spring length L1 in the standby state, and spring length L2 when the injection needle hits the skin for Examples 1-2 to 1-5 and Comparative Example 1 are as shown in Table 1. The springs used in Examples 1-2 to 1-5 and Comparative Example 1 are round wire coil springs with standard inner diameters manufactured by MISUMI Group Inc., and have the following model numbers: Example 1-2: VUY12-65 Example 1-3: VUY12-42.5 Example 1-4: VUY12-40 Example 1-5: VUY12-40 Comparative Example 1: VUY12-30

[0104] Examples 2-1 to 2-5 and Comparative Example 2 A syringe made of polypropylene (PP) (HJ5010-LL, Henke-Sass, Wolf) was used as the syringe, and the spring constant, free length of the spring L0, length of the spring in the standby state L1, and length of the spring when the injection needle hits the skin L2 were set as shown in Table 2. Except for this, an injection device and a holder similar to those in Example 1-1 were prepared.

[0105] Examples 3-1 to 3-6 and Comparative Example 3 A syringe made of cycloolefin polymer (COP) (Clear Ject 0.5 mL LL T2, Taisei Chemical Co., Ltd.) was used as the syringe, and the spring constant, the free length of the spring L0, the length of the spring in the standby state L1, and the length of the spring when the injection needle hits the skin L2 were set as shown in Table 3. Except for this, an injection device and a holder similar to those in Example 1-1 were prepared.

[0106] [Evaluation of administration] The administration of each example and comparative example was evaluated by the following method. <Skin preparation> Skin excised from a Göttingen 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. Wrap film was adhered to the thawed excised skin using double-sided tape (Nicetack NW-F30, Nichiban Co., Ltd.). Then, with the surface of the excised skin to which the wrap film was adhered facing up, the excised skin was placed on top of a Kimtowel (Nippon Paper Crecia) or urethane foam (P20-25, P10-25, Hikari Co., Ltd.).

[0107] <Determination of Administration Location> The hardness of the excised skin placed as described above was measured using a muscle hardness meter (digital display NEUTONE muscle (soft tissue) hardness meter, manufactured by Triall) to determine the administration location. Specifically, measurements were taken three times at each of multiple locations on the excised skin using the muscle hardness meter, and the site showing an average hardness of approximately 15 to 45 (site having a hardness equivalent to that of a human upper arm) was determined as the administration location.

[0108] <Measurement of wheal size and leakage amount> The microprotrusions of the syringe were punctured perpendicularly into the excised skin using a holder, and the entire amount of medicinal solution in the syringe was injected. The puncture speeds for each Example and Comparative Example are shown in Tables 1 to 3. After injection of the medicinal solution, the holder was removed from the administration site, the microprotrusions were extracted, and the presence or absence of a wheal and leakage of liquid onto the skin surface were immediately confirmed. Figure 8 shows a schematic plan view of a wheal. In Figure 8, reference numeral 91 indicates the outline of the wheal, and reference numeral 92 indicates the liquid within the wheal. If a wheal was formed, the major axis length A and minor axis length B of the wheal were measured using a vernier caliper (Mitutoyo Corporation) (see Figure 8). The average of the major axis length A and the minor axis length B was taken as the wheal size. If liquid leakage was observed on the skin surface, the skin was soaked with a Kimwipe whose mass had been measured in advance, and the mass of the Kimwipe after absorption was measured using an electronic balance (AG135, Mettler Trade Co., Ltd.). The amount of leakage was calculated by subtracting the mass of the Kimwipe before absorbing water from the mass of the Kimwipe after absorbing water. The drug solution was administered three times, and the wheal size and leakage amount were measured for each administration. The results are shown in Tables 1 to 3. In Tables 1 to 3, "none" indicates that the entire administered amount leaked and no wheal was observed.

