Patent Publication Number: US-2023149631-A1

Title: Pre-filled syringe

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a bypass continuation of PCT Application No. PCT/JP2021/030194, filed on Aug. 18, 2021, which claims priority to Japanese Patent Application No. JP2020-139686, filed on Aug. 20, 2020. The contents of these applications are incorporated by reference in their entireties. 
    
    
     BACKGROUND 
     The present application relates to a prefilled syringe in which a plunger is attached to a gasket. 
     A drug is housed in a sterile state inside a prefilled syringe in advance. Then, the prefilled syringe directly punctures a patient, injects the drug into a medical container, or is attached to a syringe pump to administer the drug to the patient. 
     In one type of prefilled syringe, a plunger is not attached to a gasket in advance, but is attached at a time of use. In another type of prefilled syringe, a plunger is attached to a gasket in advance. 
     For the prefilled syringe of the type in which the plunger is attached to the gasket in advance, a so-called “vacuum capping” may be used to insert the gasket. Vacuum capping includes filling a drug in an outer cylinder whose distal end opening is sealed in a sterile environment and under a depressurized atmosphere (a vacuum atmosphere), disposing a gasket at an opening part of the outer cylinder, then producing a normal pressure state, and thereby inserting the gasket into the outer cylinder. Then, the plunger is attached to the gasket to manufacture the prefilled syringe. 
     The prefilled syringe in which a plunger has already been attached to a gasket makes it difficult to dispose the gasket at an opening part of an outer cylinder, and therefore the above-described capping work is performed using the gasket alone. Therefore, a prefilled syringe generally requires a subsequent plunger attachment process. 
     Furthermore, a label that describes a drug name, a drug amount, and the like is generally pasted on an outer surface of an outer cylinder of a prefilled syringe, and the label often makes it impossible to visually check a gasket position. 
     Japanese Patent Publication No. H08-504354-A (“Patent Literature 1”)(corresponding with PCT Publication No. WO94-013340, U.S. Pat. No. 5,370,621, and U.S. Pat. No. 5,472,431) discloses a prefilled syringe. This publication uses a plunger illustrated in  FIGS.  3 ,  8 , and  10   . The illustrated plunger includes four disc-shaped parts that can be inserted into an outer cylinder. 
     SUMMARY 
     Technical Problem 
     In the prefilled syringe according to Patent Literature 1, the plunger includes the four disc-shaped parts around a longitudinal axis, and the three disc-shaped parts are located in the outer cylinder in  FIG.  11   . 
     In a case where, for example, the third disc-shaped part is exposed from the outer cylinder in a state illustrated in  FIG.  11   , the gasket has moved backward from a state in which the gasket is positioned in the syringe. However, Patent Literature 1 does not recognize such a case, and it is likely that, even in a case where the third disc-shaped part is not exposed from the inside of a syringe main body, the gasket has moved backward from the state in which the gasket is positioned in the syringe. Furthermore, the four disc-shaped parts have the same shape, and, even in a case where the third disc-shaped part is exposed from the outer cylinder, a user cannot recognize based on the exposure of the third disc-shaped part that the gasket has moved backward from the state in which the gasket is positioned in the syringe. 
     Furthermore, the gasket is likely to move backward before use. This is considered to be mainly due to a user’s unnecessary operation of moving the plunger backward immediately before administration. Furthermore, backward movement of the plunger (backward movement of the gasket) is also likely to occur due to deviation from environmental conditions such as a temperature environment at a time of manufacturing, a time of transportation, and a time of storage of the prefilled syringe. 
     When the plunger moves backward, in other words, the gasket moves backward beyond a certain level, a negative pressure may be generated in the syringe, and air may flow into a drug solution of the prefilled syringe from between the gasket and the outer cylinder, and thereby contaminate the drug solution. 
     An object of the present invention is to provide a prefilled syringe in which a plunger has been attached to a gasket, and that makes it possible to easily and reliably visually determine when the plunger moves backward beyond an allowable level. 
     According to one embodiment, a prefilled syringe includes: an outer cylinder; a gasket that is slidably housed in the outer cylinder; a plunger that presses the gasket; a sealing member that seals a distal end part of the outer cylinder; and a drug that is housed in the outer cylinder, the outer cylinder includes a flange part that is provided at a proximal end part, the gasket includes a plunger distal end part attachment part, the plunger includes a gasket pressing part that is provided at a distal end part of the plunger, a shaft part that extends in a proximal end direction from the gasket pressing part, and a pressing operation part that is provided at a proximal end part of the shaft part, the shaft part includes on a proximal side of the gasket pressing part an indicator part that can be recognized by visually checking an external appearance, the plunger is attached to the gasket, and the indicator part is located in the flange part of the outer cylinder, and cannot be recognized by visually checking the external appearance in a state in which the plunger has been attached to the gasket, and is exposed behind the flange part, and can be recognized by visually checking the external appearance when the plunger moves backward. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    is a front view of a prefilled syringe according to an embodiment of the present invention. 
         FIG.  2    is a partial cross-sectional view taken along line A-A in  FIG.  1   . 
         FIG.  3    is a back view of the prefilled syringe illustrated in  FIG.  1   . 
         FIG.  4    is a perspective view illustrating the prefilled syringe illustrated in  FIG.  1    from a lower end side. 
