Improved injection system for drug delivery device

Abstract

The present invention relates to a device for transdermal drug delivery, the device comprising: a housing, the lower shell (107) of which defines a skin connection surface having an opening (106) for the passage of a transdermal injection cannula (122); a reservoir (203, 215) containing the active ingredient to be administered; a pump system (200) comprising a pump body (201), a valve piston (202) and / or a pump piston (205) axially movable in the pump body (200) by at least one drive system (240, 250); a transdermal injection system (100) and an electronic control system (310) for operating the drive system (240, 250) of the pump system (200) and for releasing the transdermal injection system (100). The invention is characterized in that the injection system (100) is controlled by a translating element which interacts with a connecting member (105) interposed between the pump piston (205) or the motorized valve piston (202) on one side and the injection system (100) on the other side, the connecting member (105) being movable between a first position in which the pump piston (205) or the motorized valve piston (202) is inserted and a second, irreversible position in which the pump piston (205) or the motorized valve piston (202) is inserted, the connection member assumes the first position until the injection system (100) is activated, the connection member is switched into the second, irreversible position by triggering the injection system (100), and in the second position, the connection member is retracted so as to no longer have any zone that is likely to interact with the piston (202, 205) throughout the stroke of the piston (202, 205).

Description

Technical Field

[0001] The present invention relates to the field of external drug delivery systems, in particular transdermal drug delivery systems, including pump systems and transdermal delivery systems. Typically, the system is integrated into a housing, the interior of which maintains the sterility of a separate fluid part, which is adhered to the abdomen or chest or body part of a patient and delivers the substance to the patient via a cannula inserted subcutaneously into the patient's body.

[0002] Medical treatment of many diseases requires continuous infusion of drugs via subcutaneous and intravenous injections, especially for drugs containing large molecules that cannot be digested when administered orally, such as insulin, biologics, and biosimilars.

[0003] Patients with chronic diseases (such as immuno-oncology) or who need repeated postoperative treatment need bolus injections that are usually administered by nursing staff. The amount of these injections can vary from a few milliliters to tens of milliliters. Since the flow rate is limited to the flow rate that the patient can tolerate, the injection time increases in proportion to the amount of injection, and has a direct impact on the workload of the nursing staff. Automatic drug injection pumps have been developed to free up the time of nursing staff when the administration via the pump must be supervised by trained personnel, and enable patients to safely self-administer medication thanks to a simplified automatic system, thereby giving them conventional autonomy and significantly reducing the frequency with which they need to go to the hospital.

[0004] Basal and bolus doses must be administered in precise doses according to individual prescriptions. Therefore, drug infusion pumps must be highly reliable, ensuring that patients and caregivers can monitor the correct dose.

[0005] These pumps are also used to infuse biologic drugs or active anticancer ingredients that require shorter infusion times, from tens of minutes to hours, at less frequent intervals (weekly or monthly).

[0006] To avoid the problem of re-sterilization of mobile devices for home treatment, disposable devices are preferred. Therefore, simplicity of the components of the device is crucial to ensure that the sales price is not too high.

[0007] Typically, the patient fills the reservoir with an active ingredient, such as from a vial, attaches a needle and dosing tube to the reservoir outlet, and then inserts the reservoir into the pump housing. After purging air from the reservoir, tube, and needle, the patient inserts the needle assembly, puncture element, and cannula into a selected location on their body, and removes the puncture element. To avoid irritation and infection, the subcutaneous cannula should be replaced and discarded with the empty reservoir.

[0008] Alternatively, the patient or caregiver can use an additional transfer station to automatically transfer the contents of the vial to the internal reservoir of the medical device. To do this, the user typically needs to connect the vial (and vial adapter if not already integrated into the transfer station) to the transfer station on one side and the medical device to the transfer station on the other side and then start the transfer sequence.

