• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    double chamber preloadable syringe, and, aripiprazole loaded into a syringe a double chamber preloadable syringe (100) includes: a barrel (10) which has a bypass portion (11); a hub luer lock (20); a front cap (30); a middle plug (40) which seals a preparation(s) which seals a solvent (1) together with the middle plug (40); a finger grip (60); and a piston rod (70) which is connected to the end cap from the rear end side. a female screw portion (64) which is screwed around the centerline is formed on an inner circumferential surface of the finger grip (60), and a male screw portion (73) which is capable of being screwed to the female screw portion is formed on an outer circumferential surface of the piston rod (70).
    公开号:BR112013011289B1
    申请号:R112013011289-1
    申请日:2011-11-16
    公开日:2021-06-01
    发明作者:Makoto Kakiuchi
    申请人:Otsuka Pharmaceutical Co., Ltdq；
    IPC主号:
    专利说明:

    Field of Invention
    [001] The present invention relates to a pre-loadable syringe which is filled with and contains and protects a liquid preparation in advance, and can be used promptly after being removed from the package before use.
    [002] In addition, the invention relates to aripiprazole filled in a syringe, which is a pre-loadable syringe filled with aripiprazole.
    [003] Priority is claimed in Japanese Patent Application No.2010-256188, filed November 16, 2010. The contents of which are incorporated herein by reference. Description of Related Art
    [004] Pre-fillable syringes are pre-filled with a liquid preparation in advance, and thus these can be readily used without troublesome operation after being removed from the pack in medical institutions. As described above, pre-filled syringes are excellent in terms of convenience and significantly contribute to the reduction in the workload of people related to medical services such as doctors and nurses, and so there are employees in many hospitals.
    [005] Hitherto, as a type of pre-fillable syringe, dual-chamber pre-fillable syringes have been known in which a preparation and a solvent or solution (dispersion medium) are separately filled.
    [006] The double-chamber preloadable syringe has a front cap inserted into the front end side of a cylinder and an end cap inserted into the rear end side of the cylinder, and a middle cap inserted into the center of the interior of the cylinder, the cylinder is divided into two front and rear chambers. In addition, a deflection portion which is formed so that the inner circumferential surface of the cylinder protrudes partially outwardly is formed in a portion positioned closer to the front end than the middle cap of the cylinder. Additionally, a powder is sealed in the front chamber on the front end side of the middle cap, and the front end is sealed by the front cap. A solvent is sealed in the rear chamber on the rear end side of the middle plug, and the rear end is sealed by an end plug. A plunger rod is attached to the rear end of the end cap.
    [007] When the double-chamber preloadable syringe having such a configuration is used, the end cap is advanced into the cylinder by pressing the plunger rod into the cylinder. Therefore, the pressing force by advancing the end cap is transmitted to the middle cap through the solvent, and thus the middle cap also advances with the advancement of the end cap. When the middle plug reaches the bypass portion, the front chamber and rear chamber communicate with each other through the projecting portion of the bypass portion. Appropriately, the solvent in the rear chamber flows into the front chamber and is mixed with the preparation in the front chamber, and thus the injection is reconstituted.
    [008] Aripiprazole which is used as an active component of a pharmaceutical composition is known as a typical antipsychotic drug which is useful for the treatment of a schizophrenic and is expressed by the following structural formula (for example, in reference to Patent Document 1 ): [Formula 1]

    [009] When a preloadable syringe containing aripiprazole, i.e., aripiprazole filled into a syringe is used, for example, a bolus composition is reconstituted which is obtained by suspending a pharmaceutical composition by a dispersing means and then freezing by drying the suspension. When the cake composition is used, it is mixed with a desired dispersion medium (injectable liquid) to be resuspended, and the resuspension is injected to a patient intramuscularly or hypodermicly (for example, in reference to the Patent Document two).
    [0010] In addition, Patent Document 3 discloses a preloadable dual-chamber syringe called a "two-chamber syringe" in which a dry frozen material is reconstituted by freeze-drying a solution in the syringe and is then sealed by a rubber housing, and an injectable liquid is sealed in another partition chamber on the syringe. List of Citation Patent Documents
    [0011] Patent Document 1: US Patent No. 5006528 Patent Document 2: Japanese Patent Application Publication No.2007-509148 Patent Document 3: Japanese Patent Application Publication No. 8-112333 Invention Summary Technical Problem
    [0012] In the dual chamber preloadable syringe described above, in order to properly mix the solvent and preparation, the middle stopper is required to be positioned in the bypass portion until all the solvent in the rear chamber flows into the front chamber. In addition, the solvent flow is required to be controlled in the case of a preparation which is not easily dissolved.
    [0013] However, when the piston rod is pressed too early, or pressed too heavily without confirmation of the end of solvent flow to the front chamber, the middle cap moves to be closer to the front end than to the front end portion. deviation in a state in which all the solvent does not completely drain into the front chamber. Therefore, the solvent in the rear chamber remains unmixed with the preparation.
    [0014] In this way, due to incorrect operation of the piston rod, a useless solvent, which was not prepared with the preparation, is generated, and as a result, problem occurs because an injection having a predetermined concentration cannot be reconstituted and the preparation is not sufficiently dissolved by the solvent.
    [0015] In the case of aripiprazole filled in a syringe described above, the residue caused by incomplete suspension on resuspension became a problem.
    [0016] The invention is designed in such problems, and an object of the invention is to provide a pre-loadable dual chamber syringe in which a solvent and a preparation can be safely and properly mixed together according to properties of the same.
    [0017] In addition, an object of the invention is to provide aripiprazole filled in a syringe which is adapted to reduce the residue caused by incomplete suspension in the resuspension. Solution to Problem
    [0018] In order to solve the problems described above, the invention proposes the following means.
    [0019] That is, a dual-chamber preloadable syringe includes: a cylinder which has a cylindrical shape with a centerline as a center and has an offset portion formed by protruding a portion of an inner circumferential surface towards the exterior; a luer hub lock which is provided at the front end of the cylinder; a finger grip which is provided at the rear end of the cylinder; a front cap which is fitted to the front end side of the bypass portion on the cylinder; a middle plug which is fitted to the rear end side of the bypass portion on the cylinder to seal a preparation together with the front plug; an end cap which is fitted to the rear end side of the middle cap on the cylinder to seal a solvent together with the middle cap; a plunger rod which is connected to the end cap from the rear end side by insertion into the finger grip; a female screw portion which is formed to be screwed around the centerline to an inner circumferential surface of the finger grip; and a male screw portion which is shaped to be able to screw together with the female screw portion into an outer circumferential surface of the piston rod.
    [0020] When the double chamber preloadable syringe having such characteristics is used, the plunger rod can be rotated according to screwing the male screw portion to the female screw portion. Appropriately, the piston rod gradually advances in accordance with the steps of the male screw portion and the female screw portion. Therefore, it is possible to avoid excessive advance speed of the piston rod, and thus it is possible to allow the middle cap to remain in the bypass portion. Suitably, the solvent flow rate to the front chamber can be easily adjusted and kept constant, and it is possible to efficiently mix the preparation in the solvent.
    [0021] In addition, in the double-chamber preloadable syringe according to the invention, when the middle cap which is advanced by pressing the plunger rod enters the bypass portion, the front end of the male screw portion preferably reaches the rear end of the female screw portion and can be screwed to it.
