Injection kit and holding instrument

Abstract

To provide an injection kit which facilitates a puncture with a fine protrusion for injection to an appropriate depth and enables efficient intradermal administration.SOLUTION: An injection kit includes an injection tool and a holding instrument for holding the injection tool. The injection tool 40 includes an injection needle 41 having a fine protrusion 44 and a medicinal solution storage part 52 for storing a medicinal solution. The fine protrusion 44 has an opening hole. The holding instrument 1 includes an energizing member 30 for energizing the injection tool 40 in a puncture direction of the injection needle 41. In the injection kit, weight of the injection tool 40 and kinetic energy in puncturing a skin with the fine protrusion of the injection tool energized by the energizing member 30 satisfy the following formula (1). E≥0.0077ln(x)+0.0057...(1) (In the formula, E expresses the kinetic energy, and x expresses weight of the injection tool.)SELECTED DRAWING: Figure 1

Description

[Technical Field]

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

[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 that a microneedle is inserted into the skin using a holder that moves the microneedle toward the skin. For example, Patent Document 1 describes the use of an action assisting device for puncture and injection to insert 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 multiple 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 Document 3 describes a method in which a microneedle device equipped with microneedles is accelerated to a desired speed by a microneedle delivery device and pressed against the stratum corneum of the skin. The document also describes a method in which, after the microneedles have penetrated the stratum corneum and are removed from the skin, a drug is applied to the skin and passed through the through-holes formed in the skin. The document also describes a method in which a piston is used to provide sufficient acceleration to reach the desired speed, and the maximum speed obtained by the piston is preferably 20 m / s or less, and the minimum speed obtained by the piston is preferably 2 m / s or more per second. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2015 / 151516 [Patent Document 2] Japanese Patent Application Laid-Open No. 2016-144690 [Patent Document 3] US Patent Application Publication No. 2005 / 0261631 Summary of the Invention [Problem to be solved by the invention]

[0007] 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 present inventors have found that simply specifying the microneedle insertion 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.

[0008] Therefore, an object of the present invention is to provide an injection kit and holder that allows the microprotrusions for injection to be easily inserted to an appropriate depth and enables efficient intradermal administration. [Means for solving the problem]

[0009] The present invention provides an injection kit having an injection device and a holder for holding the injection device. In one embodiment, the injection device preferably includes an injection needle having fine projections and a medicinal solution container in which a medicinal solution is contained. In one embodiment, the microprojections preferably have apertures. In one embodiment, the holder preferably has a biasing member that biases the syringe in the puncture direction of the syringe needle. In one embodiment, it is preferable that 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) (In the formula, E represents the kinetic energy, and x represents the mass of the syringe.)

[0010] The present invention provides a holder for holding an injection device. In one embodiment, the injection device preferably includes an injection needle having fine protrusions and a drug solution container capable of containing a drug solution. In one embodiment, the microprojections preferably have apertures. In one embodiment, the holder preferably has a biasing member that biases the syringe in the puncture direction of the syringe needle. In one embodiment, it is preferable that 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) (In the formula, E represents the kinetic energy, and x represents the mass of the syringe.) [Effects of the Invention]

[0011] 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. [Brief explanation of the drawings]

[0012] [Figure 1]FIG. 1 is a perspective view of a holder according to a preferred embodiment of the present invention. [Figure 2] FIG. 2 is a cross-sectional view taken along line II-II in FIG. [Figure 3] 3 is a schematic enlarged cross-sectional view of an injection needle provided in an injection device attached to the holder shown in FIG. [Figure 4] 4(a) to (c) are enlarged schematic cross-sectional views of the protrusions of the injection needle shown in FIG. 3, where FIG. 4(a) is an enlarged schematic cross-sectional view of the fine protrusion, FIG. 4(b) is an enlarged schematic cross-sectional view of the stimulation protrusion, and FIG. 4(c) is an enlarged schematic cross-sectional view of the control protrusion. [Figure 5] FIG. 5 is a diagram showing a state in which the microprotrusions have been punctured into the skin using the holder shown in FIG. 1, and is a cross-sectional view that schematically shows a cross section along the thickness direction of the skin. [Figure 6] FIG. 6 is a schematic cross-sectional view for explaining a method for measuring the puncture speed. [Figure 7] FIG. 7 is a schematic diagram for explaining the amount of compression of a spring. [Figure 8] FIG. 8 is a diagram for explaining the length of the major axis and the length of the minor axis of a wheal. [Figure 9] FIG. 9 is a graph plotting the kinetic energy at the time of puncturing on the vertical axis and the mass of the syringe on the horizontal axis for each example and each comparative example. [Figure 10] FIG. 10 is a graph showing an enlarged portion of FIG. [Figure 11] FIG. 11 is a graph plotting the kinetic energy at the time of puncturing on the vertical axis and the mass of the syringe on the horizontal axis for each test example. [Figure 12] FIG. 12 is a graph showing an enlarged portion of FIG. [Figure 13] 13 is a perspective view showing the syringe attached to the holder shown in FIG. 1. FIG. [Figure 14] 14 is a perspective view showing the syringe needle of the syringe shown in FIG. 13 in an unconnected state. [Figure 15] FIG. 15 is an enlarged view of the fine protrusions as viewed from the side where the apertures are formed. [Figure 16]FIG. 16 is a perspective view schematically showing another embodiment of the injection kit of the present invention. [Figure 17] 17 is a perspective view showing the main body of the holder shown in FIG. 16 with the slider in the advanced state. [Figure 18] 18 is a perspective view showing a main body of the holder shown in FIG. 17 with the slider retracted. [Figure 19] FIG. 19 is a cross-sectional view taken along CC in FIG. [Figure 20] FIG. 20 is a cross-sectional view taken along line DD in FIG. [Figure 21] FIG. 21 is an explanatory diagram of the locked state by the locking mechanism. [Figure 22] 22 is a perspective view showing the retainer shown in FIG. 16 with the slider retracted. DETAILED DESCRIPTION OF THE INVENTION

[0013] 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 parts.

[0014] 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.

[0015] 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 syringe 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 syringe holder 20 into the guide hole 11, the movement direction of the syringe holder 20 is restricted to the axial direction X of the main body 10 of the holder 1. The syringe holder 20 is disposed inside the main body 10 of the holder 1.

[0016] The holder 1 also has a stopper mechanism for maintaining the compressed state of the spring 30, which is a biasing member. The stopper mechanism maintains the compressed state of the spring 30 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.

[0017] 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 connected in a detachable manner. When calculating kinetic energy, which will be described later, 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 injection device 40 typically has a base part 47 between the microprojections 44 and the drug solution supply device 50. The base part 47 typically directly or indirectly supports the microprojections 44. The outer surface of the base part typically has a luer lock. FIG. 13 shows a specific example of an injection device 40 in which an injection needle 41 and a drug solution supplier 50 are connected.