         FIG.  5    is a front view of a plunger used in the prefilled syringe illustrated in  FIG.  1   . 
         FIG.  6    is a cross-sectional view taken along line B-B in  FIG.  5   . 
         FIG.  7    is a perspective view of the plunger illustrated in  FIG.  5   . 
         FIG.  8    is a longitudinal cross-sectional view of a gasket used in the prefilled syringe illustrated in  FIG.  1   . 
         FIG.  9    is an explanatory view of an outer cylinder used in the prefilled syringe illustrated in  FIG.  1   . 
         FIG.  10    is a front view of a prefilled syringe according to another embodiment of the present invention. 
         FIG.  11    is a partial cross-sectional view taken along line C-C in  FIG.  10   . 
         FIG.  12    is a front view of a plunger according to the another embodiment used in the prefilled syringe of the present invention. 
         FIG.  13    is a front view of the plunger according to another example used in the prefilled syringe of the present invention. 
         FIG.  14    is a front view of the plunger according to the another example used in the prefilled syringe of the present invention. 
         FIG.  15    is a front view of the plunger according to the another example used in the prefilled syringe of the present invention. 
         FIG.  16    is a front view of the plunger according to the another embodiment used in the prefilled syringe of the present invention. 
         FIG.  17    is a front view of the plunger according to the another example used in the prefilled syringe of the present invention. 
         FIG.  18    is a right side view of the plunger illustrated in  FIG.  5   . 
         FIG.  19    is a plan view of the plunger illustrated in  FIG.  5   . 
     
    
    
     DETAILED DESCRIPTION 
     Hereinafter, a prefilled syringe will be described using embodiments illustrated in the drawings. 
     As illustrated in  FIGS.  1  to  4   , a prefilled syringe  1  according to the present invention includes an outer cylinder  2 , a gasket  3  that is slidably housed in the outer cylinder  2 , a plunger  4  that presses the gasket  3 , a sealing member  5  that seals a distal end part of the outer cylinder  2 , and a drug  9  that is housed in the outer cylinder  2 . 
     The outer cylinder  2  includes a flange part  6  that is located at a proximal end part, the gasket  3  includes a plunger distal end part attachment part  35 , and the plunger  4  includes a gasket attachment distal end part  42 , a gasket pressing part  43  that is provided at a proximal end of the gasket attachment distal end part  42 , a shaft part  41  that extends in a proximal end direction from the gasket pressing part  43 , and a pressing operation part  44  that is provided at a proximal end part of the shaft part  41 . 
     The shaft part includes at a proximal side of the gasket pressing part  43  indicator parts  45   a ,  45   b ,  45   c , and  45   d  that can be recognized by visually checking an external appearance, the plunger  4  is attached to the gasket  3 , and the indicator parts  45   a ,  45   b ,  45   c , and  45   d  are located in the flange part  6  of the outer cylinder  2 , and cannot be recognized by visually checking the external appearance in a state in which the plunger  4  has been attached to the gasket  3 , and are exposed behind the flange part, and can be recognized by visually checking the external appearance when the plunger moves backward. 
     As illustrated in  FIGS.  1  to  4   , the prefilled syringe  1  according to the present invention includes the outer cylinder  2 , the gasket  3  that is slidably housed in the outer cylinder  2 , the plunger  4  that presses the gasket  3 , the sealing member  5  that seals the distal end part of the outer cylinder  2 , and the drug  9  that is housed in the outer cylinder  2 . In addition,  FIG.  2    illustrates cross sections of the outer cylinder and the sealing member taken along line A-A in  FIG.  1   , and illustrates external appearances of the plunger and the gasket. 
     In the prefilled syringe  1  according to this embodiment, the plunger  4  can be attached to the gasket  3  by being rotated, and, when the plunger  4  is loosened from the gasket  3 , the loosening can be resolved by rotating the plunger. 
     According to this embodiment, as illustrated in  FIGS.  1  to  4  and  9   , the outer cylinder  2  includes an outer cylinder main body  20 , and an attachment member  60  that is attached to a proximal end part of the outer cylinder main body  20 . 
     The outer cylinder main body  20  includes a hollow main body part  21 , a hollow distal end part  22  that extends from a distal end part of the hollow main body part  21 , and an outer cylinder flange  24  that is provided at a proximal end part of the hollow main body part  21 . In this embodiment, the attachment member  60  is fixed to the outer cylinder flange  24 , and both of the attachment member  60  and the outer cylinder flange  24  form the flange part  6 . 
     More specifically, the attachment member  60  is fixed to a bottom surface part of the flange  24  of the outer cylinder main body  20 . The attachment member  60  is not limited to such a type, and may sandwich the flange  24 . 
     In the prefilled syringe  1  according to this embodiment, the attachment member  60  includes retaining parts  64   a  and  64   b  that retains the plunger  4  in the outer cylinder  2 . The plunger  4  includes a disc-shaped gasket pressing part  43 , and this gasket pressing part  43  can abut on the retaining parts  64   a  and  64   b  of the attachment member  60 , and has a function of retaining the plunger  4 . 
