Administration device

Abstract

Provided is an administration device having a novel structure with which makes it possible for any user to effectively administer a substance to be administered such as a powdery drug to the site called the olfactory region in the nasal cavity. This device includes: a gas generator; a valve part; an injection cylindrical body 50; a flexible portion 51 formed on the distal side of the injection cylindrical body 50; a nozzle end portion 53 having a discharge port 54; and a posture control projection portion 52. When the posture control projection portion 52 is positioned on the nostril floor, the flexible portion 51 deforms along the contour in the external nostril formed between the nasal septal cartilage and the upper lateral cartilage, while the nozzle end portion 53 is positioned on the nose-dorsum side around the region in the external nostril in which the upper lateral cartilage meets the nasal bone.

Description

Administration device

[0001] The present invention relates to an administration device, and more particularly to the structure of an administration device for administering a predetermined dose of a drug or the like to the nasal cavity or the like.

[0002] Generally, a treatment method of administering a powder drug into the nasal cavity to a patient having a disease such as rhinitis or nasal allergy is known. In this treatment method, a powder drug filled in a capsule is administered into the nasal cavity using a dedicated drug administration device. Further, conventionally, drug administration devices used for this treatment method have been devised (see, for example, Patent Documents 1 to 3).

[0003] Such nasal administration of a powder drug or the like is not only for local treatment such as rhinitis treatment, but in recent years, it is also for preventing or treating systemic diseases, central nervous system diseases, infectious diseases, etc., and further, attempts have been made to use it for brain transfer called Nose-to-Brain delivery. Along with this, various nasal administration preparations and nasal administration devices have been provided (see FIG. 29).

[0004] The brain transfer called Nose-to-Brain delivery is, for example, administering a drug to a part of the mucosa in the upper part of the nasal cavity where there is an olfactory epithelium that controls olfaction (referred to as the olfactory part), and delivering the drug from the olfactory part to the brain (see FIG. 1). In this case, drug candidates do not pass or hardly pass through the blood-brain barrier (BBB). By delivering such a drug from the olfactory part to the brain, it is expected to have the effect of directly delivering the drug from the olfactory part to the brain without going through the blood (see FIG. 29). In such Nose-to-Brain delivery, how to efficiently administer a powder drug or the like to the olfactory region is one of the important points.

[0005] Japanese Patent No. 6339371, Japanese Patent No. 6959708, US Patent Application Publication No. 2016 / 0129205

[0006] However, the structure of the external nostrils and nasal cavity is complex, and the olfactory region in particular is located in a deep, narrow area in the upper part of the nasal cavity, with a very limited surface area. Therefore, there is a challenge in delivering drugs to the olfactory region with general administration devices (see Figure 25(B)). Furthermore, compared to liquid drugs, powdered drugs tend to scatter due to airflow when sprayed from an administration device, which easily hinders delivery to the target olfactory region. Against this backdrop, there is currently no administration device suitable for efficiently delivering powdered drugs to the olfactory region in a predetermined amount to the nasal cavity, and there is room for improvement in this respect.

[0007] Therefore, the present invention aims to provide a novel administration device with a structure that allows any user to efficiently administer a substance, such as a powdered drug, to a part of the nasal cavity called the olfactory region.

[0008] To solve these problems, the inventors conducted various studies. One of the characteristics considered important for efficiently administering a substance to the olfactory region within the nasal cavity is the spray characteristics of the administration device. This can be described as an approach that involves calculating a suitable range by focusing on various parameters such as the air pressure during spraying, the time to reach the maximum air pressure, and the time during which the spray is performed at an air pressure of 10 kPa or more, and then creating a device that can realize such spray characteristics. However, the inventors have now considered another important factor, in addition to these characteristics, focusing on the position and orientation (position and direction of the nozzle inside the nostril) when spraying the powdered formulation. In other words, focusing on three important points (see Figure 14), (1) ensuring the nozzle tip reaches a predetermined position inside the nostril, (2) ensuring that the administered substance, such as powdered drugs, can be administered while avoiding the inner wall of the nostril formed between the nasal septum cartilage and the superior lateral nasal cartilage (see Figures 30 and 31), and (3) ensuring that the position and orientation of the nozzle can be appropriately controlled while the nozzle is inserted into the nostril without causing pain to the user, we conducted repeated tests and studies, keeping in mind the structure of the nostril and nasal cavity, and found that it is preferable to spray the powdered formulation by positioning the nozzle for spraying the powdered drug on the dorsal side of the nose, around the area inside the nostril where the superior lateral nasal cartilage and the nasal bone intersect, rather than aiming directly at the olfactory region from the nostril, and then spraying so that the powdered drug is delivered to the olfactory region along the upper ridge inside the nostril and nasal cavity after spraying (see Figure 1).

[0009] One aspect of the present invention, based on such findings, is an administration device for administering a predetermined amount of a substance to be administered, such as a powdered drug, to the olfactory region of the nasal cavity, comprising: a gas generator that generates air or gas; a valve that is opened when the gas generator is operated by a user or the like; a spray cylinder that communicates with the gas generator via the valve and extends at least in part along a predetermined axis; a flexible portion formed on the tip side of the spray cylinder, which is at least in part flexible; a nozzle end formed at the tip of the spray cylinder and having an outlet for ejecting the substance to be administered; and a posture control projection formed on a part of the spray cylinder, which is sized to be inserted into the nasal cavity through the user's external nares, wherein by positioning the posture control projection at the nostril floor, the flexible portion is positioned to contact the nasal septal cartilage and the upper lateral nasal cartilage. This administration device is configured such that the nozzle tip is positioned around the area within the nostril where the upper lateral cartilage and the nasal bone intersect on the dorsum of the nose side, while deforming to conform to the shape of the inside of the nostril formed between the nostril and the cartilage.

[0010] With this configured administration device, the spraying cylinder, including the nozzle end and the flexible posture control projection, is inserted into the user's nostril. By positioning the posture control projection at the bottom of the nostril, the flexible portion deforms to conform to the shape of the nostril formed between the nasal septal cartilage and the upper lateral cartilage. The nozzle end is positioned around the area of ​​the nostril where the upper lateral cartilage and the nasal bone intersect on the dorsum of the nose side. This clears the three important points mentioned above and makes it easier to adopt a posture that sprays powdered drugs along the upper ridge of the nostril and nasal cavity.