[0018] In this embodiment, the chemical solution supplier 50 is a syringe 51. More specifically, the chemical solution supplier 50 is typically a syringe 51 having a syringe barrel 51a and a plunger 58. Syringe 51 typically includes a medicinal solution storage section 52 capable of storing a medicinal solution therein. Syringe barrel 51a preferably includes, at one end in the longitudinal direction thereof, a liquid inlet 53 for supplying the medicinal solution to fine protrusions 44, and a connection section 54 for connecting to base component 47 that supports injection needle 41. Syringe 51 typically includes a cylindrical syringe barrel 51a. Syringe barrel 51a preferably includes, at one longitudinal end, a tip portion 51b having a connection portion 54. Syringe barrel 51a preferably includes, at the other longitudinal end, a flange portion 56. Inlet 53 is typically disposed at tip 51b. Inlet 53 is typically cylindrical with a diameter smaller than that of the portion of syringe barrel 51a that contains drug solution storage portion 52, and is open at its tip. Connecting portion 54 preferably has a female thread ridge 54a on its inner circumferential surface. Thread ridge 54a is preferably capable of threadably engaging with protruding portion 49 of base component 47. The syringe barrel 51a is made of, for example, glass or synthetic resin, but is not limited to these. The plunger 58 typically includes an operating rod 59 and a gasket 59a. Gasket 59a is typically provided at the tip of operating rod 59 and disposed inside syringe barrel 51a. Gasket 59a is preferably capable of being pushed into syringe barrel 51a. The operating rod 59 preferably has a pressing operation part 59b at its rear end, which is pressed with a finger when injecting the medicinal liquid. The operating rod 59 is preferably made of a synthetic resin material and is formed in a rod shape.

[0019] 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 the drug solution is supplied from injection port 53 provided at tip end 51b to fine protrusion 44 of injection needle 41.

[0020] The injection needle 41 is configured to include a fine protrusion device 42 and a base part 47. The injection device 40 is used for intradermal administration of a medicinal solution. Here, intradermal administration means administration of a medicinal solution into the epidermis or dermis. In the present invention, it is preferable to administer the medicinal solution into the epidermis. The injection device 40 being used for intradermal administration of a medicinal solution means that the microprojections 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 microprojections 44 will be described later.

[0021] The main body 21 of the syringe holder 20 is configured so that the tip portion 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 syringe 40 is attached to the syringe holder 20 by inserting the tip portion of the syringe 51 and the base part 47 of the injection needle 41 into the main body 21 of the syringe holder 20 and connecting the tip portion of the syringe 51 and the base part 47 of the injection needle 41.

[0022] 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 arranged at an intermediate position that is lower than the tip position of the micro-protrusion 44 and higher than the base surface 43.

[0023] The microprojections 44 of the injection needle 41 have openings 44a through which liquid can be ejected. The microprojections 44 are hollow. The microprojections 44 are preferably conical in shape and have openings 44a at their tips. The tip of the microprojections 44 refers to the region on the tip side of the midpoint of the projection height H1 from the base surface 43 to the tip of the microprojection 44 (see FIG. 4(a)). The openings 44a may be formed at the tip of the microprojection 44 or on the side surface. The hollow portions 44b of the microprojections 44 communicate with the outside via the openings 44a of the microprojections 44. The openings 44a are through-holes that penetrate the microprojections 44 in the thickness direction and are preferably located on the side surface of the conical microprojections 44. The hollow portions 44b of the microprojections 44 function as passages for liquid to be ejected from the openings 44a to the outside. The microprojections 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.

[0024] The stimulation protrusion 45 is a protrusion without an opening. The stimulation protrusion 45 has a cone shape. The cone shape of the stimulation protrusion 45 may be a substantially circular cone shape or a substantially polygonal cone shape. The tip surface of the control protrusion 46 is flat, i.e., linear and 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 in 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 a substantially cylindrical shape, or may be a substantially polygonal prism shape such as a square prism.

[0025] 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 the medicinal solution is injected from the fine-protrusion device 42. It should be noted that the micro-projection device 42 does not necessarily have to have the stimulation projections 45 and the control projections 46 .

[0026] 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 drug solution is supplied to the hollow portion 47b using a syringe 51. The other opening functions, for example, as a supply port when the drug solution supplied from the syringe 51 is supplied to the fine protrusion device 42.

[0027] A method for injecting a medicinal liquid into the skin using the injection kit 100 will now be described. First, the syringe 51 is filled with the drug solution. Specifically, with the tip opening of the syringe 51 immersed in the drug solution, the plunger 58 inserted into the syringe 51 is pulled up, and the drug solution is drawn into the syringe 51. The injection needle 41 is attached to the syringe 51 filled with the drug solution, forming the injection device 40. The plunger 58 of the syringe 51 is pressed down, and the drug solution is filled 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 that biases 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 projections 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 fixation of the guide projections 22 of the injection device holder 20 is released. Then, the injection device holder 20 holding the injection device 40 is urged toward the skin, and the fine projections 44 of the injection device 40 puncture the skin (see FIG. 5). Thereafter, the plunger 58 of the syringe 51 is pressed down to inject the medicinal liquid into the skin.

[0028] To efficiently perform intradermal administration, it is necessary not only to simply puncture the skin with the microprojections 44 of the injection device 40, but also to puncture the microprojections 44 to an appropriate depth that allows intradermal administration. Specifically, when the microprojections 44 puncture the skin, it is preferable that the openings 44a of the microprojections 44 reach the layer S12, which is inner than the stratum corneum S11 in the epidermis S1 (see FIG. 5). Note that the openings 44a of the microprojections 44 may extend beyond the epidermis S1 and reach the dermis S2. Even when the openings 44a of the microprojections 44 reach the dermis S2, the medicinal liquid ejected from the openings 44a penetrates not only the dermis S2 but also the epidermis S1, so that the medicinal liquid can 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 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.

[0029] As a result of careful investigations by the inventors, it was found that by satisfying a certain relationship between the kinetic energy when the micro-projections 44 puncture (hereinafter also referred to as "kinetic energy at puncture") and the mass of the injection device 40, the micro-projections 44 can be punctured to an appropriate depth, and intradermal administration can be carried out efficiently.

[0030] 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).

[0031] If the kinetic energy at the time of puncturing and the mass of the injection device 40 satisfy the above-mentioned formula (1), when the microprojections 44 of the injection device 40 are punctured into the skin by the holder 1, the microprojections 44 will be more likely to penetrate the stratum corneum of the skin and reach the epidermis. Therefore, the microprojections 44 will be more likely to puncture to an appropriate depth, and intradermal administration can be performed efficiently.

[0032] Furthermore, from the viewpoint of making it easier for the fine protrusions 44 to reach the epidermis 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) (In the formula, E represents the kinetic energy at the time of puncture, and x represents the mass of the syringe.)

[0033] Furthermore, it is preferable that the kinetic energy at the time of puncturing and the mass of the injection tool 40 satisfy the following formula (3). E≦0.05ln(x)+0.075 (3) (In the formula, E represents the kinetic energy at the time of puncture, and x represents the mass of the syringe.) When the kinetic energy at the time of puncture and the mass of the injection device 40 satisfy equation (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.

[0034] 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 tool 40 satisfy the following formula (4). E≦0.05ln(x)+0.055 (4) (In the formula, E represents the kinetic energy at the time of puncture, and x represents the mass of the syringe.)

[0035] Moreover, 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 tool 40 satisfy the following formula (5). E≦0.05ln(x)+0.015 (5) (In the formula, E represents the kinetic energy at the time of puncture, and x represents the mass of the syringe.)

[0036] From the viewpoint of making it easier for the micro-projections 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).

[0037] 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.

