Administration device and method for manufacturing administration device

Abstract

[Problem] To provide an administration device capable of preventing excessive release of a substance to be administered in an initial stage after placement, and a method for manufacturing the administration device. [Solution] An administration device 100 has a plug 170 mounted so as to close an opening 113a provided at the other end 113 in the longitudinal direction of a body portion 110. The plug has: a communication passage 175 communicating with a second region S2; and a discharge port 176 provided at the other end of the communication passage and discharging the substance 150 to be administered to the outside as a piston slides toward the other end side. The substance to be administered is held across from the second region to at least a part located on the one end side of the communication passage. A non-holding region 175 where the substance to be administered is not held is provided on the other end side of the communication passage.

Description

Dosing device and method for manufacturing the same

[0001] The present invention relates to an administration device that administers a substance such as a drug solution while being placed in a living body, and a method for manufacturing the administration device.

[0002] Patent Document 1 discloses a sustained administration type administration device that is capable of sustainedly releasing a drug solution, which is an administered substance, over a predetermined period of time while being placed (implanted) in a living body.

[0003] The device of Patent Document 1 has a hollow container, a piston slidably held within the container, an osmotic agent (working agent) that serves as a driving source for pressing the piston, a semipermeable membrane that allows liquid components in the body fluid to pass through, thereby enabling the body fluid to come into contact with the osmotic agent, and a delivery orifice (release portion) that is positioned at the tip side of the container and releases the medicinal liquid pressed by the piston.

[0004] The interior of the container of the device is divided into two regions by a piston: one region is a drug solution storage space located at the distal end of the container with the piston as the boundary, and the other region is an osmotic agent storage space located at the proximal end of the container, opposite the first region with the piston as the boundary.

[0005] The device of Patent Document 1 utilizes the principle of osmotic pressure to bring the liquid components of the body fluid that have permeated the semipermeable membrane into contact with an osmotic agent when releasing the drug solution. The osmotic agent swells upon contact with the liquid components, increasing the internal pressure of the osmotic agent-containing space. As the internal pressure of the osmotic agent-containing space increases, the piston slides toward the distal end, releasing the drug solution contained in the drug solution-containing space, which is partitioned distal to the osmotic agent-containing space, into the living body.

[0006] JP 2017-57212 A

[0007] Among the medicinal liquids selected as the substances to be administered in the administration device of Patent Document 1 and the like, while they are expected to have a significant therapeutic effect, some may cause serious side effects if released in excess of the prescribed dosage. Furthermore, some of these medicinal liquids may expand in volume when the temperature rises due to the body temperature or the like after the administration device is placed in the living body. An administration device equipped with such a medicinal liquid that expands in volume with a temperature rise may release an excessive amount of medicinal liquid into the living body in an amount greater than the expected release amount per unit time in the early stages after placement.

[0008] The present invention has been made in consideration of the above-mentioned problems, and aims to provide an administration device that can prevent excessive release of the administered substance in the early stages after placement, and a method for manufacturing such an administration device.

[0009] The present invention can be achieved by any one of the following means (1) to (6).

[0010] (1) An administration device that releases an administration substance while being placed in a living body, comprising: a main body portion having a cavity extending in the longitudinal direction; a liquid-permeable portion that is arranged on one longitudinal end side of the main body portion and is capable of allowing permeation of liquid components contained in bodily fluids in the living body in response to osmotic pressure; an active agent that is filled in a first region defined on the other longitudinal end side of the main body portion relative to the liquid-permeable portion and increases in volume as it comes into contact with the liquid component; a piston that is arranged on the other end side of the main body portion relative to the first region and slides toward the other end side as the volume of the active agent increases; the administration substance that is filled in a second region defined on the other end side of the main body portion relative to the position where the piston is arranged; and a plug attached to close an opening provided at the other end of the main body portion, wherein the plug has a communication passage that communicates with the second region, and a release port that is arranged at the other end of the communication passage and releases the administration substance to the outside as the piston slides toward the other end side of the main body portion, The substance to be administered is held over at least a portion of the second region located on one end side of the communicating passage, and a non-holding region in which the substance to be administered is not held is provided on the other end side of the communicating passage.

[0011] (2) The administration device described in (1) above, wherein the object to be administered is composed of a medicinal liquid whose volume expands due to the temperature difference between a predetermined storage temperature and a planned use temperature, and the non-retaining area of ​​the communicating passage has a flow path volume larger than the volume expansion amount of the medicinal liquid.

[0012] (3) The administration device described in (2) above, wherein the volume expansion amount (Q1) of the medicinal liquid, the flow path cross-sectional area (S) of the communicating passage, the length (L) of the non-retaining area of ​​the communicating passage, and the initial filling amount (Q2) of the medicinal liquid filled in the second area before volume expansion satisfy the relationship of the following formula (1).

[0013] Q1≦S×L≦Q2...(1) (4) An administration device described in any one of (1) to (3) above, wherein the communicating passage has a spirally extending groove portion formed on the outer surface of the plug.