[0011] In the above-described administration device, a bent portion may be formed in the middle of the spray cylinder.

[0012] In the above-described administration device, the bent portion may be formed such that the spray cylinder bends in the direction opposite to the direction in which the attitude control projection protrudes.

[0013] In the above-described administration device, the relative bending angle of the bent portion with respect to the non-bent portion may be 17.5 degrees or more and 55 degrees or less.

[0014] In the above-described administration device, the attitude control protrusion may be formed such that, in the cross-section at the maximum protrusion of the attitude control protrusion, the length from the side of the spray cylinder to the maximum protrusion is greater than that of the external nostril.

[0015] In the above-described administration device, the maximum protrusion of the posture control projection may be formed in a rounded shape.

[0016] In the above-described administration device, a notch may be provided in the portion of the posture control projection that is closer to the proximal end than the maximum protrusion.

[0017] In the above-described administration device, multiple notches may be provided.

[0018] In the above-described administration device, a movable piece may be provided between the multiple incisions.

[0019] In the above-described administration device, the flexible portion may be made of a flexible material.

[0020] In the above-described administration device, the nozzle end may have a length sufficient to allow the outlet to reach a predetermined position inside the nostril.

[0021] In the above-described administration device, the flexible portion may be flattened such that the direction in which the posture control protrusion protrudes is wider.

[0022] In the above-described administration device, the surface of the flexible portion may have irregularities formed on it.

[0023] In the above-described administration device, the uneven portion may be formed in a pleated manner by a plurality of grooves that are continuous in the longitudinal direction of the flexible portion.

[0024] In the above-described administration device, the groove may extend in the width direction of the flexible portion.

[0025] In the above-described administration device, the groove may encircle the flexible portion.

[0026] In the above-described administration device, the grooves may be inclined with respect to a direction perpendicular to the longitudinal direction of the flexible portion.

[0027] In the above-described administration device, the groove may be inclined in a direction perpendicular to the longitudinal direction of the flexible portion, such that when the flexible portion bends within the nostril, the nozzle moves away from the user's maxilla.

[0028] In the above-described administration device, a guard portion may be formed around the nozzle end outlet, protruding outward from the outlet.

[0029] In the above-described administration device, the gas generator may be a pump member that deforms and reduces its internal volume when pressed by the user or the like, thereby generating air.

[0030] According to the present invention, it is possible to provide a novel administration device with a structure that allows any user to efficiently administer a substance, such as a powdered drug, to a part of the nasal cavity called the olfactory region.

[0031] This figure illustrates how powdered drug sprayed from an administration device is delivered to the olfactory region along the ridge of the upper nasal cavity. This is a perspective view showing an example of the structure of an administration device according to one embodiment of the present invention. This is an exploded perspective view of the administration device. This is an exploded perspective view of the administration device viewed from the bottom side. This is a perspective view showing an example of the configuration of a holder (guide member) and a piercer (perforating member). (A) Plan view, (B) Front view, (C) Side view of the holder. This is a longitudinal cross-sectional view of the holder along line VII-VII in Figure 6(A). This is a longitudinal cross-sectional view of the holder along line VIII-VIII in Figure 6(A). This is a bottom view of the holder. (A) Plan view, (B) Longitudinal cross-sectional view along line bb, (C) Bottom view of the piercer. This is a perspective view of the piercer viewed from the proximal end side. This is a longitudinal cross-sectional view of the piercer and holder along line XII-XII in Figure 5. This is a longitudinal cross-sectional view of the piercer and holder along line XIII-XIII in Figure 5. (A) A view of the inside of the nostril showing the state when the nozzle end of the administration device is inserted into the external nostril, and (B) an enlarged view thereof. Figures illustrating the control of the orientation of the nozzle end based on its shape: (A) the administration device of this embodiment, (B) a conventional device shown as a reference example, and (C) a device without a stopper shown as a reference example. (A) A figure illustrating the force acting on the administration device when inserted into the nostril and its direction, and (B) a figure showing the state when powdered drug is sprayed from the nozzle end. (A) A figure showing how the flexible part of the administration device bends along the structure inside the nostril, and (B) and (C) reference figures showing the state when a non-flexible nozzle end is inserted into the nostril. Figures (A) to (E) show various shapes of the uneven parts formed by grooves in the spray cylinder of the administration device. Perspectives showing examples of the shape around the nozzle end's outlet, respectively (A) and (B). Perspectives showing examples of the stopper's shape, respectively (A) and (B). Figures showing the general shape of the nostril / nasal cavity portion, respectively (A) viewed from above, (B) viewed from the front, and (C) viewed from the side.The diagram shows the change in shape of the administration device inside the nostril when the administration device is inserted: (A) Cross-sectional view of the left nostril cut at five different positions, (B) Diagram showing the cross-sectional surface of the administration device inserted into the left nostril, cut at the five positions, with the cross-sections shown in gray, and (C) A superimposed view of (A) and (B). The diagram also explains the effect of deformation inside the nostril due to the pleated shape of the flexible portion formed by multiple grooves: (A) Diagram showing the administration device with the flexible portion inserted inside the nostril, (B) Diagram showing a suitable example of a flexible portion with a pleated shape that naturally conforms to the shape inside the nostril, (C) Diagram showing how the flexible portion shown in (B) naturally conforms to the shape inside the nostril, along with a cross-section along line XII-XII, (D) Diagram showing an example of a flexible portion with a different pleated shape, and (E) Diagram showing how the flexible portion shown in (D) looks when inserted into the nostril, along with a cross-section along line XII-XII. Figures (A) to (C) show the behavior of the stopper (posture control projection) when the flexible part of the administration device is inserted into the nostril. (A) is a figure illustrating the difference in the distribution behavior of the sprayed powdered drug between the administration device of this embodiment and (B) a conventional device. This is a front view showing the behavior of the administration device of this embodiment when inserted into the nostril. This is an exploded perspective view showing an example of the configuration of an administration device that employs a canister as a gas generator, such as a container capable of supplying air or gas. (A) is a side view showing an example of the configuration of an administration device that employs a canister as a gas generator, and (B) is a cross-sectional view along the bb line. This is a figure illustrating the general process from when the powdered drug sprayed into the nasal cavity is absorbed in the olfactory region and delivered to the brain. This is a front view of the area around the nose on the face, illustrating the nasal septum cartilage and the superior lateral nasal cartilage. This is a side view of the area around the nose on the face, illustrating the superior lateral nasal cartilage, the dorsum of the nose, and the nasal bone. These are (A) a side view and (B) a front view of the skull, illustrating the maxilla.