    [0022] When the middle cap is advanced through the end cap and the solvent by pressing the plunger rod, the front end of the male screw portion is placed in contact with the rear end of the female screw portion when the middle cap enters the deviation portion. Suitably, even when the piston rod is further depressed, the piston rod does not advance further, and the middle cap does not advance either. Therefore, it is possible to prevent the middle cap from being excessively advanced to the front end side of the deflection portion due to excessive force applied to the piston rod.
    [0023] In addition, after the front end of the male screw portion is placed in contact with the rear end of the female screw portion as described above, the piston rod is gradually advanced in accordance with the bolting between the male screw portion and the female screw portion by rotation of the piston rod. When the middle plug advances with the advancement of the piston rod and completely enters the bypass portion, solvent is introduced to the preparation through the bypass portion, and both of them are mixed. The solvent flow for the preparation is adjusted by the steps of the male screw portion and the female screw portion, and thus the speed can be adjusted to a speed at which the preparation is easily dissolved.
    [0024] Appropriately, as the plunger rod can be rotated according to screwing between the male screw portion and the female screw portion only when the middle cap reaches the bypass portion and the solvent is introduced for the preparation, only a piston rod pressing preparation can be carried out until a part of the middle cap reaches the bypass portion. Therefore, it is possible to avoid the manipulation of the double chamber preloadable syringe from the problem that has arisen.
    [0025] The meaning of "when the middle cap enters the bypass portion" includes when the front end of the middle cap reaches the rear end of the bypass portion, when a portion of the middle cap enters the bypass portion, and immediately before the end front of the middle cap reaches the rear end of the bypass portion. That is, a configuration can be provided in which the front end of the male screw portion reaches the rear end of the female screw portion just before the front end of the middle cap reaches the bypass portion.
    [0026] Additionally, the dual-chamber preloadable syringe according to the invention preferably further includes: a guide groove which is formed in the female screw portion and extends parallel to the centerline; and a guide plate which is formed on the rear end side of the male screw portion on the outer circumferential surface of the piston rod and is guided in accordance with the guide groove.
    [0027] When the piston rod is rotated and advanced according to screwing between the male screw portion and the female screw portion, the male screw portion of the piston rod passes through the female screw portion of the finger grip, and so the bolting between the male screw portion and the female screw portion is released. Appropriately, the piston rod can be depressed. At this time, for example, the piston rod is stopped in a position in which the guide plate of the piston rod and the guide groove formed in the female screw portion can be fitted together. Therefore, by pressing the piston rod, the piston rod can be guided in the direction in which the guide groove extends. Appropriately, the piston rod can be safely switched to go straight from rotation, and allowing the piston rod to go straight, discharging bubbles into the cylinder and injecting a liquid preparation into a patient. performed safely.
    [0028] Additionally, the pre-loadable dual-chamber syringe according to the invention preferably additionally includes: a first protrusion which is formed at the rear end of the finger grip and with which the guide plate is brought into contact so as to be able to overcome in it when at least a part of the middle cap which is advanced by rotation of the piston rod in accordance with the female screw portion and the male screw portion moves by the deflection portion.
    [0029] When a part of the middle cap advancing on the cylinder moves by the offset portion by the rotation and advancement of the piston rod in accordance with the bolting between the male screw portion and the female screw portion, the rod guide plate of the plunger is placed in contact with the first protrusion. Appropriately, a healthcare worker can easily recognize that as a part of the middle plug moves through the bypass portion, the space between the middle plug and the front plug, i.e. the space in which the solvent and preparation are mixed is fenced off again. At this point, the healthcare worker shakes the pre-fillable dual-chamber syringe, and thus an injection can be reconstituted in which the preparation is completely mixed, dissolved or suspended in the solvent.
    [0030] Additionally, in the double-chamber preloadable syringe according to the invention, after the guide plate overcomes the first protrusion by rotating the plunger rod according to the female screw portion and the male screw portion, the screwing between the male screw portion and the female screw portion is preferably released.
    [0031] Appropriately, after a part of the middle cap moves through the deflection portion due to the rotation and advancement of the piston rod in accordance with the bolting between the male screw portion and the female screw portion, the piston rod can be pressed. That is, as the plunger rod is rotated only when solvent is introduced for the preparation, and then the operation is switched to a plunger press preparation, it is possible to simplify the handling of the preloadable dual chamber syringe. In addition, as the guide plate is placed in contact with the first protrusion before the bolting between the male screw portion and the female screw portion is released, a healthcare worker can detect the end of the piston rod rotation early.
    [0032] In addition, the double-chamber preloadable syringe according to the invention preferably additionally includes: a second protrusion which is formed at the rear end of the finger grip and is brought into contact at a position in which the guide plate which overcomes the first protrusion can be snapped into the guide groove with the guide plate.
    [0033] When the guide plate overcomes the first protrusion as described above, the screwing between the male screw portion of the piston rod and the female screw portion of the finger grip is released, and thus the advance due to the rotation of the piston rod. spool is switched to advance due to forward travel. In addition, at this point, the guide plate is brought into contact with the second protrusion, and so the health worker recognizes that the plunger rod can be depressed. That is, the operation of the piston rod can be safely switched by contacting the guide plate with the second protrusion. Furthermore, in this state, the guide plate and the guide groove can be adjusted to each other. Appropriately then, by pressing the piston rod, the piston rod can be advanced together with the guide plate.
    [0034] In addition, the double-chamber preloadable syringe according to the invention is particularly suitable when the preparation includes aripiprazole.
    That is, although aripiprazole is difficult to dissolve in the solvent, the preparation can be suitably dissolved in the solvent in the pre-fillable double chamber syringe having the configuration described above. Therefore, even when aripiprazole is used as a preparation, aripiprazole can be easily suspended in the solvent.
    [0036] In addition, aripiprazole filled into a syringe according to the invention includes: aripiprazole; a cylinder which has a cylindrical shape with a centerline as a center and has an offset portion formed due to protruding a portion of an inner circumferential surface towards the outside; a luer hub lock which is provided at the front end of the cylinder; a finger grip which is provided at the rear end of the cylinder; a front cap which is fitted to the front end side of the bypass portion on the cylinder; a middle plug which is fitted to the rear end side of the bypass portion on the cylinder to seal the aripiprazole together with the front plug; an end cap which is fitted to the rear end side of the middle cap on the cylinder to seal a solvent together with the middle cap; a plunger rod which is connected to the end cap from the rear end by inserting the finger grip; a female screw portion which is formed to be screwed around the centerline to an inner circumferential surface of the finger grip; and a male screw portion which is shaped to be capable of being screwed to the female screw portion on an outer circumferential surface of the piston rod.
    [0037] When aripiprazole filled in a syringe according to the invention is used, the plunger rod is rotated according to the screw-in between the male screw portion and the female screw portion. Appropriately, the piston rod gradually advances in accordance with the steps of the male screw portion and the female screw portion. Therefore, it is possible to avoid excessive advance speed of the piston rod, and thus it is possible to allow the middle cap to stay in the bypass portion. Suitably, the solvent flow rate to the front chamber can be easily adjusted and kept constant, and it is possible to reduce the residue in the resuspension.
