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`US 20050182370Al
`
`(19) United States
`(12) Patent Application Publication
`Hato
`
`(10) Pub. No.: US 2005/0182370 Al
`Aug. 18, 2005
`( 43) Pub. Date:
`
`(54) PREFILLED SYRINGE WITH PLUNGER
`BACKWARD MOVEMENT LIMITING
`MECHANISM
`
`(76)
`
`Inventor: Seiichi Hato, Kanagawa (JP)
`
`Correspondence Address:
`DAVID W. HIGHET VP & CHIEF IP
`COUNSEL
`BECTION DICKINSON AND COMPANY
`1 BECTON DRIVE MC 110
`FRANKLIN LAKES, NJ 07417-1880 (US)
`
`(21) Appl. No.:
`
`10/507,767
`
`(22) PCT Filed:
`
`Mar. 11, 2003
`
`(86) PCT No.:
`
`PCT/JP03/02851
`
`(30)
`
`Foreign Application Priority Data
`
`Mar. 15, 2002
`
`(JP) ......................................... 2002-72083
`
`Publication Classification
`
`Int. CI.7 .................................................... A61M 5/178
`(51)
`(52) U.S. Cl. .............................................................. 604/213
`
`(57)
`
`ABSTRACT
`
`A risk of injection liquid contamination due to contact of
`injection liquid in an injection-liquid filled area in a barrel
`with the surface in an injection-liquid unfilled area in the
`barrel by causing a plunger of a prefilled syringe to be
`inadvertently withdrawn by mishandling which may leads to
`medical malpractice, is eliminated by the invention. With(cid:173)
`drawal of a plunger 14 is limited by engagement of a barrel
`12 in which a withdrawal-limiting member 48 is provided
`and a the plunger 14 in which a withdrawal-limiting member
`54 is provided. As a result of this, contact of the injection
`liquid L prefilled to a liquid-filled area 32 in the barrel 12
`with the surface of a liquid-unfilled area 34 in the barrel by
`withdrawal of the plunger 14 is prevented.
`
`Regeneron Exhibit 1047.001
`
`

`

`Patent Application Publication Aug. 18, 2005 Sheet 1 of 2
`
`US 2005/0182370 Al
`
`Regeneron Exhibit 1047 .002
`
`

`

`Patent Application Publication Aug. 18, 2005 Sheet 2 of 2
`
`US 2005/0182370 Al
`
`56
`
`Regeneron Exhibit 1047 .003
`
`