[0038] 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. When the syringe 51 is not filled with the 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 a syringe> First, syringe 51 is filled with the drug solution. Then, injection needle 41 is attached to syringe 51 filled with the drug solution, forming injection device 40. Then, plunger 58 is pressed down to remove air from syringe 51. Specifically, the plunger is pressed down until the amount of drug solution filled in syringe 51 reaches a predetermined amount (e.g., 100 μL). Then, excess drug solution adhering to the tip of microprojections 44 of injection needle 41 is removed by absorbing it with Kimwipes. Then, the mass of injection device 40 after removing the air is measured using an electronic balance (AG135, Mettler Trade Co., Ltd.). The mass is measured five times, and the average value is defined as the mass of the injection device.

[0039] 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.

[0040] 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.

[0041] 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 achieving both making it easier for the microprotrusions 44 to reach into the epidermis, preventing the microprotrusions 44 from puncturing too deeply, and preventing pain during puncturing.

[0042] The kinetic energy at the time of puncturing can be calculated by squaring the speed at which the microprojections 44 puncture (hereinafter also referred to as "puncturing speed"), multiplying this value 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 microprojections 44 to an appropriate depth and efficiently administering intradermally.

[0043] Specifically, it is preferable that the puncture speed and the mass of the injection tool 40 satisfy the following formula (6). S≧-750ln(x)+3850···(6) (In the formula, S represents the puncture speed, and x represents the mass of the injection device 40.)

[0044] When the puncture speed and the mass of the injection device 40 satisfy formula (6), the microprojections 44 easily penetrate the stratum corneum of the skin and reach the epidermis when the microprojections 44 of the injection device 40 are punctured into the skin by the holder 1. Therefore, the microprojections 44 are more likely to puncture to an appropriate depth, and intradermal administration can be performed efficiently.

[0045] Furthermore, from the viewpoint of making it easier for the fine projections 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 syringe.)

[0046] 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.

[0047] If the puncture speed is too high, the fine protrusions 44 may puncture too deeply, which may prevent the medicinal liquid 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.

[0048] 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 microprotrusions 44 to reach into the epidermis, preventing the microprotrusions 44 from puncturing too deeply, and preventing pain during puncture.

[0049] The puncture speed can be measured, for example, by the following method. <Method for measuring puncture speed> First, syringe 51 is filled with the drug solution. Then, injection needle 41 is attached to syringe 51 filled with the drug solution, thereby forming injection device 40. After that, plunger 58 is pressed down to remove air from inside syringe 51. Specifically, the plunger is pressed down until the amount of drug solution filled in syringe 51 reaches a predetermined amount (for example, 100 μL). Then, excess drug solution adhering to the tip of microprojections 44 of injection needle 41 is removed by absorbing it with Kimwipes.

[0050] Next, the syringe 40 after deairing 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 standby state of the holder 1 is released.

[0051] 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 fine protrusions 44 puncture the sponge 7. The sampling period of the laser displacement meter is, for example, 20 μs.

[0052] 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 as the 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 taken as the puncture speed.

[0053] 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).

[0054] 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.

[0055] As described above, the injection device 40 is used for intradermal administration of a medicinal solution. Here, the fact that the injection device 40 is used for intradermal administration of a medicinal solution means that the openings 44a of the microprojections 44 of the injection device 40 are located in a position suitable for intradermal administration. To ensure that the openings 44a are located in a position suitable for intradermal administration, the centers of the openings 44a are 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 centers of the openings 44a are preferably located 200 μm or more and 1000 μm or less below the tips of the microprojections 44. That is, the distance H4 from the tips of the microprojections 44 to the center positions of the openings 44a (see FIG. 4(a)) (hereinafter also referred to as the "center positions 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. 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.

[0056] From the viewpoint of facilitating the discharge of the liquid medicine contained in the liquid medicine containing portion 52 from the opening 44a, the opening 44a of the fine projection 44 has an area X of the opening (hereinafter also referred to as hole area X) calculated from the width L4 and the length L3 of the opening 44a, which is preferably 500 μm 2 More than 1250 μm, preferably 2 From the viewpoint of preventing leakage of liquid onto the skin surface after puncture, it is preferable that the thickness is 6100 μm or more. 2 Less than or equal to 4800 μm, 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 More than 4800μm 2 The following applies (see FIG. 15): 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.

[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 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.

[0058] 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, 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.

[0059] It is preferable that the width L4 of the opening 44a is 25 μm or more and 100 μm or less and the vertical width L3 of the opening 44a is 25 μm or more and 200 μm or less, it is more preferable that the width L4 is 40 μm or more and 60 μm or less and the vertical width L3 is 40 μm or more and 200 μm or less, and it is even more preferable that the width L4 is 40 μm or more and 60 μm or less and the vertical width L3 is 80 μm or more and 100 μm or less. The width L4 and the length L3 of the opening 44a are measured as follows: The opening area X is calculated as follows.

[0060] <Method of measuring the width and length of the opening 44a> All of the syringes 40 to be manufactured are inspected with a camera during manufacturing, and the dimensions of the openings 44a formed on the outer surfaces of the fine projections 44 (dimensions along the opening surfaces) are measured from the inspection images.

[0061] <How to calculate hole area X> The opening 44a is regarded as an ellipse (including a perfect circle), and the width L4 and the length L3 are measured, and the width L4 and the length L3 are calculated using the following formula (13). Pore ​​area X(μm 2 )=π×(L4 / 2)×(L3 / 2) ···(13) The opening 44a preferably has a circular or elliptical shape when viewed from the front.

[0062] 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 have a blood flow promoting effect, thereby promoting the immune induction effect. Therefore, according to 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 promoting effect can be determined by various known methods, for example, by determining whether or not a flare reaction occurs in the skin, or by visualizing the blood flow distribution using a laser blood flowmeter.

[0063] 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 puncture 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 puncture depth of the fine protrusions 44 and the stimulation protrusions 45. In other words, the fine protrusion device 42 of this embodiment is configured to be able to control the puncture depth of the fine protrusions 44 and the stimulation protrusions 45 into the skin.

[0064] 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, in other words, 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)). Moreover, the difference H1-H3 is preferably 5000 μm or less, more preferably 4000 μm or less, from the viewpoint of not damaging the dermis more than necessary. 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 caused by the blood flow promoting effect of the stimulation protrusion 45, suppressing the second protrusion from failing to puncture due to the elasticity of the skin, and enabling the second protrusion to penetrate the skin sufficiently, it is preferable that the protrusion height H2 of the stimulation protrusion 45 (see Figure 4(b)) is 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 it is more preferable that H2 > H3. From the same viewpoint, the difference H2-H3 is preferably 0 or more, more preferably 100 μm or more, and even more preferably 400 μm or more. Moreover, the difference H2-H3 is preferably 5000 μm or less, and more preferably 4000 μm or less, from the viewpoint of not damaging the skin more than necessary. The difference H2-H3 is preferably 0 to 5000 μm, more preferably 100 to 5000 μm, and even more preferably 400 to 4000 μm.

[0065] From the viewpoint of ensuring a more reliable blood flow promoting effect, ensuring reliable puncturing by the fine protrusions 44, and suppressing leakage of the medicinal solution caused by insufficient puncturing, it is preferable that the fine protrusions 44 be taller than the stimulation protrusions 45. More specifically, the difference H1-H2 between the protrusion height H1 of the fine protrusions 44 and the protrusion height H2 of the stimulation protrusions 45 is preferably 1 μm or more, and more preferably 5 μm or more. Moreover, from the viewpoint of easily achieving both ease of injection of the liquid and the effect of promoting blood flow, the difference H1-H2 is preferably 5000 μm or less, and more preferably 4000 μm or less. The difference H1-H2 is preferably 1 μm or more and 5000 μm or less, and more preferably 5 μm or more and 4000 μm or less.

