WO1998013088A9 - Systeme de seringue comportant deux cylindres preremplis, separes, prevus pour deux constituants - Google Patents

Systeme de seringue comportant deux cylindres preremplis, separes, prevus pour deux constituants

Info

Publication number
WO1998013088A9
WO1998013088A9 PCT/US1997/017194 US9717194W WO9813088A9 WO 1998013088 A9 WO1998013088 A9 WO 1998013088A9 US 9717194 W US9717194 W US 9717194W WO 9813088 A9 WO9813088 A9 WO 9813088A9
Authority
WO
WIPO (PCT)
Prior art keywords
barrel
chamber
fluid
stopper
reciprocable stopper
Prior art date
Application number
PCT/US1997/017194
Other languages
English (en)
Other versions
WO1998013088A1 (fr
Filing date
Publication date
Application filed filed Critical
Priority to JP10515890A priority Critical patent/JP2001502938A/ja
Priority to EP97945280A priority patent/EP0936934A1/fr
Priority to CA002265806A priority patent/CA2265806C/fr
Priority to AU46515/97A priority patent/AU738397B2/en
Publication of WO1998013088A1 publication Critical patent/WO1998013088A1/fr
Publication of WO1998013088A9 publication Critical patent/WO1998013088A9/fr

Links

Definitions

  • This invention relates to a syringe system for packaging, mixing and delivering two constituents or components that are stored separately in isolation from each other but which must be combined or mixed together prior to delivery.
  • the invention is particularly suitable for use with a medicament, such as a drug in powder form, which must be dissolved and diluted in a liquid prior to delivery.
  • the present invention provides an improved packaging, mixing and delivery system which can accommodate embodiments having the above-discussed benefits and features.
  • the present invention provides a syringe system for storing two components or constituents in isolation from each other.
  • the system can be subsequently operated for combining or mixing the two constituents and for then delivering the combination.
  • the syringe system includes first and second prefilled containers which each includes first and second prefilled syringe barrels, respectively.
  • the first barrel includes an open end and an opposite substantially closed delivery end.
  • the delivery end defines a delivery passage or dispensing passage to accommodate the delivery or dispensing of fluid from the first barrel.
  • a first removable closure is provided to occlude the delivery passage.
  • a reciprocable stopper or moveable seal is slidably disposed in the first barrel to define a first chamber.
  • the first chamber is preferably prefilled with a first constituent between the reciprocable stopper and the delivery end.
  • the second barrel is sized to be disposed in the first barrel and has an open end and an opposite substantially closed discharge end having a discharge passage to accommodate the discharge of fluid from the second barrel.
  • a second removable closure is provided to occlude the discharge passage.
  • a slidable plunger is sealingly disposed within the second barrel to define a second chamber.
  • the second barrel is preferably prefilled with a liquid second constituent in the second chamber between the discharge end and the slidable plunger.
  • the second closure In order to combine the two constituents, the second closure, if any, is first removed from the second barrel discharge end.
  • the first barrel reciprocable stopper and the second barrel discharge end are engageable to cooperatively define a coupling or fluid transfer connector means for accommodating the flow of the liquid second constituent from the second chamber into the first chamber.
  • This can include (a) connecting means for connecting the second barrel with the reciprocable stopper in the first barrel, and (b) fluid communicating means for establishing fluid communication between the first and second chambers.
  • the liquid constituent As the second barrel discharge end and plunger are moved closer together, the liquid constituent is moved (i.e., pushed) from the second chamber into the first chamber where the liquid second constituent mixes with the first constituent.
  • the assembly may be shaken to promote mixing.
  • the first closure can be removed from the first barrel.
  • the second barrel which is engaged with the reciprocable stopper, can be pushed inwardly. This movement carries both the second barrel and coupled reciprocable stopper inwardly into the first chamber. This coupled movement dispenses the mixed contents of the first chamber through the delivery passage.
  • FIG. 1 is a partial cross-sectional view of a first embodiment of the syringe system of the present invention showing the first and second containers before the container barrels are coupled together;
  • FIG. 2 is a greatly enlarged, fragmentary, cross-sectional view of the discharge end of the second barrel
  • FIG. 3 is a view of the components of FIG. 1 in a coupled condition with the reciprocable stopper in the first barrel penetrated by the piercing needle of the second barrel just prior to the plunger of the second barrel being moved toward the discharge end
  • FIG. 4 is a view similar to FIG. 3, but FIG. 4 shows the liquid contents of the second barrel completely discharged into the first barrel;
  • FIG. 5 is a greatly enlarged, fragmentary, cross-sectional view of the delivery end of the first barrel shown with the first closure removed and replaced with a needle;
  • FIG. 6 is a cross-sectional view of a second embodiment of the present invention showing the separate first and second barrels of the containers prior to being coupled together;
  • FIG. 7 is a greatly enlarged, fragmentary, cross-sectional view of the conduit assembly and reciprocable stopper in the first barrel of the second embodiment
  • FIG. 8 is a perspective view of the valve member employed in the reciprocable stopper of the second embodiment
  • FIG. 9 is ' a top plan view of the valve member shown in FIG. 8;
  • FIG. 10 is a view similar to FIG. 7, but FIG. 10 shows a third embodiment of the present invention having a modified reciprocable stopper
  • FIG. 10A is a fragmentary, bottom plan view taken along the plane 10A-10A in FIG. 10;
  • FIG. 11 is a cross-sectional view of a fourth embodiment of the present invention showing the separate first and second barrels of the containers prior to being coupled together;
  • FIG. 12 is a greatly enlarged, fragmentary, cross-sectional view of a portion of the assembled components of the fourth embodiment showing the second barrel being operated to open the mixing valve of the first barrel;
  • FIG. 13 is a cross-sectional view of a fifth embodiment of the present invention showing the separate first and second barrels of the containers prior to being coupled;
  • FIG. 14 is a greatly enlarged, fragmentary, cross-sectional view of a portion of the assembled components of the fifth embodiment showing the second barrel being operated to open the mixing valve of the first barrel;
  • FIG. 15 is a cross-sectional view taken generally along the plane 15-15 in FIG. 14;
  • FIG. 16 is a cross-sectional view taken generally along the plane 16-16 in FIG. 15;
  • FIG. 17 is a fragmentary, cross-sectional view of a portion of the assembled components of a sixth embodiment of the present invention showing the second barrel being operated to open the mixing valve in the first barrel.