     The outer cylinder main body  20  includes the hollow distal end part  22  that includes an opening at a distal end, a lock adapter  8  that covers a nozzle part of the hollow distal end part  22 , the hollow main body part  21 , and the flange  24  that is provided at a proximal end of the hollow main body part  21 . The nozzle part can be connected with another medical instrument (e.g., an injection needle, a connector, or a three-way stopcock). The lock adapter  8  includes on an inner surface a screw part that can be screwed with medical instrument (e.g., a rib or a screw part formed on a flange of an injection needle, a connector, a three-way stopcock, or the like) connected to the nozzle part. 
     The hollow main body part  21  of the outer cylinder main body  20  is formed in a cylindrical shape having a relatively small diameter, and is filled with a small amount (more specifically, 0.5 ml to 2 ml) of a drug solution or the like in a first embodiment, and the outer diameter of the hollow main body part  21  is 6 to 12 mm. 
     The outer cylinder flange  24  includes an arc-shaped outer edge that is formed protruding in a direction perpendicular to a center axis of the hollow main body part from an entire circumference of the proximal end of the hollow main body part  21 . Furthermore, as illustrated in  FIG.  9   , the flange  24  includes four recess parts  26   a ,  26   b ,  26   c , and  26   d . Furthermore, as illustrated in  FIG.  9   , the attachment member  60  includes four protrusions  62   a ,  62   b ,  62   c , and  62   d  that are provided on an upper surface of a plate-shaped part  61  and fit to the four recess parts of the flange  24 . Furthermore, the attachment member  60  is attached to the flange  24  of the outer cylinder main body  20  by fitting the above protrusions and recess parts. 
     Furthermore, the attachment member  60  includes a plunger insertion cutout part  63  that extends in a center direction from an outer part, and the width of the plunger insertion cutout part  63  is smaller than an outer diameter of the gasket pressing part  43  of the plunger  4 . Furthermore, the retaining parts  64   a  and  64   b  are formed by facing inner edge parts of the plunger insertion cutout part  63 . Therefore, when the plunger  4  moves backward, the gasket pressing part  43  abuts on the retaining parts  64   a  and  64   b , and is regulated from moving backward more and being detached from the outer cylinder. 
     The hollow distal end part  22  has a diameter that is smaller than the outer diameter of the hollow main body part  21 , and is reduced toward the distal end. The hollow distal end part  22  includes at a distal end a distal end opening part for discharging a drug solution or the like in the outer cylinder. Furthermore, the hollow distal end part  22  includes a locking rib that can be locked with the lock adapter  8  at a proximal end part (slightly distal of the distal end of the hollow main body part  21 ). In this embodiment, the locking rib is an annular rib. 
     Furthermore, the lock adapter  8  is a cylindrical member, and is attached to the hollow distal end part  22  of the outer cylinder main body  20 . Furthermore, a lower part of the lock adapter  8  is held by the locking rib provided to the hollow distal end part  22 . Furthermore, the lock adapter  8  includes an adapter side screw part that can be screwed with a sealing member side screw part of the sealing member (cap)  5  described later. In this first embodiment, the screw part is formed by two spiral ribs. 
     The sealing member  5  includes a main body part  51  that has a lower hollow part that houses the nozzle part of the hollow distal end part  22 , and a seal member  52  that is housed in the main body part  51  and disposed at an upper end part of the lower hollow part. Furthermore, the sealing member side screw part is formed on an outer surface of the lower hollow part. 
     Examples of materials for forming the outer cylinder main body  20  include various resins such as polypropylene, polyethylene, polystyrene, polyamide, polycarbonate, polyvinyl chloride, poly-(4-methylpentene-1), acrylic resin, acrylonitrile-butadiene-styrene copolymer, polyester such as polyethylene terephthalate, cyclic polyolefin polymer, and cyclic olefin copolymer. Among these resin materials, resins such as polypropylene, cyclic polyolefin polymer, and cyclic olefin copolymer are easy to mold and have heat resistance, and therefore are preferable. Note that the cyclic olefin polymer and the cyclic olefin copolymer that have such high transparency that a drug solution filled inside can be visually checked from an outside, and have heat resistance for withstanding autoclave treatment is particularly preferable as the materials for forming the outer cylinder main body  20 . 
     As a material for forming the lock adapter  8 , rigid resins such as polyvinylidene fluoride, polypropylene, polycarbonate, or polyamide are preferably used. As a material for forming the attachment member  60 , the sealing member  5 , and the plunger  4  described later, rigid or semirigid resins such as high density polyethylene, polypropylene, polystyrene, or polyethylene terephthalate are preferably used. 
     As a material for forming the seal member  52 , elastic materials such as synthetic rubbers such as natural rubber, isoprene rubber, butyl rubber, butadiene rubber, fluororubber, or silicone rubber, and thermoplastic elastomers such as olefin-based elastomer or styrene-based elastomer are preferable. 
     The gasket  3  includes a gasket main body  31  that includes a closed distal end part  33 , an opening proximal end part, an inner cavity part that extends distally from the opening proximal end part, and the inner cavity side screw part (a spiral recess part or the plunger distal end part attachment part)  35  that is provided on an inner surface of the inner cavity part. 
     The gasket  3  is housed in a proximal end part of the outer cylinder main body  20 , more specifically, at a position that is located a predetermined length toward the distal side from a proximal end opening of the outer cylinder main body  20 . A distance between a proximal end of the gasket  3  and the proximal end of the outer cylinder main body  20  is preferably 10 to 25 mm. 
