WO2011073174A1

WO2011073174A1 - Syringe

Info

Publication number: WO2011073174A1
Application number: PCT/EP2010/069595
Authority: WO
Inventors: Tony Bedford; Duncan Bishop; Andrew Gow; Dave Harris; Nick Hawson; Dominic Lloyd-Lucas; Martin Murphy; Christophe Royer
Original assignee: Novartis Ag
Priority date: 2009-12-15
Filing date: 2010-12-14
Publication date: 2011-06-23

Abstract

A syringe (2) for dispensing a fluid, the syringe including a barrel (4) including a discharge end (5) defining a discharge passage, and a plunger disposed within the barrel (4), the plunger being adapted to move axially within the barrel (4) such that the plunger and discharge end (5) define a variable volume chamber within the barrel and the plunger includes an axial stop (30) adapted to move axially between a prime stop position and a dose stop position disposed rearwardly of the prime stop position, whereby the prime stop position defines the end of a priming stroke and the dose stop position defines the end of a dosing stroke.

Description

Syringe

The present invention relates to a syringe and, in particular, to a syringe adapted to permit priming, followed by dosing of a pre-determined dose.

It is often desirable to deliver a relatively small volume of fluid from a syringe in a method that is both accurate and reproducible. Typically, syringes containing fluids are first primed, to ensure that no air or other gas is present in the syringe and then a second, delivery (dosage) step is performed to deliver the required volume of fluid. However, it is difficult to deliver accurately a relatively small volume of fluid during the delivery step using a conventional syringe.

WO01/62319, US3,934,586 and WO03/004080 all describe dual stage syringes, but none of them addresses the issue of delivering accurately and reproducibly a relatively small volume of a fluid.

According to a first aspect of the present invention, there is provided a syringe for dispensing a fluid, the syringe including a barrel including a discharge end defining a discharge passage, and a plunger disposed within the barrel, the plunger being adapted to move axially within the barrel such that the plunger and discharge end define a variable volume chamber within the barrel and the plunger includes an axial stop adapted to move axially between a prime stop position and a dose stop position disposed rearwardly of the prime stop postion, whereby the prime stop position defines the end of a priming stroke and the dose stop position defines the end of a dosing stroke.

By having a movable axial stop, a priming stroke can be defined in which the plunger is moved from a start position to the axial stop disposed in the prime stop position. The axial stop can then be moved axially rearwards to the dose stop position. When the axial stop is disposed in the dose stop position, the syringe may be used to deliver a dose of fluid contained therein by further movement of the plunger from the prime stop position to the axial stop, i.e. to the dose stop position. The spacing between the prime stop position and the dose stop position corresponds to a fixed dose for a given internal diameter of the barrel. Thus, the dose stop position is disposed rearwardly on the plunger from the prime stop position and the spacing between the prime stop position and the dose stop position defines the dosing stroke of the plunger. l Providing an axial stop adapted to move axially relative to the plunger between a prime stop position and a dose stop position means that it is possible to achieve accurate and reproducible dosing of relatively small doses of the fluid by controlling the spacing between the stop positions.

The barrel typically defines a stop surface adapted to engage the axial stop and thereby prevent further movement of the plunger. In an embodiment of the invention defined hereinabove, the dose stop position is spaced from the rearward end of the plunger.

In this embodiment, the axial stop provides a well defined dose stop position. In the art, the dose stop is often defined by indicia carried by the syringe barrel which rely upon the user stopping the dose stroke at the appropriate point, or by a plunger button engaging or contacting the barrel body. However, this opens up the possibility that the user delivers an incorrect dose, particularly when a relatively small dose is to be administered. For example, it may be the case that the user does not fully displace the plunger, resulting in an underdose being delivered. Additionally or alternatively, there is the possibility of foreign material becoming lodged at the rear of the barrel, which would prevent complete displacement of the plunger to the dose stop. This would also result in an underdose being delivered. For doses having relatively small volumes, it is important that the dose stroke is well defined.