  • FIGS. 1-5 A first embodiment of the prefilled syringe system of the present invention is illustrated in FIGS. 1-5 and is designated generally therein by the reference number 20.
  • the system may be generally characterized as including two "containers" for separately storing two constituents or components in isolation from each other, but which can be subsequently operated to combine or mix the components for delivery.
  • the first container includes a first barrel 22 having an open end 24 and an opposite, substantially closed, dispensing end or delivery end 26 defining a delivery passage or dispensing passage 28.
  • the first barrel 22 is preferably fabricated from a synthetic polymer, such as a thermoplastic material, but the barrel may be made of other suitable material such as glass.
  • a first constituent or component 40 is provided in the first barrel 22.
  • the constituent 40 in the preferred embodiment contemplated for use in medical applications, can be a drug or other medicament in granular form, powder form, or other particulate form.
  • the first constituent may also be a liquid. It is contemplated that the constituent 40 in the first barrel 22 would typically be a drug which, if in solid form, requires reconstitution, or if in liquid form, requires dilution.
  • the system of the present invention will be useful in the containment of hazardous drugs such as are used in oncological applications or in biotechnology delivery applications.
  • the delivery end 26 defines an exterior thread form 30 for receiving a threaded cap or first removable closure 32 and for subsequently receiving, upon removal of the closure 32, a suitable dispensing component, such as a hollow needle 34 described hereinafter in detail with reference to FIG. 5. Any other suitable conventional or special capping system may be employed.
  • a reciprocable stopper 42 is slidably disposed in the first chamber 24 above the first constituent 40.
  • the reciprocable stopper 42 is fabricated from a resilient, elastomeric material.
  • the reciprocable stopper 42 has an uncompressed diameter somewhat larger than the diameter of the chamber 2 .
  • a friction-fit engagement is established between the stopper 42 and the chamber 24 that is sufficient to hold the stopper 42 in place on top of the constituent 40 during normal packaging, shipping and handling.
  • the force of engagement is sufficiently low ⁇ fco permit sliding of the stopper 42 along the chamber 24 when the stopper 42 is subjected to a sufficiently high axial force as described in detail hereinafter.
  • the reciprocable stopper 42 may be alternatively described as a moveable seal, slidable seal, piston, or grommet . All of these terms may be regarded as interchangeable herein.
  • the term "moveable seal” has been used in the above-identified parent patent application Serial No. 08/408,463. However, the term “reciprocable stopper” is generally used herein to define the same or analogous components.
  • cover 44 may be an adhesive backed, flexible web that can be readily pulled off just prior to use of the system.
  • the first barrel 22 may be regarded as a first container together with the closure 32, stopper 42, and cover 44 for storing the first component 40 and subsequently mixing the first component 40 with another component as explained in detail hereinafter.
  • a second constituent or component 46 in the form of a liquid, is sealed within a second barrel 48.
  • the liquid constituent 46 would typically be a diluent for diluting and/or reconstituting the first constituent 40.
  • the second barrel 48 may be formed from the same synthetic polymer materials as used for the first container 22.
  • the second barrel 48 preferably includes a generally cylindrical wall portion 50 that is sized to be disposed in the first container 22 (FIGS. 3 and 4) . Initially, in the pre-assembled condition, the second barrel 48 is preferably encased in a protective sleeve 52 which must be removed prior to use.
  • the second barrel 48 also includes a plunger assembly or plunger assembly or plunger 64 which is slidably disposed within the cylindrical barrel 50.
  • the plunger 64 includes a plunger shank or stem 70 with a thumb push flange at one end and a piston 68 at the other end slidably received within the barrel cylindrical wall portion 50.
  • the piston 68 is preferably elastomeric and is initially located at the upper end of the second barrel 48 in contact with the liquid second constituent 46 as illustrated in FIG. 1.
  • the plunger shank 70 may be provided with a threaded end or snap-fit end 72 for engaging a mating thread form or snap- fit form in the top of the piston 68.
  • Such a structure permits packaging of the system components with the plunger shank 70 not initially connected or assembled with the piston 68.
  • the user can thread or snap-fit the shank 70 into the piston 68.
  • the second barrel 48 has a discharge end 56 defining a discharge passage communicating through the discharge end to accommodate the discharge of fluid from the barrel 48.
  • the second barrel discharge passage is defined by the hollow interior of a piercing needle 60 which is mounted in the discharge end of the second barrel 48.
  • the second barrel 48 is initially provided to the user with a second cap or removable closure 62 mounted to the second barrel discharge end 56 over the piercing needle ' 60 as shown in FIG. 2.
  • the second closure 62 may be held on the discharge end of the second container by means of a snap-fit (or by other means, e.g.; a threaded engagement (not illustrated).
  • the second barrel 48 may be regarded as a second container together with the closure 62 and plunger 64 for storing and subsequently functioning as a syringe to discharge the liquid second constituent 46 into the first container barrel 22 as will be explained in detail hereinafter.