     As illustrated in  FIGS.  1  and  2   , the gasket  3  according to this embodiment includes a cylindrical main body part that extends with substantially the same outer diameter, and a tapered closed part that extends in a distal end direction from the main body part. Furthermore, on an outer side surface of the main body part, a plurality of annular ribs (the number of which is three in this embodiment, yet may be an appropriate number as long as the number is two or more and liquid tightness and slidability can be satisfied) are formed. These ribs come into liquid-tight contact with an inner surface of the outer cylinder main body  20 . 
     Furthermore, the gasket  3  includes a recess part that extends inside the cylindrical main body part and in the distal end direction from the proximal end opening part. This recess part can house the gasket attachment part (gasket attachment distal end part)  42  of the plunger  4 . Furthermore, on an inner surface of the recess part (an inner surface of the cylindrical main body part), the gasket side screw part (plunger distal end part attachment part)  35  is formed. The gasket side screw part  35  can be screwed with a plunger side screw part formed on the outer surface of the gasket attachment part  42  of the plunger  4 . By screwing both of the gasket side screw part  35  and the plunger side screw part, the plunger  4  is not detached from the gasket  3 . 
     As materials for forming the gasket  3 , rubbers having elasticity (e.g., butyl rubber, latex rubber, silicone rubber, and the like), synthetic resins (e.g., styrene-based elastomers such as an SBS elastomer and an SEES elastomer, and olefin-based elastomers such as an ethylene-α-olefin copolymer elastomer), and the like are preferably used. 
     Furthermore, a distal side portion of the gasket main body may be coated with a low drug adsorbent substance or the like. 
     As a material of a low drug adsorbent layer, a known material conventionally used for a laminate gasket can be used. Examples of the material of the low drug adsorbent layer include polyolefin-based resins, fluorine-based resins, and polyester-based resins. More specifically, the polyolefin-based resins are preferably polypropylene, ultra-high molecular weight polyethylene, poly(4-methylpentene-1), cyclic polyolefin, and the like, and the fluorine-based resins are preferably tetrafluoroethylene-perfluoroethoxyethylene copolymer, polytetrafluoroethylene, tetrafluoroethylene/perfluoroalkyl vinyl ether copolymer, tetrafluoroethylene/hexafluoropropylene copolymer, and the like. 
     Furthermore, it is preferable to apply a lubricant to the outer surface of the gasket main body  31 , that is, at least the surfaces of a distal side annular rib  36  and a proximal side annular rib  37 . Furthermore, the lubricant may be applied to the inner surface of the outer cylinder. As the lubricant, silicone oil is suitable. Furthermore, the surface of the gasket main body may be provided with a silicone-based resin layer solidified and formed on the surface, or a layer made of the above-described ultra-high molecular weight polyethylene or the fluorine-based resin so as not to use a lubricant such as silicone oil. 
     As illustrated in  FIGS.  1  to  7 ,  18 , and  19   , the plunger (syringe plunger)  4  includes the gasket attachment part  42  that is provided at an upper end, the gasket pressing part  43  that is located at a lower end of the gasket attachment part  42 , the shaft part  41  that extends downward from the gasket pressing part  43 , and the pressing operation part  44  that is provided near the proximal end of the shaft part  41 . 
     The gasket attachment part  42  is a protruding part that is provided at a distal end part of the plunger  4 , and can enter an inner cavity part  34  of the gasket  3 . The gasket attachment part  42  protrudes in the distal end direction from a vicinity of a center of the disc-shaped gasket pressing part  43 . The gasket attachment part  42  is desirably a cylindrical part, yet may be a rod-like part. Furthermore, the gasket attachment part  42  may be a cylindrical part that includes a cross-shaped reinforcing part inside. 
     Furthermore, the outer surface of the gasket attachment part  42  includes the plunger side screw part that is screwed with the gasket side screw part  35  formed on the inner surface of the inner cavity part  34  of the gasket  3 . The plunger side screw part is formed by a spiral rib. In this embodiment, the plunger side screw part includes two strips (two rows) of spiral ribs so as to match the spiral screw part of the gasket  3 . The spiral rib may be only one strip (one row). Furthermore, in the prefilled syringe according to this embodiment, both of the gasket  3  and the plunger  4  are placed in the attached state by rotating the plunger  4 . 
     The gasket pressing part  43  is a plate-like part that has a substantially perfect circular shape, and has a diameter that is slightly smaller than the inner diameter of the outer cylinder main body  20 . The gasket attachment part  42  is provided such that the center of the gasket attachment part  42  is located on a center axis of the gasket pressing part  43 . 
     The shaft part  41  is formed by three or more (four in this embodiment) flat plate parts extending from the gasket pressing part  43  to a proximal end direction side and in parallel to a center axis of the plunger  4 . As illustrated in  FIGS.  1  to  7 ,  18 , and  19   , and  FIG.  6    in particular, the shaft part  41  according to this embodiment is formed by the four flat plate parts extending radially at equal angles (more specifically, at intervals of 90 degrees,) from a center axis of the shaft part  41 . Furthermore, as illustrated in  FIG.  6   , a bonding part of each flat plate part of the shaft part  41  according to this embodiment is provided with an axial direction reinforcing part that extends over the entire length of the flat plate part. Therefore, the shaft part  41  has a thick center part, in other words, has a thick shaft axis. 
