Applicator and applicator cartridge

Abstract

To achieve an applicator that is convenient to use though the needle size is small.SOLUTION: In an applicator of the present invention, a medicine housing part 46 for housing a medicine to be administered, a plurality of microneedles 62 with hollow holes to be connected to the medicine housing part, and a gasket 41 provided on a straight line with the medicine housing part in a first direction, which hermetically seals the medicine housing part are composed as a cartridge part 4 of a single unit. The cartridge part 4 is attached to a body part having an attaching part 5 to which the cartridge part is removably attached and a moving part capable of moving the gasket in the first direction.SELECTED DRAWING: Figure 6

Description

[Technical Field]

[0001] The present invention is suitable for application to an applicator and an applicator cartridge for transdermal administration in medical applications using, for example, microneedles. [Background technology]

[0002] Conventionally, applicators using so-called microneedles with micro-sized diameters have been known as applicators for transdermally administering drugs (see, for example, Patent Document 1). It is expected that the use of these microneedles will significantly reduce pain during transdermal administration.

[0003] In an applicator using this microneedle, a small-diameter through-hole is formed to match the size of the microneedle, and it is assumed that the drug to be administered will be administered into the body through the through-hole. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent Publication No. 2020-32232 Summary of the Invention [Problem to be solved by the invention]

[0005] This applicator is required to solve various problems that arise due to the small size of the microneedles and that do not exist in syringes that use conventional needles.

[0006] The present invention has been made to solve such problems, and its object is to provide an applicator and an applicator cartridge that use microneedles and are easy to use. [Means for solving the problem]

[0007] In order to solve such problems, the applicator of the present invention comprises: a drug storage section for storing an administration drug; A plurality of microneedles having hollow holes connected to the drug storage portion; a cartridge portion having a gasket that is aligned with the medicine storage portion in a first direction and seals the medicine storage portion; a detachable mounting portion for detachably mounting the cartridge portion; When the cartridge part is attached, The gasket is disposed in a direction intersecting the axial direction of the microneedle. a moving part that is movable in a first direction; a main body having Equipped with child It is characterized by the following.

[0008] The applicator cartridge of the present invention comprises: a drug storage section for storing an administration drug; A plurality of microneedles having hollow holes connected to the drug storage portion; The medicine storage unit; Intersecting the axial direction of the microneedle a gasket that is aligned in a first direction, seals the medicine container, and is movable toward the medicine container; The gasket is movable in the first direction. an attachment portion for attachment to a main body portion having a moving portion; The axial direction of the plurality of microneedles is A direction intersecting the first direction It is characterized by: [Effects of the Invention]

[0009] The present invention can realize an applicator and an applicator cartridge that are easy to use even when the needle size is small. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 is a schematic diagram showing a configuration (1) of an applicator according to a first embodiment. [Figure 2]FIG. 2 is a schematic diagram showing a configuration (2) of the applicator in the first embodiment. [Figure 3] FIG. 3 is a schematic diagram showing a configuration (3) of the applicator in the first embodiment. [Figure 4] FIG. 4 is a schematic diagram showing a configuration (4) of the applicator in the first embodiment. [Figure 5] FIG. 5 is a schematic diagram showing a configuration (5) of the applicator in the first embodiment. [Figure 6] FIG. 10 is a schematic diagram showing a configuration (6) of an applicator in the second embodiment. [Figure 7] FIG. 10 is a schematic diagram showing a configuration (1) of an applicator according to a second embodiment. [Figure 8] FIG. 10 is a schematic diagram showing a configuration (2) of an applicator according to a second embodiment. [Figure 9] FIG. 10 is a schematic diagram showing a configuration (3) of an applicator according to a second embodiment. [Figure 10] FIG. 10 is a schematic diagram showing a configuration (4) of an applicator in the second embodiment. [Figure 11] FIG. 10 is a schematic diagram showing the configuration (1) of an applicator according to another embodiment. [Figure 12] FIG. 10 is a schematic diagram showing a configuration (2) of an applicator according to another embodiment. [Figure 13] FIG. 10 is a schematic diagram showing the configuration (3) of an applicator according to another embodiment. [Figure 14] FIG. 10 is a schematic diagram showing a configuration (4) of an applicator according to another embodiment. [Figure 15] FIG. 10 is a schematic diagram showing the configuration (5) of an applicator according to another embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0011] First Embodiment Hereinafter, embodiments of the present invention will be described with reference to the drawings.

[0012] Figures 1 to 6 show an applicator 1 of the present invention as a whole. Figure 1 is a perspective view of the applicator 1 as seen from the upper right, Figure 2 is a perspective view as seen from the lower right, Figure 3 is a perspective view as seen from the upper right when the cartridge portion 4 is removed, Figure 4 is a side view when the cartridge portion 4 is removed, Figure 5 is a side view, and Figure 6 is a cross-sectional view taken along the center line in the front-to-rear direction.

[0013] 1 to 5, the applicator 1 has a main body 2 and a cartridge 4 that is detachable from the main body 2. The main body 2 has a housing 20 on the right side and an attachment portion 5 that protrudes to the left below the housing 20.

[0014] The housing 20 has a semi-elliptical cylindrical shape, formed by cutting an elliptical cylinder with an elliptical bottom along its short axis, and has a flat bottom. The upper side has a lock groove 21, a slide groove 22, and a slider 23 (described in detail below).

[0015] The lower plate 50 has a plate shape and constitutes the mounting portion 5 that protrudes from the underside of the housing portion 20, and the underside of the entire applicator 1 is flat. The mounting portion 5 has a circular installation hole 54 cut out, and recesses 56 and 57 are formed on the left and right sides of the installation hole 54, respectively. In addition, a guide hole 59 is formed near the right end of the cartridge portion 4.

[0016] The cartridge portion 4 has a cylindrical installation protrusion 65 that protrudes downward from the cartridge body 40. The installation protrusion 65 is formed so that the diameter of its bottom surface is slightly (0.05 mm to 1.0 mm) smaller than the installation hole 54, and protrusions 66 and 67 are formed on the left and right sides. In addition, a guide protrusion 49 is formed near the lower right end of the cartridge portion 4.