`

`US 2005/0182370 Al
`
`Aug. 18, 2005
`
`1
`
`PREFILLED SYRINGE WITH PLUNGER
`BACKWARD MOVEMENT LIMITING
`MECHANISM
`
`TECHNICAL FIELD
`
`[0001] The present invention relates to a syringe in which
`injection liquid is pre filled (pre filled syringe), and more
`particularly, the prefilled syringe which is provided with a
`means for preventing contamination of the pre filled injection
`liquid.
`
`BACKGROUND TECHNIQUE
`
`[0002] For a conventional type of prefilled syringe, injec(cid:173)
`tion liquid is filled into the syringe barrel and a sliding plug
`( of the liquid-injecting plunger) is inserted in the barrel,
`usually under a sterilized condition, and thereafter, a plunger
`rod is fixed to the sliding plug and works such as labeling
`and packaging are done for shipment under a non-sterilized
`condition.
`
`[0003] A syringe in which some specific injection liquid is
`prefilled may be finally sterilized by heating using an
`autoclave etc. after packaging. However, in other type of
`syringe in which injection liquid unable to be sterilized by
`heating is prefilled, bacteria or other microorganisms are
`considered to have started to adhere to the syringe imme(cid:173)
`diately after it was brought out from the sterilized condition.
`Namely, in such condition, only the liquid-filled space
`sealed by the sliding plug ( of the plunger) in the barrel is
`kept sterilized, and there is a possibility that microorganisms
`adhere to the backward area of the sliding plug, even if the
`backward area is inside the barrel, before the prefilled
`syringe is used.
`
`[0004] Consequently, in case of the above-mentioned
`syringe, when the sliding plug is withdrawn backward, there
`is a risk that bacteria or other microorganisms adhering to
`the inner surface of the barrel may contaminate injection
`liquid and the syringe is therefore hazardous. The control of
`such risk has been depending on the careful handling of the
`prefilled syringe by care providers such as physicians and
`nurses, but their mishandling has been reasonably antici(cid:173)
`pated. However, in reality, injection liquid was contaminated
`due to the mishandling, that may result in medical malprac(cid:173)
`tice. Even if such contamination of injection liquid and
`medical malpractice due to it occur, it was difficult to
`determine that such malpractice was attributable to the
`mishandling of the prefilled syringe and the problem has
`therefore not been clearly recognized.
`
`[0005] The invention is intended to clarify where the
`problem exists and to provide a prefilled syringe entirely
`free from a risk of injection liquid contamination due to
`mishandling and resultant medical malpractice.
`
`DISCLOSURE OF THE INVENTION
`
`[0006] The invention provides the prefilled syringe com(cid:173)
`prising a barrel having a closed front-end wall with a small
`passageway through which injection liquid is discharged and
`a rear opening, a plunger including a sliding plug liquid(cid:173)
`tightly contacting with the inner surface of the barrel and
`partitioning the inside of the barrel into a liquid-filled area
`which is formed between the plunger and the closed front(cid:173)
`end wall and in which injection liquid is filled and sealed and
`
`a liquid-unfilled area in the back of the liquid-filled area and
`a plunger rod extending backward from the sliding plug
`through the rear opening of the barrel, and a plunger
`withdrawal-limiting member fixed to the barrel, which limits
`withdrawal of the plunger by engaging the plunger and
`prevents injection liquid from contacting with the surface of
`the liquid-unfilled area in the barrel.
`[0007] Referring more particularly, the plunger with(cid:173)
`drawal-limiting member which is provided at the rear open(cid:173)
`ing of the barrel and extends from the rear opening to the
`inside of the barrel for a certain length, can contact with the
`backward-moving sliding plug of the plunger so that with(cid:173)
`drawal of the plunger is limited.
`[0008]
`It is also possible that the plunger withdrawal(cid:173)
`limiting member provided at the rear opening of the barrel
`is in the form of an annular withdrawal-limiting flange
`comprising an opening for the plunger rod which extends
`inwardly in the radial direction from the periphery of the rear
`opening of the barrel and is sized to allow the plunger rod
`to pass therethrough, while a stopper member extending
`outwardly in the radial direction from the plunger rod is
`provided. As a result of this, withdrawal of the plunger is
`limited by engagement of the stopper member with the
`withdrawal-limiting flange.
`[0009]
`In the above case, it is possible to stably push and
`handle the plunger by allowing at least a portion of the outer
`peripheral surface of the withdrawal-limiting member to
`closely contact with the inner peripheral surface of the
`barrel. It is also possible that the position in which the
`withdrawal-limiting member is fixed to the plunger rod is
`adjusted at needs in accordance with the quantity of injec(cid:173)
`tion liquid to be prefilled.
`[0010]
`In other form of embodiment, the withdrawal(cid:173)
`limiting member may be made in the form of a cylindrical
`member in which a male screw is provided on the outer
`peripheral surface thereof, and on the other hand, the
`plunger withdrawal-limiting member may be formed in the
`form of an annular flange in which the inner peripheral
`surface of the flange defines an opening having a size
`corresponding to the plunger withdrawal-limiting member,
`the annular flange being provided at the rear end opening of
`the barrel and extending inwardly in a radial direction from
`the peripheral edge of the opening and a female screw to be
`mated with the male screw is formed on the inner peripheral
`surface of the flange. In this form of syringe, when the
`plunger is withdrawn for a predetermined distance over a
`predetermined position, the stopper member engages the
`withdrawal-limiting member, thus preventing withdrawal of
`the plunger. If the male screw of the stopper member is
`further turned and fitted into the female screw on the plunger
`withdrawal-limiting member the plunger can be further
`withdrawn.
`[0011] Additionally, it is possible that the stopper member
`is formed in the form of a leaf spring shaped member which
`extends diagonally backward from a predetermined location
`in the plunger rod so that when the plunger rod is inserted
`into the barrel through the opening for the plunger rod the
`leaf spring is deflected by the surface of the opening for the
`plunger rod and after passing through the same opening the
`leaf spring returned to its original shape to act the function
`to limit plunger withdrawal.
`[0012] Furthermore, it is possible that the stopper member
`is formed in a member projecting radially outward from the
`
`Regeneron Exhibit 1047 .004
`
`

