WO2023078826A1

WO2023078826A1 - Prefilled syringe (pfs) with removable piston rod that can be stored along the syringe barrel

Info

Publication number: WO2023078826A1
Application number: PCT/EP2022/080340
Authority: WO
Inventors: Jeff Tonnar; Cédric PENARD
Original assignee: Laboratoire Aguettant
Priority date: 2021-11-03
Filing date: 2022-10-31
Publication date: 2023-05-11
Also published as: FR3128644A1

Abstract

. The invention relates to a syringe (1) of the prefilled syringe type (PFS) comprising: - a syringe barrel (2) internally comprising a chamber to store a liquid pharmaceutical product that is to be injected; - a seal (6) positioned in the chamber of the barrel and forming a piston head; - a piston connector (13; 14) that is fixed to or formed integrally in the seal; - a plunger (5; 56) forming a piston rod of which one end (510, 520; 560) is designed to be fixed to the connector and the other end is configured as a thumb rest for at least one of the user's digits, the plunger being removable and configured in such a way as to adopt: • an inactive storage position in which it is physically separated from and complements part of the barrel, and • an active position of use in which it is fixed to the connector (13; 14) in order to cause the seal the slide inside the barrel.

Description

Title: Pre-filled syringe (PFS) with removable plunger rod, storable along the syringe barrel.

Technical area

The present invention relates to the field of packaging injectable drugs for parenteral or enteral administration in liquid form.

More particularly, the invention relates to pre-filled syringes (PFS) in which drugs are packaged and which require aseptic presentation, that is to say that the drug transfer interface to its place of administration (site of injection into a patient) must be sterile at the time of use.

The invention aims to propose a solution for improving the compactness of an injection device, in particular of a PFS syringe, in its packaging/storage configuration before its use.

Prior technique

A pre-filled syringe is a syringe in which a drug in liquid form has been packaged and sterilized, before or after filling the syringe, with a view to its storage, which may be long term. This avoids a sampling step in a vial or in an ampoule at the time of use, for the purpose of immediate administration.

This ready-to-use packaging avoids the preparation of the drug before its injection and the associated risks of error.

To prevent the drug from flowing out while it is stored in the syringe, the syringe is plugged at one end of the volume containing the drug by a seal mounted on the plunger of the syringe, and at the other end by a tip with a removable cap. The plug with ruptile shutter can advantageously be like those described respectively in the patent applications EP1973592, EP3829681 and that filed on November 26, 2020 under the ri FR2012159.

There is shown in Figure 1, a prefilled hypodermic syringe 1 according to the state of the art of axisymmetric shape around a longitudinal axis X.

Syringe 1 comprises a tubular body 2 of generally cylindrical shape with two open longitudinal ends 3, 4.

A rod forming a pusher 5 passes through the opening of the first end 3 of the tubular body 2. The end of the pusher 5 mounted in the tubular body 2 is surmounted by a seal 6. The pusher 5 and the seal 6 form a piston which is adapted to slide inside the tubular body 2 along the longitudinal axis X.

The gasket 6 forming the piston head is preferably provided with peripheral ribs directly in surface contact with elastic deformation against the inside of the body 2 to guarantee sealing.

The pusher 5 forming the piston rod allows a user to actuate the translational movement of the piston to release the packaged liquid, once the syringe is open.

The tubular body 2 has, at the first end 3, a support flange 7 which projects outwards. Thus, a user's fingers come to rest under the collar 7, while another finger, generally the thumb, moves the pusher 5 and therefore the piston with its seal 6 by pressing on the end 50 of the pusher 5 opposite to that forming the piston.

The second end 4 of the tubular body comprises a substantially transverse wall 8 open at its center and which is extended by a connection piece 9 of the Luer-lock or Luer or NR Fit or EN Fit type (or other specific connectors developed for applications allowing keying with other existing connectors).

The tip 9 comprises a tubular inner part 10 and an outer part 11, coaxial with the inner part, which forms a neck and whose internal surface is threaded to allow the screwing of a tip of complementary shape for connection to a needle or an infusion line or a catheter or a device known by the English designation “Luer Activated Device” (LAD) or any other connector on the market, once the syringe 1 has been opened.