In a further embodiment of the invention as defined anywhere herein, the axial stop includes a stop element slidably coupled to the plunger, wherein the stop element includes a releasable lock adapted selectively to lock the stop element in the prime stop position and the dose stop position. In such embodiments, the stop element defines the prime and dose positions and the releasable lock permits the stop element selectively to be retained in one of the prime and dose positions or to move between them. Thus, the lock typically includes a lock position in which axial movement of the stop element relative to the plunger is prevented and a release position in which axial movement of the stop element relative to the plunger is permitted.

The plunger may include one or more protrusions or recesses and the stop element may include a complimentary locating element adapted to engage the protrusion(s) or recess(es), whereby the stop element defines the prime position or the dose position when engaged with the corresponding protrusion or recess.

In a yet further embodiment of the invention as defined anywhere herein, the axial stop includes a captive nut and the plunger includes a threaded portion wherein one end (i.e. the forward end) of the threaded portion defines a first rotational limit and the other end (i.e. the rearward end) of the threaded portion defines a second rotational limit, wherein the captive nut disposed at the first rotational limit defines the prime stop position and the captive nut disposed at the second rotational limit defines the dose stop position and the captive nut engages the threaded portion of the plunger such that rotation of the captive nut causes axial movement of the captive nut relative to the plunger.

The syringe according to the first aspect of the invention may define a plurality of dose stop positions, spaced successively rearwardly from the prime stop position or the preceding dose stop position. Thus, the axial stop may define a plurality of dose positions and is adapted to move sequentially from the prime stop position to each successive dose stop position.

Where a plurality of dose stops positions is provided, the syringe may be adapted to provide an audible or visual indication that the axial stop is disposed in a dose stop position. Thus, the axial stop may emit an audible sound, such as a click, when disposed in a dose stop position and/or it may include a window or aperture through which a visual indication may be seen by a user when the axial stop is disposed in a dose stop position.

Additionally or alternatively, the axial stop may be adapted to provide a tactile indication that it is disposed in a dose stop position. Such an indication may include one or more detents provided on the syringe which are capable of being felt by a user when moving the axial stop. Thus, in embodiments where the axial stop includes a captive nut and the plunger includes a threaded portion, the threaded portion may include one or more detent positions and the captive nut may include a pawl adapted to engage the detent positions, wherein each detent defines a dose stop position. The detent(s) may be formed, for example, by providing a notch in a portion of the thread.

In a further embodiment of the invention as defined anywhere herein, the plunger includes a shaft connected at one end to a piston disposed in use within the barrel and connected at the other end to a push button, and the axial stop is adapted to move axially (i.e. longitudinally) relative to the shaft.

The barrel may include a collar comprising a collar body which defines therethrough a shaft guide channel, wherein the shaft of the plunger is slidably retained within the guide channel. The collar body may further define the stop surface adapted to engage the axial stop.

In order to maintain the plunger in a fixed axial orientation relative to the barrel, for example during the priming step, the shaft of the plunger may include an orientation controlling element which is adapted to maintain the axial orientation of the plunger shaft relative to the guide channel. This ensures that the plunger remains in the desired axial orientation until the priming step is complete and the axial stop in the prime stop position has engaged the stop surface. In an embodiment of the invention as defined anywhere herein, the orientation controlling element includes a spline (a longitudinally extending rib) carried by the plunger shaft which is located in use within a spline channel defined through the collar.

The interaction of the spline carried by the plunger shaft with the spline channel prevents unwanted movement, e.g. rotation, of the plunger relative to the barrel.

The skilled person will appreciate that the plunger may include more than one spline, wherein the splines are circumferentially offset from each other. In such an embodiment, the barrel and/or collar typically includes corresponding spline channels for each spline.

A common arrangement for plungers is to include a cruciform-shaped shaft. Thus, in an embodiment of the invention as defined anywhere herein, the plunger shaft has a cruciform cross sectional configuration. In such an embodiment, the collar body may define a guide channel having complimentary cruciform shape.