[0009] These devices are equipped with an internal energy source that provides power for the internal workings when the drug is injected into the patient. Since these devices can be stored for long periods of time, it is critical to conserve power during this time and power the system only when needed. Prior art

[0010] It is known from the prior art that the applicant's patent application US2019365993 describes a drug delivery device, which includes a percutaneous drug delivery system having a needle actuation mechanism and a needle guiding element, the needle actuation mechanism being configured for percutaneous insertion of a cannula, and the needle guiding element being used to guide the axial movement of the needle and the cannula. The needle actuation mechanism includes a cam element capable of rotating relative to the needle guiding element. The guiding element guides the needle attached to the needle holder and the cannula attached to the cannula holder. The needle holder and the cannula holder each include an engagement portion, wherein the engagement portion of the needle holder is configured to engage with a first cam surface and a second cam surface, and the engagement portion of the cannula holder is configured to engage with a locking surface.

[0011] It is also known that patent application US20200108201A1 describes a therapeutic substance administration device, which includes a fluid path having a reservoir needle, a main body needle, a main body needle injection mechanism and a pumping assembly, the pumping assembly (a) being configured to pump a substance from a reservoir to an object, (b) being shaped to define a pump chamber, and (c) including a plunger disposed in the pump chamber. The plunger moves back and forth through a plurality of discrete motion stages. The first motion stage of the plunger actuates a first operation in a set of operations, the set of operations including (a) driving the reservoir needle to penetrate the reservoir, (b) advancing the main body needle into the body of the object, (c) extracting the substance from the reservoir, (d) pumping the substance into the object, and (e) retracting the main body needle. The second motion stage of the plunger actuates a second operation in the set of operations.

[0012] Patent application US20210330893A1 describes a manual automatic injector for drug administration. The automatic injector includes a housing, a syringe holder configured to receive a syringe, a first drive module adapted to move the syringe holder relative to the housing, and a rigid needle shield remover comprising a first portion adapted to separate the rigid needle shield from the syringe.

[0013] Disadvantages of existing technology

[0014] In the solution described in patent EP3354303, although the device features two electromagnetic actuators, it is not possible to control the needle and cannula actuation mechanism independently of the operation of the pump. The mechanism is actuated by a prestressed spring and is locked in place by a rod of the pump's piston before the first use. When the pump is used for the first time, the rod releases the lock on the needle and cannula actuation mechanism, which then cannot return to the standby position.

[0015] The solution proposed in patent application US20210330893A1 is not entirely satisfactory. The same motorized element actuates the pump and the injection needle trigger system in a series of continuous movements of gradually increasing amplitude, but is always limited by the activation position of the first trigger of the ejection mechanism and the second trigger thereafter. Therefore, this solution does not make full use of the motorized stroke, which is limited by the position of the first trigger for needle extension and the second trigger for needle retraction. Therefore, during the drug injection phase via the needle inserted into the patient's body, the stroke available for pumping is reduced and limited by the needle movement mechanism, and therefore more cycles are required, which increases the power consumption of the motor; unless the volume of the pump body is increased, but this is not ideal because it forces the device to take up more space.

[0016] Furthermore, in order to fully utilize the available stroke, the movement must be controlled very precisely, since any error will result in unintentional triggering of the needle extension and retraction mechanism.

[0017] The solution provided by the present invention

[0018] In order to overcome the disadvantages of the prior art, the present invention in its most general sense relates to a transdermal drug delivery device having the features according to claim 1 .

[0019] The system includes:

[0020] a housing whose lower shell defines a skin-engaging surface having an opening for passage of a percutaneous injection cannula,

[0021] a reservoir containing the active ingredient to be administered,

[0022] a pump system comprising a pump body, a valve piston and / or a pump piston, which is axially movable in the pump body by means of at least one drive system,

[0023] a transcutaneous injection system and an electronic control system for operating the drive system of the pump system and for releasing the transcutaneous injection system,

[0024] Characterized in that the injection system is controlled by a translation element which interacts with a connecting member inserted between the pump piston or the motor valve piston on one side and the injection system on the other side, the connecting member being movable between a first position and a second, irreversible position, the connecting member occupying the first position until the injection system is activated, the connecting member being switched into the second, irreversible position by triggering the injection system, and in the second position the connecting member retracts so that over the entire stroke of the piston there is no longer any zone with which it could interact.