The tubular inner part 10 is of substantially frustoconical shape and opens, on the side of its largest diameter which coincides with the opening of the transverse wall 8, on the inside of the tubular body 2.

A cap 12 is screwed into the threaded part 11 of the end piece 9, thereby closing the tubular inner part 10 of the end piece 9. The tubular body 2, the piston with its seal 6, the endpiece 9 and the stopper 12 delimit a sealed space serving as a reservoir for a liquid to be administered to a patient.

To make the syringe 1 operational, the cap 12 is unscrewed which opens the syringe, then a needle or an infusion line or a catheter or an LAD device or any other connector on the market, is connected to the tip 9.

Once the needle or the infusion line or the catheter or other market connector has been implanted in a patient, a user can actuate the pusher 5 which administers the liquid contained in the reservoir to the patient.

The primary advantage of a PFS pre-filled syringe is that the user does not have to transfer medication from any container into the syringe prior to use. In other words, a pre-filled syringe limits preparation, confusion, and the risk of contamination at the time of injection, because all contact areas are sterile. Thus, a PFS syringe allows rapid and safe administration of the drug. Such a PFS syringe generally comprises a graduation allowing the desired dosage.

Prefilled syringes are often filled at a production facility, packaged, and then shipped to a medical facility or healthcare facility. Once in this facility/establishment, these syringes are often placed in storage locations, such as cupboards, on operating theater trolleys, within a central pharmacy of a hospital location, etc., controlled and/or or locked to reduce the theft of the syringes themselves and/or the theft of the contents of these syringes.

Space inside these controlled storage locations is often limited. However, due to their storage position in which the piston rod is deployed outside the cylinder, the PFS syringes each take up a significant amount of space.

There is therefore a need to reduce the storage space required to contain a given prefilled syringe. This is all the more true as some drugs require a large dose volume and therefore increase the intrinsic volume of the syringe barrel in which the drug is contained.

More generally, there is a need to provide an injection device that can be packaged/stored in a very compact manner, in particular as soon as it is prefilled.

Several tappet (piston rod) and related assembly solutions have already been proposed. on PFS syringe barrels to reduce the overall length and volume of the syringe in its storage position.

Thus, the patents DE188449, US4011868A, EP2760511B1 each disclose a piston rod (pusher) in the form of a single arm mounted pivoting about a hinge between its storage position along a syringe and its use position. wherein it is locked by locking in an adapter/connector attached to the syringe stopper.

Patents EP2467182B1, EP2632511B1 and EP2760510B1 disclose a piston rod solution in one or two parts that can be folded down along the syringe barrel in a storage position of a PFS syringe but permanently connected with a hinge to an adapter/ connector fixed in the stopper of the syringe. Locking the hinge to guarantee the alignment of the previously folded piston rod.

All these solutions involve the implementation of a hinge which complicates and increases the production, the assembly of the syringes as well as their cost. In addition, the blocking of the hinge on the syringe barrel is not necessarily easy and quick to achieve by an uninformed user, who may, through improper handling, lead to a malfunction of the syringe or even to the impossibility of s use it, especially if the hinge breaks. Finally, because of the hinge, the feeling of pushing by a user may not be satisfactory, i.e. different from that with a usual piston rod directly pre-assembled in the cylinder, surmounted by the seal.

Consequently, there is a need to propose a solution which makes it possible to reduce the storage space required to contain a syringe, in particular a PFS prefilled syringe, which is simple and quick to use, even for an uninformed, robust user, of lower implementation cost, and which does not affect the feeling of pushing on the piston rod (pusher) by a user.

The object of the invention is to meet this need at least in part.

Disclosure of Invention

To do this, the invention relates, in one of its aspects, to a syringe of the pre-filled syringe (PFS) type, comprising:

- a syringe cylinder comprising inside a chamber for storing a liquid pharmaceutical product to be injected, - a seal arranged in the cylinder chamber forming a piston head;

- a piston connector fixed or formed integrally in the seal;

- a pusher forming a piston rod, one end of which is adapted to be fixed to the piston connector and the other end is shaped as a support zone for at least one user's finger, the pusher being removable and configured to take : an inactive storage position in which it is physically separated and hugs a part of the syringe barrel, and an active use position in which it attaches to the connector to cause the seal to slide inside the syringe barrel.