[0066] The protrusion height H1 of the micro-protrusions 44 is preferably 10 μm or more, and more preferably 20 μm or more, from the viewpoint of preventing the penetration from being hindered due to deformation of the skin when the micro-protrusions 44 are pressed against the skin, improving the puncture performance, and reliably injecting the medicinal solution into the skin S. Moreover, 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, the protrusion height H1 of the fine projections 44 is preferably 10 μm or more and 5000 μm or less, and more preferably 20 μm or more and 4000 μm or less, from the viewpoint of achieving both improved puncture performance and minimal invasiveness.

[0067] The protruding height H2 of the stimulating projections 45 is preferably 10 μm or more, and more preferably 20 μm or more, from the viewpoint of stimulating the skin by pressing it against the skin and promoting blood flow. Moreover, from the viewpoint of minimal invasiveness, the protrusion height H2 of the stimulation protrusion 45 is preferably 5000 μm or less, and more preferably 4000 μm or less. Furthermore, the protrusion height H2 of the stimulating projection 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 being minimally invasive. The distance H3 from the base surface 43 to the lancing depth control section 46a is preferably 5 μm or more, and more preferably 10 μm or more. Moreover, from the viewpoint of improving the puncture performance of the fine projections 44, the distance H3 is preferably 4000 μm or less, and more preferably 3000 μm or less. The distance H3 is preferably 5 μm or more and 4000 μm or less, and more preferably 10 μm or more and 3000 μm or less.

[0068] Next, the material of which the fine protrusions 42 are made will be described. The fine protrusion 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 fine protrusions 44 to facilitate injection of liquid. The injection needle is more preferably formed from a base sheet containing a thermoplastic resin. The thermoplastic resin may include one or more selected from polyolefin, polyester, polyamide, polyamideimide, polyetheretherketone, polyetherimide, polyvinyl chloride, acrylic resin, polystyrene resin, and the like. The polyolefin may include one or more selected from polypropylene, polyethylene, and the like. The polyester may include one or more selected from polyethylene terephthalate, polyfatty acid ester, polylactic acid, polycaprolactone, polybutylene succinate, and the like. The polyamide may include one or more selected from nylon and the like. From the viewpoint of biodegradability, it is preferable that the composition contains a polyfatty acid ester. Specifically, the polyfatty acid ester may include one or more selected from polylactic acid and polyglycolic acid.

[0069] The ratio of the mass of the thermoplastic resin contained in the micro-projection device 42 to the total mass of the micro-projection device 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. 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 such as antibacterial agents, disinfectants, moisturizing agents, flow improvers, antistatic agents, and colorants.

[0070] The medicinal liquid to be injected into the skin by the fine protrusion tool 42 can be selected appropriately depending on the intended use of the injection needle 41. According to this embodiment, the medicinal liquid can be easily administered intradermally, and therefore the medicinal liquid 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, so it is expected that the effectiveness of the vaccine will be improved. 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.

[0071] The medicinal solution may contain one or more selected from, for example, vaccines for preventing infectious diseases such as hepatitis A, hepatitis B, hepatitis C, influenza, COVID-19, respiratory syncytial virus (RS) virus, tuberculosis, rabies, polio, chickenpox, rubella, measles, tetanus, shingles, and malaria; vaccines for treating chronic hepatitis B, tuberculosis, rabies, malignant neoplasms, shingles, and the like; analgesics for cancer patients; insulin; biological products; gene therapy drugs; injectables; and skin-applied preparations. Since the micro-projections 44 of the micro-projection device 42 puncture the skin, the micro-projection device 42 can be applied to pharmacologically active substances that require subcutaneous injection in addition to pharmacologically active substances used for conventional transdermal administration. The skin S into which the medicinal liquid is injected by the fine protrusion tool 42 may be human skin or may be the skin of an animal other than a human.

[0072] The holder preferably stores energy for moving the injection device 40 in the biasing member by, for example, contracting a spring, holds the injection device 40 in 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.

[0073] 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, such as holder 1a shown in Figures 16 to 22. The holder 1 a preferably includes a slider 120 and a main body portion 130 . The slider 120 is preferably capable of removably fixing the injection tool 40 thereto. The slider 120 is preferably disposed inside the main body portion 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 moving back and forth direction X. Furthermore, the same direction in the main body 130 as the slider moving back and forth direction X is also referred to as the axial direction X of the main body.

[0074] The slider 120 typically has an elongated shape extending in the advancing / retreating direction X, and the length in the axial direction X is longer than the length in the width direction Y perpendicular to the axial direction. The slider 120 preferably has an arc-shaped cross section, with a portion of the peripheral wall of the cylinder cut out continuously along the axial direction of the cylinder. The cutout portion of the cylinder preferably forms a side opening 123 extending along the forward / backward direction X of the slider 120. The slider 120 preferably has a liquid medicine supply device housing portion 121. The liquid medicine supply device housing portion 121 typically houses a syringe 51 which is the liquid medicine supply device 50. It is preferable to provide a fixing protrusion 122 for restraining a portion of the base part 47 of the injection tool 40 on the skin side of the drug solution feeder housing part 121 . It is preferable that the length of drug solution feeder housing 121 along the circumferential direction of syringe 40 is equal to or less than half the circumference of syringe 40, from the viewpoint of facilitating attachment of syringe 40. It is preferable that fixing protrusion 122 has an arc shape in a cross section perpendicular to the one direction. It is preferable that fixing protrusion 122 has a smaller radius of curvature than drug solution feeder housing portion 121. It is preferable that fixing protrusion 122 has a pair of gripping protrusions 122a at both ends in the circumferential direction. It is preferable that the length of fixing protrusion 122 along the circumferential direction of injection device 40, including the pair of gripping protrusions 122a, is longer than half the length of the restrained portion of the injection device 40.

[0075] 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. The constricted portion 48 preferably serves as an engagement groove that engages with the fixing protrusion 122 and / or the pair of gripping protrusions 122a. The outer diameter of the constricted portion 48 is smaller than the outer diameter of the large-diameter portion 47c and the tip end 51b. The constricted portion 48 preferably serves as a restrained portion that is restrained by the fixing protrusion 122. In this case, simply by pushing the constricted portion 48 of the injection needle 41 into the fixing protrusion 122 from the side where the side opening 123 is open, the constricted portion is restrained by the fixing protrusion 122. Thus, rattle is less likely to occur between the injection needle 41 and the fixing protrusion 122. The engagement groove that engages with the fixing protrusion 122 and / or the pair of gripping protrusions 122a is hereinafter also referred to as a restraining engagement groove. The restraining engagement groove is preferably disposed between the fine protrusion 44 and a 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), but may also be formed by other methods. For example, a ring-shaped groove may be formed around the large-diameter portion 47c, and the groove may be used as the engagement groove. When connecting base component 47 and drug solution feeder 50 such as syringe 51 with luer connectors, the male connector and female connector are preferably luer lock connectors. Luer lock connectors are preferred because they are difficult to disconnect and difficult to release the state in which syringe 40 is held by slider 120. The restraining engagement groove is not limited to having a length the entire circumference of syringe 40, and may have a length that does not correspond to the entire circumference of syringe 40, for example, a length of half the circumference.