  • FIG. 2 The first stage of the operation is illustrated in FIG. 2.
  • the second closure 62 is removed to expose the piercing needle 60.
  • the second barrel 48 is inverted (so that the piercing needle 60 is pointing generally upwardly) . This will ensure that the liquid constituent 46 cannot drip out. However, even if the second barrel 48 is not inverted, the liquid constituent 46 will not drip out. This is because the second barrel 48 has no vent system. A vent system would admit ambient air into the second barrel 48 so as to permit the liquid constituent to flow out through the needle 60 solely under the influence of gravity.
  • the liquid constituent 46 remains in the second barrel 48 and is not able to flow out through the piercing needle 60.
  • the first barrel 22 is inverted and aligned with the second barrel 48. Then relative movement is effected so as to locate the distal end of the second barrel 48 in the first barrel 22.
  • the second barrel 48 is inserted into the first barrel 22 until the piercing needle 60 engages, and penetrates completely through, the reciprocable stopper 42 of the first barrel 22.
  • the moveable plunger 64 is not moved relative to the second container 48.
  • the plunger 64 remains in the initial, outermost orientation.
  • the plunger 64 is pushed inwardly within the second barrel 48 (i.e., toward the discharge passage in the needle 60 of the second barrel 48) .
  • the plunger movement causes the liquid second constituent 46 to flow out through the hollow piercing needle 60 to mix with the first constituent 40 within the first chamber 24.
  • the hydraulic pressure within the first chamber 24 acts on the stopper 42 and the abutting distal end of the second barrel 48.
  • the increasing pressure moves (i.e., pushes) the reciprocable stopper 42 and the second barrel 48 outwardly relative to the first barrel 22. It will be appreciated that the ambient atmospheric pressure bears on the outside surface of the plunger piston 68, and this additional pressure is effective in aiding the discharge of the liquid second constituent 46 into the first chamber 24.
  • the first closure 32 is removed from the first barrel 22, and the delivery end 26 can be connected to a receiving component or discharge component, such as a flexible container or tubing set (not illustrated) .
  • a hollow needle 34 is mounted at the distal end of the first barrel delivery end 26.
  • the needle 34 may be of a conventional, single-ended type with a straight, hollow, stainless steel shaft, typically 20 gauge in size.
  • the needle 34 may be provided with a swaged or molded hub 74 (FIG. 5) for engagement with the bottom, distal end of the delivery end 26 of the first barrel 22.
  • the needle 34 When properly mounted on the first barrel 22, the needle 34 is in alignment with the delivery passage 28, and fluid communication is established between the delivery passage 28 and the needle 34.
  • the plunger 64 and second barrel 43 can be moved forward by applying an axial force. This causes the combined constituents in the first chamber 24 to be dispensed or expelled from the chamber 24 through the needle 34.
  • first barrel stopper 42 has a central portion which is fully penetratable by the needle 60. That stopper central portion and the second barrel piercing needle 60 cooperatively define a fluid transfer connector means or coupling means incorporating ⁇ a) fluid communicating means and (b) connecting means.
  • the fluid communicating means includes the flow passage through the needle 60 which is operative to accommodate the flow of the liquid second constituent from the second barrel 48 into the first chamber 24 of the first barrel 22.
  • the connecting means includes the sealing engagement between the exterior of the needle 60 and the stopper 42 which accommodates the movement of the stopper 42 together with the second barrel
  • FIGS. 6- 9 An alternate second embodiment of the syringe system of the present invention is illustrated in FIGS. 6- 9. Elements in the alternate embodiment which are the same as, or which function in an analogous manner to, elements of the first embodiment illustrated in FIGS. 1-5 are designated with three digit reference numbers wherein the last two digits are the same as the two digits of the reference number of the corresponding element in the first embodiment .
  • the second embodiment of the syringe system includes a first barrel 122 and a second barrel 148.
  • the first barrel 122 has an open upper end which is initially sealed with a removable cover 144.
  • the first barrel 122 contains a first component or constituent 140.
  • the first constituent 140 is deposited in the bottom of the first barrel 122 which defines a dispensing end or delivery end 126 having a dispensing passage or delivery passage 128 communicating through the dispensing end or delivery end 126 to accommodate the dispensing of fluid from the first chamber 124.
  • the closed delivery end 126 preferably includes a concentrically extending collar with an interior threaded form for receiving a first removable closure 132 as shown in FIG. 6. Upon removal of the closure 132, the delivery end 126 can be threadably mated with a suitable receiving component, such as a stopcock or an IV administration set (not illustrated) .
  • a suitable receiving component such as a stopcock or an IV administration set (not illustrated) .
  • a reciprocable stopper 142 is slidably disposed in the first barrel 122 and, together with the first barrel 122, defines a first chamber 124 which is initially filled with the first constituent 140.
  • the stopper 142 is 1 retained with sufficient frictional engagement to prevent its movement within the first barrel 122 during normal storage, transport, and handling.
  • the reciprocable stopper 142 may be alternatively described as a moveable seal, slidable seal, piston, or grommet. All of these terms may be regarded as interchangeable herein.
  • the term "moveable seal” has been used in the above-identified parent patent application Serial No. 08/408,463. However, the term “reciprocable stopper” is generally used herein to define the same or analogous components.
  • the reciprocable stopper 142 is fabricated from a resilient elastomeric material.
  • the reciprocable stopper 142 has an uncompressed diameter somewhat larger than the diameter of the first barrel 122 for a friction-fit slidable engagement with the first barrel 122.
  • the reciprocable stopper 142 is retained with sufficient frictional engagement to prevent its movement with the first barrel 122 during normal storage, transport, and handling.