According to a second aspect of the invention, there is provided a plunger assembly for use with a syringe barrel, the assembly including a collar adapted to engage one end of the barrel; and a plunger including a piston adapted to be located within the barrel, an elongate shaft extending from the piston and a push button at the end of the shaft opposite to the piston, wherein the elongate shaft is slidably retained within the collar, and wherein the elongate shaft includes an axial stop adapted to move axially between a prime stop position and a dose stop position disposed rearwardly of the prime stop postion, whereby the prime stop position defines the end of a priming stroke and the dose stop position defines the end of a dosing stroke.

The additional features described and defined herein in connection with the first aspect of the invention may apply equally to the second aspect of the invention. Thus, the second aspect of the invention may include any, some or all of the additional features described

hereinabove.

According to a third aspect of the invention, there is provided a syringe kit including a syringe barrel and a plunger assembly according to the second aspect of the invention.

According to a fourth aspect of the invention, there is provided a pre-filled syringe for dispensing a fluid, the syringe including a barrel including a discharge end defining a discharge passage, the barrel containing therein a medicament in fluid form; and a plunger disposed within the barrel, the plunger being adapted to move axially within the barrel such that the plunger and discharge end define a variable volume chamber within the barrel and the plunger is capable of displacing fluid from the chamber through the discharge end;

wherein the plunger includes an axial stop adapted to move axially between a prime stop position and a dose stop position disposed rearwardly of the prime stop postion, whereby the prime stop position defines the end of a priming stroke and the dose stop position defines the end of a dosing stroke.

The additional features described and defined herein in connection with the first aspect of the invention may apply equally to the fourth aspect of the invention. Thus, the fourth aspect of the invention may include any, some or all of the additional features described hereinabove.

As used herein, the term "forward" means towards the discharge end of the syringe and the term "rearward" means away from the discharge end of the syringe.

The skilled person will appreciate that the features specified above in connection with embodiments of the invention may be combined with each other and any of the aspects of the invention as defined. Thus, the present invention includes within its scope an aspect of the invention combined with two or more of the features described anywhere herein as optional features. All such combinations of features described herein are considered to be made available to the skilled person.

Embodiments of the invention will now be described in detail, by way of example only, with reference to the accompanying drawings in which:

Figure 1 is a perspective view of a syringe according to a first embodiment of the invention; and

Figure 2 is side elevational view of the syringe shown in Figure 1.

For the avoidance of doubt, the skilled person will appreciate that in this specification, the terms "up", "down", "front", "rear", "upper", "lower", "width", etc. refer to the orientation of the components as found in the syringe when installed for normal use as shown in the Figures.

A syringe 2 according to the invention is shown in Figures 1 and 2. The syringe 2 includes a barrel 4 defining a cylinder therein. Located at the rear of the barrel 4 is a collar 6 and at the opposite end, i.e. the front, of the barrel 4 is a discharge end 5 which defines therein a discharge passage. Secured to the discharge end 5 is a connecting collar 8 of a hypodermic needle 10.

The skilled person will appreciate that the hypodermic needle connecting collar 8 may be a simple friction fit with the discharge end 5 of the barrel 4 or it may be a locking collar, such as a Luer-Lok collar. Alternatively, the needle connecting collar 8 may be adhered to the barrel 4. The connection of hypodermic needles to syringe barrels is well known in the art and will not be described in detail herein.

The syringe 2 further includes a plunger assembly 12. The plunger assembly 12 consists of a plunger shaft 14 which terminates at its rearward end in a push button 16 and terminates at its forward end in a piston (not shown) located within the cylinder defined by the barrel 4. The plunger shaft 14 is slidably retained within the collar 6.