[0017] Therefore, the cartridge unit 4 is attached to the attachment unit 5 with the guide projections 49 fitting into the guide holes 59 and the protrusions 66 and 67 fitting into the recesses 56 and 57. At this time, the guide holes 59 and the recesses 56 and 57, and the guide holes 59 and the protrusions 66 and 67 are located at different positions in the left-right and front-rear and bottom directions, and the lower surfaces of the recesses 56 and 57 are continuous with the lower plate 50, so that the cartridge unit 4 is positioned in five directions: left-right, front-rear and bottom.

[0018] The installation protrusion 65 is formed so that its thickness in the vertical direction is slightly (0.05 mm to 1.0 mm) smaller than the thickness in the vertical direction of the attachment part 5. Therefore, as shown in Figure 5, only a part of the microneedle sheet 63 attached to the tip of the installation protrusion 65 and the microneedles 62 protruding from the microneedle sheet 63 protrude from the lower surface of the lower plate 50.

[0019] 6, a spring 24 and a spring receiving portion 25 are housed inside the housing portion 20. A slider 23 extends from the upper right end of the spring receiving portion 25.

[0020] A slide groove 22 extending in the left-right direction and a lock groove 21 extending rearward from the right end of the slide groove 22 are formed on the upper side of the housing 20, and the slider 23 is attached so as to be movable along the slide groove 22 and the lock groove 21. Figure 6 shows the state in which the slider 23 is positioned in the lock groove 21, with the spring receiving portion positioned at the rightmost position and the spring 24 compressed.

[0021] The cartridge unit 4 has a gasket 41 and a drug storage unit 46 inside. The right side of the administered drug stored in the cylindrical drug storage unit 46 is sealed by the gasket 41. A drug supply path 47 is formed near the lower left end of the drug storage unit 46. The drug supply path 47 connects the drug storage unit 46 and the drug ejection space 48, and supplies the administered drug to the microneedle sheet 63.

[0022] A plurality of microneedles 62 are formed on the underside of the microneedle sheet 63. For example, 25 microneedles 62 are formed in a 5×5 matrix, and are arranged in a square shape at equal intervals. These microneedles 62 are hollow microneedles each having a through-hole (not shown) that penetrates from the back surface of the microneedle sheet 63 to the tip of the microneedle 62. The microneedles 62 eject the administered drug, which is supplied from the drug storage section 46 via the drug supply path 47 and the drug ejection space 48, from the tip (underside) of the through-hole. There is no limit to the number of microneedles 62, and it may be selected appropriately (for example, 9 to 500) depending on the application, the required ejection amount, etc.

[0023] The cartridge unit 4 ejects the administered drug supplied from the drug storage unit 46 to the tip back surface 4B via the tips 11A of the microneedles 62 formed on the tip surface 4A. The height of the microneedles 62 (the height from the flat surface of the microneedle sheet 63 to the tips of the microneedles 62) is 30 to 2000 μm, more preferably 50 to 1200 μm, or 100 to 900 μm, from the viewpoints of ensuring ease of manufacture and safety while still fulfilling the role of the microneedles 62.

[0024] The applicator 1 of the present invention can be used for transdermal absorption, subcutaneous injection, and intradermal injection, but for subcutaneous injection, the height of the microneedle is preferably 1000 μm or more. For transdermal absorption and intradermal injection, the height of the microneedle is preferably 100 μm to 1000 μm to ensure passage through the stratum corneum. Considering that the microneedle 62 does not penetrate the skin for approximately 50 to 200 μm from its base, it is preferable to form the microneedle 62 at a height that is 50 to 200 μm above the depth of the area where the administered drug is to be ejected.

[0025] The through-holes are formed around the central axis of the microneedle 62 or at a position offset from the central axis, and the central axis of the through-holes 12 is located at the tip 11A of the microneedle 62 or near the tip (the central axis is closer to the tip than 1 / 2 of the height of the microneedle 62). There are no restrictions on the shape of the through-holes 12, and they may be formed to have approximately the same size overall (i.e., a columnar shape such as a cylindrical or prismatic shape), or to become larger towards the base (i.e., a pyramidal shape such as a conical or triangular pyramid shape).

[0026] There is no limit to the size of the through-holes 12, but in order to ensure the strength of the microneedles 62 and the amount of liquid passing through them, the diameter of the narrowest part is preferably about 1 / 20 to 1 / 2, and particularly preferably about 1 / 10 to 1 / 3, of the diameter of the microneedles 62. Specifically, the diameter of the base of the microneedles 62 is preferably about 100 to 900 μm, and more preferably about 200 to 600 μm. The average diameter from the base to the tip of the through-hole is preferably 10 to 200 μm, and even more preferably 20 to 100 μm. The total average cross-sectional area of ​​the through-holes from the base to the tip is 0.0110 to 0.110 mm2, and more preferably 0.0165 to 0.055 mm2.

[0027] Although there is no limitation on the viscosity of the administered drug, the effects of the applicator 1 of the present invention can be adequately achieved by using a low-viscosity liquid as the administered drug. A low-viscosity liquid is one whose viscosity at 60 rpm (L-type viscometer / 25°C) is preferably 150 mPa·s or less, and more preferably 80 mPa·s or less. Similarly, it is preferable that the thixotropy is low, and that the viscosity at 6 rpm / 60 rpm is 3.0 or less, and more preferably 2.0 or less.

[0028] There is no limit to the number of microneedles 62, and any number can be used. There is also no limit to how the microneedles 62 can be arranged, and they can be arranged regularly, randomly, or freely. For example, they can be arranged in a circular, elliptical, or polygonal shape.

[0029] Here, when the user presses the microneedle 62 against the administration target site and moves the slider 23 from the lock groove 21 to the slide groove 22, i.e., forward, the compressed spring 24 expands, and its left end moves together with the spring receiving portion 25 into the inside of the cartridge portion 4, pushing the gasket 41 to the left and forcing the administration drug in the drug storage portion 46 into the drug supply path 47. As a result, the administration drug is administered transdermally to the administration target site via the through-hole of the microneedle 62.

[0030] Here, the cross-sectional area A1 of the drug storage section 46 in the up-down and front-rear direction is formed to be larger than the cross-sectional area A2 of the drug supply path 47 in the left-right up-down direction. The area ratio (A1 / A2) of the cross-sectional area A1 to the cross-sectional area A2 is preferably 2.0 or more, and more preferably 10.0 or more. Furthermore, by adjusting the relationship between the area ratio (A1 / A2) and the extension force N of the spring 24, it is possible to adjust the discharge speed of the administered drug from the drug supply path 47, i.e., the ejection speed of the administered drug administered transdermally from the microneedle 62.