`

`US 2005/0182370 Al
`
`Aug. 18, 2005
`
`2
`
`plunger rod and a notch through which the stopper member
`passes may be formed at the opening of the withdrawal(cid:173)
`limiting flange so that the function of plunger withdrawal
`can be released.
`
`BRIEF EXPLANATION OF THE DRAWINGS
`
`[0013] FIG. 1 is a sectional side elevational view of a
`prefilled syringe arrangement in accordance with the first
`embodiment of the invention;
`
`[0014] FIG. 2 is a sectional side elevational view of a
`prefilled syringe arrangement in accordance with the second
`embodiment of the invention;
`
`[0015] FIG. 3 is a sectional side elevational view of a
`prefilled syringe arrangement in accordance with the third
`embodiment of the invention;
`
`[0016] FIG. 4 is a schematic illustration view of a prefilled
`syringe arrangement in accordance with the fourth embodi(cid:173)
`ment of the invention;
`
`[0017] FIG. 5 is a schematic illustration view of a prefilled
`syringe arrangement in accordance with the fifth embodi(cid:173)
`ment of the invention; and
`
`[0018] FIG. 6 is a schematic illustration view of the
`prefilled syringe according to the sixth embodiment of the
`invention in which the side view of the withdrawal-limiting
`flange is also shown.
`
`BEST MODE FOR CARRYING OUT THE
`INVENTION
`
`[0019] The mode for carrying out the prefilled syringe
`according to the invention is explained below, referring to
`the attached drawings.
`
`[0020] FIG. 1 shows the first mode for carrying out the
`prefilled syringe 10 according to the invention. As illus(cid:173)
`trated, the prefilled syringe 10 has a barrel 12 in a cylindrical
`form and the plunger 14 to be inserted into the barrel. The
`barrel has the front-end wall 16, the tip of which has a small
`passageway (not shown in the FIG. 1) through which the
`injection liquid is discharged, and the rear opening 18
`through which the plunger 14 is received. A barrel tip cover
`20 is mounted on the outer surface of the tip of the front-end
`wall 16. The plunger 14 has a sliding plug 22 at its tip which
`is able to slidably move along the inner surface of the barrel
`12 and a plunger rod 24 which extends outwardly from the
`sliding plug 22 to the outside of the barrel through the rear
`opening 18 at the rear end of the barrel. FIG. 1 shows the
`completed prefilled syringe before use. In this state, the
`sliding plug 22 partitions the inside of the barrel 12 into a
`liquid-filled area 32 where the injection liquid Lis filled and
`sealed and a liquid-unfilled area 34 in the back of the area
`32. In the illustrative embodiment shown in the FIG. 1, the
`sliding plug 22 has a generally cylindrical form and three
`ring-shaped ribs 26, 28 and 30 are provided around the outer
`surface of the sliding plug with keeping predetermined
`spaces in the axial direction therebetween. As the ribs
`liquid-tightly contact with the inner surface of the barrel 12,
`so that the liquid-filled area 32 in which the injection liquid
`is filled and sealed is formed between the front-end wall 16
`of the barrel and the sliding plug 16. Namely, in this state,
`the liquid-filled area 32 is formed between the front-end wall
`
`16 and the right side rib 30 and the liquid-unfilled area 34 is
`formed between the right side rib 30 and the rear opening 18
`of the barrel.
`[0021] As illustrated in the FIG. 1, a withdrawal-limiting
`member 36 to limit withdrawal of the plunger 14 is provided
`around the rear opening 18 of the barrel. The withdrawal(cid:173)
`limiting member has a base plate 40 in an annular form,
`which is abutted to the end edge of the rear opening 18, a
`outer cylindrical portion 42 which extends from the base
`plate toward the tip of the barrel along the outer surface of
`the barrel and an inner cylindrical portion 44 which extends
`longer than the outer cylindrical portion 42 from the base
`plate toward the tip of the barrel around the inner surface of
`the barrel. These outer and inner cylindrical portions are
`secured to the barrel by pinching the side wall of the barrel.
`[0022] The front-end of the inner cylindrical portion 44 is
`spaced from the rear end of the sliding plug 22 for a distance
`of d. Therefore, the sliding plug 22 is able to move rearward
`by the distance d from the predetermined position shown in
`FIG. 1 and when the sliding plug is moved rearward for the
`distance d it abuts or engages the front end of the inner
`cylindrical portion 44 of the withdrawal-limiting member
`36, thus further withdrawal being prevented. The distance d
`is determined to be shorter than a distance D between the
`front-end of the sliding plug (more accurately, the position
`where the left side rib 26 liquid-tightly contacts with the
`inner surface of the barrel) and the position where the rear
`end of the right side rib 30 liquid-tightly contacts with the
`inner surface of the barrel so that when the sliding plug is
`withdrawn no contact between injection liquid L and the
`inner surface in the liquid-unfilled area in the barrel.
`[0023] For the above-mentioned prefilled syringe, the
`plunger 14 and the withdrawal-limiting member 36 may be
`formed from a general-purpose resin such as polypropylene
`and polyethylene using injection molding and the sliding
`plug 22 is preferably be made from rubber or similar
`materials.
`[0024] FIG. 2 shows other mode for carrying out the
`prefilled syringe 10 according to the invention.
`[0025]
`In this type of prefilled syringe, an annular with(cid:173)
`drawal-limiting flange 48 is integrally molded with the
`cylindrical barrel 12 in the rear end therefore and an opening
`through which the plunger rod 24 passes is provided in the
`central portion of the withdrawal-limiting flange 48. In
`addition, a pair of notches 50 and 52 are formed diametri(cid:173)
`cally in the diameter of the inner peripheral edge of the
`flange 48. On the other hand, on the surface of the plunger
`rod 24, a withdrawal-limiting member 54 extends backward
`from the rear-end of the sliding plug 22. The withdrawal(cid:173)
`limiting member 54 has a shape and a size corresponding to
`that of the notches 50 and 52 so that the member 54 is able
`to pass through the notches. Therefore, after injection liquid
`is prefilled and the sliding plug 22 is loaded, the plunger rod
`24 is inserted into the barrel with the withdrawal-limiting
`part 54 passing through the notch 50 or 52, and then the
`front-end of the plunger rod can be connected to the sliding
`plug 22. Between the rear-end of the withdrawal-limiting
`member 54 and the inner surface of the withdrawal-limiting
`flange 48, the space d keeping the same relation of D>d as
`shown in the embodiment in FIG. 1 is provided.
`[0026] FIG. 3 shows the third mode for carrying out the
`prefilled syringe according to the invention.
`
`Regeneron Exhibit 1047 .005
`
`