  • a novel conduit and valve assembly 176 is mounted in the reciprocable stopper 142.
  • the conduit and valve assembly 176 includes a generally elongate conduit 177 (which may be in the form of a luer socket) extending through the stopper 142 and defining an internal flow passage 178 having an inlet 177A and an outlet 177B.
  • the conduit and valve assembly 176 includes a laterally projecting boss 180 defining a receiving cavity 181 for receiving a ribbed anchor portion 184 of a valve member insert 185.
  • the valve member insert 185 includes a transversely oriented, resilient, spring member 186 extending from the lower end of the anchor portion 184.
  • a frusto-conical, flapper valve member 187 projects upwardly from the spring member 186.
  • the exterior surface of the valve member 187 is adapted to seal against the conduit outlet 177B.
  • the spring member 186 normally biases the valve member 187 in tight sealing engagement against the conduit outlet end 177B as illustrated in FIG. 7. This defines a one-way flow valve.
  • the inlet end of the conduit and valve assembly 176 includes a standard female luer socket which defines the inlet 177A and from which extends a connector flange 179, such as is employed in conventional connection systems marketed under the trademark LUER-LOK. This accommodates connection of the conduit and valve assembly 176 to the second barrel 148 as described in detail hereinafter. Other suitable conventional or special connecting systems may be employed.
  • the first barrel 122 may be regarded as a container together with the closure 132, reciprocable stopper 142, conduit and valve assembly 176, and cover 1 44 for storing, and subsequently mixing, the first component 140.
  • the second barrel 148 is preferably initially provided with a surrounding, protective sleeve 152 which is removed and discarded subsequent to use.
  • the second barrel 148 preferably has a cylindrical barrel portion 150 containing a liquid second constituent 146 that is retained within the barrel portion 150 by a plunger assembly or plunger 164 which includes a stem or shank having a piston 168 at one end slidably disposed within the barrel portion 150 and having a thumb push flange at the other end.
  • the bottom end of the second barrel 148 defines a discharge end 156.
  • the end 156 includes an outwardly projecting discharge conduit 158 (which is preferably in the form of a standard luer nozzle) defining an internal discharge passage 159 communicating through the discharge end 156 to accommodate the discharge of fluid from the barrel portion 150 of the second barrel 148.
  • the conduit 158 accommodates fluid-tight connection with the female luer socket which defines the inlet 177A of the coaduit assembly 176 in the first barrel 122.
  • An axia ly extending collar 161 is spaced from, and surrounds, the discharge conduit 158.
  • the collar 161 defines an internal thread form of the type that is employed in connection systems marketed under the trademark LUER-LOK.
  • the collar 161 can be threadingly engaged with the thread flange 179 at the inlet end of the conduit and valve assembly 176 which projects from the reciprocable stopper 142 in the first barrel 122.
  • the second barrel projecting conduit 158 is adapted to enter into the inlet 177A of the conduit and valve assembly 176 to form a leak-tight seal with the conduit 177.
  • the second barrel collar 161 and conduit 158, and the first barrel conduit and valve assembly 176 thus function as a cooperating fluid transfer connector means or coupling means for connecting the second barrel 148 with the first barrel 122 first chamber 124 through the reciprocable stopper 142.
  • Other suitable connection structures could be used in place of the specific form of the collar 161, conduit 158, and conduit and valve assembly 176 illustrated.
  • a secondary, removable closure member 162 in the form of a threaded plug, is threadingly engaged with the collar 161, and it must be removed prior to use. This prevents ingress of contaminants and insures that the liquid second constituent will not leak out of the second barrel 148.
  • the liquid second constituent 146 cannot leak out of a small diameter passage 159 because there is no vent system that would admit ambient air into the second barrel 148 so as to permit the liquid constituent 146 to flow out solely under the influence of gravity.
  • the second barrel 148 may be regarded together with the closure member 162 and plunger 164 as a second container or syringe for holding, and subsequently discharging, the liquid second constituent 146.
  • both barrels are preferably held in an inverted position.
  • the closure 162 is removed from the second barrel 148.
  • the second barrel 148 is inserted into the first barrel 122 to connect the second barrel discharge conduit 158 with the first barrel conduit assembly 176.
  • the second barrel luer nozzle conduit 158 is inserted into the female luer socket inlet 177A of the first barrel conduit and valve assembly 176.
  • the thread in the second barrel collar 161 is then engaged with- the flange 179 on the first barrel conduit and valve assembly 176.
  • relative rotation between the two barrels is effected to complete the threaded engagement.
  • the second barrel plunger 164 can be pushed toward the discharge passage 159.
  • the liquid second constituent 146 flows from the second barrel 148 through the conduit and valve assembly 176 (where the valve member 187 opens) into the first barrel 122, and the reciprocable stopper 142 moves outwardly in the first barrel 122 along with the second barrel 148 connected to the assembly 176.
  • the first barrel 122 and second barrel 148 could also merely be pulled outwardly relative to each other while ambient air pressure acts on the exterior surface of the plunger piston 168 and is transferred to the liquid second constituent 146.
  • the stopper 142 is pulled outwardly, the volume beneath the stopper 142 within the first barrel chamber 124 increases while the pressure within the chamber 124 decreases. This results in a pressure differential which opens the valve member 187 as the liquid second constituent 146 flows into the first barrel 122 to combine with the first constituent 140.
  • the outward movement of the two barrels 122 and 148 relative to each other is continued until the bottom interior surface of the plunger piston 168 engages the bottom, interior surface of the second barrel 148. At this point, all of the liquid second constituent 146 has been expelled from the barrel portion 150 of the second barrel 148 into the first barrel 122.
  • the assembly can be shaken to ensure good mixing.