[0025] Additionally, the electronic system may:

[0026] only the pumping function or the valve function is controlled over a limited portion of the nominal axial stroke of the pump piston or the valve piston, and

[0027] ● Over at least an additional portion of the stroke, the axial displacement of the pump piston or the valve piston is controlled so as to drive an additional function independent of the pumping function or the valve function, the additional function being not activated during this axial displacement of the pump piston or the valve piston over the nominal stroke.

[0028] In particular, the additional function may be triggering the transdermal injection system.

[0029] In this case, the transdermal injection system may include:

[0030] a mechanism for actuating an assembly comprising a needle connected to a needle holder, said cannula connected to a cannula holder and a guide element configured to guide an axial displacement of the needle and the cannula,

[0031] The actuation mechanism comprises:

[0032] a cam element which is rotatable relative to the needle guiding element, the needle holder and the cannula holder each comprising a protrusion which cooperates with a rib of the guiding element,

[0033] ●A preload spring for imparting a rotational movement to the cam element relative to the needle guide element, for sequentially controlling the needle insertion and needle retraction movements, so that the needle and the cannula move from the retracted position to the extended position when the cam element rotates through a first predetermined angle through the cooperation between the protrusion of the needle holder and the cannula holder and the rib-shaped member of the cam element, and so that the needle returns to the retracted position through the cooperation between the protrusion of the needle holder and the rib-shaped member of the cam element when the cam element further rotates through a second predetermined angle, whereby during the rotation through the second predetermined angle, the protrusion of the cannula holder is maintained in the extended position by cooperating with the cam element.

[0034] In a variant, the injection system is provided with locking means which abut against a wall of the cam element in order to prevent said cam element from rotating due to the action of said preload spring.

[0035] In particular, the locking device is provided with a connecting member capable of rotating around an axis and a translation element capable of translating in a plane orthogonal to the axis, the distal end of the translation element being in contact with the wall of the cam element, the proximal end being resting on the surface of the connecting member, the opposite surface of the connecting member being resting on the raised surface of the lower shell, thereby preventing any translational movement of the translation element, and is characterized in that the end of the rod of one of the pistons can be moved by the additional stroke to a position where the end contacts the connecting member to impart a rotational movement to the connecting member, the rotational movement causing the release of the locking device by releasing the contact between the proximal end of the translation element and the surface of the connecting member.

[0036] In another variant, the additional function is to trigger a system for perforating a membrane separating a recess for a cartridge containing the active ingredient from the internal space of the housing.

[0037] "Independent" means that one function does not necessarily drive other functions in a systematic, coordinated way. The lever can:

[0038] During the "nominal stroke", in addition to this additional function, the pumping is controlled separately,

[0039] The triggering of the additional function is controlled only in the supplementary part of the stroke.

[0040] The rod may also control pumping during this additional portion of the stroke, or may not control pumping, or may control pumping only over a limited portion of the additional stroke.

[0041] DETAILED DESCRIPTION OF A NON-LIMITING EXEMPLARY EMBODIMENT

[0042] For a better understanding of the invention, and in order to show how embodiments of the invention may be implemented, reference will now be made by way of example to the accompanying drawings, in which:

[0043] 1.[ Figure 1 ] shows a top view of the locking device of the insertion mechanism in its initial state,

[0044] 2.[ Figure 2 ] shows a top view of the locking device of the insertion mechanism in its final state,

[0045] 3.[ Figure 3 ] shows the needle insertion mechanism alone in perspective and in partial cross-section,

[0046] 4.[ Figure 4] shows a perspective view in partial cross-section of a locking mechanism associated with the pump system and housed in the lower shell of the housing,

[0047] 5.[ Figure 5 ] shows a side view of a pump system associated with a locking mechanism,