[0031] For example, the discharge rate of the administered drug can be slowed by increasing the area ratio (A1 / A2) and decreasing the stretching force N, and conversely, the discharge rate of the administered drug can be increased by decreasing the area ratio (A1 / A2) and increasing the stretching force N. Furthermore, by increasing the area ratio (A1 / A2) and increasing the stretching force N, the administered drug can be discharged slowly and with high pressure.

[0032] There is no limit to the extension force N of the spring 24, but it is preferable to use one having a force of 5 N or more, and more preferably 10 N or more. Instead of the spring 24, it is also possible to use various elastic bodies such as a leaf spring.

[0033] The cross-sectional area of ​​the through-hole in the microneedle 62 (the sum of the smallest parts) is appropriately selected depending on the amount of drug to be administered and the expected depth (the distance from the skin surface to the tip of the microneedle 62). The average flow rate of the drug to be administered ejected from the microneedle 62 is determined by the relationship between the extension force N of the spring 24 and the cross-sectional area of ​​the through-hole. The average flow rate is preferably 5.0 μl / sec or more, and more preferably 10.0 μl / sec or more. In particular, when performing intradermal injection, it is preferably 10.0 μl / sec or more, and more preferably 15.0 μl / sec or more.

[0034] When removing the cartridge unit 4, the user moves the slider 23 from the left side to the right side of the slide groove 22 and pushes it into the lock groove 21 at the right end. This causes the spring 24 to contract again, and the protruding spring 24 and spring receiving portion 25 return to the inside of the housing unit 20.

[0035] Furthermore, the applicator 1 has a clamping plate portion 3 hanging downward from the main body portion 2. The clamping plate portion 3 has a strip-shaped clamping connection portion 32 that connects to the main body portion 2, and a facing plate 31 that is a round flat plate provided at the tip of the clamping connection portion 32. It is preferable that the facing surface 31A of the facing plate 31 is a smooth flat surface. Note that a convex portion may be formed on the periphery of the facing plate 31.

[0036] The clamping connection part 32 is made of elastic material such as plastic or sheet metal, and holds the opposing plate 31 in a movable state so that it can come into contact with the microneedles 62. In a free state where no load is applied to the opposing plate 31, the distance between the tip of the microneedle 62 and the opposing plate 31 is preferably 0.5 cm to 5 cm, and more preferably 1 cm to 3 cm, so that the user can easily operate it with one hand and grasp the skin. Note that the clamping connection part 32 may also be made of a non-elastic material such as string or cloth.

[0037] The user pinches the skin while grasping the underside of the opposing plate 31 and the upper side of the main body 2, thereby firmly pinching and pressurizing the skin between the opposing surface 31A and the left side of the lower plate 50 (the part where the microneedles 62 are formed). In this state, when the user pushes the slider 23 located in the lock groove 21 into the slide groove 22, the action of the above-mentioned spring 24 causes the administered drug to be ejected from the microneedles 62 in a pressurized state, allowing transdermal administration.

[0038] In this way, in applicator 1, spring 24 having a locking mechanism, gasket 41, and drug storage section 46 are arranged in a straight line, and the administered drug is ejected using the extension force N of spring 24. This allows the user to perform transdermal administration by simply releasing the locking mechanism while holding applicator 1 in one hand.

[0039] Furthermore, in applicator 1, drug storage section 46 and gasket 41 are arranged in one columnar space, and cartridge section 4, which has hollow microneedles 62 at the tip of drug ejection space 48 connected to drug storage section 46, is detachably attached to main body section 2 configured to push out gasket 41. This allows main body section 2 to be used repeatedly by simply replacing cartridge section 4, thereby improving hygiene and reducing costs.

[0040] Furthermore, the applicator 1 has an opposing plate 31 that can be placed opposite the microneedles 62 at a close distance (1 mm or less). This allows the user to press the tip of the microneedle 62 against the skin by pressing the skin against the opposing plate 31, making it possible to fix the highly flexible skin and to properly insert the microneedles 62 into the skin.

[0041] <Second embodiment> Next, a second embodiment will be described with reference to Figures 7 to 9. In the second embodiment, parts corresponding to those in the first embodiment are given reference numerals with 100 added, and descriptions of the same parts will be omitted.

[0042] 7, applicator 101 has upper plate portion 150 and lower plate portion 130, which have approximately the same length L and width W, connected by connecting portion 140, and main body portion 102 is installed on top of upper plate portion 150. Main body portion 102 is installed near the right-hand tip, and connecting portion 140 is formed toward the left side (to the left of 1 / 2 of the length L of upper plate portion 150 in the left-right direction, and approximately 1 / 3 of the way from the left end).

[0043] 8, the connecting portion 140 has a connecting protrusion 152 protruding from the upper plate portion 150 and a connecting protrusion 132 protruding from the lower plate portion 130 formed at positions offset in the front-to-rear direction. The connecting protrusions 152 and 132 are provided with connecting hole portions 153 and 133, respectively, and the connecting hole portions 153 and 133 are rotatably connected by a thin rod-shaped pin 139 having a circular cross section.

[0044] Although there are no restrictions on the position of the connecting portion 140, it is preferable that the connecting portion 140 be installed at 1 / 4 to 2 / 5 of the length L from the left end of the upper plate portion 150 and the lower plate portion 130, due to the relationship between the size of the gap distance at the right ends of the upper plate portion 150 and the lower plate portion 130 and the angle of inclination when the upper plate portion 150 and the lower plate portion 130 are closed. Although not shown, an extension plate may be provided so that the angle opens to the left of the upper plate portion 150 and the lower plate portion 130. In this case, the extension plate is not included in the upper plate portion 150 and the lower plate portion 130, and the positions of the left ends of the upper plate portion 150 and the lower plate portion 130 do not change.

[0045] There are no limitations on the dimensions of the applicator 1, but from the standpoint of operability, it is preferable that the length L in the left-right direction of the upper plate portion 150 is 2 to 5 cm, the width W in the front-to-back direction is about 1 to 3 cm, and the thickness T1 in the up-down direction is 0.1 to 0.5 cm. Similarly, from the standpoint of operability, the length L and width W of the lower plate portion 130 are almost the same as those of the upper plate portion 150, but preferably there is a step of about 2 mm so that the right side is thicker than the left side, and the thickness T2 on the left side is about 0.1 to 0.5 cm, and the thickness T3 on the right side is about 0.3 to 1.0 cm.