    [0038] According to the double-chamber preloadable syringe of the invention, it is possible to avoid the excessive advance speed of the plunger rod, and thus it is possible to prevent the middle stopper from being advanced excessively and moving out of the bypass portion . Appropriately, it is possible to allow the middle plug to be easily in the bypass portion, and the solvent flow rate to be adjusted by the steps of the male screw portion and the female screw portion, while it is possible to properly mix the solvent and the preparation.
    [0039] In addition, according to aripiprazole filled into a syringe, it is possible to reduce residue and incomplete dissolution in the resuspension. Brief Description of Drawings
    [0040] FIG. 1 is a longitudinal sectional view of a dual chamber preloadable syringe (aripiprazole filled in a syringe) according to an embodiment.
    [0041] FIG. 2A is a perspective view illustrating a finger grip.
    [0042] FIG. 2B is a longitudinal sectional view illustrating a finger grip.
    [0043] FIG. 3 is a side view of a piston rod.
    [0044] FIG. 4 is a side view of the piston rod.
    [0045] FIG. 5 is a perspective view of the piston rod.
    [0046] FIG. 6A is a view illustrating a method of using the dual chamber preloadable syringe according to the embodiment.
    [0047] FIG. 6B is a view illustrating a method of using the dual chamber preloadable syringe according to embodiment.
    [0048] FIG. 6C is a view illustrating a method of using the dual chamber preloadable syringe according to the embodiment.
    [0049] FIG. 7A is a view illustrating a method of using the dual chamber preloadable syringe according to the embodiment.
    [0050] FIG. 7B is a view illustrating a method of using the dual chamber preloadable syringe according to the embodiment.
    [0051] FIG. 8 is a perspective view of the finger grip and the plunger rod which is inserted into the finger grip.
    [0052] FIG. 9A is a view of the finger grip of a modified embodiment.
    [0053] FIG. 9B is a view of the finger grip of a modified embodiment. Description of Modalities
    [0054] Hereinafter, a preloadable dual-chamber syringe and eripiprazole filled into a syringe according to embodiments of the invention will be described in detail with reference to the drawings.
    [0055] As shown in FIG. 1, a double-chamber preloadable syringe (aripiprazole filled in a syringe) 100 is provided with a cylinder 10, a luer hub 20, a front cap 30, a medium cap 40, an end cap 50, a luer handle. finger 60, and a plunger rod 70. In this preloadable dual-chamber syringe 100, a preparation S and a solvent L to be mixed together to reconstitute injection M (see FIG. 7A) are filled in a separate state .
    [0056] The double-chamber preloadable syringe 100 of this modality is suitable for use in the injection of a material such as preparation S which is not easily dissolved in solvent L, and even in this case, preparation S can be easily and smoothly safely dissolved and suspended in solvent L. Particularly, when aripiprazole is used as preparation S which is not easily dissolved in solvent L, the value of the prefillable dual chamber syringe 100 of this embodiment is demonstrated.
    [0057] Aripiprazole, i.e. 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydrocarbostyril, or 7-{4-[4-( 2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2(1H)-quinolinone is a typical antipsychotic drug which is useful for the treatment of schizophrenics, and has the following structural formula:

    [0058] The cylinder 10 is molded from clear glass, and has an approximately cylindrical shape that extends along the centerline O. An approximately central part of the cylinder 10 in the direction of the centerline O is formed as a portion of offset 11 in which a part of the outer circumferential surface and the inner circumferential surface of the cylinder 10 in the circumferential direction protrude outwards in the radial direction over a predetermined dimension in the direction of the centerline O. The position of the offset portion 11 in the direction of centerline O can be set appropriately according to the project.
    [0059] In addition, a cylindrical part of the cylinder 10 on the front end side of the diverter portion 11 is formed as a front end side cylinder portion 12, and a cylindrical part of the diverter portion 11 on the rear end side is formed as a rear end side cylinder portion 13. That is, the cylinder 10 has the front end side cylinder portion 12 which is disposed on the front end side with the offset portion 11 as a limit and the rear end side cylinder portion 13 which is disposed on the rear end side. That is, in the cylinder 10, an area on the front end side is formed as the front end side cylinder portion 12, an area on the trailing end side is formed as the rear end side cylinder portion 13, and an area between the area on the front end side and the area on the rear end side is formed as the bypass portion 11.
    [0060] In addition, a ring-shaped front end side protrusion 14 which protrudes outwards in the radial direction over the entire area in the circumferential direction is formed on the outer circumference at the front end of the cylinder 10. Additionally, a protrusion of ring-shaped rear end side 15 which protrudes outwardly in the radial direction over the entire area in the circumferential direction is formed on the outer circumference at the rear end of the cylinder 10.
    [0061] Hub 20 Luer Lock is molded from a clear synthetic resin having appropriate rigidity, and has a multi-stage cylindrical outer shape with centerline O as a center. The hub Luer lock 20 is provided with a base end portion 21 having a cylindrical shape, a cylinder portion 22 which is coupled to the front end side of the base end portion 21 so as to be reduced by one stage. in diameter, and a Luer tip 23 which is formed on the front end side of the cylinder portion 22 to have a smaller diameter than the cylinder portion 22.
    [0062] A fitting hole 24 which is open to the rear end side of the hub Luer latch 20 is formed within the base end portion 21, and a bypass chamber 25 having the shape of a hole with a bottom is formed on the front side of the fitting hole 24, i.e. within the cylinder portion 22. A front end surface 25a with which the front end of the front cap 30 is placed in contact is formed in a position touching the portion. of the deflection chamber 25. The front end surface 25a is formed into a conical surface shape of which the diameter is gradually reduced towards the front side.
    [0063] In addition, an insertion hole 23a penetrated along the centerline O is formed within the Luer tip 23. One end of the insertion hole 23a is open to the front end of the Luer tip 23, and the other end is open to the center of the front end surface 25a of the bypass chamber 25. An injection needle 27 (omitted in FIG. 1, see FIG. 7B) extending to the front end side along centerline O is attached at one end, i.e. the front end side of the insertion hole 23a so as to communicate with it. A cap 110 is fitted to the Luer tip 23.
    [0064] The fitting hole 24 is a hole formed to attach the hub Luer lock 20 to the cylinder 10, and the inner diameter thereof is shaped to be approximately the same as the outer diameter of the cylinder 10. The luer lock of hub 20 is attached to the front end side of cylinder 10 by enclosing the front end of cylinder 10 with fitting hole 24.
    [0065] In addition, an annularly recessed ring-shaped groove 24a is formed in the front end portion of the inner circumferential wall of the socket hole 24 with the centerline O as a center. When the hub Luer latch 20 is attached to the front end side of the cylinder 10, the ring-shaped front end side protrusion 14 of the cylinder 10 is fitted to the ring-shaped groove 24a, and thus the hub Luer latch 20 is integrally fixed with cylinder 10 air-proof, liquid-proof, and strongly.
    [0066] The bypass chamber described above 25 is a hole with a bottom, the inner diameter of which is smaller than the diameter of the plug hole 24 by one stage, and the inner circumferential wall thereof has a bypass groove 26 formed in it. The deflection groove 26 comprises a linear groove 26a and an annular groove 26b.
    [0067] More than one linear groove 26a is formed at regular intervals in the circumferential direction so as to extend parallel to the axis line O on the inner wall surface of the bypass chamber 25, and the front end sides of these linear grooves 26a are respectively connected to the introduction port 23a extending to the front end surface 25a from the inner wall surface of the bypass chamber 25 and formed within the Luer tip 23.