[0032] The configuration of the present invention will be described in detail below based on an example of an embodiment shown in the drawings.

[0033] [Example of administration device configuration] The administration device 1 is a transnasal administration device for administering a predetermined amount of a substance to be administered, such as a powdered drug, into the olfactory region of the nasal cavity (see Figure 3, etc.). The administration device 1 in this embodiment is configured to include a pump member 10, a piercer 20, a holder 30, a lid member 40, a spray cylinder 50, etc. (see Figure 2, etc.).

[0034] The pump member 10 functions as a gas generator for supplying air. When the administration device 1 is in use, it supplies air to eject the substance to be administered, such as powdered drug M, from the nozzle 54 of the spray cylinder 50. In this embodiment, the pump member 10 is a component in which the bellows-shaped container is crushed in the axial direction of the central axis (axis) 1C by the user pressing the pressure-receiving portion 12 at the bottom 13 with their finger, thereby reducing the internal volume (see Figure 2, etc.). The pump member 10 has an opening 11, a pressure-receiving portion 12, a bottom 13, a bellows portion 14, and a shoulder portion 15. Although the posture in which the administration device 1 is used is not strictly limited, it is generally assumed that it is used in a posture in which the spray cylinder 50 is above the pump member 10. In this embodiment, the position in which the injection cylinder 50 is above the pump member 10 is conveniently designated as the operating position, and in this position, the upper part is positioned as "up" and the opposite side (towards the bottom 13) as "down" along the central axis (axis line) 1C, and the explanation below will proceed accordingly (see Figure 2, etc.).

[0035] The specific shape of the pump member 10 is not particularly limited, but as an example, in this embodiment, a pump with a tapered vertical cross-section is used, which narrows as it approaches the bottom 13 of the pump member 10 from the shoulder portion 15 formed at the lower part of the opening 11 (see Figures 2 to 4). In order to efficiently produce jet air from a small pump, it is preferable to make the pump a shape that is easily contractible (easily crushed) so that the air corresponding to the volume of the pump can be used as jet air as possible. When the pump member 10 is tapered in this way, the overlap of the peaks of the bellows portion 14 when the pump member 10 is contracted shifts slightly, so the pump can be efficiently contracted with a small reaction force (the force that causes the pump to return to its original shape). As a result, even with a small pump, the user can produce jet air with little force. In addition, when the bottom 13 is narrow, the position where the user places their thumb is more uniform when using it, so when the pump member 10 is contracted, the movement of the bottom 13 from side to side is suppressed, and the contraction operation is stabilized. Therefore, there is also the advantage that differences in the shrinking behavior from one user to another will be less likely to occur.

[0036] The shoulder portion 15 of the pump member 10 is shaped to allow users such as patients (including doctors who administer medication to patients) to easily grip it with their fingers, especially their index and middle fingers (see Figures 2 to 4). Users can easily grip the shoulder portion 15, which is located on either side of the lid portion 40, with their index and middle fingers, and press the bottom portion 13 with their thumb to contract the pump member 10. The surface of the shoulder portion 15 may be provided with grooves or other features that function as an anti-slip surface 17 to prevent fingers from slipping.

[0037] The cross-sectional shape of the pump member 10 (the shape of the cross section perpendicular to the central axis 1C) is also not limited and may be circular, for example, but in this embodiment, a pump with a cross-sectional shape that is roughly oval or elliptical, or a shape that is flattened in one direction, is used (see Figures 2 to 4).

[0038] The opening 11 of the pump member 10 is located above the pump member 10. The opening 11 is provided with a projection, such as a male screw 16, for attaching the lid member 40. The pressed portion 12 is located at the bottom 13 and is shaped to be easily pressed by the user with their finger, for example, flat or gently concave.

[0039] As long as it functions as described above, the specific shape, structure, and materials of the pump member 10 are not particularly limited. For example, in this embodiment, a pump member 10 made of a blow-molded product is used, but instead, a pump member 10 made of an injection-molded product, which has better molding accuracy than blow molding, may be used.

[0040] The piercer (perforating member) 20 moves in conjunction with the contraction operation of the pump member 10 and perforates a hole in the seal member 70 during this movement. The piercer 20 in this embodiment has a shaft portion 21, an upward-facing tip portion 22, and a base portion 28 that is pressed when the pump member 10 contracts. The tip portion 22 has a shape that facilitates perforation of the seal member 70, for example, a conical shape that tapers from the edge portion 25 towards the tip (see Figures 3, 4, 10, etc.).

[0041] The shaft portion 21 of the piercer 20 has a groove portion 26 that extends along the direction of movement of the piercer 20. In this embodiment, a piercer 20 is used in which the shaft portion 21 has a cross shape in cross shape and groove portions 26 are formed on all four sides (see Figures 3 and 4).

[0042] The back side of the tip portion 22 of the piercer 20 is the back surface portion 24. The back surface portion 24 is formed so as to direct a portion of the air that flows into the cylindrical space 42 of the lid member 40 through the perforation provided in the sealing member 70 by the tip portion 22 radially outward. For example, the back surface portion 24 of the administration device 1 of this embodiment is inclined like an umbrella so that it approaches the tip portion as it moves from the radially outward to the inward (see Figures 10, 11, etc.). The back surface portion 24 of the piercer 20 formed in this way directs a portion of the air flowing into the cylindrical space 42 radially outward while creating a downward airflow, thereby reducing the residual powdered drug M in the filling space 42.

[0043] The guide member (hereinafter also referred to as "holder") 30 functions as a member that holds the piercer 20 and guides the piercer 20 while restricting the radial movement during the movement of the piercer 20. The holder 30 of the present embodiment has a large-diameter portion 31 and a sleeve-shaped small-diameter portion 32, and is formed by a stepped cylindrical body provided with a tip-side opening 35 in the large-diameter portion 31 and a base-end-side opening 36 in the small-diameter portion 32 (see FIGS. 3 and 4). In the large-diameter portion 31, a pair of slits 37 penetrating from the inner wall to the outer wall are provided at opposing positions (see FIGS. 5, 6, etc.). These slits 37 are locked to the locking protrusions 44b provided on the sleeve portion 44 of the lid member 40, so that the guide member 30 is locked to the lid member 40.

