Stopper for a medical infusion device

Abstract

The present invention relates to a stopper (1) configured to be positioned within a barrel (101) of an injection device (100) for injecting at least one composition, the stopper (1) comprising a gasket (10) having a proximal end (11), a distal end (12), a lateral wall (13), and a through hole (14, 71) extending from the proximal end to the distal end, and an insert (50) inserted into the through hole (14, 71), the stopper being adapted to transform between a closed configuration in which the gasket (10) cooperates with the insert to hermetically close the through hole (14, 71) to prevent flow of the composition between the proximal end (11) and the distal end (12) of the gasket (10), and an open configuration in which the gasket (10) cooperates with the insert to open a fluid passage in the through hole (14, 71) between the proximal end (11) and the distal end (12) of the gasket (10) to allow flow of the composition.

Description

Technical Field

[0001] Technical Field of the Invention The present invention relates to a stopper for a medical infusion device and a medical infusion device comprising said stopper for infusing at least one composition.

Background Art

[0002] Technical Background Prefilled infusion devices are common containers for delivering drugs or vaccines to patients and include syringes, cartridges, auto-injectors, and the like. These typically include a plunger stopper that engages slidably within the container, which is filled with a pharmaceutical composition for the purpose of providing healthcare providers with an infusion device that is immediately available for use by the patient.

[0003] The container has a substantially cylindrical shape and includes a proximal end that can be sealed by a plunger stopper, a distal end from which the pharmaceutical composition is discharged, and a transverse wall extending between the proximal and distal ends of the container. In practice, the plunger stopper is intended to move from the proximal end of the container towards the distal end of the container by the pressure applied by the plunger, thereby discharging the drug contained within the container.

[0004] Prefilled infusion devices are widely known and used and can be used to perform the infusion of multiple compositions to a patient. In that case, the container comprises two chambers, a first chamber adapted to contain a first composition and a second chamber adapted to contain a second composition. The two chambers are separated by a second stopper, commonly referred to as a plug or diaphragm, which prevents the compositions from passing from one chamber to the other and mixing.

[0005] WO 02 / 076534 discloses an apparatus for dispensing two viscoelastic solutions. The apparatus comprises a movable diaphragm separating two chambers, each containing a solution. The movable diaphragm is provided with an opening of small diameter, which is sufficient to prevent mixing of the two solutions before the first solution is injected, while allowing subsequent injection of the second solution. SUMMARY OF THE INVENTION PROBLEM TO BE SOLVED BY THE INVENTION

[0006] This document also discloses passing the second solution through the movable diaphragm via an opening formed in the diaphragm itself. For the purpose of ensuring the sealing property of the first chamber in consideration of the second solution, the opening has a small diameter. This makes it difficult to inject the solution because of the force required to be applied on the plunger to pass the second solution through the opening and discharge it.

[0007] Such drawbacks are particularly important when the composition has a high viscosity, which is usually the case for viscoelastic solutions, and / or when the injection is carried out manually by a user who cannot push the plunger strongly enough with a finger. When a medical professional repeatedly injects a viscous pharmaceutical composition into a patient, the repetition of the same gesture may also cause repetitive strain injury.

[0008] European Patent No. 1 844 804 discloses a multi-chamber syringe comprising a barrel and a plug separating two chambers each containing a solution. The plug has two flanges adapted to contact the inner surface of the barrel. The proximal flange is provided with an eccentric projection extending in the distal direction. At the end of the injection of the first solution, the eccentric projection abuts against the distal end of the barrel, which induces pivoting of the plug relative to the barrel. Thereby, the second solution may pass through the space formed between each of the two flanges of the plug and the inner surface of the barrel and through a fluid passage formed in the transverse wall of the plug between the flanges. Performing an injection using this syringe also requires significant effort on the part of the user.

[0009] Furthermore, the seal of the two chambers provided by the plug may not be sufficient to prevent mixing of the two solutions during the injection of the first solution.

[0010] Another problem not solved by any of the prior art relates to dead volume. At the end of the injection of the second solution, in the more distal chamber, a small volume of the second solution remains in the chamber. This small volume is referred to as dead volume. This dead volume must be taken into account when a very precise volume of solution has to be injected, which requires additional calculations and may introduce an error in the volume of the solution effectively injected. Also, this small volume may be costly for the pharmaceutical industry. Means for Solving the Problems

[0011] Brief Description of the Invention The present invention aims to provide a stopper for a medical injection device for sequentially injecting at least one composition, preferably at least two compositions, which may be pharmaceutical compositions, overcoming the drawbacks of known devices, and an injection device comprising said stopper.