    [0068] In addition, the annular groove 26b is an annular groove extending in the circumferential direction with the axis line O with a center, and is formed in the vicinity of the boundary between the fitting hole 24 and the deflection chamber 25 on the surface of inner wall of the diverter chamber 25. The annular groove 26b is connected to the respective rear ends of the plurality of linear grooves 26a described above, and thus the respective linear grooves 26a are connected through the annular groove 26b.
    [0069] The front cap 30, the middle cap 40, and the end cap 50 are molded from medical rubber having corrosion resistance for preparation S, solvent L, and injection M, and has an approximately cylindrical shape, which has an outer diameter slightly larger than the inner diameter of cylinder 10, with centerline O as a center.
    [0070] The front cap 30 is fitted to the front end side of the diverter portion 11 of the cylinder 10, i.e. fitted to the front end side cylinder portion 12.
    [0071] In addition, the middle cap 40 is fitted to the rear end side of the offset portion 11 of the cylinder 10, i.e. fitted to the rear end side cylinder portion 13. Particularly, the middle cap 40 of this mode is arranged so that the front end of the middle cap 40 is positioned at the boundary between the diverter portion 11 and the rear end side cylinder portion 13 which is the front end of the rear end side cylinder portion 13. The preparation in powder S is sealed so as to be sandwiched between the middle plug 40 and the front plug 30 in the cylinder 10. That is, the preparation S is filled into a front chamber F formed by the inner circumferential surface of the cylinder 10, the rear end surface. of the front cap 30, and the front end surface of the middle cap 40.
    [0072] The end cap 50 is fitted on the additional rear end side of the middle cap 40 of the rear end side cylinder portion 13 of the cylinder 10 while being spaced from the middle cap 40 in the direction of centerline O. Solvent L having a liquid form is sealed to be sandwiched between the end cap 50 and the middle cap 40 described above. That is, solvent L is filled into a rear chamber B formed by the inner circumferential surface of cylinder 10, the rear end surface of the middle plug 40, and the front end surface of the end plug 50. A female screw hole ( omitted) in which a connecting portion 76 of the piston rod 70 to be described later is screwed on is formed in the rear end of the end cap 50.
    [0073] In this way, in the double chamber preloadable syringe 100, the preparation S and the solvent L are sealed separately in the front chamber F and the rear chamber B divided by the middle stopper 40.
    [0074] As shown in FIGS. 2A and 2B, finger grip 60 is provided with an engaging portion 61, a flange portion 62, and a cylinder portion 63.
    [0075] The engagement portion 61 has an approximately cylindrical shape with the centerline O as a center, and a engagement hole 61a to which the rear end of the cylinder 10 is fitted is formed on the inner circumferential side thereof. An annularly recessed ring-shaped groove 61b is formed in the inner circumference at the rear end of the socket hole 61a with the centerline O as a center. As shown in FIG. 1, when the finger grip 60 is attached to the rear end of the cylinder 10, the ring-shaped rear end side protrusion 15 of the cylinder 10 is fitted into the ring-shaped groove 61b, and thus the finger grip 60 is tightly secured. integrally with cylinder 10.
    [0076] The flange portion 62 projects in the diametric direction from the rear end of the socket portion 61, that is, from the vicinity of the boundary between the socket portion 61 and the cylinder portion 63 with the axis line O as a center, and has an approximately rectangular shape when viewed in the direction of centerline O. The flange portion 62 supports a health worker's fingers when the preloadable dual chamber syringe 100 is used, and thus acts to manufacture the handling of the preloadable dual chamber syringe 100 by the healthcare worker with ease.
    [0077] The cylinder portion 63 has an approximately cylindrical shape with the centerline O as a center, and extends further towards the rear side from the rear end of the fitting portion 61. The cylinder portion 63 has a diameter which is smaller than the inner diameter of the fitting portion 61 by a stage, and a step portion at the boundary between the cylinder portion 63 and the fitting portion 61 is placed in contact with the rear end of the cylinder 10. Female screw portion 64 which is screwed around centerline O is formed on the inner circumferential surface of cylinder portion 63. Female screw portion 64 is made up of two socket screws which are screwed in the clockwise direction (here hereafter referred to as the direction of screw rotation) toward the front end side from the rear end side of the finger grip 60, and each female screw extends to rotate around, for example 360°, the inner circumferential surface of the cylinder portion 63.
    [0078] In addition, a guide groove 65 which is recessed outwardly (outward in the radial direction of the centerline O) in the radial direction of the female screw portion 64 and extends parallel to the centerline O is formed in the inner circumferential surface of cylinder portion 63, i.e. on female screw portion 64. Guide groove 65 extends over all areas of barrel portion 63 and female screw portion 64 in the direction of centerline O, and a pair of guide grooves 65 are provided to be opposite each other with an interval of 180° between them in the circumferential direction of the female screw portion 64, i.e. opposite each other in the diametric direction of the female screw portion 64.
    [0079] In addition, a pair of first protrusions 66 and a pair of second protrusions 67 are provided at the rear end of the cylinder portion 63. The pair of first protrusions 66 are provided to be opposed to each other with a 180° gap between them. in the circumferential direction of the cylinder portion, that is, opposite each other in the diametric direction of the cylinder portion. In addition, the pair of second protrusions 67 are also provided to be opposite each other with an interval of 180° between them in the circumferential direction of the cylinder portion, i.e. opposite each other in the diametric direction of the cylinder portion.
    [0080] The first protrusion 66 is formed in a part on the rear side of the pair of guide grooves 65 of the rear end surface 63a of the cylinder portion 63 in the direction of rotation of the screw to be in protrusion to the rear side along the line of axis O from rear end surface 63a. In addition, the second protrusion 67 is formed in a part on the front side of the pair of guide grooves 65 of the rear end surface 63a of the cylinder portion 63 in the direction of rotation of the screw to protrude to the rear side along the axis line O from rear end surface 63a. That is, the first and second protrusions 66 and 67 are adjacent to the guide grooves 65 for sandwiching the guide grooves 65 between them in the circumferential direction of the centerline O.
    [0081] Here, a surface of the first protrusion 66 which faces the rear side in the screw rotation direction is formed as a slightly sloping surface 66a which is gradually slanted towards the rear side along the centerline O from the rear end surface 63a that faces the front side in the direction of screw rotation. In addition, a surface facing the front side in the direction of rotation of the screw of the first protrusion 66 is formed as a sharply sloping surface 66b which is gradually slanted towards the front side along the centerline O which faces the front side in the direction of rotation of the screw. The steeply sloping surface 66b has a steeper slope than the above mentioned gently sloping surface 66a.
    [0082] Additionally, a surface of the second protrusion 67 which faces the rear side in the direction of rotation of the screw is formed as a vertical surface 67a which extends vertically to the rear side along the centerline O from the surface of rear end 63a of cylinder portion 63 connected to guide grooves 65.
    [0083] The second protrusion 67 is formed to be larger than the first protrusion 66, i.e. the top portion of the vertical surface 67a of the second protrusion 67 is positioned closer to the rear side in the direction of the axis line O than the top portion of the first protrusion 66.