     The pressing operation part  44  is provided at the proximal end of the shaft part  41 . The pressing operation part  44  is formed in a disk shape, and is used as a plunger pressing part. The pressing operation part  44  according to this embodiment has a disk shape that has a larger diameter than that of the above-described disc-shaped gasket pressing part  43 . 
     Furthermore, according to this embodiment, there are disc-shaped, in other words, four ¼ circular reinforcing parts  46  located in the middle of the shaft part  41 , more specifically, on a distal side from the center. Therefore, each flat plate part includes distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d , and proximal side flat plate parts  41   e ,  41   f ,  41   g , and  41   h . Furthermore, the distal side flat plate part  41   a  and the proximal side flat plate part  41   e  are aligned on the same straight line. Similarly, the distal side flat plate part  41   b  and the proximal side flat plate part  41   f , the distal side flat plate part  41   c  and the proximal side flat plate part  41   g , and the distal side flat plate part  41   d  and the proximal side flat plate part  41   h  are also aligned on the same straight line. 
     In other words, the reinforcing parts  46  partition each flat plate part into the distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d  and the proximal side flat plate parts  41   e ,  41   f ,  41   g , and  41   h . The proximal side flat plate parts  41   e ,  41   f ,  41   g , and  41   h  extend from the proximal ends (reinforcing parts  46 ) of the distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d  to the pressing operation part  44  in parallel to the center axis of the plunger. Note that, according to this embodiment, the distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d  are thicker than the proximal side flat plate parts  41   e ,  41   f ,  41   g , and  41   h . 
      Furthermore, the distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d  have a predetermined thickness that is relatively thick, and extend toward the proximal end direction side from the gasket pressing part  43  and in parallel to the center axis of the plunger  4 . 
     Furthermore, the shaft part  41  includes indicator parts  45   a ,  45   b ,  45   c , and  45   d  that are located on the proximal side of the gasket pressing part  43 , are located on the distal side of the reinforcing parts  46 , and can be recognized by visually checking an external appearance. 
     The indicator part can be formed by a unique outer shape part that has a different shape from that of another portion of the shaft part (more specifically, the flat plate part) and therefore is visually recognizable, a unique outer surface part that has a different surface state from that of the other portion of the shaft part (more specifically, the flat plate part) and therefore is visually recognizable, and the like. Furthermore, the indicator part may be formed by a unique outer shape part and a unique outer surface part that have a different surface state and shape from those of the other portion of the shaft part. 
     In this embodiment, the indicator parts  45   a ,  45   b ,  45   c , and  45   d  are formed by inclined parts that are formed on an outer surface of the shaft part, more specifically, outer side surfaces of the distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d . Furthermore, in this embodiment, the indicator parts (unique outer shape parts)  45   a ,  45   b ,  45   c , and  45   d  include vertex plane parts that extend in an axial direction of the plunger  4 , and inclined side surface parts that are provided on both sides of the vertex plane parts. 
     Therefore, the indicator parts  45   a ,  45   b ,  45   c , and  45   d  are easily visually recognized. Note that, in this embodiment, the distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d  each include in the entire length thereof the vertex plane part, and the inclined side surface part that are provided on both sides of the vertex plane parts. Note that only the indicator parts  45   a ,  45   b ,  45   c , and  45   d  portions may each include the vertex plane part that extends in the axial direction of the plunger  4 , and the inclined side surface part that is provided on the both sides of the vertex plane part. 
     Furthermore, inclination angles of the indicator parts  45   a ,  45   b ,  45   c , and  45   d  with respect to the center axis of the plunger  4  are preferably 6 to 27 degrees, and are particularly preferably 9 to 22 degrees. Furthermore, the length of each indicator part in the axial direction of the plunger is preferably in a range of 1 to 6 mm, and more preferably 2 to 6 mm. Furthermore, the length of the indicator part in the axial direction of the plunger is preferably an allowable plunger moving distance, in other words, a moving distance of the plunger that does not cause an influence in keeping a sterilized state. 
     In the prefilled syringe  1  according to the present invention, when the gasket unnecessarily moves by a time of an administration operation, the indicator parts  45   a ,  45   b ,  45   c , and  45   d  are located behind the flange part  6 , and can be visually recognized behind the flange part  6 . Consequently, a person who performs the administration operation can grasp the likelihood that the gasket  3  has moved. Particularly when the entire indicator parts  45   a ,  45   b ,  45   c , and  45   d  are located behind the flange part  6 , and are visually recognizable, it is likely that a movement amount of the gasket is large, air flows from the side surface of the gasket  3  into the outer cylinder  2 , and the sterilized state is not kept, and it is possible to easily grasp such a likelihood. 
     Note that, in the prefilled syringe  1  according to this embodiment, the plunger  4  and the gasket  3  are coupled by screwing. It is also likely that loosening of attachment (more specifically, loosening of screwing) of the plunger  4  to the gasket  3  makes the plunger move backward. Therefore, when the indicator parts  45   a ,  45   b ,  45   c , and  45   d  are housed in the flange part  6  by rotating the plunger  4 , it is possible to check that the gasket  3  has not unnecessarily moved backward. 