[0014] (5) A method for manufacturing an administration device according to any one of (1) to (4) above, comprising the steps of: filling the second region with an amount of the substance to be administered that will overflow from the opening when the plug is attached while the substance to be administered is heated to a temperature at which the substance is to be used; attaching the plug to the main body to allow the substance to flow into the communicating passage; and cooling the main body to a predetermined storage temperature that is lower than the temperature at which the substance is to be used.

[0015] (6) A method for manufacturing the administration device described in any one of (1) to (4) above, comprising the steps of: heating the main body with the substance to be administered filled in the second region and the plug attached to the main body to a planned use temperature of the substance to be administered, and releasing at least a portion of the substance to be administered through the communication path and the release port; and cooling the main body to a predetermined storage temperature that is lower than the planned use temperature.

[0016] According to the above administration device, a non-retention area is provided in a portion of the other end of the communicating passage, so even if the volume of the administered substance expands in the early stages after placement, the expanded volume of the administered substance can be absorbed (retained) by an amount corresponding to the flow path volume of the non-retention area. Therefore, excessive release of a larger volume of the administered substance than expected can be prevented in the early stages after placement. Furthermore, according to the above administration device, there is no unfilled space (area) in the second region where the administered substance is not filled, and the administered substance is continuously retained between the second region and a portion of the one end of the communicating passage, so gas such as air is not trapped in the second region. Therefore, the above administration device can prevent excessive release of the administered substance due to volume expansion of gas such as air trapped in the second region in the early stages after placement.

[0017] FIG. 1 is a schematic cross-sectional view of an administration device according to an embodiment; FIG. 2 is a schematic cross-sectional view of an administration device according to an embodiment, showing the state when administering a substance to be administered; FIG. 3 is an enlarged view of dashed line portion 3A in FIG. 1; FIG. 4 is a perspective cross-sectional view showing an enlarged view of the vicinity of the other end of the administration device according to an embodiment; FIG. 5 is a view for explaining a manufacturing method of an administration device according to an embodiment; FIG. 6 is a view for explaining a manufacturing method of an administration device according to an embodiment; FIG. 7 is a view for explaining a manufacturing method of an administration device according to an embodiment; FIG. 8 is a view for explaining another example of a manufacturing method of an administration device according to an embodiment; FIG. 9 is a perspective cross-sectional view showing an enlarged view of the vicinity of the other end of an administration device according to Modification 1; FIG. 10 is a perspective cross-sectional view showing an enlarged view of the vicinity of the other end of an administration device according to Modification 2.

[0018] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. The embodiments shown here are merely examples for embodying the technical concept of the present invention and are not intended to limit the present invention. Furthermore, all other embodiments, examples, and operational techniques that can be conceived by those skilled in the art without departing from the spirit of the present invention are included within the scope and spirit of the present invention, as well as within the scope of the claims and their equivalents.

[0019] Furthermore, for the convenience of illustration and ease of understanding, the drawings attached to this specification may be represented schematically with the scale, aspect ratio, shape, etc. appropriately changed from the actual product, but these are merely examples and do not limit the interpretation of the present invention.

[0020] Furthermore, in the following description, when ordinal numbers such as "first" and "second" are used, unless otherwise specified, they are used for convenience and do not stipulate any particular order.

[0021] In the administration device 100 of the embodiment described below, the "one end side (base end side)" is the side where the liquid permeable portion 120 is disposed, and is indicated by the arrow X1 in the figure. The "other end side (tip end side)" is the side opposite the one end side where the plug 170 is disposed, and is indicated by the arrow X2. The longitudinal direction of the main body portion 110 (the direction along the central axis c1) is indicated by the arrows X1-X2.

[0022] An administration device 100 according to an embodiment will be described.

[0023] <Administration Device 100> The administration device 100 is a device that is placed in a living body and is continuously driven non-electrically to enable continuous administration of an administration subject 150 based on predetermined administration conditions.

[0024] Fig. 1 shows a longitudinal cross-sectional view of the administration device 100 before administering the substance 150. Fig. 2 shows the administration device 100 placed in a living body administering the substance 150.

[0025] The administration device 100 can release (administer) the substance to be administered 150 into a living body under predetermined administration conditions (administration conditions such as administration period and dosage) for sustained administration of the substance to be administered 150 into a living body. The administration device 100 can be configured to sustainedly administer the substance to be administered 150 over a long period of time (at least several weeks to several months, or even several years).

[0026] The administration device 100 according to this embodiment will be generally described with reference to FIGS. 1, 3, and 4, and comprises a main body 110 having a lumen 115 extending in the longitudinal direction, a liquid-permeable portion 120 arranged on one end 111 side of the main body 110 in the longitudinal direction and capable of allowing the passage of liquid components contained in bodily fluids in a living body in accordance with osmotic pressure, and a liquid-permeable portion 120 filled in a first region S1 partitioned on the other end 113 side of the main body 110 in the longitudinal direction. The device has an actuator 130 that increases the volume, a piston 140 that is positioned closer to the other end 113 of the main body 110 than the first region S1 and slides toward the other end 113 as the volume of the actuator 130 increases, an administered substance 150 filled in a second region S2 that is defined closer to the other end 113 of the main body 110 than the position where the piston 140 is positioned, and a plug 170 that is attached to close an opening 113a provided in the other end 113 of the main body 110.