    [0084] The piston rod 70 is a member connected to the end cap 50 to move the end cap 50 to the front side of the cylinder 10. As shown in FIGS. 3 to 5, the piston rod 70 is provided with a long rod portion 71 which extends along the axis line O, a connecting portion 76 which is provided on the front end side of the rod portion 71 and has a male screw shape connected to the end cap 50, and a pressing portion 77 which is provided on the rear end side of the rod portion 71 and by which the health worker applies pressure when pressing the end cap 50.
    [0085] In addition, a male screw portion 73 which is screwed around the axis line O is formed on the outer circumferential surface of the shank portion 71. The male screw portion 73 is made up of two core screws which are screwed on in the clockwise direction (screw rotation direction) towards the front end side from the rear end side of the piston rod 70. Such male screw portion 73 is formed over a predetermined strip in the direction of the centerline More on the front end side than a central portion of the shank portion 71 in the direction of the centerline O.
    [0086] The shank portion 71 has a pair of cutout portions 74 which are formed by cutting a predetermined strip in the circumferential direction over substantially the entire area in the direction of the axis line O. The pair of cutout portions 74 is formed with a 180° gap between them in the circumferential direction of the shank portion 71. Suitably, the shank portion 71 may be molded using a split mold.
    [0087] By the cutout portions 74, the male screw portion 73 is divided into two parts in the circumferential direction of the shank portion 71.
    [0088] In the cutout portion 74, a rib 74a is formed which protrudes outwardly in the radial direction of the centerline O from a bottom surface of the cutout portion 74, i.e., from a surface of the cutout portion 74. cut-out portion 74 that faces outwardly in the radial direction of centerline O to extend parallel to centerline O. The strength of rod portion 71 is maintained by rib 74. In addition, two ribs 74a are arranged in parallel on the direction of the axis line O in the respective cutout portions 74. Due to the configuration in which the rib 74a on the front end side and the rib 74a on the rear end side are divided in this way, a part of the solvent L that remains in the protruding part of the deflection portion 11 can be prevented from reaching rib 74a on the rear end side through rib 74a on the front end side and sticking to the hand of the health worker.
    [0089] In addition, an area on the front end side of the area in which the male screw portion 73 of the shank portion 71 is formed as a shank front end portion 71a having a cylindrical outer circumferential surface, and an area on the side The rear end portion of the area in which the male screw portion 73 is formed is formed as a shank trailing end portion 71b having the same cylindrical outer circumferential surface.
    [0090] The shank front end portion 71a and the shank rear end portion 71b are formed to have an outer diameter which is the same or slightly smaller than the inner diameter of the female screw portion 64 of the cylinder portion 63 of the finger grip 60. In this way, the shank front end portion 71a and the shank trailing end portion 71b can be inserted into the female screw portion 64 in the direction of the axis line O.
    [0091] Additionally, a pair of guide plates 75 is formed with a 180° gap between them in the circumferential direction of the rod portion 71 on the outer circumferential surface of the rear end portion of rod 71b. These guide plates 75 have a shape that protrudes rectangularly outwards in the radial direction of the shank portion 71 in a cross section perpendicular to the centerline O, and extends parallel to the centerline O over a predetermined strip.
    [0092] Next, a method of using the dual chamber preloadable syringe 100 having the configuration described above will be described with reference to FIGS. 6A to 7B.
    [0093] First, as shown in FIG. 6A, the connecting portion 76 at the front end of the piston rod 70 is screwed into a female screw hole of the end cap 50, and thus the piston rod 70 is connected to the end cap 50. In this state, the end portion The shank front 71a of the shank portion 71 is inserted into the female screw portion 64 of the finger grip 60.
    [0094] Next, the pressing portion 77 of the plunger rod 70 is pressed from the rear end side into a state in which the health worker's fingers are placed on the flange portion 62 of the finger grip 60. The force of pressing is transmitted to the middle cap 40 through the end cap 50 and the solvent L. That is, the piston rod 70 advances due to the pressing force described above, and the middle cap 40 also advances into the side cylinder portion. of rear end 13 of cylinder 10.
    [0095] As shown in FIG. 6B, at the time when a part of the middle cap 40 (in this embodiment, half of the middle cap 40 on the front end side towards the axis line O) enters the offset portion 11, the front end of the male screw portion 73 of the shank of plunger 70 is placed in contact with the rear end of the female screw portion 64 of the finger grip 60. The male screw portion 73 can be brought into contact with the female screw portion 64 when the front end of the middle cap 40 reaches the rear end of the bypass portion 11, or the male screw portion 73 can reach the female screw portion 64 just before the front end of the middle cap 40 reaches the rear end of the bypass portion 11. Placing the male screw portion 73 and the female screw portion 64 in contact with each other in this way, the male screw portion 73 and the female screw portion 64 become interruptions in the advancement of the piston rod 70. Next, the interruption Plunger 70 cannot be advanced even when piston rod 70 is depressed.
    [0096] In addition, by placing the male screw portion 73 and female screw portion 64 in contact with each other in this way, the male screw portion 73 and the female screw portion 64 can be screwed together. Suitably, when the piston rod 70 is rotated to the forward side in the direction of screw rotation in this state, the male screw portion 73 and the female screw portion 64 are screwed together, and the piston rod 70 moves forward. according to the steps of the same. End cap 50 also advances with advancement of piston rod 70. As shown in FIG. 6C, when the entire length of the middle cap 40 in the direction of centerline O enters the interior of the deflection portion 11, the front chamber F and the rear chamber B communicate with each other through the outwardly projecting area of the cylinder 10 in the portion. deviation 11.
    [0097] Suitably, the solvent L from the rear chamber B can be allowed to flow into the preparation S from the front chamber F. Furthermore, when the piston rod 70 is further rotated in the direction of screw rotation and gradually advances, more than pressing force which is applied to the solvent L due to the advancement of the piston rod 70 is converted to pressure to allow the solvent L to flow into the front chamber F. Therefore, the middle plug 40 is in the bypass portion 11 with little advance.
    [0098] Next, at the moment when the front end of the end cap 50 is placed in contact with the rear end of the middle cap 40 due to the advancement of the piston rod 70, all the solvent L in the rear chamber B is introduced to the preparation S of the front chamber F, and thus the rear chamber B is eliminated. Furthermore, when the piston rod 70 is further rotated in the direction of screw rotation and gradually advances, the middle cap 40 which is placed in contact with the end cap 50 is also simultaneously advanced through the end cap 50.
    [0099] Next, as shown in FIG. 7A, at the moment a portion of the middle cap 40 (in this embodiment, half of the middle cap 40 on the front end side in the direction of the centerline O) enters the front end side cylinder portion 12 of the cylinder 10, i.e. , at the moment when a portion of the middle cap 40 moves out of the deflection portion 11, the guide plate 75 of the plunger rod 70 is brought into contact with the slightly sloping surface 66a of the first protrusion 66 of the finger grip 60 in order to be able to overcome it from the rear side in the direction of rotation of the screw. At this time, the front chamber F is resealed and the health worker shakes the pre-loadable dual chamber syringe 100 under this circumstance, so that preparation S is completely dissolved by solvent L and the preparation of injection M is completed.