[0012] The present invention particularly aims to provide such a stopper and an injection device that enable a user to easily perform the injection of a second composition contained in the barrel of the injection device and ensure an optimal sealing property to prevent the two compositions from mixing before the first composition is completely injected.

[0013] The present invention also aims to provide such a stopper that exhibits a lower volume compared to stoppers of the prior art and enables a reduction in the dead volume of the injected composition.

[0014] For this purpose, one object of the present invention is a stopper configured to be positioned inside the barrel of an injection device for injecting at least one composition, the stopper comprising: - a gasket having a proximal end portion, a distal end portion, a transverse wall, and a through-hole extending from the proximal end portion to the distal end portion; - an insertion portion inserted into the through-hole. The stopper is - adapted to deform between a closed configuration in which the gasket cooperates with the insert to airtight close the through-hole and prevent the flow of the composition between the proximal end portion and the distal end portion of the gasket, and - an open configuration in which the gasket cooperates with the insert to open a fluid passage in the through-hole between the proximal end portion and the distal end portion of the gasket and allow the flow of the composition. In some embodiments, the stopper comprises the following features:

[0015] - the proximal end portion of the gasket comprises a membrane; - the insert comprises an inner chamber having a distal opening and at least one lateral opening; - the gasket comprises cavities extending around each lateral opening of the insert; - in the closed configuration, the membrane cooperates with the insert to close the cavities in order to prevent the flow of the composition between the proximal end portion and the distal end portion of the gasket; ​- In the open configuration, the membrane deforms towards the cavity under a positive difference in pressure applied to the membrane between the composition located at the proximal end from the proximal end of the gasket and the fluid present at the distal end from the distal end of the gasket, opening the fluid passage between the proximal end of the gasket, the cavity, the inner chamber and the distal end of the gasket.

[0016] In some embodiments, the gasket comprises an inner groove, and the insert comprises a flange extending from its transverse wall and inserted into the inner groove of the gasket to axially hold the insert with respect to the gasket.

[0017] In some embodiments, the stopper has the following features: - In the closed configuration, the outer surface of the insert engages in a sealing state with the inner surface of the through-hole to prevent the flow of the composition between the proximal end and the distal end of the gasket, and the protruding portion of the insert protrudes distally from the distal end of the gasket, and - In the open configuration, the protruding portion of the insert is configured to abut against the distal end inside the barrel of the injection device, and the outer surface of the insert disengages from the inner surface of the through-hole to open the fluid passage between the insert and the barrel to allow the flow of the composition between the proximal end and the distal end of the gasket.

[0018] In some embodiments, the insert is in the form of a pin having an elongated cylindrical or frustoconical body.

[0019] In other embodiments, the insert is in the form of a ball.

[0020] In some embodiments, the protruding portion of the insert comprises two legs, preferably three legs, protruding distally from the ball.

[0021] In some embodiments, in the open configuration, the protruding portion of the insert is configured to abut against the inner wall of the barrel of the injection device.

[0022] In some embodiments, the protruding portion of the barrel protrudes from the distal end to the proximal end of the inner wall of the barrel of the medical infusion device, - In the closed configuration, the outer surface of the insert engages in a sealing state with the inner surface of the through hole to prevent the flow of the composition between the proximal end and the distal end of the gasket, - In the open configuration, in order to allow the flow of the composition between the proximal end and the distal end of the gasket, the protruding portion of the barrel abuts against the proximal end of the insert, and the outer surface of the insert disengages from the inner surface of the through hole to open the fluid passage between the insert and the barrel. In some embodiments, the gasket comprises a holder having a through hole fixedly inserted therein and adapted to receive the insert.

[0023] The gasket may comprise an inner groove, and the holder comprises a transverse wall and a flange extending from the transverse wall, and the flange is inserted into the inner groove of the gasket to axially hold the holder with respect to the gasket.

[0024] In some embodiments, the transverse wall of the gasket comprises one or more ribs extending therefrom, and the ribs are adapted to contact the inner surface of the barrel.

[0025] Another object is a medical infusion device for injecting at least one composition, - A barrel extending from the proximal end to the distal end, - A plunger rod adapted to be translatable inside the barrel, - A stopper as described above, disposed between the distal end of the barrel and the plunger rod and adapted to be translatable inside the barrel, wherein the transverse wall of the stopper engages in a sealing state with the inner surface of the barrel. The present invention relates to a medical infusion device comprising a stopper.