[0048] 6.[ Figure 6 ] shows a perspective view of the complete fluid system integrated in the lower shell of the housing,

[0049] 7.[ Figure 7 ] shows a side cross section of the pump,

[0050] 8.[ Figure 8 ] shows a top view of the pump body from which the valve piston emerges,

[0051] 9.[ Fig. 9 ] shows a front cross-sectional view of the pump,

[0052] 10.[ Fig.10 ] shows two pump hole shapes for connecting pipes and the fluid flow cross sections obtained for different valve piston positions,

[0053] 11.[ Fig.11 ]、

[0054] 12.[ Fig.12 ]and

[0055] 13.[ Fig.13 ] shows a perspective view of a fluid system compatible with an external vial for various steps of vial insertion, wherein [ Fig.11 ] shows all components before assembly, [ Fig.12 ] shows a vial positioned in an adapter, and [ Fig.13 ] shows the vial and adapter assembly assembled to the dock and in the final position,

[0056] 14.[ Fig.14 ] shows a cross-sectional side view of the adapter and the docking piece,

[0057] 15.[ Fig.15 ] shows a side view of the docking piece,

[0058] 16.[ Fig.16 ]and

[0059] 17.[ Fig.17 ] shows a top view of the docking piece integrated into the lower housing in the initial position and the final position of the activation stroke, respectively,

[0060] 18.[ Fig.18 ]and

[0061] 19.[ Fig.19 ] shows a cross-sectional top view of the docking piece integrated into the lower housing in the initial position and final position of the activation stroke, respectively.

[0062] General principles of the trigger injection system

[0063] First, the preferred embodiment of the present invention involves a solution using a cannula and a needle. Then, the injection mechanism operates in multiple steps:

[0064] Insert the needle surrounded by the cannula,

[0065] - once the cannula-needle assembly reaches its position in the patient, the needle alone is removed, the cannula remaining implanted in the patient,

[0066] - During treatment, the drug is transferred through the cannula, with the needle locked in the withdrawn position and the cannula locked in the inserted position,

[0067] - After treatment, the cannula is removed by removing the device.

[0068] However, the present invention is not limited to this preferred embodiment and may also provide a more basic mechanism as proposed in patent application US20210330893A1, which consists in simply moving a hollow needle that remains implanted in the patient's body.

[0069] The invention is based on the intervention of a connecting member (105) which is inserted between the motorized pump piston (205) or valve piston (202) on the one hand and the injection system (100) on the other hand.

[0070] The connecting member (105) is capable of moving between a first position and a second, irreversible position, the connecting member occupying the first position until the needle or needle-cannula assembly is commanded to extend, the connecting member being switched to the second, irreversible position by triggering the injection system (100), and the connecting member ultimately being irreversibly retained in the second, irreversible position.

[0071] In this second position, the connecting member (105) is eliminated so that there is no longer any area that may interact with the piston (202, 205) over the entire stroke of the piston. The entire stroke includes the nominal stroke and the release stroke. In contrast to the solution proposed in US20210330893A1, in which once the connecting member (105) has been removed, the area of ​​interaction must remain in order to trigger the retraction of the needle, the entire stroke of the piston (202, 205) can be used for valve operation or pumping purposes.

[0072] In the example described showing an embodiment of the connecting member (105), the connecting member takes the form of an element capable of rotating around an axis (154). In its initial position, it blocks the translation element (104), which locks the injection system (100). When the piston comes into contact with the connecting member (105), the piston causes the connecting member to tilt around the axis (154), thereby releasing the translation element, which allows the operation of the injection system (100) to proceed freely and moves the connecting member (105) into its second position in which it is permanently retained. This is ensured, for example, by ribs (171, 172) that guide the portion into its second position in which it is retained by an elastic return member. In this second position, the connecting member (105) is finally removed to allow the piston to move through its entire stroke to ensure pumping without any further direct or indirect interaction with the injection system (100).

[0073] It should be noted that the present invention is not limited to drug delivery devices implementing such a trigger mode of the injection system, and includes inventive technical options associated with such a trigger mode in an exemplary embodiment, but can also be used without such a trigger mode.