    [00100] Here, the state in which the guide plate 75 is placed in contact with the first protrusion 66 in order to be able to overcome it means a state of contact at a level where even if a resistance occurs in the rotation of the rod of plunger 70 due to the guide plate 75 placed in contact with the slightly sloping surface 66a of the first protrusion 66, the guide plate 75 can overcome the first protrusion 66 towards the front side in the direction of screw rotation by the strong rotation of the rod. Plunger 70. Such a state of contact can be accomplished by molding the plunger rod 70 and the finger grip 60 with a flexible material such as a synthetic resin.
    [00101] In the contact state described above, when the guide plate 75 overcomes the first protrusion 66 as shown in FIG. 8 by strong rotation of the piston rod 70, the guide plate 75 is then brought into contact with the vertical surface 67a of the second protrusion 67 from the rear side in the direction of rotation of the screw. Suitably, the movement of the guide plate 75 to the front side in the direction of rotation of the screw is inhibited. That is, the piston rod 70 can no longer be rotated to the front side in the direction of screw rotation. Even when the piston rod 70 is rotated in the reverse rotation direction of the bolt, the guide plate 75 is brought into contact with the sharply inclined surface 66a of the first protrusion 66, and thus rotation is inhibited.
    [00102] Additionally, after the guide plate 75 overcomes the first protrusion 66 as described above, the male screw portion 73 passes through an area in which the female screw portion 64 is present. That is, the bolting between the male screw portion 73 and the female screw portion 64 is released. In addition, when guide plate 75 is positioned between the first and second protrusions 66 and 67, the position of guide plate 75 in the circumferential direction coincides with that of guide groove 65 of finger grip 60. That is, the plate guide groove 75 and guide groove 65 can be adjusted to each other.
    [00103] Appropriately, the piston rod 70 can be pressed again to go straight.
    [00104] Next, when the piston rod 70 is pressed, the guide plate 75 of the piston rod 70 is fitted into the guide groove 65 of the finger grip 60, and the piston rod 70 advances to be guided into the groove. guide tube 65. The pressing force which is generated by pressing the piston rod 70 at this time is transmitted to the front cap 30 through the end cap 50, the middle cap 40, and the injection M, and the front cap 30 advances on cylinder 10.
    [00105] When the front cap 30 enters the bypass chamber 25 as a result of the advancement of the front cap 30 described above, the front chamber F in which the injection M is present communicates with the introduction hole 23a of the Luer tip 23 through the bypass groove 26. Suitably, bubbles remaining in cylinder 10 are discharged to the outside, and thus injection M can be introduced to injection needle 27, and injection M can be injected into a patient.
    [00106] Next, in the injection of injection M, the piston rod 70 is further pressed, and thus the injection M of the front chamber F is introduced into the injection needle 27 through the deflection groove 26 and the introduction hole 23a. Furthermore, when the piston rod 70 is fully depressed, as shown in FIG. 7B, the entire injection M is injected into a patient through injection needle 27, and the front end of the middle cap 40 and the rear end of the front cap 30 are brought into contact with each other, while the front chamber F is eliminated. As described above, the injection of the M injection into a patient ends.
    [00107] According to the double chamber preloadable syringe 100 of this modality having the configuration described above, when the plunger rod 70 is rotated according to the screwing between the male screw portion 73 and the female screw portion 64, the piston rod 70 gradually advances in accordance with the steps of the male screw portion 73 and the female screw portion 64. Appropriately, it is possible to avoid the excessive advance speed of the piston rod 70, and it is possible to allow the middle buffer 40 is in the bypass portion 11. Properly, it is possible to catch the communication state between the front chamber F and the rear chamber B, and thus it is possible to properly (or completely) mix the solvent L and the preparation S.
    [00108] Here, when aripiprazole is employed as preparation S, it is difficult to dissolve in solvent L. However, in the dual-chamber preloadable syringe 100 of this embodiment, preparation S can be properly (or completely) dissolved in solvent L. Therefore, even when aripiprazole is employed as preparation S which is difficult to dissolve in solvent L, aripiprazole can be easily suspended in solvent L.
    [00109] In addition, when the middle cap 40 is advanced through the end cap 50 and the solvent L by pressing the plunger rod 70, the male screw portion 73 is brought into contact with the female screw portion 64 when a part of the middle cap 40 enters the deflection portion 11. Properly, even when the piston rod 70 is further depressed, the piston rod 70 does not advance, and the middle cap 40 does not advance either. Therefore, it is possible to prevent the middle stopper 40 from being advanced too far to the front end side of the deflection portion 11 due to an excessive force applied to the piston rod 70.
    [00110] In addition, the dual-chamber preloadable syringe 100 of this modality has a configuration in which, as described above, when a part of the middle stopper 40 that is advanced by pressing the plunger rod 70 enters the diverter portion 11, the end The front end of the male screw portion 73 reaches and is screwed to the front end of the female screw portion 64. A configuration can also be provided in which the front end of the male screw portion 73 reaches the front end of the female screw portion 64 just before from the front end of the middle cap 40 enters the bypass portion 11.
    [00111] Suitably, as the piston rod 70 can be rotated according to screwing between the male screw portion 73 and the female screw portion 64 only when the middle cap 40 reaches the deviation portion 11 and the solvent L is introduced in preparation S, only a pressing preparation of the plunger rod 70 can be carried out until a part of the middle stopper 40 reaches the bypass portion 11. Thus, it is possible to simplify the handling of the pre-loadable double chamber syringe 100.
    [00112] Additionally, in the double chamber preloadable syringe 100 according to this modality, when the plunger rod 70 is rotated and advanced according to the screwing between the male screw portion 73 and the female screw portion 64, the male screw portion 73 of piston rod 70 passes through female screw portion 64 of finger grip 60, and thus the screwing between male screw portion 73 and female screw portion 64 is released. At this time, the guide plate 75 of the piston rod 70 is brought into contact with the second protrusion 67 of the finger grip 60, and the piston rod 70 can no longer be rotated. Therefore, the healthcare worker can easily perceive that the bolting between the male screw portion 73 and the female screw portion 64 has been released.
    [00113] In addition, as the bolting is released in this way, piston rod 70 can be depressed. At this time, the piston rod 70 is interrupted in a position in which the guide plate 75 of the piston rod 70 and the guide groove 65 formed in the female screw portion 64 can be adjusted to each other, and so when the piston rod Plunger 70 is biased, piston rod 70 can be guided in the direction in which guide groove 65 extends. Appropriately, the plunger rod 70 can be let go straight, and the same operation as in the case of normal syringes can be performed.
    [00114] In addition, in this mode, in the case where the piston rod 70 is rotated according to the screwing between the male screw portion 73 and the female screw portion 64, the guide plate 75 of the piston rod 70 is placed in contact with the first protrusion 66 so as to overcome it when the middle plug 40 that goes straight on the cylinder 10 moves out of the bypass portion 11. Appropriately, the health worker can easily perceive that the front chamber F is resealed as a part of the middle stopper 40 moves through the bypass portion 11. At this time, the health worker shakes the pre-loadable double chamber syringe 100 so that injection M in which preparation S is completely dissolved in solvent L can be reconstituted.
    [00115] Additionally, in this mode, as described above, the configuration is provided in which the guide plate 75 overcomes the first protrusion 66 by rotating the piston rod 70 according to the bolting between the female screw portion 64 and the portion of male screw 73, and then the bolting between the male screw portion 73 and the female screw portion 64 is released.