[0026] In some embodiments, the medical infusion device is adapted to sequentially infuse two compositions, and the stopper separates two chambers of the barrel including a first chamber between the stopper and the end of the barrel containing the first composition and a second chamber between the stopper and the plunger rod containing the second composition.

[0027] Brief Description of the Drawings Further features and advantages of the present invention will become apparent from the following detailed description when taken in conjunction with the accompanying drawings.

Brief Description of the Drawings

[0028]

Figure 1

Figure 2

Figure 3

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Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

Figure 16

[0029] The same reference numerals from one figure to another refer to similar elements or elements performing the same function. As a result, said elements may not be fully described again.

[0030] The figures are only intended to illustrate examples of embodiments of the stopper and are not intended to be limiting. In particular, the features of the various embodiments can be combined at any time if technically possible.

[0031] DETAILED DESCRIPTION OF THE EMBODIMENTS OF THE INVENTION The present invention relates to a stopper configured to be disposed inside a barrel of an injection device for injecting at least one composition, preferably for sequentially injecting at least two compositions. Such an injection device is particularly suitable for medical personnel to inject a pharmaceutical composition into a patient or, in the case of self-injection, for the patient himself to inject a pharmaceutical composition. An embodiment of the medical injection device of the present invention is shown in FIG. 3 and will be further described in the following text.

[0032] The composition is a fluid and may be a liquid such as a pharmaceutical composition, a pharmaceutical agent, a vaccine, etc. Also, when the barrel is filled with the composition, a gas such as air, nitrogen, or another gas or a mixture thereof may be present (in the form of small bubbles) in the barrel.

[0033] The stopper 1 includes a gasket 10 and a pin 50. The pin is configured to be inserted into the gasket, and the stopper is configured to be inserted into the injection device.

[0034] Referring to FIG. 3, the injection device 100 is a syringe including a barrel 101 extending from a proximal end portion 103 to a distal end portion 104. The distal end portion includes a tip 105 surrounding a channel 106 for the passage of the composition. The stopper 1 is configured to be disposed inside the barrel 101 of the injection device 100 for injecting at least one composition, preferably for sequentially injecting at least two compositions.

[0035] The injection device 100 includes a plunger rod 111 fixed to a plunger stopper 107 adapted to be translatable inside the barrel for injecting the composition.

[0036] Embodiments of the stopper 1 are shown in FIG. 1 where the gasket 10 and the pin 50 are separated from each other and in FIG. 2 where the pin 50 is inserted into the gasket 10, and the stopper is thus in a usable state.

[0037] The gasket 10 has a substantially cylindrical shape, which corresponds to the shape of the barrel 101 of an injection device such as a syringe, where the stopper is intended to be inserted.

[0038] The gasket comprises a proximal end portion 11, a distal end portion 12, and a transverse wall 13 extending between the proximal wall and the distal wall.

[0039] The transverse wall 13 defines a through hole 14 extending from the proximal end portion 11 forming the proximal inlet 20 to the distal end portion 12 forming the distal outlet 21. This through hole has a substantially cylindrical or frustoconical shape.

[0040] The gasket 10 is axially symmetric with respect to the longitudinal axis passing through the center of the through hole 14.

[0041] The proximal end portion 11 of the gasket 10 comprises a membrane 16, which has a proximal face 22 and a distal face 23.

[0042] The membrane 16 extends radially inwards from the transverse wall 13 of the gasket and partially covers the through hole 14 at the proximal inlet 20.

[0043] Advantageously, the membrane 16 of the gasket may have a thickness composed of 0.1 mm to 1.0 mm. The stopper may be used in an injection device having an injection volume composed of 1 ml to 20 ml, preferably 1 ml to 3 ml.

[0044] The transverse wall 13 comprises an outer seal surface 25 configured to engage in a sealed state with the inner wall of the barrel.

[0045] The seal surface 25 is continuous, which means that it continuously extends along the circumference of the gasket 10 to form a ring. Since the continuous surface extends between the outer surface of the transverse wall of the stopper 1 and the inner surface 102 of the barrel of the medical container, any passage of the composition between the stopper 1 and the barrel 101 is prevented. Optimal sealing performance is thus ensured.

[0046] According to a preferred embodiment, the seal surface 25 may comprise one or more seal ribs 18. Each rib 18 extends outwardly from the transverse wall 13 of the gasket and is adapted to contact the inner surface 102 of the barrel. Not only the number of ribs, but also the dimensions of each rib, such as height, width, and the distance between two adjacent ribs, may be adapted to further optimize the sealing performance depending on the dimensions of the gasket and the barrel.