     Furthermore, in the prefilled syringe  1  according to this embodiment, the plunger  4  is attached to the gasket  3 , and the indicator parts  45   a ,  45   b ,  45   c , and  45   d  are entirely located in the flange part  6  of the outer cylinder  2  in a state in which the plunger  4  has been attached to the gasket  3 . Furthermore, the proximal ends of the indicator parts  45   a ,  45   b ,  45   c , and  45   d  are located at the same positions as or slightly on an inner side of a proximal end of the flange part  6  of the outer cylinder  2 . 
     Furthermore, in the prefilled syringe  1  of this embodiment, as described above, the flange part  6  is formed by the attachment member  60  fixed to the outer cylinder flange  24 , the attachment member  60  includes the plunger insertion cutout part  63  that extends from the side part to the center part of the attachment member  60 , and, instead of all the indicator parts, part of all the indicator parts, more specifically, the indicator part  45   d  that is part of the indicator parts is visually recognizable through the plunger insertion cutout part  63 . However, the rest of the indicator parts  45   a ,  45   b , and  45   c  cannot be visually recognized. Consequently, the visually recognizable indicator part  45   d  makes it possible to recognize the presence of the indicator part, and the rest of the indicator parts  45   a ,  45   b , and  45   c  cannot visually checked, so that it is possible to easily recognize that the gasket does not unnecessarily move. 
     Furthermore, the prefilled syringe  1  according to this embodiment further includes a label  27  that is pasted on an outer surface of the outer cylinder  2 , and the gasket  3  cannot be visually recognized due to the label  27 . Therefore, according to this prefilled syringe  1 , whether or not the gasket moves cannot be visually recognized. However, the prefilled syringe  1  according to this embodiment includes the above-described indicator parts, so that, even when the gasket  3  itself cannot be visually recognized, it is possible to visually recognize unnecessary backward movement of the gasket  3 . 
     The drug solution  9  to be filled in a space formed by the outer cylinder main body  20 , the gasket  3 , and the sealing member  5  may be any drug and, for example, a drug solution such as cyclosporine, a benzodiazepine-based drug, a sodium chloride injection solution, vitamins, or minerals, a powdery or lyophilized drug such as an antibiotic or a protein preparation, or a solution is used. 
     Furthermore, the prefilled syringe according to the present invention may be a prefilled syringe  1   a  illustrated in  FIGS.  10  and  11    in which an outer cylinder  2   a  does not include an attachment member. In the prefilled syringe  1   a  according to this embodiment, a flange part is formed by a flange  24   a  of the outer cylinder  2   a . In addition,  FIG.  11    illustrates cross sections of the outer cylinder and a sealing member taken along line C-C in  FIG.  10   , and illustrates external appearances of a plunger and a gasket. 
     Only differences between the prefilled syringe  1   a  according to this embodiment and the above-described prefilled syringe  1  are that whether or not there is the attachment member, and the gasket  3  and the plunger  4  are located slightly on the distal side of the outer cylinder. The rest is the same as those of the above-described prefilled syringe  1 . 
     Furthermore, in the prefilled syringe  1   a  according to this embodiment, too, the plunger  4  is attached to the gasket  3 , and the indicator parts  45   a ,  45   b ,  45   c , and  45   d  are entirely located in the flange  24   a  of the outer cylinder  2   a  in a state in which the plunger  4  has been attached to the gasket  3 . Furthermore, the proximal ends of the indicator parts  45   a ,  45   b ,  45   c , and  45   d  are located at the same positions as or slightly on an inner side of a proximal end of the flange  24   a  of the outer cylinder  2   a . Furthermore, all the indicator parts  45   a ,  45   b ,  45   c , and  45   d  cannot be visually recognized due to the flange  24   a  of the outer cylinder  2   a . 
     Note that, in the prefilled syringe  1   a  according to this embodiment, distal ends or distal end parts of the indicator parts  45   a ,  45   b ,  45   c , and  45   d  may be visually recognizable from the outer surface of the outer cylinder  2   a  at the proximal end part of the hollow main body part  21  (a boundary part with the flange  24   a ) of the outer cylinder  2   a . Such a prefilled syringe makes it possible to recognize presence of the indicator parts, and makes it possible to easily recognize that the gasket does not unnecessarily move because parts other than the distal end parts of the indicator parts  45   a ,  45   b ,  45   c , and  45   d  cannot be visually recognized. 
      Furthermore, an aspect of the indicator parts in the prefilled syringe according to the present invention may include indicator parts included in a plunger  4   a  illustrated in  FIG.  12   . 
     Similarly to the above-described indicator parts  45   a ,  45   b ,  45   c , and  45   d , indicator parts  48   a ,  48   b ,  48   c , and  48   d  (not illustrated) included in the plunger  4   a  according to this embodiment are each a unique outer shape part that is visually recognizable because each indicator part has a different shape from that of the other portion of the shaft part (more specifically, the flat plate part). 
     Furthermore, in this embodiment, the indicator parts (unique outer shape parts)  48   a ,  48   b ,  48   c , and  48   d  (not illustrated) are each formed by a recess part that extends a predetermined length from a vertex of each flat plate part toward a proximal end side of the flat plate part, and the recess part in particular has a rectangular shape. The depth of the recess part is preferably in a range of 0.3 to 0.6 mm, and more preferably 0.4 to 0.5 mm. 