    [00116] Appropriately, after a part of the middle cap 40 moves out of the deflection portion 11 due to the rotation of the piston rod 70, the pressing operation of the piston rod 70 can be carried out. In addition, after the guide plate 75 overcomes the first protrusion 66, the guide plate 75 is brought into contact with the second protrusion 67, and thus the rotation of the piston rod 70 is stopped. This position becomes a position in which feed due to rotation and feed due to going straight are switched.
    [00117] In this way, the plunger rod 70 is rotated only when the solvent L is introduced into the preparation S, and then the operation can be switched to a preparation by pressing the plunger rod 70. It is possible to simplify the handling of the pre-syringe. chargeable dual chamber 100.
    [00118] In addition, in this embodiment, when the guide plate 75 is placed in contact with the second protrusion 67 by rotating the piston rod 70, the guide plate 75 of the piston rod 70 can be fitted in the guide groove 65 of the finger grip 60. Appropriately thereafter, by depressing the piston rod 70, the piston rod 70 can be let go straight.
    [00119] As described above, the twin-chamber preloadable syringe 100 of this modality is used to allow the plunger rod 70 to go straight when used in this way to allow the middle stopper 40 to enter the bypass portion 11, thereby allowing the solvent L flows safely into the preparation S and sufficiently dissolves or suspends the preparation S. Here, when the plunger rod 70 just goes straight, the force to press the plunger rod 70 is difficult to adjust, and so there is possibility that the middle plug 40 may pass through the bypass portion 11.
    [00120] In this mode, by contacting the male screw portion 73 with the female screw portion 64, the health worker can detect a position in which the middle cap 40 enters the bypass portion 11. In addition, the subsequent advancement of the rod of piston 70 is performed by rotation according to screwing between the male screw portion 73 and the female screw portion 64, and thus the speed can be easily adjusted and the feed rate does not increase to a feed rate or greater. Appropriately, it is possible to prevent the middle stopper 40 from passing through the bypass portion 11. Particularly, the double-chamber preloadable syringe 100 of this embodiment is suitable to be applied when preparation S is special and takes a long time to dissolve the preparation S.
    [00121] In addition, it is considered that if the guide plate 75 and the second protrusion 67 are not present when the male screw portion 73 passes through the female screw portion 64 and the tightness between the male screw portion 73 and the female screw portion 64 ends, the health worker cannot detect the release of the bolting between the male screw portion 73 and the female screw portion 64, and in that position, the piston rod 70 is rotated again and again. In addition, when the healthcare worker notices the release of the bolting described above and presses the plunger rod 70 in a hurry, the injection M is instantly pressed as the plunger rod 70 can be let go straight through freely, and so the front cap is dropped into bypass chamber 25 and the seal on the front end portion of cylinder 10 is released. Whereas, when the syringe is shaken, there is a concern that solvent L or injection M will fly out of the injection needle 27.
    [00122] In this regard, in this modality, the guide plate 75 is placed in contact with the second protrusion 67 to stop the rotation of the piston rod 70, and thus it is possible to allow the health worker to detect the release of the screw described. above. Appropriately, the healthcare worker may recognize that it is necessary not to press down on the plunger rod 70 without concerned consideration, it is necessary to sufficiently dissolve and suspend the preparation S by stirring the preparation S and also the solvent L, and it is necessary to operate the Plunger rod 70 carefully to discharge bubbles from that position and inject the drug into a patient.
    The dual chamber preloadable syringe (aripiprazole filled in a syringe) 100 which is an embodiment of the invention has been described in detail. However, the invention is not limited to this without departing from the technical idea of the invention, and some design modifications and the like can be made.
    [00124] For example, the pitches of the male screw portion 73 and female screw portion 64 can be properly designed, and thus the advance speed of the plunger rod 70 can be adjusted, and the speed of dissolution or suspension of the preparation S by solvent L can be freely adjusted.
    [00125] Furthermore, in the case where the double chamber preloadable syringe 100 is packaged in a state in which the plunger rod 70 is connected to the end cap 50, even when the plunger rod 70 is pressed with little care during transport and the like, further advancement of the piston rod 70 is inhibited as the male screw portion 73 is brought into contact with the female screw portion 64. In a suitable manner, it is always possible to safely hold the separation state of the solvent L and preparation S, and the danger can be avoided.
    [00126] It is preferable that the respective end portions of the female screw portion 64 and the male screw portion 73 in the circumferential direction are formed into a tapered shape. Suitably, the female screw portion 64 and the male screw portion 73 can be easily screwed together, and thus the operation can be carried out smoothly.
    [00127] It is possible to use a 60 finger grip as shown in FIGS. 9A and 9B, for example, as the finger grip 60 of a modified embodiment. In this finger grip 60 of the other embodiment, the flange portion 62 is provided on a rear end side of the cylinder portion 63, different from the embodiment in which the cylinder portion 63 is projecting rearwardly from the flange portion 62 In other words, in the case of the modified modality, the cylinder portion 63 is buried in the socket portion 61.
    [00128] Accordingly, as the cylinder portion 63 having female screw portion 64, the first protrusions 66, the second protrusions 67 and the guide groove 65 do not protrude from the flange portion 62, it is possible to avoid that handling the preloadable dual chamber syringe becomes problematic due to the health worker's fingers touching the cylinder portion 63.Examples
    [00129] Here below, examples will be described.
    [00130] A bulk powder of aripiprazole hydrate was suspended in a dispersion medium to obtain a concentration of 30% by weight as aripiprazole anhydride. The concentrations of other additives in the obtained suspension were as follows. The concentration of sodium carboxymethylcellulose was about 1.248% by weight, the concentration of mannitol was about 6.24% by weight, and the concentration of sodium dihydrogen phosphate monohydrate was 0.111% by weight. In addition, the pH of the suspension was adjusted to about 7 by the addition of aqueous sodium hydroxide. The suspension was wet milled by a high shear rotary homogenizer (CLEARMIX, M Technique Co., Ltd.) and repeatedly wet milled at 550 bar by a high pressure homogenizer (Niro Inc.). The primary principal particle size of the obtained suspension was 2 to 3 µm.
    [00131] 1.5 ml of the suspension (about 450 mg, as aripiprazole anhydride) was filled into a freeze-drying beaker made of polyethylene, and moved to a freeze dryer. The suspension was freeze-dried according to the following cycle of (a) and (b) to obtain a cake composition: (a) Heat Treatment: The beaker filled with the suspension was frozen for about 4 hours at one temperature of shelf kept at about -40oC; and(b) Primary drying: Primary drying was continued for about 40 hours at a chamber pressure increased to about 13 Pa and a shelf temperature increased to about -5oC
    [00132] After freezing by drying, the bottom of the cup was pressed and a freeze-dried cake was taken.