[0047] The presence of one or more ribs reduces the contact surface between the transverse wall 13 of the gasket and the inner surface 102 of the barrel of the injection device as compared to the straight transverse wall of the stopper, and thus improves the sliding performance of the gasket 10 with respect to the barrel 101. As a result, the force required to act thereon to displace the stopper 1 inside the barrel is reduced, which facilitates injection for the user and usually prevents the stick-slip phenomenon caused by the stopper sliding with respect to the barrel. Moreover, when there are a plurality of ribs 18, the greater the distance between the ribs, the better the stability of the stopper.

[0048] The gasket 10 may be made of any material having elastomeric properties commonly used in the manufacture of stoppers for medical injection devices. For example, the gasket may be made of polyisoprene, elastomer, rubber, thermoplastic elastomer, and liquid silicone rubber.

[0049] The pin 50 has a substantially cylindrical or frustoconical shape corresponding to the shape of the through-hole 14 of the gasket, and it is intended to form the stopper 1 by inserting the pin therein. The pin 50 may be made of polypropylene.

[0050] The pin 50 includes a transverse wall 55 that defines an inner chamber 51, which forms a hollow volume. The inner chamber 51 has a terminal opening 52 and at least one lateral opening 53 that are in fluid communication with each other. In FIGS. 1 and 2, the terminal opening 52 and the at least one lateral opening 53 are circular, but of course other shapes are possible.

[0051] Preferably, the inner chamber has two to four lateral openings.

[0052] According to a preferred embodiment, as shown in FIGS. 1 and 2, the pin 50 has two lateral openings 53 that are diametrically opposed to each other with respect to the inner chamber 51.

[0053] The pin may include a flange 54 extending from its transverse wall 55 along the entire circumference of the transverse wall or only a part thereof. The flange is adapted to be inserted into an inner groove 19 provided on the inner surface of the transverse wall 13 of the gasket. In this way, when the pin 50 is inserted into the gasket 10, the pin is axially held with respect to the gasket. The flange 54 may be continuous or discontinuous.

[0054] For the same purpose, the pin 50 may include two parts, a proximal part 56 and a distal part 57, and the distal part has a smaller diameter than the proximal part. The diameter of the through hole 14 of the gasket 10 is also reduced in the region of the distal end to match the diameter of the distal part of the pin. In this way, the pin 50 is axially held in the distal direction with respect to the gasket 10.

[0055] The chamfer 58 preferably smoothes the angle between the proximal part and the distal part.

[0056] The pin 50 may include a head 59 having a larger diameter than the rest of the pin. Therefore, when the pin 50 is inserted into the gasket 10, due to the abutment of the head 59 against the proximal end 11 of the gasket 10, the pin is axially held in the distal direction with respect to the gasket.

[0057] In some embodiments, the inner surface of the gasket includes a ridge positioned at the proximal end of the gasket, preventing the insert from moving in the proximal direction.

[0058] Referring to FIG. 2, the gasket 10 may further include a cavity 15 that extends into the gasket around the lateral opening 53 of the pin. When the pin 50 includes two lateral openings 53, the gasket 10 includes two cavities 15, both of which extend into the gasket around the corresponding lateral openings 53 of the pin.

[0059] More precisely, the cavity 15 communicates with the lateral opening 53.

[0060] As a result, a fluid passage, called the first fluid passage, is provided between the end end 12 of the gasket, the inner chamber 51 of the pin, and the cavity 15. This first fluid passage communicates with the membrane 16 of the gasket.

[0061] The membrane forms a valve configured to open or close the cavity 15 in response to a positive pressure difference exerted on the membrane by a composition positioned at the proximal end from the proximal end 11 of the gasket and a fluid present at the distal end from the distal end 12 of the gasket.

[0062] By being deformable between a closed configuration and an open configuration, the gasket 10 allows or prevents the composition located on the proximal side of the stopper 1 from entering the gasket through the membrane 16 and flowing through the first fluid passage to the distal side of the stopper 1.

[0063] In the closed configuration, the membrane 16 cooperates with the pin 50 to close the cavity 15. The flow of the composition between the proximal end 11 and the distal end 12 of the gasket is thus prevented.

[0064] In the open configuration, the membrane 16 deforms towards the cavity 15, i.e., towards the distal direction, under the positive pressure difference described above. The deformation of the membrane forms a fluid passage, called the second fluid passage, between the proximal end 11 of the gasket and the cavity 15, which opens onto the first fluid passage, and the composition may flow through the stopper for injection.