Advantageously, the PFS syringe includes a closure cap for the chamber at its distal end and in the inactive storage position, the support zone partially covers said closure cap.

Alternatively, the cylinder comprises, at its proximal end, a support flange which projects outwards and, in the inactive storage position, the support zone partly covers said support flange.

The covering by the support zone of the pusher according to one or the other of the alternatives makes it possible to further reduce the storage space of a syringe according to the invention.

According to an advantageous variant embodiment, the connector and the pusher comprise clipping/fitting means adapted to cooperate with each other so as to secure the pusher to the connector.

According to a first advantageous embodiment of the invention, the pusher comprises, between its two ends, a deployable body with two cylindrical portions interconnected by hinges, of the film hinge type, so that:

- in its inactive storage position, one of the cylindrical portions of the body is folded inside the other cylindrical portion and matches the part of the circumference of the syringe barrel and;

- In its active position of use the previously folded cylindrical portion is deployed around the hinges so as to form a cylinder with a diameter of the order of that inside the connector. According to this first embodiment, the connector advantageously comprises at least two clipping/snapping reliefs projecting from the cylinder when the pusher is in its storage position.

Also according to this first mode, each of the cylindrical portions comprises at least one latching relief in which a latching relief of the connector is snapped when the pusher is in its position of use.

According to a second advantageous embodiment of the invention, the pusher comprises, between its two ends, a rigid body with ribs, part of which is shaped as a cylinder portion adapted to match the part of the syringe barrel in the storage position .

According to this second embodiment, the connector advantageously comprises an annular ring comprising a body extended by a skirt forming tabs separated by slots, the end of each tab ending in a snap-in relief.

Also according to this second mode, the end of the rigid body of the pusher advantageously comprises at least one latching relief in which a latching relief of one of the legs of the connector is snapped when the pusher is in its position of 'use.

According to an advantageous embodiment, the end of the rigid body of the pusher comprises at least two ribs, preferably three ribs regularly spaced angularly adapted to be inserted individually into a slot delimited by two adjacent legs of the annular ring.

Advantageously, the piston connector is clipped/snapped or screwed into the seal.

The invention therefore consists essentially in making a pre-filled syringe PFS, the piston rod (pusher) is to be fixed in a removable manner, preferably by clipping/snapping into a mechanical adapter/connector itself already positioned and fixed to the joint of seal which seals the chamber of the syringe body which contains the drug to be injected. In addition, the shape and dimensions of the pusher allow it to closely fit the rest of the syringe in a storage position, which guarantees great compactness to the dismantled assembly.

And when you want to use the PFS syringe, that is to say when a user needs to inject the product contained in the syringe body, he removes the pusher from its storage position and then attaches it directly to the mechanical connector/adapter: the pusher then extends along the longitudinal axis of the syringe and the user only has to slide it as usual in the syringe barrel for injecting the product. The mechanical connection of the plunger in the connector/adapter is very simple and quick even for an untrained user and once this connection has been made, the plunger cannot be easily removed, which guarantees the reliability of the syringe.

The mechanical snap-on connection can be configured so that a sound indicates to even the uninformed user, such as a healthcare professional, that the pusher is securely snapped into the connector.

And, unlike the PFS syringes according to the state of the art with removable pusher with one or two arms, which is permanently connected to the seal by a hinge, thanks to the invention, delicate positioning is avoided. which can lead to inoperability or even breakage of part of the syringe.

Other advantages and characteristics of the invention will emerge better on reading the detailed description of examples of implementation of the invention given by way of illustration and not limitation with reference to the following figures.

Brief description of the drawings

[Fig 1] Figure 1 is a longitudinal sectional view of a prefilled syringe according to the state of the prior art in the configuration filled before use.

[Fig 2] Figure 2 is a side view of a prefilled syringe according to a first embodiment of the invention showing the pusher (piston rod) in its inactive storage position.

[Fig 3] Figure 3 repeats Figure 2 but in another side view.

[Fig 4] Figure 4 repeats Figure 2 but in perspective view. [Fig 5] Figure 5 is a side view of the prefilled syringe according to Figures 2 to 4 but with the pusher in its active position of use.

[Fig 6] Figure 6 repeats Figure 5 but in perspective view.