    [00133] As a preparation S, the freeze-dried cake was placed in the front chamber (space between the front stopper 30 and the middle stopper 40) of the preloadable dual chamber syringe 100 of the modality. The back chamber (space between the middle buffer 40 and the end buffer 50) was filled with 2.0 ml of purified water as a L solvent. 1. Measurement of Amount Remaining in Dead Space in Preloadable Dual Chamber Syringe
    The end cap 50 was pressed until the purified water from the rear chamber drained into the front chamber via bypass 11. After the purified water flowed into the front chamber, the freeze-dried cake was resuspended by sufficient agitation. In the suspension after resuspension, pieces of powder and the like due to residue caused by incomplete dissolution were not shown. The suspension was discharged from the Luer tip introduction port 23a 23, which was the discharge port at the front end of the double chamber preloadable syringe 100, by further depressing the end cap 50. After discharge , the dual chamber preloadable syringe 100 was disassembled, and the amount of drug remaining in the dual chamber preloadable syringe 100 was quantified. The average of it was about 19 mg. As the suspension was well shaken and evenly resuspended, the amount of drug is the amount remaining in the Dead Space in the syringe.2. General Piston Rod Resuspension
    [00135] A general plunger rod (with a screw tap portion 73 formed therein) only for unidirectional pressing in the discharge direction was attached to the end cap 50 to make a preloadable double chamber syringe of a comparative example, and the end cap 50 was pressed to allow purified water to rapidly drain into the front chamber in the same manner as described above. Then, the syringe was left for 5 seconds without complete agitation, and the suspension was discharged from the introduction port 23a of the Luer tip 23. After discharge, the preloadable double chamber syringe was disassembled, and the amount of drug remaining in the preloadable dual-chamber syringe was quantified. The average of it was about 195 mg. It was found that about 176 mg, which is a difference with the remaining amount described above, remains in the syringe as the residue caused by incomplete dissolution.3. Screw-type Plunger Rod Resuspension
    [00136] The screw-type plunger rod 70 of this embodiment has been attached to the end cap 50 to allow purified water to rapidly drain into the front chamber while turning the screw as described above in this embodiment. Then, the syringe was left for 5 seconds without complete agitation, and the suspension was discharged from the introduction port 23a of the Luer tip 23. After discharge, the preloadable double chamber syringe was disassembled, and the quantity of drug remaining in the preloadable dual-chamber syringe was quantified. The average of it was about 62 mg. It was found that about 43 mg, which is a difference with the remaining amount described above, remains in the syringe as the residue caused by incomplete dissolution.
    [00137] The test result described above is shown in Table 1. From the result, it was found that the resuspension can be performed efficiently by performing a resuspension process with the screw-type piston rod 70 of this modality. In general, in the double chamber preloadable syringe, there is a concern that when resuspension by shaking is required as in the case of the preparation used in this test, the injection can be performed without a shaking process in actual clinical practice. When the agitation process is forgotten, a significant dose reduction is shown when using the general plunger rod. However, through the use of the plunger rod 70 of this modality, the significant reduction in dose becomes smaller even when agitation is forgotten. In addition, as the plunger rod 70 is operated differently before and after the resuspension process as opposed to a general plunger rod just for pressing, it is possible to request the health worker to recognize the resuspension process, and it is possible to reduce a risk of dose reduction due to forgetfulness of agitation.
    Industrial Applicability
    [00138] According to the double-chamber preloadable syringe of the invention, it is possible to properly mix the solvent and the preparation. In addition, according to aripiprazole filled in a syringe, it is possible to reduce the residue and incomplete dissolution in the resuspension. Reference Signal List 10 cylinder, 11 bypass portion, 12 front end side cylinder portion, 13 cylinder portion of rear end side protrusion, 14 ring-shaped front end side protrusion, 15 ring-shaped rear end side protrusion, 20 hub Luer latch, 21 base end portion, 22 cylinder portion, 23 Luer tip , 24 fitting hole, 25 deflection chamber, 25a front end surface, 26 deflection groove, 26a linear groove, 26b annular groove, 27 needle, 30 front cap, 40 middle cap, 50 end cap, 60 finger grip , 61 socket portion, 62 flange portion, 63 cylinder portion, 64 female screw portion, 65 guide groove, 66 first protrusion, 66a slightly sloped surface, 66b sharply sloped surface, 67 second protrusion , 67a vertical surface, 70 piston rod, 71 rod portion, 71a rod front end portion, 41b rod rear end portion, 73 male screw portion, 74 notch portion, 74a rib, 75 guide plate, 76 connecting portion, 77 pressing portion, 100 double chamber preloadable syringe, O axis line, S preparation, L solvent, M injection, F front chamber, B rear chamber.
    权利要求:
    Claims (5)
    [0001]
    1. Dual chamber preloadable syringe (100), comprising: a cylinder (10) which has a cylindrical shape with a centerline (O) as a center and has a bypass portion (11) formed due to the protruding a part of an inner circumferential surface to the outside; a luer hub lock (20) which is provided at the front end of the cylinder; a finger grip (60) which is provided at the rear end of the cylinder; front (30) which is fitted to the front end side of the bypass portion in the cylinder; a middle cap (40) which is fitted to the rear end side of the bypass portion in the cylinder to seal a preparation (S) together with the front cap; an end cap (50) which is fitted to the rear end side of the middle cap on the cylinder to seal a solvent together with the middle cap; a piston rod (70) which is connected to the end cap from the rear end side by in section of the finger grip and which is provided with a long shank portion which extends along the axis line, a connecting portion which is provided on the front end side of the shank portion and has a male screw shape connected to the end cap, and a pressure portion which is provided on the rear side of the rod portion; a female screw portion (64) which is formed to be screwed around the centerline on an inner circumferential surface of the finger grip ; and a male screw portion (73) which is formed along a predetermined interval in the direction of the centerline, more on the front side, than a central portion of the shank portion, in the direction of the centerline and to be capable of being screwed together with the female screw portion on an outer circumferential surface of the piston rod, characterized by the fact that a guide groove (65) which is formed in the female screw portion and extends parallel to the centerline a guide plate (75) which is formed on the rear end side of the male screw portion on the outer circumferential surface of the piston rod and is guided in accordance with the guide groove; and a first protrusion (66) which is formed at the rear end of the finger grip and with which the guide plate is brought into contact so as to be able to overcome it when at least a part of the middle plug is advanced through. of the rotation of the piston rod according to the female screw portion and the male screw portion moves by the deflection portion.
    [0002]
    2. Double-chamber preloadable syringe according to claim 1, characterized in that the front end of the male screw portion is arranged to reach the rear end of the female screw portion, and can be screwed to it when a middle cap, which is advanced by pressing the plunger rod, enters the bypass part.
    [0003]
    3. Double-chamber preloadable syringe according to claim 1 or 2, characterized in that the screw between the male screw portion and the female screw portion are arranged to be released after the guide plate overcomes the first protrusion through, rotating the piston rod in accordance with the female screw portion and the male screw portion.
    [0004]
    4. Double-chamber preloadable syringe according to claim 3, characterized in that it further comprises: a second protrusion (67) which is formed at the rear end of the finger grip and is arranged to be brought into contact with a position in which the guide plate which overcomes the first protrusion can be fitted to the guide groove.
    [0005]
    5. Double-chamber preloadable syringe according to any one of claims 1 to 4, characterized in that the preparation includes aripiprazole.
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    同族专利:
    公开号 | 公开日
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    法律状态:
    2018-12-18| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-09-17| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-06-23| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |
    2020-11-17| B07E| Notice of approval relating to section 229 industrial property law [chapter 7.5 patent gazette]|
    2021-05-04| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-06-01| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 16/11/2011, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    JP2010256188|2010-11-16|
    JP2010256188|2010-11-16|
    PCT/JP2011/076385|WO2012067141A1|2010-11-16|2011-11-16|Two-chambered container-cum-syringe and syringe-filled aripiprazole|
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