The push button 16 defines a rearward facing push button surface 16a which is substantially planar. The plunger shaft 14 is cruciform in cross-section and defines a pair of opposed vertical splines 18 and a pair of opposed horizontal splines 20. The collar 6 includes a body which defines therein a plunger shaft guide channel in the form of a cruciform aperture 22 substantially about the longitudinal axis of the barrel 4. Each of the four arms of the cruciform-shaped aperture 22 has a height which is slightly greater than the height of the corresponding spline 18, 20 and a width which is slightly greater than the width of the corresponding splines 18, 20, such that the plunger shaft 14 is able to slide axially relative to the collar 6 within the aperture 22, but is unable to rotate about its longitudinal axis within the aperture 22.

The body of the collar 6 about the cruciform aperture 22 defines a stop surface. An axial stop in the form of a captive nut 30 cooperates with a threaded portion 36 provided on the plunger shaft 14. The captive nut 30 includes a rearward facing wall 32 and a forward facing peripheral edge portion 34. The threaded portion includes at its forward end a front stop element (not shown) and at its rearward end a rear stop element 38. In use, the captive nut is rotated until it engages the front stop element of the threaded portion 36 (as shown in Figure 2). In this configuration, the captive nut 30 is in the prime stop position. The plunger assembly 12 is then drawn backwards by a user to introduce a medicament in fluid form into the cylinder defined within the barrel 4. The syringe 2 is then held substantially vertically, with the needle 10 uppermost, and tapped to release any trapped gas in the medicament. A user initiates a priming step to remove any gas or dead volume from within the barrel by urging the plunger assembly 12 forward via the rearward facing push button surface 16a. This causes the piston within the barrel 4 to move forward, expelling the unwanted gas and priming the syringe. The priming stroke is continued until the forward facing peripheral edge portion 34 of the captive nut 30 engages the stop surface defined by the body of the collar 6. This defines the end of the priming stroke.

The user then rotates the captive nut until it engages the rear stop element 38 of the threaded portion 36 (i.e. the dose stop position). The hypodermic needle 10 is then inserted into or through the skin of a patient and the dose stroke is commenced. The dose stroke is defined by the relatively short distance between the forward facing peripheral edge portion 34 of the captive nut 30 in the prime position and the forward facing peripheral edge portion in the dose position. In other words, the dose stroke is defined as the axial distance by which the captive nut is displaced. At the end of the dose stroke, the forward facing peripheral edge portion 34 of the captive nut 30 engages the stop surface defined by the body of the collar 6 to prevent any further forward movement of the plunger assembly 12.

The skilled person will appreciate that the actual dose delivered by the syringe during the dose stroke is a function of the internal diameter of the barrel 4 and the spacing between the prime stop position and the dose stop position. The delivery dose can be varied by varying one or both of these physical properties.

Example 1 Tests of the syringe described above were carried out as follows: Test Apparatus

The syringe plunger and collar as described above were assembled to a sample 1 ml syringe barrel. A needle was fitted to the discharge end of the syringe barrel.

Preparation and Measurement

The syringe was filled with a nominal volume of RO/DI water, held vertically and tapped to release air bubbles, and primed to the prime stop position. A clean Eppendorf Tube was tared on an analytical balance. The captive nut was rotated to the dose stop position as described above, and the plunger depressed to the dose stop, discharging the dose into the vial.

The vial was then closed and weighed. The test was repeated, re-using the syringe, but taking a clean vial each time. Calculation

Dose mass was calculated from the difference in weight of the vial.

Dose volume was calculated from the mass by dividing by density.

Density = 998.022kg/m³ at lab conditions of 21°C and 42%RH Apparatus

Sartorius ME235S-OCE analytical balance (5 decimal places / 1 g)

300 μΙ Eppendorf Tubes

Syringe Device as described above

Results

Table 1

The results from N = 10 measurements

The dose delivered by the prototype in the tests is in the range 47.41 ± 3.24μΙ i.e. 44.17 to 50.65μΙ.