[Fig 7] Figure 7 is a perspective view of the prefilled syringe according to Figures 5 and 6 but with the pusher in its active position once the syringe has been used.

[Fig 8], [Fig 9], [Fig 10] Figures 8, 9 and 10 correspond respectively to Figures 2, 3 and 4 with an alternative embodiment of the pusher.

[Fig 11], [Fig 12], [Fig 13] Figures 11, 12 and 13 correspond respectively to Figures 4, 5 and 6 with the alternative embodiment of the pusher according to Figures 8 to 10.

[Fig 14] Figure 14 is a side view of the pusher, in its folded storage position, according to the first mode.

[Fig 14A] Figure 14A is a cross-sectional view of Figure 14.

[Fig 15] Figure 15 is a side view of the pusher, in its deployed position of use, according to the first mode.

[Fig 15A] Figure 15A is a cross-sectional view of Figure 15.

[Fig 16] Figure 16 is a perspective view of the pusher, in its folded storage position, according to the first mode.

[Fig 17] Figure 17 is a perspective view of the pusher, in its deployed position of use, according to the first mode.

[Fig 18] Figure 18 is a perspective view of a prefilled syringe according to a second embodiment of the invention showing the pusher (piston rod) in its inactive storage position.

[Fig 19] Figure 19 is an exploded view showing the pusher according to the second mode before its fixing with the subassembly consisting of the connector/adapter fixed in the seal.

[Fig 20] Figure 20 is an exploded view showing the pusher according to the second embodiment of the invention before its attachment to the subassembly. [Fig 21] Figure 21 is a perspective view showing the pusher according to the second embodiment of the invention once the attachment with the sub-assembly made.

[Fig 22] Figure 22 is a perspective view of a syringe with the pusher according to the second mode once the attachment with the sub-assembly has been made.

[Fig 23] Figure 23 is a perspective view of the prefilled syringe according to Figure 22 but with the pusher in its active position once the syringe has been used.

[Fig 24] Figure 24 is a perspective and sectional view of Figure 23 showing in detail the attachment of the pusher to the connector / adapter according to this second mode.

detailed description

The terms "lower", "upper", "above", "below", are to be understood in relation to a prefilled syringe in a vertical configuration with the cap above the tubular body of the syringe.

Figure 1 relating to a pre-filled syringe according to the state of the art has already been described in the preamble. It will therefore not be commented on below.

For the sake of clarity, the same element in a syringe according to the state of the art and according to the invention is designated by the same numerical reference.

When they are not described, the elements of a prefilled syringe according to the invention are similar to those of a prefilled syringe according to the state of the art, as shown in figure 1.

Figures 2 to 7 show a prefilled hypodermic syringe 1 according to a first embodiment of the invention, of axisymmetric shape around a longitudinal axis X.

Syringe 1 comprises a tubular body 2 of generally cylindrical shape internally delimiting a chamber for storing a liquid pharmaceutical product to be injected.

A closure cap 12 of the chamber is attached to the distal end of the latter.

A seal 6 is arranged in the cylinder chamber 2 and forms a piston head.

A piston adapter or connector 13 is preferably screwed or snapped into the seal 6. A pusher 5 forming a piston rod has a longitudinal end 510, 520 adapted to be fixed to the piston connector 13 and another longitudinal end 50 shaped as a support zone for at least one user's finger. Typically, the pusher 5 is made of plastic material, such as polypropylene (PP), advantageously biosourced PP.

According to the invention, the pusher 5 is removable and configured to take respectively:

- an inactive storage position in which it is physically separated and hugs a part of the syringe barrel with the support zone 50 partly covering the closure cap 12 (FIGS. 2 to 4);

- an active position of use in which it is fixed to the connector (13; 14) to slide the seal (6) inside the syringe barrel (figures 5 and 6).

More precisely, as illustrated in FIGS. 14 to 17, the pusher 5 comprises, between its two ends, a deployable body with two cylindrical portions 51, 52 interconnected by hinges 521, of the film hinge type.

These hinges 521 make it possible to deploy the body to obtain a substantially cylindrical final shape ready to be mechanically fixed to the connector 13.

In other words, in its inactive storage position, one of the cylindrical portions 51 of the body 5 is folded inside the other cylindrical portion 52 (FIGS. 14, 14A and 16) and matches the part of the circumference of the syringe barrel 2 (Figures 2 to 4).