[0027] 1 and 2, the main body 110 can be formed of a hollow tubular member that forms the housing of the administration device 100. An inner cavity 115 is formed inside the main body 110, extending between one end 111 and the other end 113 of the main body 110.

[0028] Because main body 110 has a cylindrical outer shape with lumen 115 extending in the longitudinal direction, it can be placed in a biological organ having a length in the longitudinal direction, such as a blood vessel or a tubular body cavity, and can suitably administer substance 150 into these biological organs. Note that the shape of main body 110 is not limited to a cylinder, and it may have, for example, a rectangular end face located at both ends in the longitudinal direction, or a prismatic shape with a polygonal cross section perpendicular to the longitudinal direction.

[0029] The administration device 100 has a liquid-permeable portion 120, an operating agent 130, a piston 140, an administration object 150, and a plug 170 arranged in this order from one end 111 to the other end 113 of the main body 110.

[0030] A base end opening 111a that connects the lumen 115 to the outside is formed at one end 111 of the main body 110. The base end opening 111a is closed by a liquid permeable portion 120 that is disposed at the one end 111.

[0031] An opening (tip opening) 113a that connects the lumen 115 to the outside is formed at the other end 113 of the main body 110. The opening 113a is closed by a plug 170 attached to the other end 113.

[0032] As shown in Figures 1, 3, and 4, when the main body 110 is in a state before the substance 150 to be administered into the living body and is filled with a predetermined amount of the substance 150 to be administered, it has a first region S1 defined on one end 111 side separated by the piston 140 and a second region S2 defined on the other end 113 side.

[0033] In the following description, the state before the administration of the substance 150 shown in Figures 1, 3, and 4 begins (for example, the state when the administration device 100 is being stored or transported, or the state before the administration of the substance 150 begins after placement in the body) is referred to as the "initial filling state."

[0034] The first region S1 is a space defined between the liquid permeable portion 120 and the piston 140 (a space between the other end of the liquid permeable portion 120 and one end of the piston 140). The first region S1 can accommodate the working agent 130.

[0035] The second region S2 is a space defined between the piston 140 and the plug 170. The second region S2 can accommodate the substance to be administered 150. A portion of the second region S2 along the longitudinal direction forms a sliding region in which the piston 140 slides along the longitudinal direction of the main body 110.

[0036] In the present embodiment, second region S2 can be defined as "a space capable of holding (filling) substance to be administered 150 located within lumen 115, which is located closer to other end 113 of main body 110 than the other end of piston 140 and closer to the base end than communication path 175 of plug 170." For example, as shown in FIGS. 3 and 4 , if one end 171 of plug 170 has a tapered shape in which the outer diameter decreases toward one end 111 of main body 110, substance to be administered 150 can be held in the space circumferentially surrounding one end 171 of plug 170. Therefore, in the present embodiment, the space circumferentially surrounding one end 171 of plug 170 can be defined as part of second region S2. For example, as shown in each of the modified examples described below (see Figures 10 and 11), if one end 171 of each plug 170A, 170B does not have a tapered shape and is configured to hold the administered substance 150 in the space closer to one end 111 of the main body 110 than one end 171 of each plug 170A, 170B, the second region S2 can be defined as "the space partitioned between the other end of the piston 140 and one end of the plug 170."

[0037] The first region S1 and the second region S2 expand or contract in longitudinal length as the piston 140 slides while the administration device 100 is in an operating state (meaning the state before, during, or after administration of the object to be administered 150). That is, the volumes of the first region S1 and the second region S2 are variable depending on the operating state of the administration device 100. More specifically, when the administration device 100 starts operating from the initial filling state shown in FIG. 1 and the piston 140 slides toward the other end 113 due to the actuating agent 130 as shown in FIG. 2, the volume of the space corresponding to the first region S1 gradually expands, while the volume of the space corresponding to the second region S2 gradually shrinks.

[0038] It is preferable that main body 110 be configured to prevent main body 110 from being crushed by buckling or the like within the range in which piston 140 slides, thereby preventing the shape of lumen 115 (for example, the cross-sectional shape intersecting the longitudinal direction) from being deformed into an unintended shape, thereby inhibiting the deterioration of the slidability of piston 140. Furthermore, since main body 110 is intended for use while being placed in a living body, it is preferable that the constituent material thereof be non-invasive or minimally invasive to the living body. Taking these points into consideration, the constituent materials of the main body 110 may be, for example, resin materials known in the medical field (acrylonitrile polymers, halogenated polymers, polyimide, polysulfone, polycarbonate, polyethylene, polypropylene, polyvinyl chloride-acrylic acid copolymer, polycarbonate-acrylonitrile-butadiene-styrene, polystyrene, etc.), or metal materials (stainless steel, titanium, nickel, aluminum, vanadium, platinum, tantalum, gold, and alloys thereof, as well as gold-plated iron alloys, platinum-plated iron alloys, cobalt-chromium alloys, and titanium nitride-coated stainless steel, etc.).