[0109] <Evaluation> Administration was deemed successful when the wheal size was 6 mm or larger and the amount leaking onto the skin surface was less than 10% of the administered amount (100 μL). Administration was deemed unsuccessful when the average diameter of the wheal was less than 6 mm or the amount leaking onto the skin surface was 10% or more of the administered amount. If the entire administered amount leaked (leakage amount 100 μL) and no puncture marks were found at the administration site, re-administration was performed at the same site. If leakage was 10% or more of the administered amount or no puncture marks were found even after re-administration, administration was deemed unsuccessful. Each example and comparative example was then evaluated according to the following criteria. The results are shown in Tables 1 to 3. <<Criteria>> ◯: Successful administration 2 or more times out of 3 times △: Successful administration 1 time out of 3 times ×: Successful administration 0 times out of 3 times

[0110]

[0111]

[0112]

[0113] [Results] Tables 1 to 3 show the kinetic energy at the time of puncturing calculated based on the puncturing speed and the mass of the syringe. For each example and comparative example, the kinetic energy at the time of puncturing is plotted on the vertical axis and the mass of the syringe on the horizontal axis, and the results are shown in Figure 9. In Figure 9, "◯", "△", and "×" respectively indicate the following: ◯: Successful administration two or more times out of three attempts △: Successful administration once out of three attempts ×: Successful administration zero times out of three attempts As shown in Figure 9, it can be seen that the administration efficiency improves as the kinetic energy at the time of puncturing increases.

[0114] Furthermore, from the results shown in FIG. 9 , it can be seen that there is a boundary between the line connecting the points where the evaluation result is "x" and the line connecting the points where the evaluation result is "△" that determines whether or not efficient intradermal administration is possible. The line connecting the lines may be, for example, an approximation curve. The approximation curve can be calculated as a logarithmic approximation curve using, for example, Microsoft's spreadsheet software "Excel." As a result of extensive research, the inventors have found that this boundary is the curve expressed by the following formula (8) (see FIG. 10 ): E = 0.0077ln(x) + 0.0057 ... (8) Therefore, it can be seen that when the kinetic energy at the time of puncturing and the mass of the syringe satisfy the above-mentioned formula (1), the microprotrusions can be punctured to an appropriate depth, allowing efficient intradermal administration.

[0115] Furthermore, it can be seen that there is a boundary between the line connecting the points with an evaluation result of "△" and the line connecting the points with an evaluation result of "◯", which separates the administerability from "◯". As a result of extensive research by the present inventors, it was found that this boundary is a curve expressed by the following formula (9) (see FIG. 10 ): E = 0.0077ln(x) + 0.01 (9) Therefore, it can be seen that intradermal administration can be performed more efficiently when the kinetic energy at the time of puncture and the mass of the syringe satisfy the above-mentioned formula (2).

[0116] [Evaluation of Usability in Humans] The syringe needle without fine protrusions was struck against the evaluator's skin using a holder, and the pain felt at that time was evaluated. <Injection Device> The glass syringe, PP syringe, and COP syringe used in the above-described examples were used as the drug solution dispenser. A syringe without fine protrusions was used as the injection needle. <Holder> A holder having a configuration similar to that of holder 1 shown in Figure 1 was prepared. <Test> The syringe and injection needle were connected to form an injection device. Next, the injection device was attached to the holder to form an injection kit. Then, after the holder with the syringe attached was placed in standby mode, the tip of the holder was pressed against the evaluator's upper arm. Then, the guide protrusions on the syringe holder were released, and the injection needle was struck against the evaluator's upper arm. The various test conditions are shown in Tables 4 to 6. The evaluators were six healthy adults aged 20 to 59. The evaluators then scored the pain felt when the injection needle struck them on a six-point scale according to the following criteria. <<Criteria>> 0: No pain at all 1: Mild pain 2: Moderate (tolerable) pain 3: Severe pain 4: Very severe pain 5: Unbearable (worst imaginable) pain

[0117] The above evaluation was performed twice, and the average of the two results was used as the pain score. If the pain score was "3" or less, the test was performed again with the puncture speed increased. If the pain score was "4" or more, the test was terminated. The results are shown in Tables 4 to 6.

[0118]

[0119]

[0120]

[0121] [Results] Tables 4 to 6 show the kinetic energy at the time of puncture calculated based on the puncture speed and the mass of the syringe. Figure 11 shows the results of plotting the kinetic energy at the time of puncture for each test example, with the vertical axis representing the kinetic energy at the time of puncture and the horizontal axis representing the mass of the syringe. In Figure 11, "x", "△", "▲", "◯", and "●" indicate the following: x: Each evaluator's pain score was within the range of 3.00 to 3.99. △: Each evaluator's pain score was within the range of 2.50 to 2.99. ▲: Each evaluator's pain score was within the range of 2.00 to 2.49. ◯: Each evaluator's pain score was within the range of 1.00 to 1.99. ●: Each evaluator's pain score was within the range of 0.99 or less. As shown in Tables 4 to 6, with the syringe and puncture speed used in this test, no very severe pain was observed, with the average pain score of 4 or higher for the six evaluators. It can also be seen that the lower the kinetic energy during puncture, the less pain there is when the needle strikes the skin.