[0046] For example, the length L of the upper plate portion 150 in the left-right direction is approximately 2.5 cm, the width W in the front-to-back direction is approximately 1.3 cm, and the thickness T1 in the up-down direction is 0.3 cm. The length L and width W of the lower plate portion 130 are almost the same as those of the upper plate portion 150, but there is a step of approximately 2 mm so that the right side is thicker than the left side, and the thickness T2 of the left side is approximately 0.3 cm, and the thickness T3 of the right side is approximately 0.5 cm.

[0047] As shown in FIG. 9, on the left side of the connecting portion 140, a recess 157 recessed from the lower surface 150A of the upper plate portion 150 and a recess 137 recessed from the second upper surface 130B of the lower plate portion 130 are formed, and the recess 157 and the recess 137 are arranged in opposing positions. A pin 139 is installed in the recess 157 and the recess 137, and when no load is applied, the gap distance GB on the left side of the upper plate portion 150 and the lower plate portion 130 is large and the gap distance GB on the right side is small, with the pin 139 as a fulcrum. The gap distance GA is the distance between the tip surface connecting the tips of the microneedles 62 and the second upper surface 130B. When the heights of the microneedles 62 are different, the point connecting the average height positions of the microneedles 62 is called the tip surface.

[0048] Furthermore, between the upper plate portion 150 and the lower plate portion 130, the gap distance GA at the first upper surface 130A on the right side of the lower plate portion 130 is approximately 5 mm, and the gap distance GB at the second upper surface 130B is approximately 7 mm. This gap distance GA is set to be approximately the same as the expected clamping thickness when grasping the object to be clamped (for example, approximately 5 to 10 mm for the skin behind the elbow joint, or approximately 3 to 7 mm for an earlobe). In other words, when the expected clamping thickness is clamped, the angle formed between the first upper surface 130A on the right side of the lower plate portion 130 and the tip surface of the upper plate portion 150 is set to ±10°, preferably ±5°, so that they are approximately parallel.

[0049] That is, the distance from the center of the connecting holes 153 and 133 to the lower surface 150A of the upper plate 150 and the second upper surface 130B of the lower plate 130 is set to be about half the clamping thickness. This makes it possible to uniformize the pressure applied to the microneedles 162 arranged in a plane when clamping, allowing the microneedles 162 to properly pierce the skin.

[0050] Although not shown, the opening angle on the tip side when gripping regions 130X and 150X (the angle formed by lower surface 150A of upper plate portion 150 and first upper surface 130A of lower plate portion 130) is preferably 10 to 30°. If the opening angle is too small, it will be difficult to grip the skin, and if it is too large, it will be difficult to operate.

[0051] As shown in Figure 10, the main body 102 is attached by fitting the cartridge part 104 into the mounting part 105 extending from the upper plate part 150, covering the spring 124 with the spring holding part 125 protruding from the top surface of the cartridge part 104, and then fitting the cap part 120.

[0052] Specifically, upper plate portion 150 is provided with cylindrical mounting portion 105 that protrudes from upper surface 150B of upper plate portion 150, and has mounting hole 154 formed in the center thereof. Female threads 159 are formed on the outside of mounting portion 105.

[0053] Cartridge unit 104 has a cylindrical housing 142 with a bottom surface in the vertical direction, and a gasket 141 that seals housing 142 moves from top to bottom. A drug supply path 147 that is smaller than the cross-sectional area of ​​the bottom surface of drug storage unit 146 is formed on the underside of drug storage unit 146 adjacent to and below gasket 141, and a microneedle sheet 164 is attached to the underside.

[0054] The microneedle sheet 164 has an ejection space 143 connected to the drug supply path 147, and a plurality of microneedles 162 having hollow holes connected to the ejection space 143. A cylindrical spring holding part 125 having a diameter smaller than that of the attachment part 105 is fixed to the upper side of the gasket 141, and protrudes from the housing 142 of the cartridge part 104.

[0055] The upper end of housing 142 is formed thick to form protruding portion 142A that protrudes outward. The outer diameter of housing 142 is approximately the same as the inner diameter of mounting portion 105, so that housing 142 fits snugly into mounting portion 105, and protruding portion 142A is engaged with upper end 105B of mounting portion 105.

[0056] The distance from the lower surface of the protruding portion 142A to the lower surface of the cartridge portion 104 (excluding the microneedle sheet 164) is substantially the same as the distance from the upper end to the lower end of the attachment portion 105. Therefore, as shown in Figure 9, only the microneedle sheet 164 protrudes from the lower surface of the upper plate portion 150.

[0057] The cap portion 120 is attached with the spring 124 fitted into the spring holding portion 125. A male thread 129 is formed on the inside of the cap portion 120, which screws into a female thread 159 of the attachment portion 105. A recess 126 that is slightly larger in diameter than the spring 124 is formed on the upper inside of the cap portion 120, and holds the spring 124 and fixes it in the left-right and front-rear directions.

[0058] A spacer hole that connects with a hole (not shown) formed in part of the gasket 141 is formed in the housing 142 of the cartridge part 104, and a spacer plate 161 is inserted in advance. A vertical spacer hole 121 (see FIG. 8) that continues from the upper end 105B of the mounting part is formed in the mounting part 105, and the spacer plate 161 is positioned forward from the cartridge part 104, and the cartridge part 104 is attached along the vertical spacer hole 121.

[0059] When the spring 124 and the cap part 120 are placed on the mounting part 105 with the cartridge part 104 attached, the user can screw the cap part 120 onto the mounting part 105, causing the cap part 120 to move downward.

[0060] At this time, the gasket 141 does not move and the spring 124 contracts due to the presence of the spacer plate 161. With the spring 124 in a contracted state, the applicator 101 is fixed to the administration target site.

[0061] Here, connecting protrusions 152, 132 are provided protruding from the upper plate portion 150 and the lower plate portion 130 near both ends in the front-to-rear direction at a position approximately one-third of the total length from the left side of the applicator 101. Connecting holes 153, 133 are formed in the connecting protrusions 152, 132, and the upper plate portion 150 and the lower plate portion 130 are connected by a pin 139 that passes through the connecting hole portions 153, 133 so that the pin 139 serves as the center of rotation and is rotatable.