[0039] <Liquid-Permeable Section 120 > The liquid-permeable section 120 is disposed at one end 111 of the main body section 110 and separates each organ to be placed in the living body from the lumen 115 of the main body section 110 .

[0040] The liquid-permeable portion 120 has a function of selectively allowing only the liquid components contained in the body fluid in the living body to pass through. Furthermore, in the manufacturing method of the administration device 100 described below, when a liquid is used as the heating medium 210 (see FIG. 8 ), the liquid-permeable portion 120 preferably has a function of restricting the passage of the heating medium 210.

[0041] As the liquid-permeable portion 120 having the above-mentioned functions, for example, a semipermeable membrane made of a material such as a plasticized cellulose-based material, a reinforced polymethyl methacrylate (PMMA) such as hydroxylethyl methacrylate (HEMA), or an elastomer material such as polyurethanes, polyamides, polyether-polyamide copolymers, or thermoplastic copolyesters, or a mixture thereof, can be used.

[0042] <Working Agent 130> The working agent (swelling agent) 130 functions as a pressing portion that presses the piston 140 toward the other end 113 of the main body portion 110 by non-electrical continuous driving using the principle of an osmotic engine.

[0043] When the working agent 130 comes into contact with the liquid component that has permeated the liquid permeable portion 120, it gradually swells as shown by arrow a1 in Figure 2. As the working agent 130 swells, it increases the internal pressure of the first region S1. The working agent 130 exerts a pressing force as the internal pressure of the first region S1 increases, causing the piston 140 to slide toward the other end 113 of the main body 110.

[0044] The working agent 130 may be, for example, a chloride that swells upon contact with a liquid component. As the chloride, for example, a solute that can be filled into the lumen 115 of the main body 110 may be selected. Specific types of chlorides include, for example, sodium chloride, magnesium chloride, potassium chloride, sodium sulfate, magnesium sulfate, potassium sulfate, sodium phosphate, potassium phosphate, mannitol, urea, inositol, raffinose, sucrose, glucose, lactose, sorbitol, tartrates, succinates, and mixtures thereof.

[0045] In addition, the constituent materials and volume in the initial filling state of the actuator 130 can be arbitrarily set so as to achieve a predetermined pressing speed (i.e., the swelling speed of the actuator 130) according to the administration conditions of the administered substance 150.

[0046] <Piston 140> When piston 140 moves toward the other end 113 of main body 110 as active agent 130 swells, it moves the substance to be administered 150 contained in second region S2 toward the other end 113 of main body 110, as shown by arrow a2 in Figure 2.

[0047] When the piston 140 moves toward the other end 113 of the main body 110 as described above, the administration device 100 releases the administered substance 150 to the outside of the main body 110 as shown by arrow a3 in Figure 2 through a release port 176 (see Figure 4) which forms the open end of a communicating passage 175 formed in a plug 170 attached to block the opening 113a.

[0048] Piston 140 is arranged so that at least a portion of the outer circumferential surface of piston 140 is in liquid-tight contact with the inner circumferential surface of main body 110 and is slidable within bore 115. There are no particular limitations on the specific shape of piston 140, as long as it can perform the function of pushing substance to be administered 150 toward the other end 113 of main body 110 as piston 140 moves.

[0049] The piston 140 can be made of a material that maintains close contact (liquid-tightness) with the inner circumferential surface of the bore 115 of the main body 110 and has a predetermined degree of flexibility. The flexible material is preferably an elastic material. Examples of the elastic material include various rubber materials (especially vulcanized ones) such as natural rubber, isoprene rubber, butyl rubber, chloroprene rubber, nitrile-butadiene rubber, styrene-butadiene rubber, and silicone rubber; styrene-based elastomers; hydrogenated styrene-based elastomers; and mixtures of these styrene-based elastomers with polyolefins such as polyethylene, polypropylene, polybutene, and α-olefin copolymers; oils such as liquid paraffin and process oil; and powdered inorganic materials such as talc, cast iron, and mica. Furthermore, polyvinyl chloride-based elastomers, olefin-based elastomers, polyester-based elastomers, polyamide-based elastomers, polyurethane-based elastomers, and mixtures thereof can also be used as the construction material.

[0050] In particular, it is preferable to select diene rubber, styrene elastomer, or the like as the constituent material of the piston 140 from the viewpoints of having elastic properties and being able to be sterilized by gamma rays, electron beams, and high-pressure steam.

[0051] <Substance to be administered 150> Substance to be administered 150 can be composed of, for example, a fluid composition that can be released from administration device 100 continuously to produce a predetermined effect when released within a predetermined biological organ.