[0076] The fixing protrusion 122 preferably engages with an engagement groove located between the fine protrusion 44 and the drug solution feeder 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. This makes it less likely that individual differences will occur in the puncture conditions, such as the puncture angle. In addition, the syringe 40 can also be used with a syringe 51 that uses another syringe 51 with a smaller outer diameter.

[0077] The slider 120 preferably includes a rear fixing part 124 that fits around the injection device 40 on the non-skin side of the drug solution feeder housing 121. The rear fixing part 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 part 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 part of the injection device 40. Therefore, by simply pushing a part of the injection device 40 into the rear fixing part 124 from the side where the side opening 123 is open, the part can be fixed without any rattle between the rear fixing part 124 and the syringe barrel 151a.

[0078] 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 advancing / retreating direction X of the slider, 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 advancing / retreating direction X of the slider 120. 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.

[0079] According to the holder 1a, the syringe 40 can typically be attached to the slider 120 from the side of the main body 130 via the side openings 123, 133, making it easy to attach the syringe 40. This reduces the possibility of contact between the fine protrusions 44 and the holder 1a when attaching the syringe 40 to the slider 120 or when removing it after injection. This prevents damage to the fine protrusions 44, making the syringe 40 or injection needle 41 unusable, or reducing the effect 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 after the amount of drug contained in the drug solution container 52 has been optimized, the syringe 51 can be attached to the slider. When removing the injection device 40 from the slider 120 after injection, there is no need to remove the injection needle 41 from the syringe 51. This also reduces the possibility that the medicinal liquid coming out of the injection device 40 will adhere to the holder 1a. Therefore, after the injection device 40 is attached to the holder 1a and an injection operation is performed, the holder 1a can be reused by replacing only the injection device 40.

[0080] The holder 1a preferably has a guide mechanism that restricts the forward and backward movement 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 enclosing portion 131 and a guide protrusion 121a provided on the slider 120. The guide protrusion 121a preferably engages with the groove so as to be slidable in the one direction X, thereby constituting the guide mechanism. The groove typically has an opening shape that extends along the advancing / retreating direction X of the slider 120. The guide protrusion 121a inserted into the groove moves along the guide hole, thereby restricting the advancing / retreating direction X of the slider 120 to one specific direction X. The guide protrusions 121a are provided, for example, on both ends of the peripheral wall portion of the drug solution supply device accommodating portion 121 of the slider 120, 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 advancing and retreating directions of slider 120, it is preferable that the gap between the groove and guide protrusion 121a when they are engaged is greater than 0 mm and equal to or less than 1 mm. From the same viewpoint, it is preferable that the grooves and guide protrusions 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 formed by providing guide protrusions 121a on the inner wall 134 of the internal space enclosing portion 131 and grooves in the slider 120 into which the guide protrusions 121a are inserted. The guide prevents the slider from shaking during puncture and / or drug injection, and makes it easier to maintain the appropriate angle of inclination of the injection needle relative to the skin during puncture and / or drug injection.

[0081] 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 forward restriction portion 162 provided on the main body 130. An example of this is shown in FIG. 19 .

[0082] The main body 130 preferably has 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 forward position in a non-skin direction. The holding release mechanism releases the holding mechanism and moves the slider forward to the forward position. The forward position is the position where the injection needle pierces the skin. The non-skin direction is the direction away from the skin, and is typically the same direction as the retracted direction B. The holding mechanism has, for example, a holding protrusion 164 protruding from the slider 120 and a holding support 165 provided on the main body 130. When the slider 120 is moved back from a predetermined position against the biasing force of the coil spring 161, the holding protrusion 164 and the holding support 165 are configured to engage with each other. Specifically, a retaining protrusion 164 is preferably provided on the rear surface of the slider 120 . Furthermore, it is preferable that the inner wall 134 of the main body 130 is provided with a guide hole 134a that extends in the axial direction X of the main body 130 and allows the inserted holding protrusion 164 to move in the forward and backward direction X. An example of this is shown in Figures 20 and 21. The retention release mechanism preferably has a rod-shaped release member 168 that is physically linked with skin holder 71, which will be described later. When skin holder 171 is pressed against the skin, release member 168 mechanically links with it and presses a part of retention support 165. It is preferable that the mechanism is configured so that the engagement between retention protrusion 164 and retention support 165 is thereby released. Specifically, it is preferable that holding support 165 has a portion fixed to outer wall 135 and an inclined portion inclined so as to move away from outer wall 135 and approach slider 120. The inclined portion is pressed by release member 168 and displaced in direction D in the figure, thereby releasing the engagement. When holding protrusion 164 and holding support 165 are released from the engagement state, slider 120 moves forward to the advanced position due to the repulsive force of coil spring 161 in a highly compressed state, which is generated by moving slider 120 backward. In the figure, symbol A indicates the forward direction and symbol B indicates the backward direction.

[0083] The configurations of the holding mechanism and the holding release mechanism that hold slider 120 at a retracted position 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.

[0084] The holder 1a has an automatic advancement mechanism, and is configured so that the slider 120 can be advanced by a biasing force to an advanced position where the fine protrusions 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. Therefore, compared to when the slider 120 is arranged in the center of the coil springs, it is easier to form side openings 123, 133 in the main body 130 and the slider 120. Furthermore, compared to when a single coil spring 161 is arranged around the slider 120, the movement of the slider 120 in the one direction X is more stable. 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.

[0085] According to holder 1a, typically, after slider 120 is released from the retracted holding state, slider 120 automatically moves forward due to the repulsive force of compressed coil spring 161. This causes 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.

[0086] 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 supports 165. The holder 1a also typically has a holding release mechanism that releases the engagement between the holding protrusions 164 and the holding supports 165 and advances the slider 120 to the advanced position not manually but by the repulsive force of the coil spring 161. Therefore, the holding state can be released after the holder 1a has been brought close to an appropriate state for the skin to which the medicinal solution is to be administered. This makes it possible to more reliably achieve puncture of the microprotrusions 44 using the holder 1a. The retention release mechanism is preferably a mechanism that releases the engagement between retention protrusions 164 and retention support 165 by means of release member 168 that works in conjunction with skin presser 171. This is activated by pressing a part of holder 1a against the skin. Therefore, the skin area that the fine protrusions 44 come into contact with can be punctured with an appropriate amount of tension. Furthermore, it is possible to reduce individual differences in the pressure applied to the skin.

[0087] Preferably, retainer 1a has a substantially annular skin presser 171 at the end in the skin direction, i.e., the end closer to the skin in the advancing / retracting direction X of slider 120. The substantially annular skin presser is preferably arranged on the outer circumferential side of slider 120. "Arranged on the outer circumferential side of the slider" means that retainer 1a is located around slider 120 when viewed from the end side in the skin direction. More preferably, holder 1a of the present invention preferably has a substantially annular skin presser 171 that abuts against the periphery of the skin area that comes into contact with microprotrusions 44. More specifically, main body 130 preferably has, at its skin-side tip, skin presser 171 that displaces along advance / retract direction X. Displaceable skin presser 171 is constantly biased in advance direction A by a biasing member such as coil spring 161, and preferably moves backward along advance / retract direction X by pressing skin presser 171 against the skin. The term "substantially annular" may refer to a continuous annular shape, that is, a configuration that is connected 360°, and also includes a shape that is partially interrupted but can be considered to be annular as a whole. It is preferable that annular skin presser 171 has a surface parallel to a plane perpendicular to direction X of movement of slider 120 .