[0062] Recesses 157, 137 are formed near the left ends of the upper plate portion 150 and the lower plate portion 130, and the clamping spring 134 is fitted into these recesses. Therefore, when no stress is applied, the applicator 101 spreads out to the left between the upper plate portion 150 and the lower plate portion 130, and comes into contact at the right end.

[0063] Therefore, the user can open the right side by grasping the left side of the applicator 101 and narrowing the gap between the left sides of the upper plate 150 and the lower plate 130. In this state, when the user aligns the microneedle 162 with the administration target site so that it will be inserted, the right side closes due to the elasticity of the clamping spring 134, and the position of the applicator 101 is fixed.

[0064] There is no limit to the elastic force of the pinch spring 134, but it is preferable that the spring has an elastic force sufficient to hold the microneedle 162 in its inserted state.

[0065] When the user removes the spacer plate 161 , the spring 124 expands due to its elasticity, pushing the gasket 141 downward and causing the administered drug to be expelled from the microneedle 162 .

[0066] In this way, in applicator 101, by providing gripping regions 150X and 130X so as to protrude from main body portion 102, the thickness T4 of the entire gripping region can be reduced, making it easier for the user to grasp the gripping region and apply force.

[0067] Furthermore, the gap distance GA is set so that the tip surface connecting the tips of the microneedles 162 and the first upper surface 130A are approximately parallel when grasping the object to be grasped (skin), so that pressure is applied evenly to the skin from the multiple microneedles 162 formed, improving piercing performance.

[0068] In the second embodiment described above, the first upper surface 130A on the right side of the lower plate 130 protrudes, and the gap distance GA is set to be approximately the same as the expected clamping thickness when the clamped object is grasped. However, the present invention is not limited to this. For example, as shown in the applicator 101X of FIG. 12, a backing material 238X may be provided on the lower plate 130. In this case, it is preferable to set the gap distance GA small by the buffer height at which the microneedles 162 sink without piercing, depending on the hardness of the backing material 238. The backing material 238X may be configured to be replaceable, and the thickness and hardness of the backing material 238 can be configured to be changeable depending on the patient and the administration site. Furthermore, as in the applicator 101Y shown in FIG. 13, by not providing the backing material 238Y only in the area facing the microneedle 162 (i.e., making the facing surface hard), and providing the backing material 238Y in other areas, it is possible to reduce the pain felt by the user. 12 and 13, some parts are omitted. [Example]

[0069] Next, an example will be described.

[0070] Example 1 The following galantamine was prepared: The required amount of galantamine hydrobromide was weighed and pulverized in an agate mortar, then dissolved in Japanese Pharmacopoeia water for injection and diluted to the specified volume to prepare a 26.7 mg / ml aqueous solution. Drug used: galantamine hydrobromide (hereinafter referred to as galantamine in the examples) Lot number: WSEOK-AN Manufacturer: Tokyo Chemical Industry Co., Ltd.

[0071] The following experimental animals were used: Species and strain: Rat, Crl:CD (SD), SPF Weight range: Approximately 200 g Dosage: 20mg / kg (based on 200g per rat)

[0072] The following microneedle sheets were prepared (see Figure 6): PGA resin was used as the material for the microneedle sheets. H400: Cone type (manufactured by injection molding), needle height H = 400 μm, diameter at half height 1 / 2H MD = 80 μm, diameter of through-hole PD = 27 μm, number of microneedles = 6, needle distance IL = 750 μm, diameter of base part RD = 300 μm, total cross-sectional area of ​​through-hole = 0.0170 square mm H800: Conical (manufactured by injection molding), needle height H = 800 μm, diameter at half height 1 / 2H MD = 90 μm, diameter of through-hole PD = 30 μm, number of microneedles = 12, needle distance IL = 500 μm, diameter of base part RD = 150 μm, total cross-sectional area of ​​through-hole = 0.0340 square mm

[0073] As a transdermal administration applicator, applicator 101 described with reference to Figures 7 to 11 was used. As spring 124, a spring spring with a diameter of 8 mm and an elastic force of 11 N was used (the inner diameter of cartridge part 104 was Φ8.4, the same size as the inner diameter of a Terumo 2.5 mL syringe).

[0074] The back of the rat was used as the administration site, and the applicator 101 equipped with the above two types of microneedle sheets was fixed with adhesive, and galantamine was administered transdermally. The injection volume varied depending on the rat, but was 30 to 50 μl.

[0075] The results are shown in Table 1.

[0076] [Table 1]

[0077] As can be seen from Table 2, differences in absorption characteristics were confirmed depending on the microneedle needle height H. In particular, clear sustained release was confirmed in the experiment with a microneedle needle height H of 400 μm.

[0078] <Example 2> The following galantamine preparations were prepared: The required amount of galantamine was weighed and pulverized in an agate mortar, then dissolved in Japanese Pharmacopoeia water for injection and diluted to the specified volume to prepare aqueous solutions with a low volume of 5.0 mg / volume (mg / ml) and a high volume of 10.0 mg / volume (mg / ml). The concentrations of the preparations (100 μl) in Example 2 were determined so that the doses of galantamine administered to rats were 0.5 mg for the low volume and 1.0 mg for the high volume. The expected dose was 100 μl. Drug used: galantamine hydrobromide (hereinafter referred to as galantamine in the examples) Lot number: WSEOK-AN Manufacturer: Tokyo Chemical Industry Co., Ltd.

[0079] The following experimental animals were used: Species and strain: Rat, Crl:CD (SD), SPF Weight range: 100~160g

[0080] The following microneedle sheets were prepared (see Figure 5): PGA resin was used as the material for the microneedle sheets. H400: Cone type (manufactured by injection molding), needle height H = 400 μm, diameter at half height 1 / 2H MD = 80 μm, diameter of through-hole PD = 27 μm, number of microneedles = 4, needle distance IL = 750 μm, diameter of base part RD = 300 μm, total cross-sectional area of ​​through-hole = 0.0113 square mm H800: Conical (manufactured by injection molding), needle height H = 800 μm, diameter at half height 1 / 2H MD = 90 μm, diameter of through-hole PD = 27 μm, number of microneedles = 4, needle distance IL = 500 μm, diameter of base part RD = 150 μm, total cross-sectional area of ​​through-hole = 0.0113 square mm

[0081] The transdermal administration applicator used was applicator 101X described with reference to Figure 12. A spring with a diameter of 4 mm and an elastic force of 5 N was used as spring 124 (the inner diameter of cartridge portion 104 was Φ4.3, the same size as the inner diameter of a Terumo 1 ml syringe). In addition, a urethane gel (diameter 7 mm, thickness 5 mm) with a hardness of "E16" (measured by the JIS K 6253E method) was used as the backing material.