  • the first closure 132 can then be removed from the first barrel 122, and the delivery end 126 can be connected to a suitable receiving component or discharge tubing (not illustrated) .
  • a needle such as the needle 34 illustrated for the first embodiment in FIG. 5, may be attached to the first barrel 122.
  • the thumb push flange of the plunger 164 can be pushed inwardly to move the second barrel 148 and connected reciprocable stopper 142 inwardly further into the first barrel 122. This expels the combined constituents 140 and 146 from the first barrel 122.
  • first barrel conduit and valve assembly 176, second barrel collar 161, and the second barrel conduit 158 cooperatively define a fluid transfer connector means or coupling means in the form of a flow-accommodating connection which permits the liquid second constituent 146 to flow from the second barrel 148 into the first barrel 122.
  • This fluid transfer connector means or coupling means also accommodates the outward movement of the second barrel 148 relative to the first barrel 122 during the transfer of the liquid second constituent 146 from the second barrel 148 to the first barrel 122. Additionally, this fluid transfer connector means or coupling means accommodates the subsequent inward movement of the second barrel 148 during the dispensing of the combined constituents from the first chamber 124 of the first barrel 122.
  • the unique fluid transfer connector means or coupling means employed in the embodiment illustrated in FIGS. 6-9 may be characterized as including (1) a fluid communicating means, and (2) a cooperating connecting means .
  • the "fluid communicating means” includes (a) a "first fluid connector, " preferably in the form of the luer-type socket or conduit 177 defining a flow passage into the first barrel 122, and (b) a cooperating "second fluid connector” in the form of the luer-type nozzle or conduit 158 defining a flow passage out of the second barrel 148.
  • the "cooperating connecting means” may include a friction-fit connection of luer-type nozzle or conduit 158 with the luer-type socket or conduit 177.
  • the connecting means also includes the thread form on the second barrel collar 161 and the radial flange 179 on the conduit and valve assembly 176 in the first barrel 122 to cooperatively establish a threaded connection.
  • FIGS. 10 and 10A A third embodiment of the present invention, which includes a modified form of the conduit and valve assembly, is illustrated in FIGS. 10 and 10A.
  • This embodiment includes a first barrel 222 defining a first chamber 224 in which a reciprocable stopper 242 is slidably disposed above a first constituent (not visible in FIGS. 10 and 10A) .
  • a conduit 277 is mounted in the reciprocable stopper 242 and extends through the reciprocable stopper 242.
  • the conduit 277 defines an internal passage 278 and has an inlet 277A and an outlet 277B.
  • the conduit 277 defines a standard female luer socket from which extends a connector flange 279 which may be identical to the flange 179 described above with reference to the embodiment illustrated in FIGS. 6-9.
  • the bottom of the reciprocable stopper 242 has a frusto-conical shape 243 with a partial slit 289 oriented transversely to the axis of the frusto-conical shape at a outlet 277B of the conduit 277.
  • This slit defines a flap or valve member 287 which is attached with an unslit portion 290 (FIG. 10A) to the main body of the stopper 242.
  • the portion 290 is resilient and normally biases the valve member 287 upwardly against the outlet 277B of the conduit 277 to occlude the passage 278.
  • the stopper 242 and conduit 277 illustrated in FIGS. 10 and 10A are adapted to cooperate with a second container or barrel (not illustrated) that can be identical to the second barrel 148 described above with reference to the second embodiment illustrated in FIG. 6.
  • the second barrel can be inserted into the first barrel 222 and connected to the conduit 277 in the same manner as described above for the connection of the embodiment of the second barrel 148 with the first barrel 122 illustrated in FIG. 6.
  • the operation of the embodiment of the system -illustrated in FIGS. 10 and 10A with respect to combining the two constituents and subsequently dispensing them is identical with the operation of the second embodiment described above with reference to FIGS. 6-9.
  • FIGS. 11 and 12 A fourth embodiment of the syringe system is illustrated in FIGS. 11 and 12.
  • a number of the elements of the fourth embodiment of the syringe system are identical or functionally analogous to corresponding elements in the first embodiment illustrated in FIGS. 1-5.
  • the elements of the fourth embodiment illustrated in FIGS. 11 and 12 are designated by three digit reference numbers between 300 and 399.
  • the last two digits of the fourth embodiment refer.ence numbers for elements corresponding to elements in the first embodiment are identical to the last two digits of the reference numbers used to designate those corresponding elements in the first embodiment.
  • the fourth embodiment of the syringe system includes a first barrel 322 which has a first chamber 324 containing a first constituent 340.
  • the lower portion of the first barrel 322 includes a delivery end or dispensing end 326 defining a delivery passage or dispensing passage 328.
  • the delivery passage 328 is occluded with a first, removable closure 332 which may be held in a friction fit on the delivery end 326.
  • Other connection systems may be employed, such as snap-fit beads and grooves, threads, etc.
  • a reciprocable stopper 342 (which may be alternatively characterized as a moveable seal, grommet, or plunger piston) is provided above the first constituent 340 in the first chamber 324.
  • the reciprocable stopper 342 has a lower end surface defining a conical shape 343. As shown in FIG. 11, the apex of the cone has at least one slit 38.9 (or two intersecting slits, not illustrated) .
  • the single slit 389 defines two lips or flaps 387. Two intersecting slits would define four lips.
  • the lips 387 are normally biased to a closed position as illustrated in FIG. 11.
  • the upper end of the reciprocable stopper 342 has an enlarged receiving cavity 393 and a smaller entrance passage 394 which together define a retention shoulder 395.
  • the reciprocable stopper 342 is initially installed in the first barrel 322 in a frictional engagement sufficient to prevent movement of the stopper during transport, storage, and handling.