[0074] Detailed description of the multifunctional operation and release of the insertion mechanism controlled by the piston rod

[0075] Figure 1 , Figure 2 , Figure 3 , Figure 4 and Figure 5 A first embodiment of a locking device for a needle insertion mechanism according to the present invention is shown, wherein [ Figure 1 ] represents only the needle insertion mechanism as described in international patent application WO2018141697A1. Figure 2 and Figure 3 The needle locking and insertion mechanism is shown in top view, wherein [ Figure 2 ] represents a device in its initial state (called “ready”), and [ Figure 3 ] shows the mechanism after release and needle insertion. [ Figure 4 ] shows the needle locking and insertion mechanism in perspective view, and [ Figure 5 ]A needle locking and insertion mechanism without a cam element is shown in a side view.

[0076] In particular, the injection system (100) includes a needle insertion mechanism consisting of a cam element (101), and the needle insertion mechanism is [ Figure 1] is shown in more detail in a partial cross-sectional view in FIG. The cam element (101) has a rib (103) whose advantageous profile cooperates with the protrusions (111, 112) of the needle holder (120) and the cannula holder (122) so that the needle (121) and the flexible cannula (124) can be inserted during a rotational movement of the cam element (101) of less than 360° and then the needle (120) can be withdrawn alone. The cannula holder (124) has a catheter for accommodating a conduit (130) carrying a fluid to be injected through the cannula (122), the catheter being connected to the cannula (122) via an inner cavity (125). The insertion of the needle (120) and the cannula (122) is guided through a through hole (106) in the housing (107). The rotational movement of the cam element (101) is triggered by a helical spring (102) preloaded in an initial state, the cam element (101) being preloaded in an initial state. Figure 2 , Figure 3 , Figure 4 and Figure 5 The insertion sequence of the needle (120) is triggered by the release of the locking system (110), thereby allowing the cam element (101) to rotate freely and thus allowing the needle (120) to be inserted thanks to the unloading force of the spring (102). It should be noted that this movement sequence is irreversible and when it is completed, the spring (102) is in an unloaded state and opposes the movement of the cam (101) in a direction opposite to the direction used to insert the needle (120) and the cannula (122). In this way, once the sequence has been completed, the needle (120) is retracted into the medical device and cannot be deployed again, thereby putting the device in a state that avoids any risk of harming the user. The use of a retractable needle (120) contained in a flexible cannula (122) does not limit the present invention and is particularly useful for ensuring the sterility of a fluid conduit as long as the needle is located in the cannula. Other alternatives for forming a fluid interface between the device and the patient can be easily thought of by those skilled in the art.

[0077] More specifically, the locking device comprises a translational element (104) and a connection member (105) with rotational freedom, both guided in respective translational and rotational movements by a lower shell (107) of the housing.

[0078] The translation element (104) has an arm (140) and a resilient protrusion (142), the distal end of the arm resting on the wall (109) of the cam element (101) (at [ Figure 5] more clearly in the figure, and the proximal end (140) rests on the surface (150) of the connecting member (105), and the elastic protrusion ensures that the locking device (110) remains in its final position after release by cooperating with the groove (172) of the lower shell (107) of the housing. The connecting member (105) has a surface (151) opposite to the surface (150), and the opposite surface (151) rests on a protrusion of the lower shell (107) of the housing. Therefore, in the locked position, the cooperation of the translation element (104) with the connecting member (105) enables the entire preload force of the helical spring (102) applied to the cam (101) to be directly transmitted to the lower shell (107) of the housing, thereby preventing any possible movement. This also ensures a longer system life during storage, while the use of direct load transfer from the housing prevents the risk of deformation of parts over time.

[0079] The locking device (110) can be released by moving the connecting member (105). The connecting member (105) has a body (152) provided with a lever arm (153) for guiding the body (152) in rotation about an axis (154). The rotation of the connecting member (105) causes the surface (150) and the opposing surface (151) to slide on the opposing surfaces (141, 174) of the translation element (104) and the lower housing (107), respectively.