[0082] The back of the rat was used as the administration site, and the applicator 101 equipped with the above two types of microneedle sheets was fixed with adhesive, and galantamine was administered transdermally. The injection volume varied depending on the rat, but was 30 to 50 μl.

[0083] In addition, as a control experiment, galantamine was administered to rats orally, intravenously, and subcutaneously. A standard syringe with a millimeter-level needle was used. The doses were as follows: Oral administration: Dose 2 ml, 2.5 mg / ml mass / volume, 0.5 mg galantamine Intravenous and subcutaneous injection: Dose 1 ml, 2.5 mg / ml, galantamine content 0.25 mg

[0084] The results are shown in Table 2.

[0085] [Table 2]

[0086] As can be seen from Table 3, when microneedles were used, a clear sustained release was confirmed compared to oral, intravenous, and subcutaneous injections. Furthermore, the rats were still alive after 24 hours.

[0087] <Actions and effects> The following describes the features of the inventions extracted from the above-described embodiments, while indicating problems and effects as necessary. Note that, for ease of understanding, corresponding configurations in the above-described embodiments are indicated in parentheses as appropriate, but the specific configurations indicated in parentheses are not limited to these. Furthermore, the meanings and examples of terms described in each feature may also be applied as the meanings and examples of terms described in other features described in the same wording.

[0088] Conventional syringes have often been disposable for hygiene reasons. However, in order to create a sustainable society, there has been a demand for applicators that can be used as many times as possible while ensuring hygiene safety. The present invention makes it possible to realize an applicator that can be used as many times as possible while ensuring hygiene safety.

[0089] According to the above configuration, the applicator of the present invention has: a drug storage section (drug storage section 46) for storing an administration drug; A plurality of microneedles (microneedles 62) having hollow holes (through holes) connected to the drug storage section; a cartridge part (cartridge part 4) having a gasket (gasket 41) that is aligned with the medicine storage part in a first direction and seals the medicine storage part; a detachable mounting portion (mounting portion 5) for detachably mounting the cartridge portion; The gasket is characterized by comprising a moving part (spring 24) that can move the gasket in a first direction when the cartridge part is attached.

[0090] This allows the cartridge part containing the administered drug and microneedles to be replaceable, ensuring hygiene and allowing the main body part, which has moving parts that do not affect hygiene, to be used repeatedly.

[0091] In the applicator, the detachable attachment portion is The cartridge portion is fitted into a hole (installation hole 54) provided in the plate-like member. It is characterized by:

[0092] This allows the microneedles to protrude through the holes in the applicator.

[0093] In the applicator, the moving part comprises: The gasket is moved by expanding the contracted elastic body (spring 24). It is characterized by:

[0094] This allows the applicator to eject the administered medicine by applying pressure to the medicine containing section with the elastic body.

[0095] In the applicator, the first direction is: It is characterized in that it is a cross direction that intersects with the axial direction of the microneedle.

[0096] This allows the applicator to arrange the moving part so that it moves in the intersecting direction by utilizing the space in the intersecting direction.

[0097] In the applicator, The moving unit is It is housed in a housing The detachable attachment portion is The hole is formed in a plate-like member extending from the housing in the intersecting direction.

[0098] This allows the applicator to house the moving part within the housing while allowing the microneedle to protrude through the hole.

[0099] In the applicator, the moving part comprises: The gasket protrudes from the housing when it is moved, but is more than 90% housed in the housing when the cartridge part is attached or detached.

[0100] This allows the applicator to allow the user to attach and detach the cartridge part only when the moving part is stored inside the housing, and prevents malfunctions such as unintentional ejection of the administered medication when the moving part is attached to the cartridge part in a protruding state.

[0101] In the applicator, the first direction is: It is characterized in that it is approximately parallel to the axial direction of the microneedle.

[0102] This allows the applicator to arrange the moving part so that it moves in the axial direction by utilizing the axial space.

[0103] In the applicator, a housing section that houses the cartridge section and the moving section in a state where they are adjacent to each other; 2. The applicator according to claim 1, further comprising:

[0104] This allows the moving section and the cartridge section to be housed within a single housing.

[0105] Conventional syringes generally have a configuration in which the injector manually applies pressure to the syringe, thereby discharging the administered drug. However, when using microneedles, the needles have a limited penetration depth into the skin, making the application of pressure difficult. The present invention realizes a transdermal administration applicator that simplifies the application of pressure. Note that transdermal administration refers to administration routes that include drug absorption through the skin surface (which may be accompanied by absorption-enhancing techniques using electric fields, ultrasound, etc., such as iontophoresis and phonophoresis) and drug absorption via a needle subcutaneously, intradermally, or intramuscularly.

[0106] According to the above configuration, in the applicator of the present invention (applicator 1), An elastic body (spring 24) that can expand and contract in the expansion and contraction direction; a locking mechanism (slide groove 22 and lock groove 21) that holds the elastic body in a contracted state and can change the elastic body from the contracted state to an extended state; a drug storage section (drug storage section 46) for storing an administration drug; a gasket (gasket 41) provided at substantially the same position in one direction of the elastic body's expansion and contraction direction, and sealing the medicine storage section in the expansion and contraction direction; An applicator comprising a plurality of microneedles (microneedles 62) connected to the drug storage section and having hollow holes (through holes).

[0107] This allows the applicator to pressurize the drug storage section by simply stretching the elastic body that is contracted and held in place, without the user having to perform any pressure application themselves, making the pressure application operation simple.

[0108] In the applicator, a drug supply path (drug supply path 47) that connects the drug storage portion and the hollow hole and has a cross-sectional area that is 1 / 10 or less of the cross-sectional area of ​​the sealing member; 2. The applicator according to claim 1, further comprising:

[0109] This allows the administered medicine to be ejected at a flow rate that corresponds to the cross-sectional area of ​​the medicine supply path.

[0110] In the applicator, 2. The applicator according to claim 1, wherein the average flow rate of the administered drug discharged from the hollow hole is 5.0 μl / sec or more.