[0065] The membrane 16 is a one-way membrane, which means that the membrane is configured to preferably deform only when the composition flows in the terminal direction, i.e., the injection direction. In other words, the membrane 16 is configured to open only to allow the composition to flow from the proximal side of the stopper where the composition contacts the proximal end face 22 of the membrane, through the stopper 1, to the distal side of the stopper where the composition contacts the distal end face 23 of the membrane. The membrane 16 is configured to remain closed to prevent the composition from flowing from the distal side of the stopper where the composition contacts the distal end face 23 of the membrane to the proximal side of the stopper where the composition contacts the proximal end face 22 of the membrane, i.e., in the proximal direction which is opposite to the injection direction.

[0066] The membrane 16 is configured to remain closed as long as the pressure difference exerted on the membrane between the composition located proximally from the proximal end portion 11 of the gasket 10 and the fluid present distally from the distal end portion 12 of the gasket is substantially equal to zero.

[0067] The combination of the pin 50 and the cavity 15 within the gasket 10 prevents the two compositions from mixing before the first composition is completely injected by ensuring good sealing properties, while allowing for the controlled deformation and opening of the membrane 16.

[0068] The deformation of the membrane 16 towards the cavity 15 facilitates the opening of the valve and the subsequent injection of the composition located proximally from the stopper by minimizing the force required to open the valve.

[0069] The transverse wall 13 of the gasket may include an internal recess 17 configured to induce the gasket to collapse under mechanical pressure exerted in the terminal direction.

[0070] The internal recess 17 is preferably an annular groove extending along the circumference of the gasket 10 in the transverse wall 13.

[0071] The presence of the internal recess 17 allows the gasket to be crushed and thus reduces the dead volume corresponding to the volume of the composition remaining inside the barrel 101 at the end against the stopper after its injection, in contact with the stopper. This makes it possible to increase the total volume of the injected composition and prevent waste of the composition.

[0072] As can be seen in FIG. 3, the stopper 1 is arranged between the end end 104 of the barrel and the plunger stopper 107 and is translatable inside the barrel 101. The stopper 1 separates two chambers of the barrel, including a first, end, chamber 108 between the stopper 1 and the end end 104 of the barrel and a second, proximal, chamber 109 between the stopper 1 and the plunger stopper 107.

[0073] The first chamber 108 may contain a first composition intended to be injected first, and the second chamber 109 contains a second composition intended to be injected after the first composition has been injected.

[0074] The first composition and the second composition may be the same or different. Such compositions may be pharmaceutical or viscoelastic.

[0075] Alternatively, only the proximal chamber 109 may contain the composition. This embodiment is particularly advantageous for physically isolating the composition from the barrel tip, for example, to protect a needle arranged at the barrel tip from the composition, or to protect the composition from the needle material, or in the case of a staked needle, to protect the composition from the adhesive.

[0076] Note that the injection device 100 may comprise more than one stopper and may be used to inject more than two compositions.

[0077] Before injection, the cavity 15 of the gasket 10 is closed by a membrane 16 that engages the transverse wall 55 of the pin 50. This means that when the stopper 1 is inserted into the barrel 101 of the injection device, the membrane 16 is maintained in engagement with the pin 50 under radial compression of the stopper, and the stopper itself is subjected to radial compression of the barrel. The membrane 16 that closes the cavity 15 prevents the mixing of the first composition and the second composition by preventing the first composition from entering the second chamber 109 and the second composition from entering the first chamber 108.

[0078] Two or more ribs 9 of the stopper engage in a sealing state with the inner surface 102 of the barrel. Therefore, the first composition and the second composition cannot pass from one chamber to another through the passage between the stopper 1 and the barrel 101.

[0079] The functions of the stopper and the injection device provided with the stopper will then be described in the following part of the text with reference to FIGS. 4 and 5.

[0080] Figs. 4(a) and 5(a) correspond to the configuration of the injection device 100 before injection of the first composition.

[0081] In this configuration, the stopper 1 is in a closed configuration, the cavity 15 is maintained in a state of being closed at the proximal end by the membrane 16 of the gasket that cooperates with the pin 50 under radial compression of the stopper, and the plunger stopper 107 is in the proximal position. The pressure P1 in the first chamber 108 and the pressure P2 in the second chamber 109 are substantially equal, and the differential pressure ΔP = P2 - P1 is substantially zero (null), and thus much lower than the force required to open the membrane 16. Therefore, the cavity 15 remains closed.