[0052] The administered substance 150 may be, for example, a medicinal solution (liquid formulation) intended to treat a specific disease. The medicinal solution may include drugs. The drug may be any physiologically or pharmacologically active substance, particularly one known to be delivered to the human or animal body. Examples of drugs include, but are not limited to, drugs that act on peripheral nerves, adrenergic receptors, cholinergic receptors, skeletal muscle, the cardiovascular system, smooth muscle, the vascular system, synaptic sites, neurotransmitter junctions, the endocrine and hormonal systems, the immune system, the reproductive system, the skeletal system, the local hormonal system, the digestive and excretory systems, the histamine system, or the central nervous system. Examples of drugs include, but are not limited to, drugs used to treat infectious diseases, chronic pain, diabetes, autoimmune diseases, endocrine disorders, metabolic disorders, and rheumatic diseases. Additionally, drugs include, but are not limited to, peptides, proteins, polypeptides (e.g., enzymes, hormones, cytokines), nucleic acids, oligonucleotides, viruses, viral vectors, plasmids, nucleoproteins, polysaccharides, glycoproteins, lipoproteins, cells, steroids, analgesics, local anesthetics, antibiotic agents, anti-inflammatory corticosteroids, ophthalmic agents, other small molecules of pharmaceutical use, or synthetic analogs of these species, and mixtures thereof.

[0053] As will be described later, administration device 100 can prevent excessive release (initial burst) during the initial stage after placement due to volume expansion caused by a rise in temperature of administration target 150. Therefore, administration device 100 can suitably select, as the administration target, therapeutic agents for infectious diseases, cardiovascular diseases, central nervous system diseases, etc., which are relatively prone to volume expansion caused by a rise in temperature and for which excessive release may have a negative effect on the living body, among the drug solutions containing the drugs exemplified above.

[0054] <Plug 170> As shown in Figures 3 and 4, plug 170 has a communication passage 175 (orifice) that communicates with second region S2, and an outlet 176 that is provided at the other end of communication passage 175 and releases the substance to be administered 150 to the outside as piston 140 slides toward the other end 113 of main body 110.

[0055] The plug 170 has one end 171 , another end 173 , and an intermediate portion 174 extending between the one end 171 and the other end 173 .

[0056] One end 171 of the plug 170 is disposed within the second region S2.

[0057] One end 171 of the plug 170 has a tapered shape in which the outer diameter gradually decreases toward one end 111 of the body 110. Therefore, when attaching (plugging) the plug 170 to the body 110 as described below, the plug 170 can be inserted into the inner cavity 115 of the body 110 from the one end 171 side, thereby improving the workability of the attachment of the plug 170 (see FIGS. 5 and 6 ).

[0058] The other end 173 of the plug 170 can be arranged so as to be aligned in the longitudinal direction with the other end 113 of the main body 110. As shown in Figure 4, the discharge port 176 provided at the other end of the communication path 175 is arranged at approximately the same position in the longitudinal direction as the opening 113a provided at the other end 113 of the main body 110.

[0059] The intermediate portion 174 of the plug 170 is disposed so that a portion of the outer surface of the intermediate portion 174 is in close contact or pressure contact with the inner circumferential surface of the main body portion 110. The plug 170 is configured so as not to move (become displaced) in association with the sliding of the piston 140 when the piston 140 slides toward the other end portion 113 of the main body portion 110. In this way, the plug 170 functions as a plug member that closes the opening 113 a.

[0060] The communication passage 175 extends continuously from one end of the intermediate portion 174 to the other end of the other end portion 173 .

[0061] 1, 3, and 4, in the initial filling state before the start of release of the drug solution in the living body, administration device 100 holds substance 150 from second region S2 to at least a portion located on one end side of communication path 175. In other words, administration device 100 does not have an unfilled space (region) in second region S2 where substance 150 is not filled, and substance 150 is held continuously from second region S2 to a portion of the other end side of communication path 175. In each figure, substance 150 held in communication path 175 is denoted by reference numeral 150a for clarity of illustration.

[0062] As shown in Figures 3 and 4, the administration device 100 is provided with a non-retaining area 175a on the other end side of the communication passage 175 in the initial filling state, where the substance to be administered 150 is not retained.

[0063] In administration device 100, in the initial filling state as described above, non-retention area 175a is provided in a portion on the other end side of communication path 175, so even if volume expansion occurs in substance to be administered 150 in the initial stage after placement, it is possible to absorb (retain) the expanded volume of substance to be administered 150 by an amount corresponding to the flow path volume of non-retention area 175a. Therefore, it is possible to prevent excessive release of substance to be administered 150 in a volume greater than expected in the initial stage after placement.

[0064] Furthermore, in the administration device 100, in the initial filling state as described above, there is no unfilled space (area) in the second region S2 where the substance to be administered 150 is not filled, and the substance to be administered 150 is continuously held between the second region S2 and a portion of the range on one end side of the communication path 175, so that gas such as air is not trapped in the second region S2. Therefore, the administration device 100 can prevent excessive release of the substance to be administered 150 due to volume expansion of gas such as air trapped in the second region S2 in the initial stage after placement.