[0111] This allows the applicator to obtain sufficient pressure required for injection.

[0112] In the applicator, the locking mechanism comprises: A spacer (spacer plate 161) is inserted into the gasket to fix the position of the gasket. 2. The applicator of claim 1.

[0113] This allows the applicator to pressurize the administered drug storage section by simply removing the spacer from the gasket.

[0114] In the applicator, the elastic body is disposed in the other direction in the stretching direction thereof, A screw-in contraction portion (male screw 129 and female screw 159) that contracts the elastic body by screwing. The present invention is characterized by having the following.

[0115] This allows the applicator to convert rotational pressure into spring contraction through threading, so that the spring can be contracted with less force than when the spring is contracted linearly.

[0116] In the applicator, the locking mechanism comprises: a position control unit that controls the position of the elastic body in the one direction; a slide groove that is provided substantially parallel to the extension / contraction direction and allows the position control unit to slide; and a fixing portion for fixing the position control portion on the other side.

[0117] This allows the applicator to contract the spring by a simple operation of simply sliding the position control section.

[0118] In the applicator, the fixing portion comprises: The fixing groove is characterized by being bent at an angle of 70° or more from the slide groove.

[0119] This allows the applicator to extend the spring by a simple operation of simply moving the position control section from the fixed groove to the slide groove.

[0120] In the applicator, The fixing portion is The fixed groove is bent at an angle of 70° or more from the slide groove multiple times. 7. The applicator of claim 6.

[0121] This makes it necessary to move the position control unit to the slider groove after moving the applicator from the first fixed groove to the second fixed groove, thereby preventing malfunction of accidentally moving the position control unit from the fixed groove to the slide groove.

[0122] Conventional syringes generally use a single strong needle to pierce the skin. However, when using microneedles, multiple needles must be pierced into the skin at the same time, which makes piercing operation difficult. The present invention realizes a transdermal administration applicator that simplifies piercing operation.

[0123] According to the above configuration, the applicator of the present invention has: a first member (upper plate portion 150) having a first surface from which a plurality of microneedles (microneedles 162) having hollow holes (through holes) protrude; an opposing plate portion (lower plate portion 130) having a flat opposing surface; A movable connecting portion (connecting portion 140) that connects the first member and the opposing plate portion in a state in which the needle tips, which are the tips of the plurality of microneedles, and the opposing surface can be brought close to each other from a position where the needle tips and the opposing surface are separated by an open interval, A drug storage section (drug storage section 146) that stores an administration drug on the other side facing the plurality of microneedles, and a pressure section (spring 124, female screw 159, and male screw 129) that is adjacent to the drug storage section and can pressurize the drug storage section are arranged. An applicator comprising:

[0124] This allows the applicator to firmly pinch and fix the skin between the first member and the opposing plate portion, making it easier for the microneedles to pierce the skin and facilitating the piercing action.

[0125] In the applicator, The movable connection portion is The first surface and the opposing surface are rotatably connected to each other, When the direction in which the microneedles are formed is defined as the tip side and the opposite direction is defined as the base side, an elastic body sandwiched between the first surface and the opposing surface on the base side of the pivot connection part 2. The applicator according to claim 1, further comprising:

[0126] This allows the applicator to be fixed in a state where the skin is sandwiched between the first surface and the opposing surface, allowing the user to perform a pressure application operation with their hand removed from the base side.

[0127] In the applicator, the movable connection portion is The first member and the opposing plate portion are connected so that the opposing surface and the tip surface connecting the tip of the microneedle are approximately parallel with an angle of less than ±5° when the intended clamping object is clamped.

[0128] This allows the surface of the skin and the tip surface of the microneedle to be approximately parallel when the tip of the microneedle pierces the skin, making it easier to pierce.

[0129] In the applicator, the working connection comprises: The center point of rotation is set at 2 / 5 to 3 / 4 of the total length from the tip side to the base side of the first member and the opposing member.

[0130] This allows the amount of movement (opening distance) at the tip end to be greater than the amount of movement at the base end to be narrowed, making it easier to pinch the skin with a simple movement.

[0131] In the applicator, the pressure applying unit It is characterized by having an automatic pressure mechanism that can pressurize the medicine storage section by the expansion pressure of the elastic body.

[0132] This allows the user to easily administer the drug transdermally by operating the applicator at the base with one hand to pinch the skin, then releasing the hand to stretch the elastic body.

[0133] The first member is The medicine storage section and the pressurizing section are disposed on the tip side of the plate-like member.

[0134] As a result, since nothing is disposed on the base side of the applicator, the thickness of the gripping area that is gripped by the user can be reduced, thereby improving operability.

[0135] In the applicator, first and second extension members, at least one of which is inclined in a direction away from each other, are connected to the base end portions of the first member and the opposing member. It is characterized by:

[0136] This allows the area of ​​the gripping region of the applicator to be increased, improving operability.

[0137] In the applicator, Only the first extension member extending from the first member has an inclination.

[0138] This allows the bottom surface to be flat, improving operability and increasing the sense of stability when the applicator is placed on it.

[0139] In the applicator, The first member and the opposing plate portion are It is characterized by having a gripping area that protrudes further toward the base than the medicine storage section and the pressure applying section.

[0140] This allows the gripping area of ​​the applicator to be of any shape that the user grips, regardless of the shape and size of the medicine storage section and the pressure applying section, thereby improving operability.

[0141] In the applicator, the movable connection portion is It is characterized by being a plate-like member having elasticity.

[0142] This allows the applicator to have improved piercing properties with a simple configuration.

[0143] In conventional transdermal administration methods, such as patches in which a drug is applied as a liniment, the liniment must meet three essential conditions to pass through the stratum corneum, which acts as a protective membrane: 1) low molecular weight (number-average molecular weight Mn of 500 or less), 2) oil-water partition coefficient of 1 to 4, and 3) melting point of 200°C or less. In the present invention, the microneedles can pass through part or all of the stratum corneum, and the drug can be administered directly through the through-holes of the microneedles to layers deeper than the stratum corneum (epidermis or dermis). This means that the drug can be administered efficiently even if the above three conditions are not met.

[0144] <Other embodiments> In the above embodiment, the cartridge unit 4 has a removable configuration, but the present invention is not limited to this, and it may have a non-removable configuration.