[0082] The user performs the injection of the first composition. The configuration of the injection device 100 is shown in Fig. 5(b). The force applied to the plunger stopper 107 is transmitted to the second chamber 109 and further to the stopper 1, which results in a force F1 exerted by the second composition on the proximal end face of the membrane 16 of the stopper.

[0083] The displacement of the stopper 1 in the distal direction pushes the first composition in the distal direction, and the first composition is discharged from the syringe through the channel 106 at the tip.

[0084] The displacement of the stopper 1 forces the first composition to pass through the injection channel. Thus, the stopper 1 is subjected to substantially equal and opposite pressures P1 and P2 exerted on the proximal end face 22 and the distal end face 23 of the membrane 16 by the first composition and the second composition, respectively. During the displacement of the stopper 1, the differential pressure ΔP may not be substantially zero, but remains lower than the force required to open the membrane 16.

[0085] As illustrated in Fig. 5(c), the injection continues until the stopper 1 abuts against the distal end portion 104 of the barrel. A part of the first composition still remains in the first chamber 108 and the inner chamber 51 of the stopper 1.

[0086] Since the stopper 1 cannot move further distally, the pressure P2 in the second chamber 109 increases, and the force difference ΔP exceeds the force required to open the membrane 16. As a result, as shown in Fig. 4(b), the membrane 16 deforms towards the cavity 15, which means the injection direction, to open a second fluid passage between the proximal end portion 11 of the gasket and the cavity 15. The second fluid passage opens onto the first fluid passage to form a continuous fluid passage. Therefore, the second composition can flow through this continuous fluid passage to the injection channel. In this configuration, the stopper is in an open configuration.

[0087] As described above, at this point, a part of the first composition remains in the inner chamber 51. Therefore, at the start of the injection of the second composition, since both compositions are injected through the same flow path, a part of the first composition and a small amount of the second composition may be mixed.

[0088] At the end of the injection of the second composition illustrated in FIG. 5(e), the plunger stopper 107 abuts against the stopper 1. A part of the second composition remains in the first chamber 108 and the inner chamber 51.

[0089] The stopper 1 is crushed under the pressure exerted by the plunger stopper 107, and the crushing is offset by the internal recess. In this way, the stopper is in the crushed position. Therefore, when the stopper is crushed, the injection of the second composition in the inner chamber 51 becomes possible, and the dead volume can be strongly reduced.

[0090] FIG. 8 shows another embodiment of the stopper 1 including the gasket 10, the holder 70, and the insert 50. The gasket is configured to receive the holder, which in turn is configured to receive the insert. The holder is configured to be axially fixed with respect to the gasket, while the insert is axially movable in the proximal direction with respect to the holder.

[0091] The gasket has already been described above and will not be elaborated again.

[0092] The insert 50 has a frustum shape tapered in the distal direction, that is, the proximal portion 56 of the insert has a larger diameter than the distal portion 57. Contrary to that of FIG. 1, the insert is preferably a solid volume portion.

[0093] The holder 70 includes a transverse wall 72 defining a frustum-shaped through-hole 71, and distal and proximal flanges 73, 74 extending radially from both ends of the transverse wall 72. The flanges are received in corresponding internal grooves of the gasket and maintain the holder in an axially fixed position with respect to the gasket.

[0094] The transverse wall 55 of the insert 50 fits into the inner wall of the through-hole 74 of the holder and is adapted to provide a sealing state.

[0095] However, the insert is axially movable in the proximal direction with respect to the holder and the gasket. In this case, when the stopper is in the open configuration, an annular space is opened between the transverse wall of the insert and the inner wall of the holder, thereby forming a fluid passage.

[0096] Such movement of the insert in the proximal direction may be caused by the engagement between the distal portion of the insert having the protrusion 60, which extends from the distal end of the gasket to the end, and the inner surface of the distal end of the barrel.

[0097] The protruding portion of the insert is configured to avoid obstructing the fluid passage at the distal end of the barrel in order to enable the composition to be discharged from the barrel. For example, as shown in FIG. 8, the protruding portion may have a cross shape. The cross shape also has the advantage of increasing the rigidity of the insert. However, any other suitable shape may also be used as an alternative.

[0098] FIGS. 9(a) and 14(a) correspond to the configuration of the injection device before injecting the first composition.

[0099] In this configuration, the stopper 1 is in a closed configuration having a tight connection between the holder and the insert, and the plunger stopper 107 is in the proximal position. The pressure P1 in the first chamber 108 and the pressure P2 in the second chamber 109 are substantially equal, and the differential pressure ΔP = P2 - P1 is substantially zero, and thus is much lower than the force required to remove the insert from the holder.