`

`US 2005/0182370 Al
`
`Aug. 18, 2005
`
`3
`
`[0027]
`In this type of prefilled syringe, different from the
`prefilled syringe shown in FIG. 2, the withdrawal-limiting
`flange 56 is separately formed from the barrel 12 and fixed
`to a flange 58 formed radially and outwardly of and inte(cid:173)
`grally with the rear end of the barrel. It is possible that in the
`same manner as the flange holding members disclosed in the
`U.S. Pat. No. 2,814,983 and U.S. Pat. No. 2,845,426, etc.,
`the withdrawal-limiting flange 56 may be an annular form
`comprising a front annular plate 80 and a rear annular plate
`82 between which a space for holding the flange 58 of the
`barrel is provided. The withdrawal-limiting flange 56 is
`secured to the barrel in the following manner. Firstly, an
`aperture (not shown in FIG. 3) extending in radial direction
`is provided in a portion of the annular form. The withdrawal(cid:173)
`limiting flange 56 is then positioned at right angle to the axis
`of the barrel 12 with the aperture being aligned with the
`flange 58 of the barrel, and the flange 56 is pushed onto the
`aperture and then the flange 58 of the barrel and the plunger
`rod 24 are passed through the aperture into the inside of the
`withdrawal-limiting flange 56 so that the flange 58 of the
`barrel is held in the space between the front plate 80 and the
`rear plate 82.
`[0028] The withdrawal-limiting member 76 in a disc form
`is fixed to the plunger rod 24 at the distance of d from the
`rear-end annular plate 82 of the withdrawal-limiting flange
`56. In this mode of the invention, by fixing the withdrawal(cid:173)
`limiting member at a proper location in the axial direction of
`the plunger rod 24 depending on the quantity of the injection
`liquid to be filled in the prefilled syringe, it is possible to
`provide the withdrawal-limiting member 76 at the distance
`of d from the rear-end annular plate 82 of the withdrawal(cid:173)
`limiting flange. The withdrawal-limiting member 76 in this
`mode according to the invention may be in a fan shape as
`well as in a disc shape, and in either case, it is possible to
`forward the plunger 14 into the barrel 12 in a stable manner
`by keeping the outer periphery of the withdrawal-limiting
`member close to the inner surface of the barrel.
`[0029] FIG. 4 shows the fourth mode for carrying out the
`prefilled syringe according to the invention.
`[0030]
`In this type of prefilled syringe 10, a withdrawal(cid:173)
`limiting flange 64 similar to the withdrawal-limiting flange
`56 shown in FIG. 3 is mounted on the flange 58 which is
`integrally molded with the rear-end of the barrel 12 and
`radially extends. The difference of this type of prefilled
`syringe from that shown in FIG. 3 is that a female screw 66
`is formed in the inner periphery of the withdrawal-limiting
`flange 64 and a male screw 68 fitting into the female screw
`64 is correspondingly formed on a withdrawal-limiting
`member 70 which is fixed to the plunger rod 24.
`[0031] Between the rear-end of the withdrawal-limiting
`member 70 and the front surface of the rear annular plate of
`the withdrawal-limiting flange 64, a spaced is provided with
`keeping the same relation of D>d as shown in the mode in
`FIG. 1 and when the plunger 14 withdraws from a prede(cid:173)
`termined position by the distanced, the withdrawal-limiting
`member 70 abuts the withdrawal-limiting flange 64 to
`prevent further withdrawal. In order to further withdraw the
`plunger 14 and draw out the same from the barrel 12, the
`male screw of the withdrawal-limiting member 70 is turned