[0044] On the inner wall of the holder 30, as an example of fixing means for fixing the piercer 20 at a predetermined position, an upper-stage claw portion 33 for piercer fixing and a lower-stage claw portion 34 for piercer fixing are provided (see FIGS. 5 to 13, etc.). The upper-stage claw portion 33 for piercer fixing is formed by a pair of protrusions arranged to face the inner wall of the holder 30. The lower-stage claw portion 34 for piercer fixing is formed by a pair of protrusions arranged to face a position on the inner wall of the holder 30 that is closer to the base end side than the upper-stage claw portion 33 for piercer fixing (see FIG. 7, etc.). The distance (interval) between the opposing protrusions is slightly smaller than the maximum diameter of the tip portion 22 of the piercer 20, that is, the diameter of the edge portion 25 (see FIGS. 12, 13, etc.). Further, in the present embodiment, the protrusions (ribs) of the upper-stage claw portion 33 for piercer fixing and the lower-stage claw portion 34 for piercer fixing are arranged at positions 90 degrees apart in the circumferential direction (see FIG. 9, etc.), so that the circumferential positions are shifted from each other, and molding by an injection molding machine is enabled.

[0045] The upper claw portion 33 and the lower claw portion 34 for fixing the piercer have inclined surfaces that protrude more from the inner wall of the holder 30 as the piercer 20 moves from the base end to the tip end (see Figures 12, 13, etc.). The piercer 20 is positioned such that its edge portion 25 is located between the upper claw portion 33 and the lower claw portion 34 in the axial direction. When the piercer 20 is pressed toward the tip end, the edge portion 25 of the piercer 20 can move toward the tip end by overcoming the upper claw portion 33 (see Figure 13, etc.). On the other hand, even if the piercer 20 is pulled toward the base end, the edge portion 25 of the piercer 20 cannot overcome the lower claw portion 34 (see Figure 12, etc.). In this state, the piercer 20 is in a predetermined position and is configured to move when pressed. The piercer 20 and holder 30 are configured to open when operated by the user, and by opening, they form a valve section (indicated by reference numeral 60) that connects the pump member 10 and the injection cylinder 50 (see Figures 5, 12, etc.).

[0046] Furthermore, in the administration device 1 of this embodiment, the base end 28 of the piercer 20 and the bottom 13 of the pump member 10 are separated in the state before use, and a predetermined clearance is formed between them (see Figure 2). By appropriately changing the size of this clearance, the air pressure when administering the powdered drug M can be changed.

[0047] The lid member 40 is a member that can be attached to and detached from the opening 11 of the pump member 10. Inside the lid member 40, a cylindrical space 42 that can be filled with the powdery drug M is formed. The upper side of the lid member 40 is a tip cylindrical portion 43 to which the flexible injection cylindrical body 50 can be attached and detached. A flange portion 43f is provided at the tip of the tip cylindrical portion 43, so that the adhesion to the injection cylindrical body 50 is improved. On the lower side of the lid member 40, a sleeve portion 44 that fits with the large-diameter portion 31 of the holder 30 is provided. On the circumferential surface of the sleeve 44, a locking projection 44b for locking the slit 37 of the holder 30 is provided (see FIG. 4). The open end 44a of the sleeve portion 44 is sealed with a seal member 70 (see FIG. 4). The outside of the sleeve portion 44 is a lid portion 45 that engages with the opening 11 of the pump member 10. On the inner circumferential surface of this lid portion 45, a female screw portion 46 that is screwed with the male screw portion 16 of the opening 11 of the pump member 10 is provided (see FIG. 4). On the outer circumferential surface of the lid portion 45, a projection 47 that serves as an anti-slip when attaching the lid member 45 to the opening 11 of the pump member 10 is provided.

[0048] The injection cylindrical body 50 is constituted by a cylindrical member that communicates with the lid member 40. The injection cylindrical body 50 of the present embodiment is entirely formed in a cylindrical shape by a flexible material having flexibility such as a rubber material (see FIG. 2 etc.). The injection cylindrical body 50 is provided with a base-end side opening 50a, a flexible portion 51, a stopper 52, a nozzle end portion 53, a jet outlet 54, a bent portion 56, and a bridge portion 58. In the state where the injection cylindrical body 50 is attached to the lid member 40, the portion from the base-end side opening 50a to the bent portion 56 extends along the central axis (axis) 1C and has a shape that bends at the bent portion 56 (see FIG. 16 etc.). In FIG. 16, the central axis of the portion from the base-end side opening 50a extending along the central axis 1C to the bent portion 56 of the injection cylindrical body 50 is indicated by reference numeral 50C.

[0049] The base-end side opening 50a is a cylindrical portion that is attached to and detached from the outer circumference of the tip cylindrical portion 43 of the lid member 40. The injection cylindrical body 50 can be attached to the lid member 40 in an airtight manner by covering the outer circumference of the tip cylindrical portion 43 with the base-end side opening 50a.

[0050] The flexible portion 51 is a part formed on the tip side of the spray cylinder 50 that is flexible in at least part. As described above, the entire spray cylinder 50 of this embodiment is made of a flexible material such as rubber, and of these, the base end opening 50a and its surrounding area, which are placed over the outer circumference of the tip cylindrical portion 43 of the relatively rigid lid member 40, lose their flexibility, so the portion excluding the base end opening 50a and its surrounding area functions as a flexible portion 51. When the user inserts the spray cylinder 50 into the nasal cavity from the external nares, the flexible portion 51 can deform to conform to the shape of the nasal cavity. A bent portion 56 is formed in the middle of the flexible portion 51.