  • the first barrel 322 may be regarded as a first container together with the reciprocable stopper 342 and closure 332 for storing the first constituent 340.
  • the reciprocable stopper 342 is adapted to be engaged, and moved, with a second barrel 348 which includes a cylindrical barrel portion 350 sized to be disposed in the first barrel 322.
  • the barrel portion 350 has a discharge end 356 defining a discharge passage 359 communicating through the discharge end 356 to accommodate the discharge of fluid from the barrel portion 350.
  • the discharge end 356 has an enlarged head 396 and a smaller neck 398 (FIG. 11) .
  • the neck 398 and head 396 together define a transverse shoulder 399.
  • a liquid second constituent 346 is contained within the barrel portion 350 below a plunger 364 which has a piston 368.
  • a suitable closure 362 is removably mounted to the discharge end 356.
  • the closure 362 may be held on the discharge end 356 by means of a friction fit or by other suitable conventional or special means, such as threads, snap-fit beads and grooves, etc.
  • the second barrel 348 may be characterized together with the closure 362 and plunger 364 as a second container or syringe for holding and storing the liquid second constituent 346 and subsequently discharging it.
  • a protective sleeve (not illustrated) may be provided for surrounding the second barrel 348 in substantially the same manner that the sleeve 52 surrounds the second barrel 48 of the first embodiment illustrated in FIG. 1.
  • the first barrel 322 may include a removable cover (not illustrated) , such as the cover 44 shown pn the top of the first barrel 22 of the first embodiment illustrated in FIG. 1.
  • the closure 362 is removed from the second barrel 348.
  • the second barrel 348 is then disposed within the first barrel 322.
  • this step is accomplished by first inverting the second barrel 348 before the closure 362 is removed.
  • the first barrel 322 is also inverted, and the two barrels are telescopically engaged in the inverted position.
  • the second barrel 348 8/13088
  • the stopper lips, flaps, or valve members 387 remain closed so as to ensure that there will be no leakage of the liquid second constituent into the first constituent 340.
  • first and second barrels are moved outwardly relative to each other, as by pushing the second barrel plunger 364 to force the liquid second constituent 346 through the valve members 387 into the first barrel first chamber 324. This forces the second barrel 348 outwardly relative to the first barrel 322.
  • the two barrels 322 and 348 may be pulled apart.
  • Ambient air pressure acting on the plunger 368 results in the liquid second constituent 346 in the second barrel 348 being maintained under the ambient atmospheric pressure.
  • the increasing volume of the first chamber 324 under the reciprocable stopper 342 creates a negative pressure differential, and the liquid second constituent 346 forces the valve members 387 outwardly to the open position illustrated in FIG. 12.
  • the liquid second constituent 346 can thus flow into the first constituent 340.
  • the two barrels move outwardly relative to each other until the bottom surface of the plunger piston 368 engages the bottom of the cylindrical barrel portion 350 of the second barrel 348. At this point, all of the liquid second constituent 346 has been expelled into the first constituent 340 in the first chamber 324.
  • the valve lips 387 then close.
  • the assembly can then be shaken to ensure good mixing.
  • the closure 332 is removed from the " first barrel delivery end 326.
  • the first barrel delivery end 326 can then be connected to a receiving component or discharge tubing (not illustrated) or to a hypodermic needle (such as the needle 34 described above with reference to the first embodiment illustrated in FIGS. 1-5) .
  • the plunger 364 and second barrel 348 are pushed inwardly. This urges the plunger piston 368 against the bottom of the cylindrical barrel portion 350 of the second barrel 348 to move the second barrel 348 and connected reciprocable stopper 342 toward the bottom of the first container 322. This results in the combined constituents being dispensed from the first container 322.
  • FIGS. 13-16 A fifth embodiment of a syringe system, incorporating a design that may be preferred in some applications, is illustrated in FIGS. 13-16.
  • a number of the elements of the fifth embodiment of the syringe system are identical or functionally analogous to corresponding elements in the first four embodiments illustrated in FIGS. 1-12.
  • the elements of the fifth embodiment illustrated in FIGS. 13-16 are designated by three digit reference numbers between 400 and 499.
  • the last two digits of the fifth embodiment reference numbers for elements corresponding to elements in the first and fourth embodiments are identical with the last two digit /13088
  • the preferred form of the syringe system includes a first barrel 422 which has a first chamber 424 containing a first constituent 440.
  • the lower portion of the first barrel 422 includes a delivery end or dispensing end 426 defining a delivery passage or dispensing passage 428.
  • the delivery passage 428 is occluded with a first, removable closure 432 which may be held in a threaded engagement on the delivery end 426.
  • the first barrel delivery end 426 includes a tapered luer fitment 433 surrounded by an annular collar 435 defining an interior, female thread for ⁇ m 436.
  • the closure 432 includes a stem 437 for being received in the delivery passage 428 and has an exterior flange or lug 438 for engaging the female thread form 436.
  • a reciprocable stopper 442 is provided above the first constituent 440 in the first chamber 424.
  • the reciprocable stopper 442 may alternatively be characterized as a moveable seal, grommet, or plunger piston.
  • the reciprocable stopper 442 has a lower end defining an inner side or end surface 443 which has a conical shape.
  • the apex of the cone has one slit 489.
  • the slit 489 defines two lips or flaps 487 that are normally biased to a closed position as illustrated in solid line in FIG. 15.
  • the reciprocable stopper 442 has an outer side or upper end surface 439. Between the stopper outer side surface 439 and the stopper inner side surface 443 there is an enlarged receiving cavity 493 and a smaller entrance passage 494 which together define a retention shoulder 495.