[0065] In this embodiment, the administered object 150 can be composed of a medicinal solution whose volume expands due to the temperature difference between a predetermined storage temperature and the intended use temperature (the temperature at which administration of the administered object 150 begins after placement; for example, the body temperature of the living body to be placed).

[0066] Furthermore, non-retaining region 175a of communication path 175 can be configured to have a flow path volume larger than the volume expansion of the medicinal solution. By setting the flow path volume of non-retaining region 175a in this manner, it is possible to effectively prevent excessive release of substance to be administered 150 due to volume expansion in the early stage after placement.

[0067] Examples of combinations of the drug (medicinal solution) used in administration object 150 and the flow path volume of non-retention area 175a include the following.

[0068] <Example of combination> A medicinal solution containing paliperidone is used as the administration object 150. The storage temperature is 2 to 8°C. The planned use temperature is a temperature equivalent to deep body temperature. The temperature difference between the storage temperature and the planned use temperature is approximately 27 to 37°C. The amount of volume expansion is 0.91 to 1.40 mm ３ The flow path volume of the non-retaining area 175a is 0.91 to 150 mm ３ is.

[0069] The administration device 100 can be configured so that the volume expansion amount (Q1) of the medicinal liquid constituting the administered object 150, the flow path cross-sectional area (S) of the communicating passage 175, the length (L) of the non-retaining region 175a of the communicating passage 175, and the initial filling amount (Q2) of the medicinal liquid filled in the second region S2 before the volume expansion satisfy the relationship of the following formula (1).

[0070] Q1≦S×L≦Q2...(1) By configuring the administration device 100 to satisfy the above formula (1), it is possible to more effectively prevent excessive release due to volume expansion of the administered substance 150 in the initial stage after placement.

[0071] In the above formula (1), the flow path cross-sectional area (S) of the communicating passage 175 is assumed to be uniform along the extension direction of the communicating passage 175. Furthermore, the length (L) of the non-retaining region 175a of the communicating passage 175 is the effective length along the extension direction of the communicating passage 175 (for example, if the communicating passage 175 extends spirally as in this embodiment, the total length along the spiral path).

[0072] As shown in FIGS. 3 and 4, the communication passage 175 can be configured to have a spirally extending groove formed on the outer surface of the plug 170.

[0073] The communication passage 175 extends in a spiral shape around a reference axis based on the central axis c1. When the communication passage 175 is formed in a spiral shape, the pitch and angle of the spiral (the angle of inclination relative to the central axis c1 in the cross-sectional view of FIG. 1 ) can be set as desired.

[0074] Because plug 170 is configured so that communicating passage 175 has a groove that extends spirally, even when plug 170 has a relatively short longitudinal length and is formed compactly as a whole, the effective length of communicating passage 175 can be ensured to be large. This allows administration device 100 to set the flow path volume of communicating passage 175 to a size that corresponds to the amount of volumetric expansion of object 150, thereby increasing the options for drugs to be administered. Note that, as shown in the various modified examples described below, there are no particular limitations on the specific configuration (flow path shape, cross-sectional shape, number, etc.) of communicating passage 175 formed in plug 170 (see Figures 10 and 11).

[0075] <Manufacturing Method of Administration Device 100> Next, a manufacturing method of the administration device 100 according to this embodiment will be described. Note that in the method described below, for example, the components and members shown in the above-described combination example 1 can be used.

[0076] As shown in FIG. 5, the main body 110 is prepared with the liquid permeable portion 120, the working agent 130, and the piston 140 assembled thereto.

[0077] Next, as shown in Fig. 5, a step is carried out in which second region S2 (a space corresponding to second region S2 of lumen 115) is filled with an amount of substance to be administered 150 that will overflow from opening 113a when plug 170 is attached in a state in which substance to be administered 150 has been heated to the intended temperature for use of substance to be administered 150. In this step, the volume of second region S2 shown in Fig. 5 is, for example, 210 mm ３ The filling amount of the substance 150 (the amount that can overflow from the opening 113a) is, for example, 180 mm ３is.

[0078] It should be noted that the "expected operating temperature" in the administration device 100 and its manufacturing method is preferably set roughly within the range of 35 to 39°C, since the core body temperature of a typical living body (the living body of a patient who is the recipient of administration) is 35 to 39°C. However, since the core body temperature varies depending on the individual differences and physical condition of the recipient of administration, a heating temperature corresponding to the core body temperature of the living body can be set as necessary.

[0079] 6, plug 170 is attached to opening 113a of main body 110, causing substance 150 to flow into communication path 175 of plug 170. At this time, substance 150 is released from opening 113a in an amount corresponding to the volume of the portion of lumen 115 where plug 170 is inserted.

[0080] The entire plug 170 is then pushed into the lumen 115 as shown in FIG.

[0081] Next, a step of cooling the main body 110 to a predetermined storage temperature that is lower than the intended use temperature is carried out.