[0051] The stopper (posture control projection) 52 is insertable into the user's external nares, and when inserted into the external nares, it is formed to control the posture of the spray cylinder 50 so that the nozzle end 53 is located around the area within the external nares (see Figures 30 and 31) where the upper lateral cartilage and nasal bone intersect on the dorsum of the nose side. Thus, as long as it is insertable into the external nares and capable of such posture control when inserted, its shape and size are not particularly limited. As an example, in this embodiment, a roughly triangular stopper 52 is provided at a portion closer to the tip than the bent portion 56 (closer to the nozzle 54), protruding in the opposite direction to the direction in which the bent portion 56 bends (see Figure 16, etc.). The stopper 52 is formed such that the length W52 from the side portion 50s of the spray cylinder 50 to the maximum protrusion 52p is larger than a predetermined length, for example, the size of the nostrils of a user in a certain age group that could be assumed to be a user. Here, the length W52 from the side portion 50s to the maximum protrusion 52p refers to the length shown in the cross-section of the stopper 52 at the maximum protrusion 52p (see Figure 16(A), etc.).

[0052] When the stopper 52 formed in this manner is inserted into the nostril, it reaches the area at the back of the nostril called the nostril floor or nasal vestibule (see Figures 14, 15, 17, 24, 29, etc.). At this time, if the side of the spraying cylinder 50 (the side without the stopper 52) 50s, more specifically the bridge portion 58 described later, is in contact with the part of the nostril closer to the nasal tip, then that part (the part of the nostril closer to the nasal tip) becomes the point of force application and the position of the stopper 52 becomes the fulcrum, and a force acts on the nozzle end 53 that pulls it towards the dorsum of the nose (see Figure 16). As a result, the nozzle end 53 is positioned around the area within the nostril where the upper lateral cartilage and the nasal bone intersect on the dorsum of the nose side (see Figures 30, 31).

[0053] The stopper 52 possesses both flexibility and a shape that allows for smooth and painless insertion into the nostril. For example, in this embodiment, the stopper 52 is formed so that the maximum protruding portion 52p has a rounded R shape (see Figure 16, etc.). When the maximum protruding portion 52p has such a shape, the pain that the user may feel when inserting the maximum protruding portion 52p into the nostril, or when the maximum protruding portion 52p acts as a fulcrum while contacting the nostril floor or nasal vestibule, is alleviated. In addition, a plurality of notches 52k are provided in the portion of the stopper 52 that is closer to the proximal end than the maximum protruding portion 52p (in other words, the portion that faces downwards to the user when inserted into the nostril) 52b (see Figures 16, 20, etc.). With the notches 52k provided in this manner, when the stopper 52 is removed from the nostril after insertion, the stopper 52 is more likely to deform so as to tilt toward the nozzle end 53, making it easier to remove from the nostril without feeling pain. The number and shape of the notches 52k are not particularly limited; for example, they may be configured with multiple horizontal grooves (see Figure 20(A)), or they may be configured with grooves formed along the direction in which the maximum protruding portion 52p protrudes (see Figure 20(B)). Furthermore, multiple notches 52k such as these may form a movable piece 52h that is easily deformed in response to external force between these notches 52k (see Figure 20(B)).

[0054] The nozzle end 53 is the part formed at the tip of the spraying cylinder 50, and is used to eject the substance to be administered, such as powdered drug M. Of the flexible part 51, the nozzle end 53 has a flattened shape such that the direction in which the stopper 52 protrudes is wider, and it is easy to bend in the direction in which it is narrower (see Figures 2 and 23, etc.). The width of the nozzle end 53 should be such that there is very little resistance when inserting it into the nostril, and the nozzle end 53 does not move too much inside the nostril. An outlet 54 for ejecting the substance to be administered is provided at the tip of the nozzle end 53. The nozzle end 53 is long enough to allow the outlet 54 to reach a predetermined position inside the nostril, more specifically, it is long enough to direct the nozzle end 53 in the intended direction and deliver the substance to the olfactory region (see Figures 15(A) and (B)). A guard part 55 is formed around the outlet 54, protruding outward from the outlet 54 (see Figure 19).

[0055] The area around the nozzle 54 may be tapered to facilitate the administration of the drug, such as powdered medication M, into the user's nasal cavity. Additionally, the area around the nozzle 54 may be moderately rounded (see Figure 24, etc.).

[0056] The guard portion 55 prevents the nozzle 54 from being blocked by the inner wall of the nostril when the spray cylinder 50 is inserted into the nostril. The guard portion 50 may be formed by fine grooves (see Figure 19(A)) or by rounded protrusions that allow the spray cylinder 50 to be inserted more smoothly (see Figure 19(B)).

[0057] The bent portion 56 is formed in the middle of the spray cylinder 50. The spray cylinder 50 extends along the central axis 1C from the base end opening 50a to the bent portion 56, bends at the bent portion 56, and extends along the axis 50C from the bent portion 56 to the nozzle 54 (see Figure 16). The bent portion 56 is formed to bend in the opposite direction to the direction in which the stopper 52 protrudes. The range of the relative bend angle θ of the bent portion 56 with respect to the unbent portion (in other words, the angle of the axis 50C with respect to the central axis 1C) (see Figure 16) is not particularly limited, but from the viewpoint of making it easier to direct the nozzle end 53 in the intended direction after insertion into the external nostril and deliver the administered substance to the olfactory region, it is preferable that it be in the range of 17.5 degrees or more and 55 degrees or less.

[0058] The surface of the flexible portion 51 may have uneven surfaces 57. In the administration device 1 of this embodiment, the nozzle end 53 of the flexible portion 51 that is inserted into the external nostril has a fold-like uneven surface 57 formed by a plurality of grooves 57m that are continuous along the longitudinal direction (the axial direction of the axis 50C) (see Figure 16, etc.). The flexible portion 51 on which the fold-like uneven surface 57 is formed by the grooves 57m is easily bent in a direction perpendicular to the direction in which these grooves 57m extend. In this embodiment, the grooves 57m extend in the width direction of the flexible portion 51 and are formed to circumfer the flexible portion 51. These grooves 57m may be formed to extend in a direction perpendicular to the axis 50C, or they may be formed to be inclined with respect to the direction perpendicular to the axis 50C (see Figure 18). In this embodiment, the flexible portion 51 inserted into the nostril has a groove 57m that allows it to deform naturally to conform to the shape of the inner wall of the nostril, rather than being forcibly twisted against the shape of the inner wall of the nostril. In other words, the groove 57m is formed such that when the flexible portion 51 bends inside the nostril, the nozzle 54 tends to tilt away from the user's maxilla (see Figure 32) in a direction perpendicular to the axis 50C from the bent portion 56 to the tip of the spray cylinder 50 (see Figures 21 to 23, etc.). More specifically, the groove 57m is formed to slope downward to the right from the side without the stopper 52 to the side beyond the axis 50C where the stopper 52 is not provided, when viewed with the axis 50C in the vertical direction (see Figure 23(B)). The nozzle end 53 with the groove 57m formed in this way is easily deformed to conform naturally to the inner wall of the nostril (see Figure 23(C)). On the other hand, if the groove 57m is inclined in the opposite direction to the above (in the same way as above, it is inclined upward to the right) (see Figure 23(D)), when inserting the nozzle end 53 along the nostril, it may deform by twisting against the shape of the inner wall inside the nostril (see Figure 23(E)).