[0088] 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.

[0089] 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. Providing 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.

[0090] The present invention includes an injection kit including a holder, an injection device, and a medicinal solution to be filled in a medicinal solution feeder. The holder 1, 1a described above can be used as the holder included in the injection kit of the present invention. According to the holder and injection kit of the present invention, the microprotrusions for injection can be easily inserted to an appropriate depth, and intradermal administration can be carried out efficiently.

[0091] The present invention has been described above based on the preferred embodiments, but the present invention is not limited to the above-described embodiments and can be modified as appropriate. For example, in this embodiment, the biasing member possessed by the holder 1 is a spring 30, but the biasing member possessed by the holder 1 may be something other than a spring 30, such as compressed air, gunpowder, an elastic body, a rotating body, etc. Furthermore, the injection needle 41 may have projections without apertures in addition to the fine projections 44 with apertures. The projections without apertures may be solid or may be of a dissolving type.

[0092] In this embodiment, the liquid medicine container is syringe 51, but the liquid medicine container is not limited to syringe 51 and may be, for example, a tube, an electric injector, or the like.

[0093] The following supplementary notes are further disclosed regarding the above-described embodiment of the present invention. <1> An injection kit having an injection device and a holder for holding the injection device, The injection device includes an injection needle having fine protrusions and a medicinal solution storage portion in which a medicinal solution is stored, the micro-projections have apertures; the holder has a biasing member that biases the syringe in a puncturing direction of the syringe needle, An injection kit, 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) (In the formula, E represents the kinetic energy, and x represents the mass of the syringe.)

[0094] <2> The aforementioned <1> An injection kit according to claim 1, The injection kit, wherein the mass of the injection device and the kinetic energy when the fine protrusions of the injection device urged by the urging member puncture the skin further satisfy the following formula (3), preferably the following formula (4), and 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 having an injection device and a holder for holding the injection device, The injection device includes an injection needle having fine protrusions and a medicinal solution storage portion in which a medicinal solution is stored, the micro-projections have apertures; the holder has a biasing member that biases the syringe in a puncturing direction of the syringe 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 formulas (1) and (3), more preferably the following formulas (1) and (4), even more preferably the following formulas (1) and (5), still more preferably the following formulas (2) and (3), even more preferably the following formulas (2) and (4), and still more preferably the following formulas (2) and (5). E≧0.0077ln(x)+0.0057···(1) E≧0.0077ln(x)+0.01 (2) E≦0.05ln(x)+0.075 (3) E≦0.05ln(x)+0.055 (4) E≦0.05ln(x)+0.015 (5) (In the formula, E represents the kinetic energy, and x represents the mass of the syringe.) <4> The height of the fine protrusions from the base surface from which they protrude 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, 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 even more preferably 300 μm or more and 4000 μm or less. <1> ~ <3> 10. An injection kit according to any one of the preceding items. <5> The injection needle has a stimulation protrusion without an opening 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. <1> ~ <4> 10. An injection kit according to any one of the preceding items.

[0095] <6> 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; <1> ~ <5> 10. An injection kit according to any one of the preceding items. <7> The puncture speed and the mass of the injection device when the fine protrusions of the injection device urged by the urging member puncture the skin preferably satisfy the following formula (6), more preferably the following formula (7): <1> ~ <6> 10. An injection kit according to any one of the preceding items. S≧-750ln(x)+3850···(6) S≧-750ln(x)+4070···(7) (where S represents the puncture speed, and x represents the mass of the syringe.) <8> The puncture speed when the fine protrusions of the injection device urged by the urging 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, 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. <1> ~ <7> 10. An injection kit according to any one of the preceding items. <9> 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 is preferably 40.0 g or less, more preferably 30.0 g or less, even more preferably 21.0 g or less, and 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, even more preferably 3.0 g or more and 21.0 g or less. <1> ~ <8> 10. An injection kit according to any one of the preceding items. <10> The center position of the opening of the fine protrusion is preferably located 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. <1> ~ <9> 10. An injection kit according to any one of the preceding items.

[0096] <11> the injection needle has a stimulation protrusion without an opening 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, The height difference between the tip position of the stimulation protrusion and the tip position of the puncture depth control unit 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, preferably 0 or more and 5000 μm or less, more preferably 100 μm or more and 5000 μm or less, even more preferably 400 μm or more and 4000 μm or less. <1> ~ <10> 10. An injection kit according to any one of the preceding items. <12> the injection needle has a stimulation protrusion without an aperture; The height difference between the tip position of the fine protrusion and the tip position of the stimulation protrusion is preferably 1 μm or more, more preferably 5 μm or more, and is preferably 5000 μm or less, more preferably 4000 μm or less, and is preferably 1 μm or more and 5000 μm or less, more preferably 5 μm or more and 4000 μm or less. <1> ~ <11> 10. An injection kit according to any one of the preceding items. <13> The protrusion height of the fine protrusions from the base surface is preferably 10 μm or more, more preferably 20 μm or more, and is preferably 5000 μm or less, more preferably 4000 μm or less, and is preferably 10 μm or more and 5000 μm or less, more preferably 20 μm or more and 4000 μm or less. <1> ~ <12> 10. An injection kit according to any one of the preceding items. <14> the injection needle has a stimulation protrusion without an aperture; The protrusion height of the stimulation protrusion from the base surface is preferably 10 μm or more, more preferably 20 μm or more, and is preferably 5000 μm or less, more preferably 4000 μm or less, and is preferably 10 μm or more and 5000 μm or less, more preferably 20 μm or more and 4000 μm or less. <1> ~ <13> 10. An injection kit according to any one of the preceding items.

[0097] <15> the injection needle has a puncture depth control section disposed at an intermediate position that is lower than the tip position of the fine protrusion and higher than the base surface; The protrusion height of the puncture depth control unit from the base surface is preferably 5 μm or more, more preferably 10 μm or more, and is 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. <1> ~ <14> 10. An injection kit according to any one of the preceding items. <16> The apertures have a circular or elliptical shape in front view, and the width of the apertures is preferably 25 μm or more and 100 μm or less, more preferably 40 μm or more and 60 μm or less, and the vertical width of the apertures 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 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 width of the apertures is 25 μm or more and 100 μm or less and the vertical width of the apertures is 25 μm or more and 200 μm or less, more preferably the width of the apertures is 40 μm or more and 60 μm or less and the vertical width of the apertures is 40 μm or more and 200 μm or less, and even more preferably the width of the apertures is 40 μm or more and 60 μm or less and the vertical width of the apertures is 80 μm or more and 100 μm or less. <1> ~ <15> 10. An injection kit according to any one of the preceding items. <17> The area X of the aperture calculated from the width and length of the aperture is preferably 500 μm 2 More than 1250 μm, preferably 2 or more, preferably 6100 μm 2 Less than or equal to 4800 μm, preferably 2 less than 500 μm, preferably 2 More than 6100μm 2 Less than or equal to 1250 μm, more preferably 2 More than 4800μm 2 The above-mentioned <16> The injection kit according to claim 1. <18> The aforementioned <1> ~ <17> Use of the injection kit according to any one of the above for intradermal administration of a drug solution. <19> The aforementioned <1> ~ <17> A method for intradermal administration of a drug solution using the injection kit described in any one of the above.