[0145] In the above-described embodiment, the gap distance GA was adjusted by the position of the connecting portion 140 and the height of the first upper surface 130A (i.e., the step difference by which the first upper surface 130A protrudes from the second upper surface 130B, which is the base side of the lower plate portion 130), but the present invention is not limited to this, and a step difference is not necessarily required, and the upper surface of the lower plate portion 130 may be flush.

[0146] The first and second embodiments may also be combined as appropriate. For example, as shown in FIG. 11, an applicator 1X may have a lower plate portion provided below the main body portion 2, and extension plates 91 and 92 provided as gripping areas protruding from the main body portion 2 in the left-right or front-back direction. The extension plate 91 is inclined upward from the lower plate portion, while the extension plate 92 extends straight without inclining. Although not shown, a rotatable connecting portion and an elastic body are provided at its base, as in the second embodiment. Also, it is possible to connect lower plates that are long in the left-right direction, as in the second embodiment.

[0147] In the above-described embodiment, the extension force of an elastic body is used as the moving part and the pressurizing part, but the present invention is not limited to this. For example, as shown in FIG. 14, a piston 224 may be used as the moving part and the pressurizing part. Furthermore, a microneedle sheet 263 having only the microneedles 262 protruding from a flat surface may be used as appropriate. The applicator 201 has a configuration in which the gasket 241 is moved by the piston 224, and the piston 224 has a blade 224A and push-out plates 224B and 224C. The cartridge part 204 and the main body part 202 are threadedly engaged with a female thread 229 and a male thread 259.

[0148] Although the shape of the slider 23 is not particularly mentioned in the first embodiment, it is preferable to provide a handle on the top of the slider 23 that allows easy application of force in order to compress the spring 24.

[0149] In the second embodiment described above, the position of the gasket 141 is fixed by inserting the spacer plate 161, but the present invention is not limited to this. The spacer may be slid or bent so that it can be easily removed even when subjected to spring pressure.

[0150] 15, a fixture 299 can be provided in the applicator 101Z to fix the gap distance GA at a predetermined distance. The fixture 299 has locking portions at the upper and lower ends, one of which is fixed by a permanent fit, and the other of which has a lock-release mechanism (not shown). One or more fixtures 299 are provided, and they maintain the state in which the microneedles 162 are inserted into the skin. After transdermal administration, the tip end of the applicator 101Z can be opened by operating the lock-release mechanism. This allows the administered drug to be pushed into the skin hands-free, and prevents the microneedles 162 from being pulled out of the skin due to the force of the pushing, thereby improving the reliability of transdermal administration.

[0151] In the above embodiment, applicator 1 is configured as an applicator by spring 24 as an elastic body, slide groove 22 and lock groove 21 as a locking mechanism, drug storage section 46 as a drug storage section, gasket 41 as a gasket, and microneedle 62 as a microneedle, but the present invention is not limited to this. The applicator of the present invention may also be configured by locking mechanisms, drug storage sections, gaskets, and microneedles with various other configurations.

[0152] In the above embodiment, the applicator 1 is configured as an applicator by the cartridge portion 4 as a cartridge portion, the attachment portion 5 as a detachable attachment portion, and the spring 24 as a moving portion, but the present invention is not limited to this. The applicator of the present invention may be configured by a drug storage portion, a cartridge portion, an attachment portion, and a moving portion having various other configurations.

[0153] In the above embodiment, applicator 101 is configured as an applicator by upper plate 150 as a first member, lower plate 130 as an opposing plate, connecting portion 140 as a movable connecting portion, medicine containing portion 146 as a medicine containing portion, and spring 124, female screw 159, and male screw 129 as a pressure applying portion, but the present invention is not limited to this. The applicator of the present invention may be configured by a first member, opposing plate portion, connecting portion, and pressure applying portion having various other configurations. [Industrial Applicability]

[0154] The present invention can be applied to an applicator used for transdermal administration of a drug. [Explanation of symbols]

[0155] 1,101: applicator, 2,102: main body, 3: clamping plate, 4,104: cartridge, 4A: tip surface, 4B: tip back, 5,105: mounting, 11A: tip, 12: through hole, 20: housing, 21: lock groove, 22: slide groove, 23: slider, 24,124: spring, 25: spring receiving portion, 31: opposing plate, 31A: opposing surface, 32: clamping connection portion, 40: cartridge main body, 41,141: gas socket, 46, 146: drug storage section, 62, 162: microneedle, 63, 163: microneedle sheet, 120: cap section, 121: spacer vertical hole, 124: spring, 125: spring holding section, 126: recess, 129: male screw, 130: lower plate section, 132: connecting protrusion section, 134: spring, 140: connecting section, 142: housing, 142A: protrusion section, 150: upper plate section, 153: connecting hole section, 161: spacer plate

Claims

1. a drug storage section for storing an administration drug; A plurality of microneedles having hollow holes connected to the drug storage portion; a cartridge portion having a gasket aligned with the medicine storage portion in a first direction and sealing the medicine storage portion; a detachable mounting portion for detachably mounting the cartridge portion; a main body portion having a moving portion that, when the cartridge portion is attached, can move the gasket in a first direction that is a transverse direction that intersects with the axial direction of the microneedle; An applicator comprising:

2. The detachable attachment portion is The cartridge portion is fitted into a hole provided in a plate-like member.

2. The applicator of claim 1.

3. The moving unit is The gasket is moved by stretching the contracted elastic body.

3. The applicator according to claim 1, wherein the adhesive layer is a viscoelastic material.

4. The moving unit is The main body is housed in a housing, The detachable attachment portion is A hole is provided in a plate-like member extending from the housing in the cross direction.

2. The applicator of claim 1.

5. The moving unit is When the gasket is moved, it protrudes from the housing, but when the cartridge part is attached or detached, 90% or more of the gasket is housed in the housing.

5. The applicator of claim 4.

6. a housing section that houses the cartridge section and the moving section in a state where they are adjacent to each other; 2. The applicator of claim 1, further comprising:

7. a drug storage section for storing an administration drug; A plurality of microneedles having hollow holes connected to the drug storage portion; a gasket that is arranged in a straight line with the drug storage unit in a first direction intersecting the axial direction of the microneedle, seals the drug storage unit, and is movable toward the drug storage unit; an attachment portion for attaching the gasket to a main body portion having a moving portion that is movable in the first direction; The axial direction of the plurality of microneedles is A direction intersecting the first direction A cartridge for an applicator.

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