     Furthermore, the indicator parts  48   a ,  48   b ,  48   c , and  48   d  (not illustrated) portions are slightly inclined parts, yet are considerably gentler than the inclination angles of the above-described indicator parts  45   a ,  45   b ,  45   c , and  45   d , and the recess parts are more noticeable than the inclinations. 
     Only differences between the plunger  4   a  according to this embodiment and the above-described plunger  4  are the above-described forms of the indicator parts and the shapes of the distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d  on the proximal end side of the indicator parts. 
     Furthermore, an aspect of the indicator parts in the prefilled syringe according to the present invention may include indicator parts included in a plunger  4   b  illustrated in  FIG.  13   . 
     Similarly to the above-described indicator parts  45   a ,  45   b ,  45   c , and  45   d , indicator parts  49   a ,  49   b ,  49   c , and  49   d  (not illustrated) included in the plunger  4   b  according to this embodiment are each a unique outer shape part that is visually recognizable because each indicator part has a different shape from that of the other portion of the shaft part (more specifically, the flat plate part). 
     Furthermore, in this embodiment, the indicator parts (unique outer shape parts)  49   a ,  49   b ,  49   c , and  49   d  (not illustrated) are each formed by a recess part that extends a predetermined length from the vertex of each flat plate part toward a proximal end side of the flat plate part, and the recess part in particular is a recess part whose lower surface is an arc shape. The depth of the recess part is preferably in a range of 0.3 to 0.6 mm, and more preferably 0.4 to 0.5 mm. 
     Furthermore, the indicator parts  49   a ,  49   b ,  49   c , and  49   d  (not illustrated) portions are slightly inclined parts, yet are considerably gentler than the inclination angles of the above-described indicator parts  45   a ,  45   b ,  45   c , and  45   d , and the recess parts are more noticeable than the inclinations. 
     Only differences between the plunger  4   b  according to this embodiment and the above-described plunger  4  are the above-described forms of the indicator parts and the shapes of the distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d  on the proximal end side of the indicator parts. 
     Furthermore, an aspect of the indicator part in the prefilled syringe according to the present invention may include an indicator part included in a plunger  4   c  illustrated in  FIG.  14   . 
     An indicator part  47  included in the plunger  4   c  according to this embodiment is formed by a unique outer surface part that has a different surface state from that of the other portion of the shaft part and therefore is visually recognizable. The indicator part  47  (unique outer surface part) can be formed by a belt-shaped colored part, a rough surface part, a patterned part, or the like that is formed on the outer surface of the shaft part. The width (an axial direction length of the plunger  4   c ) of the belt-shaped indicator part  47  (unique outer surface part) is preferably in a range of 1 to 6 mm, and more preferably 2 to 6 mm. 
     For the colored part, a color that is an easily identifiable color and can be recognized as a warning indication is preferable, and, for example, red colors are preferable, but yellow, blue, or the like may be used. The rough surface part may be an embossed surface, a knurled surface, a surface having a large number of ribs, or the like. For the patterned surface, various patterns such as a checkered pattern, a wave pattern, and the like can be used. 
     Only differences between the plunger  4   c  according to this embodiment and the above-described plunger  4  are the above-described form of the indicator part and the shapes of the distal side flat plate parts  41   a ,  41   b ,  41   c , and  41   d  on the proximal end side of the indicator part. 
     Furthermore, an aspect of the indicator parts in the prefilled syringe according to the present invention may include indicator parts included in a plunger  4   d  illustrated in  FIG.  15   . 
     The indicator part  47  included in the plunger  4   d  according to this embodiment is formed by both of a unique outer shape part that has a different shape from that of the other portion of the shaft part and therefore is visually recognizable, and a unique outer surface part that has a different surface state and therefore is visually recognizable. As the indicator part  47 , the above-described indicator part can be suitably used. 
     The plunger  4   d  according to this embodiment includes the same indicator parts (unique outer shape parts)  45   a ,  45   b ,  45   c , and  45   d  as those of the above-described plunger  4 , and includes the belt-shaped indicator part  47  (unique outer surface part) included in the above-described plunger  4   c  at parts where the indicator parts (unique outer shape parts)  45   a ,  45   b ,  45   c , and  45   d  are provided. Consequently, it is easier to recognize the indicator parts. 
     Furthermore, an aspect of the indicator parts in the prefilled syringe according to the present invention may include indicator parts included in a plunger  4   e  illustrated in  FIG.  16   . 
     The indicator part  47  included in the plunger  4   e  according to this embodiment is formed by both of a unique outer shape part that has a different shape from that of the other portion of the shaft part and therefore is visually recognizable, and a unique outer surface part that has a different surface state and therefore is visually recognizable. As the indicator part  47 , the above-described indicator part can be suitably used. 