`and fitted into the female screw 66 of the withdrawal(cid:173)
`limiting flange.
`[0032] FIG. 5 shows the fifth mode for carrying out the
`prefilled syringe according to the invention. This type of
`
`prefilled syringe 10 is similar to that shown in FIG. 3, but
`a withdrawal-limiting member 72 fixed to the plunger rod 24
`is in the form of leaf spring projecting diagonally backward.
`That is, when the plunger rod 24 is passed into to the inside
`of the barrel through the circular opening formed in the
`withdrawal-limiting flange 56, the leaf spring of the with(cid:173)
`drawal limiting member 72 is deflected by the edge of the
`opening so that the leaf spring of the withdrawal-limiting
`member 72 passes through the opening into the barrel. After
`passage into the barrel, the leaf spring of the withdrawal(cid:173)
`limiting member is sprung back to the form projecting
`diagonally backward, as illustrated in the FIG. 5. In this
`state, when the plunger withdraws from the predetermined
`position by the distance d, the rear-end of the leaf spring of
`the withdrawal-limiting member 72 abuts the withdrawal(cid:173)
`limiting flange 56 to prevent further withdrawal.
`[0033] The prefilled syringe shown in FIG. 6 is substan(cid:173)
`tially identical to that shown in FIG. 2, but it is different
`from the syringe in FIG. 2 in the fact that only one notch 90
`is formed in the opening for the plunger rod passage in the
`withdrawal-limiting flange 56 (shown as oval-shaped in
`FIG. 6). The withdrawal-limiting member 54 fixed to the
`plunger rod 24 can pass through the notch 90 so that the
`plunger rod 24 is moved forward into the inside of the barrel
`12 and is withdrawn from the barrel.
`
`INDUSTRIAL APPLICABILTY
`[0034] The prefilled syringe according to the invention has
`the above-mentioned constitution and through its simple
`structure surely prevents accidental withdrawal of the
`plunger due to mishandling. If the plunger is inadvertently
`withdrawn beyond the predetermined position, the injection
`liquid sealed in the liquid-filled area in the barrel may
`contact with the surface of the liquid-unfilled area (which
`bacteria etc. possibly adhere to), resulting in a risk of
`contamination. The invention can totally avoid such a risk
`and therefore prevent the occurrence of medical malpractice
`attributable to the contamination.
`[0035] To prevent the contamination caused by bacteria,
`conventionally, the method involving heating sterilization
`using autoclave etc. has been employed after packing the
`produced prefilled syringe. However, it is impossible to
`apply the heating sterilization to some injection liquids and
`for the syringe prefilled with such liquids, the risk of
`contamination of such injection liquid is unavoidable.
`Therefor, the invention is especially beneficial to such
`prefilled syringe.
`[0036] Also for the prefilled syringe in which an injection
`liquid suitable for heating sterilization is sealed, the heating
`sterilization process involves incremental facility invest(cid:173)
`ment and production cost. In this regard, the invention
`makes it possible to provide users with safer prefilled
`syringes not needing such costly process and is extremely
`beneficial to them.
`
`1. A prefilled syringe comprising:
`
`a barrel having a closed front-end wall with a small
`passageway through which injection liquid is dis(cid:173)
`charged and a rear opening;
`
`a plunger including a sliding plug liquid tightly contacting
`with the inner surface of the barrel and partitioning the
`inside of the barrel into a liquid-filled area which is
`
`Regeneron Exhibit 1047 .006
`
`