[0122] From the results shown in Figure 11, it can be seen that a boundary indicating the upper limit of pain (a boundary where the pain score is 4 or more) exists above the curve connecting each of the "x" points. As a result of extensive research by the inventors, it was found that this boundary is a curve expressed by the following formula (10) (see Figure 12). E = 0.05ln(x) + 0.075 ... (10) Therefore, it can be seen that when the kinetic energy during puncturing and the mass of the syringe satisfy the above-mentioned formula (3), the microprotrusions can be punctured to an appropriate depth, and intradermal administration can be performed efficiently with less pain.

[0123] Furthermore, it can be seen that there is a boundary between the curve connecting each of the "x" points and the curve connecting each of the "▲" points that distinguishes between pain scores of 3.0 or more and 3.0 or less. As a result of extensive research, the inventors have found that this boundary is the curve expressed by the following (11) (see FIG. 12). E = 0.05ln(x) + 0.055 ... (11) Therefore, it can be seen that intradermal administration can be performed more efficiently and with less pain when the kinetic energy at the time of puncture and the mass of the syringe satisfy the above-mentioned formula (4).

[0124] Furthermore, it can be seen that there is a boundary between the curve connecting the points of the "▲" and the curve connecting the points of the "△" that separates the pain level from being 2.5 or higher to being 2.5 or lower. As a result of extensive research, the inventors have found that this boundary is the curve expressed by the following equation (12) (see FIG. 12). E = 0.05ln(x) + 0.015 (12) Therefore, it can be seen that intradermal administration can be performed more efficiently and with less pain when the kinetic energy at the time of puncture and the mass of the syringe satisfy the above-mentioned equation (5).

[0125] According to the present invention, the microprotrusions for injection can be easily inserted to an appropriate depth, and intradermal administration can be carried out efficiently.

Claims

1. An injection kit having an injection device and a holder for holding the injection device, wherein the injection device comprises an injection needle with fine protrusions and a medicinal solution container in which a medicinal solution is contained, the fine protrusions have openings, the holder has a biasing member for biasing the injection device in the puncture direction of the injection needle, and the mass of the injection device and the kinetic energy when the fine protrusions of the injection device biased by the biasing member puncture the skin satisfy the following formula (1): E ≧ 0.0077ln(x) + 0.0057 ... (1) (where E represents the kinetic energy, and x represents the mass of the injection device.) 2. The injection kit according to claim 1, wherein the micro-projections have a protruding height of 5000 μm or less from the base surface from which they protrude.

3. The injection kit according to claim 2, wherein the injection needle has a stimulation protrusion without an aperture and a puncture depth control portion disposed at an intermediate position that is lower than the tip position of the fine protrusion and higher than the base surface.

4. An injection kit according to any one of claims 1 to 3, wherein the kinetic energy is 0.014 J or more and 0.230 J or less.

5. The injection kit according to any one of claims 1 to 3, wherein the puncture speed when the microprotrusions of the injection device biased by the biasing member puncture the skin is 1700 mm / s or more and 9300 mm / s or less.

6. The injection kit according to any one of claims 1 to 3, wherein the mass of the injection device containing the medicinal solution is 1.9 g or more and 21.0 g or less.

7. A holder for holding an injection device, the injection device comprising an injection needle with fine protrusions and a drug solution storage section capable of storing a drug solution, the fine protrusions having openings, the holder having a biasing member for biasing the injection device in the puncture direction of the injection needle, and a holder in which, when the drug solution is stored in the drug solution storage section, the mass of the injection device and the kinetic energy when the fine protrusions of the injection device biased by the biasing member puncture the skin satisfy the following formula (1): E ≧ 0.0077ln(x) + 0.0057 ... (1) (where E represents the kinetic energy, and x represents the mass of the injection device.) 8. Use of the puncture kit according to claim 1 for intradermal administration of a medicinal solution.

9. A method for intradermal administration of a drug solution using the puncture kit described in claim 1.

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