[0100] The user performs the injection of the first composition. The configuration of the injection device is shown in FIG. 14(b). The force applied to the plunger stopper 107 is transmitted to the second chamber 109 and further to the stopper 1, which results in a force F1 being applied to the proximal end face of the insert by the second composition.

[0101] The displacement of the stopper 1 in the distal direction pushes the first composition in the distal direction, and the first composition is discharged from the syringe through the channel 106 at the tip. In this configuration, the stopper 1 is still in the closed configuration.

[0102] The displacement of the stopper 1 forces the first composition to pass through the channel for injection. Thus, the stopper 1 is subjected to substantially equal and opposite pressures P1 and P2 exerted on the proximal end face and the distal end face of the insert by the first composition and the second composition, respectively.

[0103] As a result, the differential pressure ΔP may not substantially become zero, but remains lower than the force required to remove the insert from the holder.

[0104] The injection continues until the projection 60 of the insert abuts against the distal end portion 104 of the barrel, as illustrated in FIG. 14(c). A part of the first composition may still remain in the first chamber 108.

[0105] Since the insert cannot move further distally, the pressure P2 in the second chamber 109 increases, and the pressure difference ΔP exceeds the force required to remove the insert from the holder. As a result, as shown in FIGS. 9(b) and 14(d), the holder 70 moves distally with respect to the insert 50 to open an annular fluid passage between the proximal end portion and the distal end portion of the stopper. In this way, the second composition can pass through this fluid passage to the injection channel. In this configuration, the stopper is in the open configuration.

[0106] At the end of the injection of the second composition illustrated in FIG. 14(e), the plunger stopper 107 abuts against the stopper 1. A part of the second composition may remain in the first chamber 108 corresponding to the dead volume.

[0107] In this embodiment of the stopper, the holder enables restricting the radial compression exerted on the insert by the gasket. As a result, the insert may be easily detached from the gasket / holder, which reduces the force applied to form the fluid passage.

[0108] However, in the alternative embodiment shown in FIG. 10, the holder may be omitted and the insert may be directly received in the through-hole of the gasket. In this case, when the protrusion of the insert engages with the inner surface of the barrel, the fitting between the insert and the gasket must be made accurate during assembly so as to easily open the fluid passage. Omitting the holder makes it possible to reduce the number of parts of the stopper and its cost.

[0109] FIG. 11 shows another embodiment of a stopper including a gasket 10, a holder 70, and an insert 50. Compared with the stopper of FIG. 8, the shape of the insert is different in that it has a spherical body and a terminal protrusion portion extending from the spherical body.

[0110] As shown in FIG. 12, when the stopper is disposed in the barrel of the injection device in the closed position, the outer wall of the spherical body of the insert fits into the inner wall of the frustum-shaped through-hole 74 of the holder to provide a sealed state.

[0111] However, the insert can axially move in the proximal direction with respect to the holder. In this case, an annular space is opened between the outer wall of the spherical body of the insert and the inner wall of the holder to form a fluid passage.

[0112] Such movement of the insert in the proximal direction may be caused by the engagement of a projection 60 of the insert extending from the end of the gasket to the end with the inner surface of the end of the barrel. In the illustrated embodiment, the projection portion comprises two legs or three legs. Preferably, the legs are arranged at regular angular intervals around the axis of the stopper. However, alternative shapes may be permitted, provided that they are configured so as not to obstruct the fluid passage at the end of the barrel in order to allow the composition to be discharged from the barrel.

[0113] As shown in FIG. 13, the holder may be omitted and the insert may be directly received in the through hole of the gasket.

[0114] In another embodiment, the projection portion is not disposed on the insert but is disposed within the barrel. This is particularly thought to be the case when the barrel is made of plastic, because plastic injection molding allows complex shapes to be formed inside or outside the barrel.

[0115] The projection portion extends from the end of the inner surface of the barrel to the proximal end. The projection portion may comprise one or more ridges. Preferably, the projection portion comprises at least two ridges arranged at regular intervals around the end channel.

[0116] As shown in FIG. 15, the insert may have a ball shape. The embodiment of FIG. 14 differs from that of FIG. 11 in that the insert does not have legs 60.

[0117] As shown in FIG. 16(a), when the stopper is disposed within the barrel in the closed position, a small portion of the outer surface of the insert protrudes from the end of the gasket.