`

`US 2005/0182370 Al
`
`Aug. 18, 2005
`
`4
`
`formed between said plunger and said closed front-end
`wall and in which the injection liquid is filled and
`sealed, and a liquid-unfilled area in the back of the
`liquid-filled area and a plunger rod extending backward
`from said sliding plug through said rear opening of the
`barrel; and
`
`a flange fixed to the rear opening of said barrel, a portion
`of which extends for a predetermined length into the
`barrel to limit plunger withdrawal so that the injection
`liquid is prevented from contacting with the surface of
`said liquid-unfilled area in the barrel by engaging said
`plunger.
`2. ( canceled)
`3. The prefilled syringe according to claim 1, wherein said
`flange has an opening for said plunger rod extending
`inwardly in the radial direction from the periphery of said
`rear end opening of the barrel and being sized to allow said
`plunger rod to pass therethrough, and said plunger has a
`stopper member extending outwardly in the radial direction
`from the plunger rod, withdrawal of said plunger being
`limited by contact of said stopper member with said flange.
`4. The prefilled syringe according to claim 3, wherein at
`least a portion of the outer peripheral surface of said stopper
`member is designed to make a close contact with the inner
`peripheral surface of said barrel.
`5. The prefilled syringe according to claim 3, wherein said
`stopper member is in the form of a plate provided at right
`angles to the axis of the plunger rod and is able to be fixed
`to a required position in the axial direction of said plunger
`rod.
`6. The prefilled syringe according to claim 3, wherein said
`stopper member is in the form of a cylindrical member
`having a male screw provided on the outer peripheral
`
`surface thereof, and a female screw mating with said male
`screw is formed at the opening for the plunger rod passage
`provided in said withdrawal-limiting flange.
`7. The prefilled syringe according to claim 3, wherein said
`stopper member is a leaf spring extending diagonally back(cid:173)
`ward from a predetermined position in said plunger rod, said
`leaf spring is adapted to be deflected by the surface of said
`opening for the plunger rod passage to be passed through the
`same opening when the plunger rod is inserted into said
`barrel through the same opening and is returned to an
`original shape after passing through the same opening.
`8. The prefilled syringe according to claim 3, wherein said
`stopper member projects radially outward from said plunger
`rod and a notch for allowing said stopper member to pass
`through is formed at said opening for the plunger rod
`passage in said withdrawal-limiting flange.
`9. The prefilled syringe according to claim 1, wherein the
`distance D between a portion on the outer peripheral surface
`of the sliding plug which is nearest to the closed front-end
`wall of said barrel and a portion on the same which is
`farthest from the closed front-end wall of the barrel and the
`distance d between the predetermined position of said
`plunger and the position where said plunger is withdrawn
`from said predetermined position and then engages said
`flange so that withdrawal of said plunger is prevented are
`adapted to keep the formula D>d.
`10. The prefilled syringe according to claim 4, wherein
`said stopper member is in the form of a plate provided at
`right angles to the axis of the plunger rod and is able to be
`fixed to a required position in the axial direction of said
`plunger rod.
`
`* * * * *
`
`Regeneron Exhibit 1047 .007
`
`