[0059] The bridge section 58 is formed by partially cutting out the inside of the side section 50s of the injection cylinder 50, either in the portion located on the opposite side of the stopper 52 across the axis 50C, or in the vicinity thereof (see Figure 16, etc.). Because the inside portion of the bridge section 58 is cut out to create space, it is more susceptible to bending when an external force is applied to the side section 50s.

[0060] The sealing member 70 is a member that seals the open end 44a of the sleeve portion 44 of the lid member 40 (see Figure 4). The sealing member 70 is preferably a moisture-proof film (for example, an aluminum sheet) that seals the internal space 42 of the cylinder and prevents the powdered chemical M from deteriorating due to air and moisture, and is also preferably a material that is easy to puncture with the tip portion 22 of the piercer 20 during use. In this embodiment, the sealing member 70 is used that maintains airtightness without tearing or peeling even when the internal pressure of the pump member 10 rises to a predetermined level.

[0061] [Operation and Operation of the Administration Device] Next, we will explain the operation of the administration device 1 and the associated operations when administering the powdered drug M.

[0062] To use the administration device 1, the user first removes the device from its box-shaped, blister-shaped, or bag-shaped package (not shown). Then, the user places their index and middle fingers on the shoulder portion 15 of the pump member 10 or the anti-slip 17 provided on the shoulder portion 15, and places their thumb on the bottom portion 1. With these fingers gripping the pump member 10, the user inserts the spray cylinder 50 into the external nostril from the nozzle 54 side (see Figure 24(A)). When the stopper 52 hits the external nares during the insertion process (see Figure 24(B)), the user inserts the spray cylinder 50 further, causing the stopper 52 to pass over the external nares and reach the area beyond, known as the nostril floor or nasal vestibule (see Figure 24(C)). In this state, the bridge portion 58 of the spray cylinder 50 comes into contact with the part of the nostril closer to the nasal tip, and is pressed and bends (see Figure 24(B)). At this time, the bridge portion 58 acts as the point of force application and the stopper 52 acts as the fulcrum, and a force acts on the nozzle end 53 toward the dorsum of the nose due to the lever principle (see Figures 16 and 24(C)). As a result of this force acting naturally, the nozzle end 53 is positioned around the area inside the nostril where the upper lateral cartilage and the nasal bone intersect on the dorsum of the nose side, and is facing the olfactory region (if there were no fulcrum, the nozzle 53' would move inside the nostril as shown in Figure 15(C), and its direction would not be fixed). In this state, when the user presses the pressed portion 12 with their thumb and pushes up the bottom 13, the powdered drug M is ejected from the nozzle 54 toward the olfactory region. According to this, it becomes possible to efficiently administer the powdered drug M to the olfactory region in nose-to-brain delivery. Moreover, a distinctive feature of the administration device 1 of this embodiment is that it does not aim linearly at the olfactory region, but rather sprays the powdered drug M so that it is carried along the ridge of the upper part of the nasal cavity (see Figure 1).

[0063] Furthermore, as already explained, when performing nose-to-brain delivery, the structure of the external nostrils and nasal cavity is complex, and in particular, the olfactory region is located in a narrow, deep area at the top of the nasal cavity, and its surface area is very limited. Therefore, a major challenge is that it is difficult to deliver drugs to the olfactory region with general administration devices (see Figures 21 and 25(B)). In this regard, with the administration device 1 as in this embodiment, the nozzle end 53 is flexible, and the pleated uneven portion 57 formed by multiple grooves 57m easily bends naturally along the structure inside the external nostril (see Figures 22, 25(A), and 26), so that the nozzle end 53 faces the olfactory region, making it possible to efficiently administer the powdered drug M to the olfactory region (see Figures 17(A), (C), etc.). If the nozzle were not flexible, the tip of the nozzle would not face the olfactory region. In this case, it is expected that the sprayed powdered drug M would hit the wall inside the nasal cavity and disperse (see Figure 17(B)).

[0064] Thus, the administration device 1 of this embodiment has features not found in conventional administration devices, such as: (1) the shape and size of the nozzle end 53 is such that the spray nozzle 54 at the tip of the nozzle end 53 is easily accessible to a predetermined position (a position where the nozzle end 53 faces the intended direction and is sufficient to deliver the powdered drug M to the olfactory region) (see the part indicated by reference numeral (1) in Figure 14); (2) the powdered drug M can be administered while avoiding the nasal septum (see the part indicated by reference numeral (2) in Figure 14); and (3) the nozzle end 53 is inserted into the external nostril in a direction that facilitates delivery of the powdered drug M to the olfactory region, and the movement of the nozzle end 53 is controlled by the stopper 52 to determine the position of the nozzle end 53 (see the part indicated by reference numeral (3) in Figure 14).

[0065] Here, we will also mention the operation of the administration device 1 when the user presses the pressure-sensitive part 12 with their thumb to push up the bottom 13. When the user presses the pressure-sensitive part 12 to push up the bottom 13, the pump member 10 contracts by the amount of clearance, and the bottom 13 comes into contact with the base end 28 of the piercer 20. After the operation of the pump member 10 begins, the piercer 20 remains held in the holder 30 until the bottom 13 comes into contact with the base end 28 of the piercer 20, and does not puncture the sealing member 70, so the air inside the pump member 10 does not flow into the lid member 40. As a result, the internal pressure of the pump member 10 increases by the amount that the pump member 10 contracts.