And, in its active position of use, the folded cylindrical portion 510 is deployed around the hinges 521 so as to form a cylinder with a diameter of the order of that inside the connector (FIGS. 15, 15A and 17), for its connection with connector 13.

To be able to carry out the easy manual deployment of the body 5, that is to say to deploy the portion 510 relative to the portion 520 around the hinges, a through hole 53 is provided. The user only has to insert a finger inside, then press on the 510 portion to cause it to deploy.

The connector 13 comprises a base 130 fixed directly in the joint 6 and two clipping/latching lugs 131, 132 in the extension of the base 130 and projecting from the cylinder when the pusher is in its storage position.

For fixing the pusher 5 to the connector 13, each of the cylindrical portions 51, 52 comprises a latching groove 510, 520 in which one of the lugs 131, 132 of the connector is snapped when the pusher is in its position of use. Figures 8 to 13 show an alternative embodiment of the pusher 52 according to which it incorporates a stiffening rib 54 arranged on the side of the support zone 50. This variant makes it possible to reinforce the pusher 52 and can be implemented for example for large volume syringes which therefore require the use of a pusher 52 also of large dimensions.

As can be seen in these figures 8 to 13, unlike the configuration of figures 2 to 7 in which the support zone covers the closure cap 12 as closely as possible in the storage position, the presence of the rib 54 slightly separates the support area 50 of cap 12 in this storage position.

Thus, a user wishing to use a PFS syringe according to the invention performs the following steps.

Beforehand, the pusher 5 is in its storage position and therefore matches a part of the cylinder 52 with the bearing zone 50 partly covering the closure cap 12 (FIGS. 2 to 4 and FIGS. 8 to 10); he separates, that is to say puts the pusher 52 at a distance from the cylinder 2. he deploys the body of the pusher 5 by inserting a finger into the hole 53 and pressing on the portion 51 which then deploys around the hinges 521.

then puts the pusher 52 opposite the connector 13 then clips/snaps the lugs 131, 132 respectively into the snap openings

510, 520. The fixing is then carried out and the pusher 5 is in its active position of use. the user then proceeds as usual by removing the cap 12 then pressing on the support zone 50 to slide the seal into the chamber of the cylinder 2 which causes the evacuation of the product contained therein.

Figures 18 to 23 show a prefilled hypodermic syringe 1 according to a second embodiment of the invention.

The pusher is here a rigid body 56 with ribs, part of which is shaped as a cylinder portion adapted to match the part of the syringe cylinder in the storage position as clearly visible in Figure 18.

The connector here is an annular ring 14 comprising a body 140 extended by a skirt forming tabs 141 separated by slots 142, the end of each tab ending in a snap-in relief 143. The end of the rigid body 56 of the pusher comprises a planar circular portion 561, as a latching relief on which a latching relief 143 of one of the lugs 141 of the connector is latched when the pusher is in its position of use.

Furthermore, the end of the rigid body 56 comprises notches 562 regularly distributed angularly and made at the distal end of the ribs. These notches 562 make it possible to avoid mechanical interference between the ribs of the body 56 and the latching lugs 141. Alternatively the ribs can be less wide over the entire length of the body.

The assembly of the pusher 56 is thus done as follows.

The rigid body 56 of the pusher is aligned with the sub-assembly made up of the adapter 14 and the joint 6 in which it is fixed (figure 19).

The rigid body 56 is then brought into contact with the adapter 14 by being inserted into the opening of the lugs 141 spaced apart from each other in their not yet snapped configuration (FIG. 20).

The clipping of the reliefs 143 of the lugs 141 on the circular portion 561 is achieved by pushing the body 56 of the pusher, the sub-assembly of the adapter 14/seal 6 being in the cylindrical body 2 of the syringe (figure 21). Thus, this thrust tightens the lugs 141 which by their reliefs 143 which block the flat circular portion 561 and therefore the pusher 56.

Thus, compared to the solution for fixing the connector according to the first mode, the annular ring 14 as proposed in this second mode allows quick and easy fixing by insertion of the piston rod 56 without the user having to carry out a determined orientation of the latter before fixing.