     The plunger  4   e  according to this embodiment includes the same indicator parts (unique outer shape parts)  49   a ,  49   b ,  49   c , and  49   d  (not illustrated) as those of the above-described plunger  4   b . The indicator parts (unique outer shape parts)  49   a ,  49   b ,  49   c , and  49   d  (not illustrated) are each formed by a recess part that extends a predetermined length from the vertex of each flat plate part toward a proximal end side of the flat plate part, and the recess part in particular is a recess part whose lower surface is an arc shape. Note that the recess part may have a rectangular shape. Furthermore, the indicator parts  49   a ,  49   b ,  49   c , and  49   d  (not illustrated) portions are slightly inclined parts, yet are considerably gentler than the inclination angles of the above-described indicator parts  45   a ,  45   b ,  45   c , and  45   d , and the recess parts are more noticeable than the inclinations. 
     The plunger  4   e  according to this embodiment includes the same indicator parts (unique outer shape parts)  49   a ,  49   b ,  49   c , and  49   d  (not illustrated) as those of the above-described plunger  4   b , and includes the belt-shaped indicator part  47  (unique outer surface part) included in the above-described plunger  4   c  at parts where the indicator parts (unique outer shape parts)  49   a ,  49   b ,  49   c , and  49   d  (not illustrated) are provided. Consequently, it is easier to recognize the indicator parts. 
     Furthermore, an aspect of the indicator parts in the prefilled syringe according to the present invention may include indicator parts included in a plunger  4   f  illustrated in  FIG.  17   . 
     The indicator part  47  included in the plunger  4   f  according to this embodiment is formed by both of a unique outer shape part that has a different shape from that of the other portion of the shaft part and therefore is visually recognizable, and a unique outer surface part that has a different surface state and therefore is visually recognizable. As the indicator part  47 , the above-described indicator part can be suitably used. 
     The plunger  4   f  according to this embodiment includes the same indicator parts (unique outer shape parts)  45   a ,  45   b ,  45   c , and  45   d  (not illustrated) as those of the above-described plunger  4 . Furthermore, upper surfaces of the indicator parts (unique outer shape parts)  45   a ,  45   b ,  45   c , and  45   d  (not illustrated) are unique outer surface parts similar to the indicator part  47 . Consequently, it is easier to recognize the indicator parts. For the unique outer surface parts, all the above-described patterns such as the colored part, the rough surface part, and the patterned part can be used. 
     The prefilled syringe according to the present invention is as follows. 
     A prefilled syringe including: an outer cylinder; a gasket that is slidably housed in the outer cylinder; a plunger that presses the gasket; a sealing member that seals a distal end part of the outer cylinder; and a drug that is housed in the outer cylinder, in which the outer cylinder includes a flange part that is provided at a proximal end part, the gasket includes a plunger distal end part attachment part, the plunger includes a gasket pressing part that is provided at a distal end part of the plunger, a shaft part that extends in a proximal end direction from the gasket pressing part, and a pressing operation part that is provided at a proximal end part of the shaft part, the shaft part includes on a proximal side of the gasket pressing part an indicator part that can be recognized by visually checking an external appearance, the plunger is attached to the gasket, and the indicator part is located in the flange part of the outer cylinder, and cannot be recognized by visually checking the external appearance in a state in which the plunger has been attached to the gasket, and is exposed behind the flange part, and can be recognized by visually checking the external appearance when the plunger moves backward. 
     According to this prefilled syringe, when the plunger attached to the gasket moves backward beyond an allowable level, the indicator parts located in the flange part of the outer cylinder are exposed to the outside from the proximal end of the flange part of the outer cylinder and can be easily visually recognized. Consequently, by visually recognizing the indicator parts, the user can easily recognize a likelihood that the gasket has moved beyond the allowable level and air has flowed into the drug, in other words, a likelihood that the drug has been contaminated. 
     Furthermore, the above embodiment may be as follows. 
     The prefilled syringe according to above ( 1 ), including a label that is pasted on an outer surface of the outer cylinder, in which the gasket cannot be visually recognized due to the label. 
     The prefilled syringe according to above ( 1 ) or (2), in which the flange part of the outer cylinder is formed by an outer cylinder flange that is provided at a proximal end part of the hollow main body part, and an attachment member that is attached to a proximal side of the outer cylinder flange. 
     The prefilled syringe according to above ( 3 ), in which the attachment member includes a plunger insertion cutout part that extends from a side part to a center part of the attachment member, and part of the indicator part is visually recognizable through the plunger insertion cutout part. 
     The prefilled syringe according to any one of above ( 1 ) to ( 4 ), in which a length of the indicator part in an axial direction of the plunger is in a range of 1 to 6 mm. 
     The prefilled syringe according to any one of above ( 1 ) to ( 5 ), in which the indicator part is formed by a unique outer shape part that has a different shape from a shape of another portion of the shaft part and is visually recognizable. 
     The prefilled syringe according to any one of above ( 1 ) to ( 5 ), in which the indicator part is formed by a unique outer surface part that has a different surface state from a surface state of another portion of the shaft part and is visually recognizable. 
     The prefilled syringe according to any one of above ( 1 ) to ( 6 ), in which the indicator part is an inclined part, a recess part, a protrusion part, or a tapered part formed on an outer surface of the shaft part. 
     The prefilled syringe according to any one of above ( 1 ) to ( 5 ), in which the indicator part is a colored part, a rough surface part, or a patterned part formed on an outer surface of the shaft part. 
     The prefilled syringe according to any one of above ( 1 ) to ( 9 ), in which the indicator part is formed by a visually recognizable different shape/state part that has a different surface state and shape from a surface state and a shape of another portion of the shaft part.