[0118] When the outer surface engages an internal ridge 110 formed inside the barrel around the end channel, the insert is moved proximally relative to the holder to form a fluid passage between the holder and the insert (see FIG. 16(b)).

[0119] Regarding the preparation of a medical infusion device for an injection to be performed, a first filling method is illustrated in FIG. 6 and a second filling method is illustrated in FIG. 7.

[0120] According to the first filling method: (a) A first composition is introduced into the barrel 101 of the infusion device 100; (b) The stopper 1 is inserted into the barrel so as to contact the first composition, partitioning a first chamber filled with the composition and a second chamber, and a second composition is introduced into the second chamber of the barrel; (c) The plunger stopper 107 is introduced into the barrel, and then the plunger rod is positioned in the barrel by engaging its end portion with the plunger stopper. The infusion device is ready for injection.

[0121] According to the second filling method: (a) The stopper 1 is inserted into the barrel 101 of the infusion device 100; (b) A first composition is introduced into the barrel, into the second chamber, the plunger stopper 107 is introduced into the barrel, and then the plunger rod is positioned in the barrel by engaging its end portion with the plunger stopper; (c) The tip of the syringe is immersed in a second composition contained in the recipient, and the second composition is sucked into the first chamber of the barrel. The infusion device is ready for injection.

Claims

1. A stopper (1) configured to be positioned inside a barrel (101) of an injection device (100) for injecting at least one composition, wherein the stopper (1) comprises: - A gasket (10) having a proximal end portion (11), a distal end portion (12), a transverse wall (13), and through holes (14, 71) extending from the proximal end portion to the distal end portion; - An insert (50) inserted into the through holes (14, 71); The stopper is adapted to deform between: - A closed configuration in which the gasket (10) cooperates with the insert to hermetically close the through holes (14, 71) to prevent the flow of the composition between the proximal end portion (11) and the distal end portion (12) of the gasket (10); - An open configuration in which the gasket (10) cooperates with the insert to open a fluid passage in the through holes (14, 71) between the proximal end portion (11) and the distal end portion (12) of the gasket (10) to allow the flow of the composition; and is adapted to deform between the two configurations, - The proximal end portion (11) of the gasket (10) comprises a membrane (16); - The insert (50) comprises an inner chamber (51) having a distal opening (52) and at least one lateral opening (53); - The gasket comprises cavities (15) extending around each lateral opening (53) of the insert; - In the closed configuration, the membrane (16) cooperates with the insert (50) to close the cavity (15) to prevent the flow of the composition between the proximal end portion (11) and the distal end portion (12) of the gasket; - In the open configuration, the membrane (16) deforms towards the cavity (15) under a positive difference in pressure exerted on the membrane between the composition located proximally from the proximal end portion (11) of the gasket (10) and the fluid present distally from the distal end portion (12) of the gasket, to open the fluid passage between the proximal end portion (11) of the gasket, the cavity (15), the inner chamber (51), and the distal end portion (12) of the gasket (10); The stopper, wherein the gasket (10) is configured to induce the gasket to collapse under mechanical pressure exerted in the terminal direction to reduce the dead volume of the composition remaining inside the barrel (101) at the terminal with respect to the stopper (1) by contacting the stopper (1) after injection of the composition, and includes an internal recess (17).

2. The stopper according to claim 1, wherein the gasket (10) is provided with an inner groove (19), and the insert (50) is provided with a flange (54) extending from its transverse wall (55) and inserted into the inner groove (19) of the gasket to hold the insert (50) axially with respect to the gasket (10).

3. The stopper according to claim 1 or claim 2, wherein the insert (50) is in the form of a pin having an elongated cylindrical or frustoconical body.

4. The stopper according to any one of claims 1 to 3, wherein the transverse wall (13) of the gasket is provided with one or more ribs (18) extending therefrom, and the ribs are adapted to contact the inner surface (102) of the barrel (101).

5. A medical injection device (100) for injecting at least one composition, comprising: - a barrel (101) extending from a proximal end to a distal end; - a plunger rod adapted to be translatable inside the barrel; - a stopper (1) according to any one of claims 1 to 4, disposed between the distal end of the barrel and the plunger rod and adapted to be translatable inside the barrel, wherein the transverse wall of the stopper (1) engages the inner surface of the barrel in a sealing state; A medical injection device comprising.

6. The medical injection device is adapted to sequentially inject two compositions, and the stopper (1) separates two chambers of the barrel including a first chamber between the stopper (1) containing the first composition and the distal end of the barrel and a second chamber between the stopper (1) containing the second composition and the plunger rod. The medical injection device according to claim 5.

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