[0098] <20> A holder for holding an injection device, The injection device includes an injection needle having fine protrusions and a medicinal solution storage portion capable of storing a medicinal solution, the micro-projections have apertures; the holder has a biasing member that biases the syringe in a puncturing direction of the syringe needle, A holder in which, when the drug solution is contained in the drug solution containing 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 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) (In the formula, E represents the kinetic energy, and x represents the mass of the syringe.) <21> the biasing member is a spring; 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, and is preferably 0.30 J or less, more preferably 0.25 J or less, even more preferably 0.22 J or less, and 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, even more preferably 0.07 J or more and 0.22 J or less. <20> The holder described in <22> The aforementioned <20> The holder according to claim 1, A holder, 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, The injection device includes an injection needle having fine protrusions and a medicinal solution storage portion capable of storing a medicinal solution, the micro-projections have apertures; the holder has a biasing member that biases the syringe in a puncturing direction of the syringe 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 formulas (1) and (3), more preferably the following formulas (1) and (4), even more preferably the following formulas (1) and (5), still more preferably the following formulas (2) and (3), even more preferably the following formulas (2) and (4), and still more preferably the following formulas (2) and (5). E≧0.0077ln(x)+0.0057···(1) E≧0.0077ln(x)+0.01 (2) E≦0.05ln(x)+0.075 (3) E≦0.05ln(x)+0.055 (4) E≦0.05ln(x)+0.015 (5) (In the formula, E represents the kinetic energy, and x represents the mass of the syringe.) <24> The height of the fine protrusions from the base surface from which they protrude 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, 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 even more preferably 300 μm or more and 4000 μm or less. <20> ~ <23> The holder according to any one of the preceding items. <25> The injection needle has a stimulation protrusion without an opening 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. <20> ~ <24> The holder according to any one of the preceding items.

[0099] <26> 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; <20> ~ <25> The holder according to any one of the preceding items. <27> the puncture speed when the microprotrusions of the injection device urged by the urging member puncture the skin and the mass of the injection device satisfy the following formula (6), preferably the following formula (7): <20> ~ <26> The holder according to any one of the preceding items. S≧-750ln(x)+3850···(6) S≧-750ln(x)+4070···(7) (where S represents the puncture speed, and x represents the mass of the syringe.) <28> The puncture speed when the fine protrusions of the injection device urged by the urging 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, 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. <20> ~ <27> The holder according to any one of the preceding items. <29> 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 is preferably 40.0 g or less, more preferably 30.0 g or less, even more preferably 21.0 g or less, and 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, even more preferably 3.0 g or more and 21.0 g or less. <20> ~ <28> The holder according to any one of the preceding items. <30> The center position of the opening of the fine protrusion is preferably located 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. <20> ~ <29> The holder according to any one of the preceding items.

[0100] <31> the injection needle has a stimulation protrusion without an opening 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, The height difference between the tip position of the stimulation protrusion and the tip position of the puncture depth control unit 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, preferably 0 or more and 5000 μm or less, more preferably 100 μm or more and 5000 μm or less, even more preferably 400 μm or more and 4000 μm or less. <20> ~ <30> The holder according to any one of the preceding items. <32> the injection needle has a stimulation protrusion without an aperture; The height difference between the tip position of the fine protrusion and the tip position of the stimulation protrusion is preferably 1 μm or more, more preferably 5 μm or more, and is preferably 5000 μm or less, more preferably 4000 μm or less, and is preferably 1 μm or more and 5000 μm or less, more preferably 5 μm or more and 4000 μm or less. <20> ~ <31> The holder according to any one of the preceding items. <33> The protrusion height of the fine protrusions from the base surface is preferably 10 μm or more, more preferably 20 μm or more, and is preferably 5000 μm or less, more preferably 4000 μm or less, and is preferably 10 μm or more and 5000 μm or less, more preferably 20 μm or more and 4000 μm or less. <20> ~ <32> The holder according to any one of the preceding items. <34> the injection needle has a stimulation protrusion without an aperture; The protrusion height of the stimulation protrusion from the base surface is preferably 10 μm or more, more preferably 20 μm or more, and is preferably 5000 μm or less, more preferably 4000 μm or less, and is preferably 10 μm or more and 5000 μm or less, more preferably 20 μm or more and 4000 μm or less. <20> ~ <33> The holder according to any one of the preceding items. <35> the injection needle has a puncture depth control section disposed at an intermediate position that is lower than the tip position of the fine protrusion and higher than the base surface; The protrusion height of the puncture depth control unit from the base surface is preferably 5 μm or more, more preferably 10 μm or more, and is 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. <20> ~ <34> The holder according to any one of the preceding items.

[0101] <36> The apertures have a circular or elliptical shape in front view, and the width of the apertures is preferably 25 μm or more and 100 μm or less, more preferably 40 μm or more and 60 μm or less, and the vertical width of the apertures 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 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 width of the apertures is 25 μm or more and 100 μm or less and the vertical width of the apertures is 25 μm or more and 200 μm or less, more preferably the width of the apertures is 40 μm or more and 60 μm or less and the vertical width of the apertures is 40 μm or more and 200 μm or less, and even more preferably the width of the apertures is 40 μm or more and 60 μm or less and the vertical width of the apertures is 80 μm or more and 100 μm or less. <20> ~ <35> The holder according to any one of the preceding items. <37> The area X of the aperture calculated from the width and length of the aperture is preferably 500 μm 2 More than 1250 μm, preferably 2 or more, preferably 6100 μm 2 Less than or equal to 4800 μm, preferably 2less than 500 μm, preferably 2 More than 6100μm 2 Less than or equal to 1250 μm, more preferably 2 More than 4800μm 2 The above-mentioned <36> The holder described in [Example]

[0102] The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these examples.

[0103] 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 tools> A glass syringe (Agilent Technologies, model number 5190-1513) was used as the drug solution supplier. After filling this syringe with the drug solution, an injection needle was connected to form the injection device. The injection needle used had a configuration similar to that of the injection needle 41 according to this embodiment. After forming the injection device, air was removed so that the amount of drug solution filled in the syringe was 100 μL. After air removal, excess liquid adhering to the injection needle was removed by absorbing it with Kimwipes. <Holder> A holder having a configuration similar to that of holder 1 shown in FIG. 1 was prepared, and an injection device 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 spring 30. The specifications of the spring in Example 1-1 are as shown in Table 1. Note that the "spring length L2 when impacting the skin" in Table 1 refers to the length of the spring when the holder with the injection device attached is placed in a standby state, the guide protrusion is released, and the injection needle is caused to impact the skin to be punctured (see FIG. 6).

[0104] [Examples 1-2 to 1-5 and Comparative Example 1] An injection device and holder similar to 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 for 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 the model numbers are as follows: 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

[0105] [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 an injection device and holder similar to those in Example 1-1 were prepared, except that 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.

[0106] [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 same injection device and holder as those in Example 1-1 were prepared, except that 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.

[0107] [Evaluation of administration] The administration properties of each example and comparative example were evaluated by the following method. <Skin Preparation> Skin removed from a Gottingen miniature pig (male, 6 weeks old, ventral part, Oriental Yeast Co., Ltd.) stored at -20°C was transferred to a refrigerator (4°C) the day before the test and thawed. A wrap film was attached to the thawed excised skin using double-sided tape (Nicetack NW-F30, Nichiban Co., Ltd.), and the excised skin was placed on a Kimtowel (Nippon Paper Crecia) or urethane foam (P20-25, P10-25, Hikari Co., Ltd.) with the surface of the excised skin with the wrap film attached facing up.