[0066] After the bottom portion 13 contacts the base end portion 28 of the piercer 20, the user's pumping force is directly transmitted to the piercer 20 via the bottom portion 13. When the user continues to press the bottom portion 13 and the pumping force exceeds a predetermined value, a force that detaches the piercer 20 ("piercer detachment force") is applied, causing the edge portion 25 of the piercer 20 to overcome the upper claw portion 33 for fixing the piercer, and the piercer 20 becomes movable relative to the holder 30.

[0067] After detaching from the holder 30, the piercer 20, if continued to be pressed, will bring its tip 22 into contact with the sealing member 70 and begin to puncture it. Consequently, air in the pump member 10 begins to flow into the lid member 40. While the piercer 20 is puncturing the sealing member 70 (but before the tip 22 has penetrated the sealing member 70), the pump force gradually increases due to the resistance from the sealing member 70, as well as the internal pressure of the pump member 10 and the reaction force of the bellows section 14. The pump force peaks just before the tip 22 of the piercer 20 penetrates the sealing member 70, and then rapidly decreases once the tip 22 has penetrated the sealing member 70. As the tip 22 of the piercer 20 penetrates the sealing member 70, air rushes into the lid member 40, and the powdered drug M is ejected from the nozzle 54 of the spray cylinder 50.

[0068] The movement of air and powdered chemical agent M during spraying will now be explained. Air inside the pump member 10 flows through the space between the groove 26 of the piercer 20 and the holder 30, passes through the perforations formed in the seal member 70, and flows into the cylindrical space 42 inside the lid member 40. At least a portion of the air that flows into the lid member 40 flows in a downward direction while moving radially outward due to the back surface 24 of the piercer 20, and then passes through the tip cylindrical portion 43 towards the spraying cylinder 50. This flow of air within the cylindrical space 42 inside the lid member 40 causes powdered chemical agent M, which tends to remain near the corners of the cylindrical space inside the lid member 40, to be sprayed out, thereby reducing the amount of powdered chemical agent M remaining in the cylindrical space 42.

[0069] Furthermore, in the administration device 1 of this embodiment, the pump member 10 and the piercer 20 are pushed in all the way to their final position (in this embodiment, the position where the bottom 13 contacts the base end opening 36 of the holder 30 and stops moving) by the momentum of the pump pressing force when it reaches its peak. Generally, differences in the magnitude and manner of change of the pump pressing force can occur due to differences in various factors such as the user and usage conditions, but with the administration device 1 of this embodiment, which realizes the operation described above, the variation in pressing force when the tip 22 of the piercer 20 penetrates the sealing member 70 is reduced, and as a result, the variation in the spraying pattern of the powdered drug M is suppressed.

[0070] After the above-described operation, the pump member 10 and the piercer 20 stop moving when they reach their final position (in this embodiment, the position where the bottom portion 13 abuts against the base end opening 36 of the holder 30 and stops moving), and the pump operation ends.

[0071] The above-described embodiment is merely one example of a preferred implementation of the present invention, and is not limited thereto. Various modifications are possible without departing from the spirit of the invention. For example, in the above-described embodiment, a pump member 10 was used as a device for generating air or gas, which serves as a medium for spraying the substance to be administered, such as a powdered drug M, but this is merely one preferred example. Instead of such a pump member 10, a container capable of supplying air or gas, such as a so-called canister 80, can be used as a gas generating device (see Figures 27 and 28). In the example administration device 1, a canister 80 is connected via a tube 81 to the opening 44a of a lid member 40, which is integrated with a sleeve-shaped outer cylinder member 90 by screwing it in place (the administration device 1 shown here is in a state where the spray cylinder 50 has been removed).

[0072] Some or all of the embodiments described above may also be described as follows. However, the present invention is not limited to the following. [Note 1] An administration device for administering a predetermined amount of a substance to be administered, such as a powdered drug, to the olfactory region of the nasal cavity, comprising: a gas generator that generates air or gas; a valve that opens when the gas generator is operated by the user, etc.; a spray cylinder that communicates with the gas generator via the valve and extends at least in part along a predetermined axis; a flexible part formed on the tip side of the spray cylinder, which is at least in part flexible; a nozzle end formed at the tip of the spray cylinder and having an outlet for ejecting the substance to be administered; and a posture control projection formed on a part of the spray cylinder, which is sized to be inserted into the nasal cavity through the user's external nares, wherein the posture control projection is positioned at the nostril floor, so that the flexible part is in contact with the nasal septal cartilage and the upper lateral nasal cartilage. An administration device configured such that the nozzle end is positioned around the region within the nostril where the upper lateral cartilage and the nasal bone intersect on the dorsum of the nose side, while deforming along the shape of the inside of the nostril formed between the nostril and the cartilage. [Note 2] The administration device according to Note 1, wherein a bent portion is formed in the middle of the spraying cylinder. [Note 3] The administration device according to Note 2, wherein the bent portion is formed such that the spraying cylinder bends in the opposite direction to the direction in which the attitude control projection protrudes. [Note 4] The administration device according to Note 2 or 3, wherein the relative bending angle of the bent portion with respect to the unbent portion is 17.5 degrees or more and 55 degrees or less. [Note 5] The administration device according to any one of Notes 1 to 4, wherein the attitude control projection is formed such that, in the cross-section of the maximum protrusion of the attitude control projection, the length from the side of the spraying cylinder to the maximum protrusion is greater than that of the nostril.[Note 6] The administration device according to Note 5, wherein the maximum protrusion of the posture control projection is formed in a rounded shape. [Note 7] The administration device according to Note 5 or 6, wherein a notch is provided in the portion of the posture control projection closer to the base end than the maximum protrusion. [Note 8] The administration device according to Note 7, wherein a plurality of the notches are provided. [Note 9] The administration device according to Note 8, wherein a movable piece is provided between the plurality of the notches. [Note 10] The administration device according to any one of Notes 1 to 9, wherein the flexible portion is formed of a flexible material. [Note 11] The administration device according to any one of Notes 1 to 10, wherein the flexible portion has a length sufficient to allow the nozzle to reach a predetermined position inside the nostril. [Note 12] The administration device according to any one of Notes 1 to 11, wherein the flexible portion is flattened so that the direction in which the posture control projection protrudes is wider. [Note 13] The administration device according to any one of Notes 1 to 11, wherein an uneven surface is formed on the surface of the flexible portion. [Note 14] The administration device according to Note 13, wherein the uneven surface is formed in a pleated shape by a plurality of grooves continuous in the longitudinal direction of the flexible portion. [Note 15] The administration device according to Note 14, wherein the grooves extend in the width direction of the flexible portion. [Note 16] The administration device according to Note 14 or 15, wherein the grooves encircle the flexible portion. [Note 17] The administration device according to any one of Notes 14 to 16, wherein the grooves are inclined with respect to a direction perpendicular to the longitudinal direction of the flexible portion. [Note 18] The administration device according to any one of Notes 14 to 17, wherein the grooves are inclined with respect to a direction perpendicular to the longitudinal direction of the flexible portion, in a direction that causes the nozzle to move away from the user's maxilla when the flexible portion is bent in the external nostril. [Note 19] The administration device according to any one of Notes 1 to 18, wherein a guard portion is formed around the nozzle end of the nozzle, protruding outward from the nozzle. [Note 20] The administration device according to any one of Notes 1 to 19, wherein the gas generator is a pump member that deforms and reduces its internal volume when pressed by a user or the like to generate air.