[0082] When the temperature of main body 110 drops to the storage temperature, substance 150, which has expanded in volume due to heating, contracts, reducing the volume of substance 150. When the volume of substance 150 decreases, substance 150 filled in communicating passage 175 moves along communicating passage 175 to a predetermined position on one end 111 side of communicating passage 175. As a result, as shown in Figure 1, it is possible to manufacture administration device 100 in an initially filled state in which substance 150 is held from second region S2 to a predetermined position on one end side of communicating passage 175, and in which non-holding region 175a where substance 150 is not held is formed on the other end side of communicating passage 175.

[0083] Next, another example of a method for manufacturing the administration device 100 will be described.

[0084] As shown in Figure 8, with the substance 150 filled in the second region S2 and the plug 170 attached to the main body 110, the main body 110 is heated to the intended temperature for use of the substance 150, and a process is carried out in which at least a portion of the substance 150 is released through the communication passage 175 and the release port 176.

[0085] The main body 110 can be heated using, for example, a heating medium 210 made of a liquid held in a liquid tank 200. However, there are no particular limitations on the heating method, and for example, heated gas or an instrument that emits radiant heat may also be used.

[0086] 9, after the substance to be administered 150 has been released through communication path 175 and release port 176, main body 110 is removed from liquid tank 200. When main body 110 is removed from liquid tank 200, substance to be administered 150 remains in communication path 175.

[0087] Next, a step of cooling main body 110 to a predetermined storage temperature that is lower than the intended use temperature is carried out. As in the manufacturing method described above, when the temperature of main body 110 drops to the storage temperature, substance 150, which has expanded in volume due to heating, contracts, and the volume of substance 150 decreases. As a result, as shown in Figure 1, administration device 100 can be manufactured in an initially filled state in which substance 150 is held from second region S2 to a predetermined position on one end side of communicating channel 175, and a non-holding region 175a where substance 150 is not held is formed on the other end side of communicating channel 175.

[0088] As described above, the administration device 100 according to this embodiment includes a main body 110 having a lumen 115 extending in the longitudinal direction, a liquid-permeable portion 120 arranged on one end 111 side of the main body 110 in the longitudinal direction and capable of allowing liquid components contained in bodily fluids in a living body to pass through in accordance with osmotic pressure, an operating agent 130 filled in a first region S1 defined on the other end 113 side of the main body 110 in the longitudinal direction relative to the liquid-permeable portion 120 and increasing in volume as it comes into contact with the liquid component, a piston 140 arranged on the other end 113 side of the main body 110 relative to the first region S1 and sliding toward the other end 113 side as the volume of the operating agent 130 increases, and ... position where the piston 140 is arranged. The piston 140 has a substance to be administered 150 filled in a second region S2 partitioned on the other end 113 side of the main body 110, and a plug 170 attached to close an opening 113a provided on the other end 113 of the main body 110, the plug 170 having a communication passage 175 communicating with the second region S2, and a release port 176 provided at the other end of the communication passage 175 for releasing the substance to be administered 150 to the outside as the piston 140 slides towards the other end 113 of the main body 110, the substance to be administered 150 being held over at least a portion located from the second region S2 to one end side of the communication passage 175, and a non-holding region 175a where the substance to be administered 150 is not held is provided on the other end side of the communication passage 175.

[0089] According to administration device 100 configured as described above, non-retention area 175a is provided in a portion of the other end side of communication path 175, so even if volume expansion occurs in substance 150 in the initial stage after placement, it is possible to absorb (retain) the expanded volume of substance 150 by an amount corresponding to the flow path volume of non-retention area 175a. Therefore, it is possible to prevent excessive release of substance 150 in a volume greater than expected in the initial stage after placement.

[0090] Furthermore, according to the administration device 100, there is no unfilled space (area) in the second region S2 that is not filled with the substance to be administered 150, and the substance to be administered 150 is continuously held between the second region S2 and a portion of the range on one end side of the communication path 175, so that gas such as air is not trapped in the second region S2. Therefore, the administration device 100 can prevent excessive release of the substance to be administered 150 due to volume expansion of gas such as air trapped in the second region S2 in the initial stage after placement.

[0091] <Variations> The configuration of the communication passage formed in the plug provided in the administration device 100 is not particularly limited as long as it connects the second region S2 to the outside of the main body 110 and can hold the administered substance 150 from the second region S2 to a predetermined position on one end side of the communication passage 175 in the initial filling state.

[0092] For example, as in Modification 1 shown in Fig. 10, the communication passage 175A can be configured to have a plurality of holes extending inside the plug 170A. Note that the flow path volume of the communication passage 175A shown in this modification can be calculated by adding up the flow path volumes of the plurality of holes.

[0093] Each hole of the communication passage 175A extends linearly along the longitudinal direction between one end 171, the other end 173, and the middle portion 174 of the plug 170.

[0094] In the initial filling state, substance 150 is held in a predetermined range on one end side of each hole of communicating passage 175A. Also, in the initial filling state, non-holding region 175a in which substance 150 is not held is provided in a predetermined range on the other end side of each hole of communicating passage 175A.