The syringe delivered a well controlled dose, within a tolerance of ± 3.24μΙ, which is within the tolerance of ± 7.5μΙ associated with the acceptance limits.

Claims

1 . A syringe for dispensing a fluid, the syringe including a barrel including a discharge end defining a discharge passage, and a plunger disposed within the barrel, the plunger being adapted to move axially within the barrel such that the plunger and discharge end define a variable volume chamber within the barrel and the plunger includes an axial stop adapted to move axially between a prime stop position and a dose stop position disposed rearwardly of the prime stop position, whereby the prime stop position defines the end of a priming stroke and the dose stop position defines the end of a dosing stroke.

2. A syringe according to Claim 1 , wherein the dose stop position is spaced from the rearward end of the plunger.

3. A syringe according to Claim 1 or Claim 2, wherein the axial stop includes a stop element slidably coupled to the plunger, wherein the stop element includes a releasable lock adapted selectively to lock the stop element in the prime stop position and the dose stop position.

4. A syringe according to Claim 1 or Claim 2, wherein the axial stop includes a captive nut and the plunger includes a threaded portion wherein one end of the threaded portion defines a first rotational limit and the other end of the threaded portion defines a second rotational limit, wherein the captive nut disposed at the first rotational limit defines the prime stop position and the captive nut disposed at the second rotational limit defines the dose stop position and the captive nut engages the threaded portion of the plunger such that rotation of the captive nut causes axial movement of the captive nut relative to the plunger.

5. A syringe according to any preceding claim, wherein the axial stop defines a plurality of dose positions and is adapted to move sequentially from the prime stop position to each successive dose stop position.

6. A syringe according to any preceding claim, wherein the axial stop is adapted to provide a visual, audible and/or tactile indication that it is disposed in a dose stop position.

7. A syringe according to Claim 6, wherein the axial stop includes a captive nut and the plunger includes an external threaded portion and wherein the threaded portion includes one or more detents which are engaged by the captive nut, whereby the captive nut is adapted to transmit a tactile and/or audible signal to a user upon engagement with a detent.

8. A syringe according to any preceding claim, wherein the plunger includes a shaft connected at one end to a piston disposed in use within the barrel and connected at the other end to a push button, and the axial stop is adapted to move axially relative to the shaft.

9. A syringe according to Claim 8, wherein the syringe barrel includes a collar

comprising a collar body which defines therethrough a shaft guide channel, wherein the shaft of the plunger is slidably retained within the guide channel.

10. A syringe according to Claim 8 or Claim 9, wherein the shaft of the plunger includes an orientation controlling element which is adapted to maintain the axial orientation of the plunger shaft relative to the guide channel.

1 1 . A syringe according to Claim 10, wherein the plunger shaft has a cruciform cross sectional configuration.

12. A plunger assembly for use with a syringe barrel, the assembly including a collar adapted to engage one end of the barrel; and a plunger including a piston adapted to be located within the barrel, an elongate shaft extending from the piston and a push button at the end of the shaft opposite to the piston, wherein the elongate shaft is slidably retained within the collar, and wherein the elongate shaft includes an axial stop adapted to move axially between a prime stop position and a dose stop position disposed rearwardly of the prime stop postion, whereby the prime stop position defines the end of a priming stroke and the dose stop position defines the end of a dosing stroke.

13. A syringe kit including a syringe barrel and a plunger assembly according to Claim 12.

14. A pre-filled syringe for dispensing a fluid, the syringe including a barrel including a discharge end defining a discharge passage, the barrel containing therein a medicament in fluid form; and a plunger disposed within the barrel, the plunger being adapted to move axially within the barrel such that the plunger and discharge end define a variable volume chamber within the barrel and the plunger is capable of displacing fluid from the chamber through the discharge end; wherein the plunger includes an axial stop adapted to move axially between a prime stop position and a dose stop position disposed rearwardly of the prime stop postion, whereby the prime stop position defines the end of a priming stroke and the dose stop position defines the end of a dosing stroke.