[0108] <Determining the 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 site. 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 (the site with hardness equivalent to that of a human upper arm) was determined as the administration site.

[0109] <Measurement of wheal size and leakage volume> The fine projections of the injection tool were punctured perpendicularly into the excised skin using a holder, and the entire amount of the drug solution in the syringe was injected. Tables 1 to 3 show the puncture speeds for each example and each comparative example. After the injection of the drug solution, the holder was removed from the administration site, the microprotrusions were extracted, and the presence or absence of a wheal and leakage of the solution 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 solution within the wheal. If a wheal was formed, the length A of the major axis and the length B of the minor axis of the wheal were measured using a vernier caliper (Mitutoyo Corporation) (see Figure 8). The average value of the length A of the major axis and the length B of the minor axis was taken as the wheal size. If there was any leakage on the skin surface, the liquid was absorbed 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 mass of the Kimwipe after absorption was subtracted from the mass of the Kimwipe before absorption, and the value obtained was used to determine the amount of leakage. The drug solution was administered three times, and the wheal size and leakage amount were measured each time. 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.

[0110] <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 (100 μL of leakage) and no puncture marks were observed at the administered site, the administration was re-administered to the same site. If the amount leaking onto the skin surface was 10% or more of the administered amount or no puncture marks were observed after re-administration, administration was deemed unsuccessful. Each example and comparative example was evaluated according to the following criteria. The results are shown in Tables 1 to 3. <<Standards>> 〇: Successful administration 2 or more times out of 3 times △: One successful administration out of three ×: 0 successful doses out of 3

[0111] [Table 1]

[0112] [Table 2]

[0113] [Table 3]

[0114] 〔result〕 Tables 1 to 3 show the kinetic energy during puncturing calculated based on the puncturing speed and the mass of the syringe. For each example and comparative example, the kinetic energy during 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 "×" indicate the following: 〇: Successful administration 2 or more times out of 3 times △: One successful administration out of three ×: 0 successful doses out of 3 As shown in FIG. 9, it can be seen that the administration property improves as the kinetic energy during puncture increases.

[0115] 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, for example, as a logarithmic approximation curve using Microsoft's spreadsheet software "Excel." As a result of extensive investigations, the present 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 if the kinetic energy at the time of puncturing and the mass of the injection device satisfy the above-mentioned formula (1), the microprotrusions can be punctured to an appropriate depth, and intradermal administration can be carried out efficiently.

[0116] 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 "〇", which separates whether the administration property is 〇 or △. As a result of intensive studies 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 carried out more efficiently when the kinetic energy at the time of puncturing and the mass of the injection device satisfy the above-mentioned formula (2).

[0117] [Evaluation of usability in humans] The needle without fine projections was struck against the skin of the evaluator using the holder, and the pain felt at that time was evaluated. <Injection tools> The liquid medicine supply devices used were the glass syringe, PP syringe, and COP syringe used in the above-mentioned examples. The syringe needles used did not have fine protrusions. <Holder> A holder having a structure similar to that of the holder 1 shown in FIG. 1 was prepared. <Test> The syringe and the injection needle were connected to form an injection device. Next, the syringe was attached to the holder to form an injection kit. Then, after the holder with the syringe attached was set to standby mode, the tip of the holder was pressed against the evaluator's upper arm. After that, the guide protrusion of the syringe holder was released, and the syringe 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 were then asked to rate the pain experienced when the needle struck them on a 6-point scale according to the following criteria. <<Standards>> 0: No pain at all 1: Mild pain 2: Moderate (tolerable) pain 3: Severe pain 4: Very severe pain 5: Unbearable (worst imaginable) pain

[0118] The above evaluation was performed twice, and the average of the two was used as the pain score. If the pain score was 3 or less, the test was repeated with an increased needle insertion speed. If the pain score was 4 or more, the test was terminated. The results are shown in Tables 4 to 6.

[0119] [Table 4]

[0120] [Table 5]

[0121] [Table 6]

[0122] 〔result〕 Tables 4 to 6 show the kinetic energy during puncture calculated based on the puncture speed and the mass of the syringe. For each test example, the kinetic energy during puncture was plotted on the vertical axis and the mass of the syringe on the horizontal axis, and the results are shown in Figure 11. In Figure 11, "x", "△", "▲", "◯", and "●" indicate the following: ×: Pain scores of each evaluator are within the range of 3.00 to 3.99. △: Pain scores of each evaluator are within the range of 2.50 to 2.99. ▲: Each evaluator's pain score is within the range of 2.00 to 2.49. ○: Each evaluator's pain score is within the range of 1.00 to 1.99. ●: Each rater's pain score is 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 among the six evaluators. It can also be seen that the lower the kinetic energy during puncture, the lower the pain upon impact with the skin.

[0123] From the results shown in Fig. 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 careful investigation by the inventors, it was found that this boundary is a curve expressed by the following formula (10) (see Fig. 12). E=0.05ln(x)+0.075 (10) Therefore, it can be seen that if the kinetic energy at the time of puncturing and the mass of the injection device 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.

[0124] Furthermore, it can be seen that there is a boundary between the curve connecting the "x" points and the curve connecting the "▲" points that separates pain scores from those that are 3.0 or higher. As a result of careful investigation, 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 with less pain when the kinetic energy at the time of puncture and the mass of the injection device satisfy the above-mentioned formula (4).

[0125] 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 careful investigation by the inventors, it was found that this boundary is the curve expressed by the following formula (12) (see FIG. 12). E=0.05ln(x)+0.015 (12) Therefore, it can be seen that intradermal administration can be performed more efficiently with less pain when the kinetic energy at the time of puncture and the mass of the injection device satisfy the above-mentioned formula (5). [Explanation of symbols]

[0126] 1 Holder 10 Main body 11 Guide hole 20 Syringe tool holder 21 Main body 22 Guide protrusion 30 Spring (biasing member) 40 Syringe 41 Syringe needle 42 Fine projection tool 43 Base 44 Fine protrusions 45 Stimulating protrusion 46 Control protrusion 47 Base Parts 51 Syringe (medicine supply device) 58 Plunger 100 injection kits

Claims

1. An injection kit having an injection device and a holder for holding the injection device, The injection device includes an injection needle having fine protrusions and a drug solution storage portion in which a drug solution is stored, the micro-projections have apertures; the holder has a biasing member that biases the syringe in a puncturing direction of the syringe needle, An injection kit, 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): E≧0.0077ln(x)+0.0057...(1) (In the formula, E represents the kinetic energy, and x represents the mass of the syringe.)

2. The injection kit according to claim 1, wherein the microprotrusions have a protruding height of 5000 μm or less from a base surface from which the protrusions protrude.

3. 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. The 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 fine protrusions 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 drug solution is 1.9 g or more and 21.0 g or less.

7. A holder for holding an injection device, The injection device includes an injection needle having fine protrusions and a medicinal solution storage portion capable of storing a medicinal solution, the micro-projections have apertures; the holder has a biasing member that biases the syringe in a puncturing direction of the syringe needle, A holder in which, when the drug solution is contained in the drug solution containing 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) (In the formula, E represents the kinetic energy, and x represents the mass of the syringe.)

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