[0095] In this modification, one end 171 of the plug 170A has a substantially constant outer diameter along the longitudinal direction. However, as in the above-described embodiment, one end 171 of the plug 170A may be formed in a tapered shape in which the outer diameter tapers toward one end 111 of the main body 110. Furthermore, there are no particular limitations on the number of holes provided in the communication passage 175A or the cross-sectional shapes of the holes (cross-sectional shape in the longitudinal direction, cross-sectional shape in a direction perpendicular to the longitudinal direction).

[0096] 11, the communication passage 175B can be configured to have a linear groove extending on the outer surface of the plug 170B. In this example, the grooves are provided at two opposing locations in the circumferential direction with the center axis c1 sandwiched therebetween.

[0097] As in the modified example described above, the flow path volume of the communication passage 175B can be calculated by adding up the flow path volumes of the multiple grooves. Furthermore, one end 171 of the plug 170B may be tapered so that the outer diameter tapers toward one end 111 of the main body 110. Furthermore, there are no particular limitations on the number of grooves or the cross-sectional shapes of the grooves (cross-sectional shapes in the longitudinal direction and cross-sectional shapes perpendicular to the longitudinal direction).

[0098] In the initial filling state, substance to be administered 150 is held in a predetermined range on one end side of each groove of communicating passage 175B. Also, in the initial filling state, non-holding region 175a in which substance to be administered 150 is not held is provided in a predetermined range on the other end side of each groove of communicating passage 175B.

[0099] The above describes the administration device and the method for manufacturing the administration device according to the present invention through the embodiments, but the present invention is not limited to the described configurations and can be modified as appropriate based on the description of the claims.

[0100] The structure of each part and the arrangement of the members described in the specification may be changed as desired. Additional members illustrated in the drawings may be omitted, or other additional members may be used as desired.

[0101] This application is based on Japanese Patent Application No. 2024-051656, filed on March 27, 2024, the disclosure of which is incorporated herein by reference in its entirety.

[0102] DESCRIPTION OF SYMBOLS 100 Administration device 110 Main body 111 One end of administration device 113 Other end of administration device 113a Opening 115 Lumen 120 Liquid permeable portion 130 Working agent 140 Piston 150 Subject to administration 170 Plug 170A Plug 170B Plug 171 One end of plug 173 Other end of plug 174 Intermediate portion of plug 175 Communication path 175A Communication path 175B Communication path 175a Non-retaining region 176 Discharge port 200 Liquid tank 210 Heating medium A Subject to administration S1 First region S2 Second region c1 Central axis of main body

Claims

1. An administration device that releases an object to be administered while placed in a living body, comprising: a main body portion with a cavity extending in the longitudinal direction; a liquid-permeable portion that is located on one longitudinal end side of the main body portion and is capable of allowing liquid components contained in body fluids in the living body to pass through in accordance with osmotic pressure; an active agent that is filled in a first region defined on the other longitudinal end side of the main body portion relative to the liquid-permeable portion and increases in volume as it comes into contact with the liquid components; a piston that is located on the other end side of the main body portion relative to the first region and slides toward the other end side as the volume of the active agent increases; the object to be administered that is filled in a second region defined on the other end side of the main body portion relative to the position of the piston; and a plug attached to close an opening provided on the other end side of the main body portion, wherein the plug has a communication passage that communicates with the second region, and a release port that is located at the other end of the communication passage and releases the object to be administered to the outside as the piston slides toward the other end side of the main body portion, The substance to be administered is held over at least a portion of the second region located on one end side of the communicating passage, and a non-holding region in which the substance to be administered is not held is provided on the other end side of the communicating passage.

2. The administration device of claim 1, wherein the object to be administered is a medicinal liquid whose volume expands due to the temperature difference between a predetermined storage temperature and a planned use temperature, and the non-retention area of ​​the communication path has a flow path volume larger than the amount of volume expansion of the medicinal liquid.

3. The administration device according to claim 2, wherein the volume expansion amount (Q1) of the medicinal liquid, the flow path cross-sectional area (S) of the communication path, the length (L) of the non-retention region of the communication path, and the initial filling amount (Q2) of the medicinal liquid filled in the second region before the volume expansion satisfy the relationship of the following formula (1): Q1≦S×L≦Q2 (1) 4. An administration device as claimed in any one of claims 1 to 3, wherein the communication passage has a spirally extending groove formed on the outer surface of the plug.

5. A method for manufacturing an administration device as claimed in any one of claims 1 to 4, comprising the steps of: filling the second region with an amount of the substance to be administered that will overflow from the opening when the plug is attached while the substance to be administered has been heated to a temperature at which the substance is to be used; attaching the plug to the main body to allow the substance to flow into the communication passage; and cooling the main body to a predetermined storage temperature that is lower than the temperature at which the substance is to be used.

6. A method for manufacturing an administration device as defined in any one of claims 1 to 4, comprising the steps of: heating the main body to a temperature at which the substance to be administered is to be used, with the second region filled with the substance and the plug attached to the main body, and discharging at least a portion of the substance to be administered through the communication path and the discharge port; and cooling the main body to a predetermined storage temperature that is lower than the temperature at which the substance to be administered is to be used.

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