Indeed, the multiplicity of lugs 141 with their fixing end 143 all around the body 140 of the ring allows fixing of the pusher 56 whatever their relative position in rotation.

In addition, to increase the mechanical holding in the fixed position of the pusher, its end 560 comprising at least two ribs 562 regularly spaced angularly adapted to be inserted individually into a slot 142 delimited by two adjacent tabs 141 of the annular ring 14, as shown in Figure 23. These ribs 562 therefore serve as holding supports.

Other variants and embodiments can be considered without departing from the scope of the invention.

In the examples illustrated, the pusher 5 or 56 is made in a single piece, preferably made of injected plastic material, such as PP, in particular biosourced or PE, or a multifunctional polymer from the cycloolefin family (COC/COP). . It is also possible to envisage a plunger in several parts to be mechanically assembled between the inactive storage position and the active use position.

In the examples illustrated, in the inactive storage position, the support zone 50 of the pusher covers the closure cap 12. An alternative can also be provided in which the support zone 50 of the pusher covers the support collar 7 which protrudes outward.

The invention applies to any embodiment of closure cap, in particular to those described in the aforementioned applications EP1973592, EP3829681 and that filed on November 26, 2020 under the ri FR2012159.

Claims

1. Syringe (1) of the pre-filled syringe (PFS) type, comprising:

- a syringe cylinder (2) comprising inside a chamber for storing a liquid pharmaceutical product to be injected;

- a seal (6) arranged in the cylinder chamber forming a piston head;

- a piston connector (13; 14) fixed or formed integrally in the seal;

- a plunger (5; 56) forming a piston rod, one end (510, 520; 560) of which is adapted to be fixed to the piston connector and the other end is shaped as a support zone for at least one finger user, the pusher being removable and configured to take: an inactive storage position in which it is physically separated and hugs a part of the syringe barrel, and an active use position in which it is fixed to the connector (13 14) to slide the seal (6) inside the syringe barrel.

2. Syringe (1) according to claim 1, comprising a closure cap (12) of the chamber at its distal end, and in the inactive storage position, the support zone (50) partly covering said closure cap (12).

3. Syringe (1) according to claim 1, the cylinder comprising at its proximal end, a support flange (7) which projects outwards and in the inactive storage position, the support zone ( 50) partially covering said support collar.

4. Syringe (1) according to one of the preceding claims, the connector and the pusher comprise clipping / snap-fastening means adapted to cooperate with each other so as to achieve the fixing of the pusher to the connector.

5. Syringe (1) according to one of the preceding claims, the pusher (5) comprising, between its two ends, a deployable body with two cylindrical portions (51, 52) interconnected by hinges (521), of the type film hinge, so that:

- In its inactive storage position, one of the cylindrical portions of the body is folded inside the other cylindrical portion and hugs the part of the circumference of the syringe barrel and; - In its active position of use the previously folded cylindrical portion is deployed around the hinges so as to form a cylinder with a diameter of the order of that inside the connector.

6. Syringe (1) according to claim 5, the connector comprising at least two reliefs clipping / snapping (131, 132) projecting from the cylinder when the pusher is in its storage position.

7. Syringe (1) according to claim 6, each of the cylindrical portions comprises at least one latching relief (510, 520) in which is snapped a latching relief of the connector when the pusher is in its position d 'use.

8. Syringe (1) according to one of claims 1 to 4, the pusher comprising, between its two ends, a rigid body (56) with ribs, part of which is shaped as a cylinder portion adapted to match the part of the cylinder syringe in the storage position.

9. Syringe (1) according to claim 8, the connector comprising an annular ring (14) comprising a body (140) extended by a skirt forming tabs (141) separated by slots (142), the end of each tab terminating in a snap relief (143).

10. Syringe (1) according to claim 9, the end of the rigid body (56) of the pusher comprising at least one latching relief (561) in which is snapped a latching relief of one of the legs of the connector when the pusher is in its position of use.

11. Syringe (1) according to one of claims 8 to 10, the end (560) of the rigid body (56) of the pusher comprising at least two ribs, preferably three ribs regularly spaced angularly adapted to be inserted individually into a slot delimited by two adjacent legs of the annular ring.

12. Syringe (1) according to one of the preceding claims, the plunger connector (13; 14) being clipped/snapped or screwed into the seal.