  • the reciprocable stopper 442 is initially installed in the first barrel 422 in a frictional engagement sufficient to prevent movement of the stopper during transport, storage, and handling.
  • the reciprocable stopper 442 is adapted to receive a support member 441.
  • the support member 441 defines a flow passage 445 and a communicating luer socket 444 which can receive a luer nozzle (as described hereinafter) .
  • the support member 441 has an enlarged head 496 arid a smaller neck 498 (FIG. 14) .
  • the neck 498 and head 496 together define a transverse shoulder 499.
  • the support member 441 can be pushed into the resilient, reciprocable stopper 442 until the support member head 496 sufficiently expands the seal entrance passage 494 and enters into the seal receiving cavity 493. In this position, the support member neck 498 is received in the smaller entrance passage 494 which, owing to the resiliency of the reciprocable stopper 442, has assumed its smaller diameter configuration whereby the reciprocable stopper retaining flange 495 engages the support member shoulder 499. This prevents separation of the support member 441 from the first barrel reciprocable stopper 442.
  • the member 441 also preferably has a support flange 457 (FIG. 14) . This prevents the reciprocable stopper 442 from being deformed to the extent that it might leak.
  • the first barrel 422 may be characterized together with the reciprocable stopper 442, support member 441, and closure 432 as a first container for storing the first constituent 440 and for subsequently mixing it with a liquid second constituent 446 contained in a second barrel 448 (FIG. 13) .
  • liquid second constituent 446 is contained within the cylindrical barrel 8/1308
  • the barrel 448 has a lower discharge end 456 defining a discharge passage 459.
  • the discharge end 456 preferably has the configuration of a luer-type nozzle for being received in the luer-type socket 444 of the support member 441.
  • a suitable closure 462 is removably mounted to the discharge end 456.
  • the second barrel 448 together with the closure 462 and plunger 464 may be characterized as a second container or syringe for storing and subsequently discharging the liquid second constituent 446.
  • a protective sleeve (not illustrated) may be provided for surrounding the second barrel 448 in substantially the same manner that the sleeve 52 surrounds the second barrel 48 of the first embodiment illustrated in FIG. 1.
  • the first barrel 422 may include a removable cover (not illustrated) , such as the cover 44 shown on the top of the first barrel 22 of the first embodiment illustrated in FIG. l.
  • the cap 462 is removed from the second barrel 448.
  • the second barrel 448 is then disposed within the first barrel 422.
  • this step is accomplished by first inverting the second barrel 448 before the closure 462 is removed.
  • the first barrel 422 is also inverted, and the two barrels are telescopically engaged in the inverted position.
  • the luer-type nozzle at the discharge end 456 of the second barrel 448 is disposed within the luer-type socket 444 of the support member 441. This may be a friction fit connection. Alternatively, a more positive mechanical connection could be employed as discussed hereinafter with respect to the sixth embodiment shown in FIG. 17.
  • the stopper flaps, lips, or valve members 487 remain closed so as to ensure that. there will be no leakage of the liquid second constituent into the first constituent 440.
  • the plunger 464 can be pushed to discharge the liquid second constituent 446 through the .reciprocable stopper slit 489 into the first chamber 424 of the first barrel 422.
  • the reciprocable stopper 442 and second barrel 448 move outwardly.
  • the first and second barrels 422 and 448 can be pulled outwardly relative to each other.
  • Ambient air pressure acting on the plunger piston 468 results in the liquid second constituent 446 being maintained under the ambient atmospheric pressure.
  • the increasing volume of the first chamber 424 under the reciprocable stopper 442 creates a negative pressure differential, and the liquid second constituent 446 forces the stopper lips or valve members 487 outwardly to the open position illustrated in FIG. 14.
  • the liquid second constituent 446 can thus flow into the first constituent 440.
  • the two barrels 422 and 448 move outwardly relative to each other until the bottom surface of the plunger piston 468 engages the bottom of the cylindrical barrel portion 450 of the second barrel 448. At this point, all of the liquid second constituent 446 has been expelled into the first constituent 440 in the first chamber 424.
  • the valve flaps 487 then close.
  • the assembly can then be shaken to ensure good mixing.
  • the closure 432 is removed from the first barrel delivery end 426.
  • the first barrel delivery end 426 can then be connected to a receiving component or discharge tubing (not illustrated) or to a hypodermic needle (such as the needle 34 described above with reference to the first embodiment illustrated in FIGS. 1-5) . Then the plunger 464 is pushed inwardly.
  • FIG. 17 illustrates a sixth embodiment of the present invention.
  • the sixth embodiment is a modification of the fifth embodiment described above with reference to FIGS. 13-16.
  • the sixth embodiment includes a support member 441A generally similar to the fifth embodiment support member 441.
  • the support member 441A includes an upwardly extending skirt 451A which has an internal, female thread form 453A.
  • a second barrel 448A is provided with a configuration generally similar to that of the fifth embodiment second barrel 448 except that the sixth embodiment second barrel 443A includes a radial lug, flange, or thread form 455A to threadingly engage the support member thread form 453A.
  • This provides a positive mechanical connection between the second barrel 448A and the support member 441A.
  • FIGS. 11-17 may be characterized as employing a unique fluid transfer connector means, or, coupling means.
  • the fluid transfer connector means or coupling means may be characterized as including (1) f ⁇ uid communicating means, and (2) cooperating connerting means.
  • the fluid communicating means include a first fluid connector in the form of a passage 359 in the second barrel discharge end 356 and a second fluid connector in the form of the flow path through the reciprocable stopper 342 and stopper flaps or lips 387.
  • the cooperating connecting means include the enlarged head 396 on the second barrel 348 and the cooperating stopper receiving cavity 393 and retention shoulder 395.