[0073] The present invention is particularly suitable for use in administration devices for administering a predetermined amount of a substance, such as a powdered drug, into the nasal cavity or the like.

[0074] 1...Administration device 1C...Central axis (axis) 10...Pump component (gas generator) 11...Opening 12...Pressed part 13...Bottom part 14...Bellows part 15...Shoulder part 16...Threaded part 17...Anti-slip 20...Piercer (perforating component) 21...Shaft part 22...Tip part 24...Back surface part 25...Edge part 26...Groove part 28...Base end part 30...Holder (guide component) 31...Large diameter part 32...Small diameter part 33...Upper claw part for fixing piercer 34...Lower claw part for fixing piercer 35...Opening on tip side 36...Opening on base end side 37...Slit 40...Lid component 42...Space inside the cylinder 43...Cylindrical tip part 43f...Flange part 44...Sleeve part 44a...Open end 44b...Locking projection 45...Lid part 46...Female thread section 47...Protrusion 50...Injection cylinder 50a...Base end opening 50C...Axis (from bent section 56 to tip) 50s...Side section 51...Flexible section 52...Stopper (attitude control projection) 52b...Base end section 52h...Movable piece 52k...Notch 52p...Maximum protrusion 53...Nozzle end 54...Outlet 55...Guard section 56...Bent section 57...Rough section 57m...Groove 58...Bridge section 60...Valve section 70...Sealing member 80...Canister (gas generator) 81...Tube 90...Outer cylinder member θ...Relative bending angle M...Powdered drug (substance to be administered) W52...Length of injection cylinder 50 from side section 50s to maximum protrusion 52p

Claims

1. An administration device for administering a predetermined amount of a substance, such as a powdered drug, to the olfactory region of the nasal cavity, comprising: a gas generator that generates air or gas; a valve that opens when the gas generator is operated by the user; a spray cylinder that communicates with the gas generator via the valve and extends at least in part along a predetermined axis; a flexible portion formed at the tip of the spray cylinder, which is at least in part flexible; a nozzle end formed at the tip of the spray cylinder and having an outlet for ejecting the substance; and a posture control projection formed in part of the spray cylinder, which is sized to be inserted into the nasal cavity through the user's external nares, wherein the posture control projection is positioned at the nostril floor, so that the flexible portion can be positioned between the nasal septal cartilage and the upper lateral nasal cartilage. An administration device configured such that the nozzle end is positioned around the area within the nostril where the upper lateral cartilage and the nasal bone intersect on the dorsum of the nose side, while deforming to conform to the shape of the inside of the nostril formed between the cartilage and the nostril.

2. The administration device according to claim 1, wherein a bent portion is formed in the middle of the spray cylinder.

3. The administration device according to claim 2, wherein the bent portion is formed such that the injection cylinder is bent in the opposite direction to the direction in which the attitude control projection protrudes.

4. The administration device according to claim 3, wherein the relative bending angle of the bent portion with respect to the non-bent portion is 17.5 degrees or more and 55 degrees or less.

5. The administration device according to claim 1, wherein the attitude control projection is formed such that, in a cross-section at the maximum protrusion of the attitude control projection, the length from the side of the injection cylinder to the maximum protrusion is greater than that of the external nostril.

6. The administration device according to claim 5, wherein the maximum protrusion of the attitude control projection is formed in a rounded shape.

7. The administration device according to claim 6, wherein a notch is provided in the portion of the attitude control projection closer to the proximal end than the maximum protrusion.

8. The administration device according to claim 7, wherein a plurality of the aforementioned incisions are provided.

9. The administration device according to claim 8, wherein a movable piece is provided between a plurality of the aforementioned notches.

10. The administration device according to claim 5, wherein the flexible portion is formed of a flexible material.

11. The administration device according to any one of claims 1 to 10, wherein the flexible portion has a length sufficient to allow the nozzle to reach a predetermined position inside the external nostril.

12. The administration device according to claim 11, wherein the flexible portion is flattened such that the direction in which the posture control protrusion protrudes is wider.

13. The administration device according to claim 11, wherein an uneven surface is formed on the surface of the flexible portion.

14. The administration device according to claim 13, wherein the uneven portion is formed in a pleated shape by a plurality of grooves that are continuous in the longitudinal direction of the flexible portion.

15. The administration device according to claim 14, wherein the groove extends in the width direction of the flexible portion.

16. The administration device according to claim 15, wherein the groove encircles the flexible portion.

17. The administration device according to claim 14, wherein the groove is inclined with respect to a direction perpendicular to the longitudinal direction of the flexible portion.

18. The administration device according to claim 17, wherein the groove is inclined in a direction perpendicular to the longitudinal direction of the flexible portion, such that when the flexible portion is bent within the nostril, the nozzle moves away from the user's maxilla.

19. The administration device according to any one of claims 1 to 10, wherein a guard portion is formed around the nozzle end of the nozzle outlet, protruding outward from the nozzle.

20. The administration device according to any one of claims 1 to 10, wherein the gas generating device is a pump member that deforms and reduces its internal volume when pressed by a user or the like to generate air.

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