  • the fluid communicating means includes the flow passage through the reciprocable stopper 442 as well as a first fluid connector in the form of the luer-type socket or conduit 444 (FIG. 14) defining a flow passage in the support member 441 and a cooperating second fluid connector in the form of the luer-type nozzle 456 defining a flow passage in the second barrel 448.
  • the cooperating connecting means may include just a friction-fit connection of luer-type nozzle 456 in the luer-type socket 444 as well as the engagement between the support member 441 and stopper 442.
  • the connecting means also includes the thread form 453A on the support member 441A and the radial flange 455A on the second barrel 448A which cooperatively establish a threaded connection.
  • the second barrel discharge end may include a closure (i.e., closure 62 illustrated in FIG. 1).
  • closures if employed, may be provided in alternate • forms such as threadable elastomeric seal members, flexible adhesive seal members, shrink wrap films, or other closure systems.
  • the above-described syringe system of the present invention provides an advantageous means for dispensing a combination of two constituents that must be kept separate from each other until they are to be used in combination.
  • the system is self-contained and sealed. Reconstitution or dilution of a drug using this system can be effected at bedside when the drug is needed.
  • the choice of the diluent liquid is not restricted or limited because the system accommodates any diluent compatible with the structural materials employed.
  • the system permits the constituents to be stored in forms in which the stability of the components is maximized. Because the reconstituted product is used immediately, provisions do not have to be made for refrigeration or other storage procedures which might otherwise be required for certain types of reconstituted products .

Abstract

L'invention porte sur un système prérempli à deux constituants qui est pourvu de premier et second réceptacles ou cylindres. Le premier cylindre comprend une première chambre présentant une extrémité de distribution ou d'administration. Cette extrémité forme un passage de distribution ou d'administration communiquant dans l'extrémité de distribution de façon à faciliter l'administration du fluide provenant de la première chambre. Un joint amovible ou bouchon est placé dans la première chambre, et un premier constituant est versé dans la première chambre entre l'extrémité de distribution et le bouchon. Un second réceptacle ou cylindre est dimensionné de façon à se placer dans le premier cylindre et comporte une extrémité d'évacuation formant un passage d'évacuation communiquant par l'extrémité d'évacuation de façon à faciliter l'évacuation du fluide du second cylindre. Un piston est disposé coulissant dans le second cylindre. Un second constituant liquide est versé dans le second cylindre entre l'extrémité d'évacuation et le piston. Le bouchon du premier cylindre et l'extrémité d'évacuation du second cylindre peuvent s'engager directement ou indirectement de façon à former un accouplement facilitant l'écoulement du second constituant liquide, du second cylindre à la première chambre du premier cylindre, au moment où le second cylindre se déplace vers l'extérieur par rapport à la première chambre.
PCT/US1997/017194 1995-03-29 1997-09-25 Systeme de seringue comportant deux cylindres preremplis, separes, prevus pour deux constituants WO1998013088A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP10515890A JP2001502938A (ja) 1996-09-27 1997-09-25 ２成分の別個の充填済みバレルを含むシリンジシステム
EP97945280A EP0936934A1 (fr) 1996-09-27 1997-09-25 Systeme de seringue comportant deux cylindres preremplis, separes, prevus pour deux constituants
CA002265806A CA2265806C (fr) 1996-09-27 1997-09-25 Systeme de seringue comportant deux cylindres preremplis, separes, prevus pour deux constituants
AU46515/97A AU738397B2 (en) 1995-03-29 1997-09-25 Syringe system accommodating separate prefilled barrels for two constituents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US72260396A 1996-09-27 1996-09-27
US722,603 1996-09-27

Publications (2)

Publication Number Publication Date
WO1998013088A1 WO1998013088A1 (fr) 1998-04-02
WO1998013088A9 true WO1998013088A9 (fr) 1998-07-30

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Country Status (4)

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EP (1) EP0936934A1 (fr)
JP (1) JP2001502938A (fr)
CA (1) CA2265806C (fr)
WO (1) WO1998013088A1 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6645181B1 (en) 1998-11-13 2003-11-11 Elan Pharma International Limited Drug delivery systems and methods
DE19947998B4 (de) * 1999-10-06 2004-04-15 Bünder Glas GmbH Injektionsspritze mit Nadelschutz
JP4112851B2 (ja) * 2001-11-27 2008-07-02 テルモ株式会社 ２室型プレフィルドシリンジ
JP6391082B2 (ja) * 2012-07-31 2018-09-19 株式会社吉野工業所 混合噴出器
CN107106771B (zh) * 2014-08-18 2021-03-19 温德加普医疗股份有限公司 便携式药物混合和递送装置及相关方法
EP3316930B1 (fr) * 2015-07-03 2019-07-31 Ferrosan Medical Devices A/S Seringue destinée à mélanger deux composants et à maintenir un vide dans une condition de stockage

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4581016A (en) * 1984-02-29 1986-04-08 Gettig Pharmaceutical Instrument Co. Dual cartridge wet/dry syringe
US4581023A (en) * 1985-02-12 1986-04-08 Kuntz David H Hypodermic syringe assembly
US5181909A (en) * 1991-05-15 1993-01-26 Mcfarlane Richard H Ampule-container medical syringe and methods
US5569193A (en) * 1995-03-22 1996-10-29 Abbott Laboratories Syringe system accommodating separately storable prefilled containers for two constituents
US5785682A (en) * 1995-03-22 1998-07-28 Abbott Laboratories Pre-filled syringe drug delivery system
US5779668A (en) * 1995-03-29 1998-07-14 Abbott Laboratories Syringe barrel for lyophilization, reconstitution and administration

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