[0080] When the rotation of the connecting member (105) is sufficient to cause the surface (150) to lose contact with the surface (141) of the translation element (104), the locking mechanism (110) is released and the translation element (104) performs a translation movement induced by the preload force of the coil spring (102). During the translation movement of the translation element (104), the curved profile (143) of the elastic protrusion (142) slides along the grooves (171, 172) of the housing (107), causing the end of the elastic protrusion to move orthogonally to the translation movement of the translation element. When the vertex (144) of the curved profile (143) passes through the interval (175) between the two grooves (171, 172), the translation element (104) is no longer in contact with the cam (101), but thanks to the release of elastic energy accumulated by the elastic protrusion (142) as the elastic protrusion (142) moves along the first groove (171), it continues to translate along the groove (172), and finally reaches [ Figure 3] shown in a stable equilibrium position. During the translational movement of the translational element (104), the lower surface (145) of the translational element (104) slides on the upper surface (155) of the connecting member (105) so as to force the connecting member (105) to move into abutment with the protrusion (173) on the lower shell (107) of the housing. The complementary profiles of the surfaces (145, 155) advantageously allow the translational element (104) to continue to translate after such movement into abutment, while at the same time as shown in [ Figure 3 ] rotational movement opposite to this abutment is prevented in the final position shown.

[0081] In this way, once the locking means have been released, the elastic projection ensures a safe end position in which the translation element ( 104 ) and the connecting member ( 105 ) are fixed, even in the event of sudden movements or shocks of the medical device.

[0082] Before the locking device is released, the translation element (104) and the connecting member (105) are held in place by the friction of the surface (150) and the opposing surface (151) on the surfaces (141, 174), respectively. The rotation of the connecting member (105) and the resulting release of the locking device are achieved by pressing the end of the pump piston (205) against the circular surface (156) of the lever arm (153). In the embodiment shown, this support is obtained over the extreme part of the displacement stroke of the pump piston (205), thereby advantageously enabling the pumping function to be performed before the locking device is released, so that, for example, an injection fluid can be transferred from an external reservoir to an internal reservoir before the device is placed on a patient. During this operation, the piston stroke of the pump can be easily limited by software.

[0083] Of course, once the locking device (110) has been triggered by the first movement of the pump piston (205) at the end part of its stroke, the pump piston (205) can benefit from the full stroke for the pumping function and thus increase the amount transferred from the internal reservoir to the patient for each pump cycle.

[0084] Note that the pump piston (205) only ensures the rotational movement of the connecting member (105) until the locking mechanism (110) is released, as described above. In order to ensure the free movement of this piston on this end stroke, after releasing the locking device (110), it is necessary to keep the connecting member (105) in the safe position allowed here by its cooperation with the translation element (104).

[0085] Detailed description of the pump body with rectangular holes

[0086] One embodiment of the pump system (200) is Figures 6 to 10 Shown in [ Figure 6] shows a pump system (200) integrated into the lower housing (107), which is connected to a reservoir (203) for the fluid to be extracted and to an internal reservoir (215). [ Figure 7 ] shows a cross-sectional side view of the pump system (200), revealing the fluid circuit. [ Figure 8 ] shows a side view of the pump body (201) from which the valve piston (202) emerges. [ Fig. 9 ] shows a radial cross-section of a pump system (200) in which the pump body (201) is cut in two axially offset planes to simultaneously reveal ports (212 and 213). Fig.10 a to Fig.10 d highlights the geometry of the three ports (21, 212, 213) of the pump body (201) and their advantages over those used in international patent application WO2018141697A1.

[0087] More specifically, and as Figure 6 and Figure 7 As shown, the pump consists of a pump body (201) and two pistons (pump piston (205) and valve piston (202)), defining a variable volume inner chamber (208) between them. The two pistons are each connected to a rack (248, 258), which can be set to axial motion by a drive system (240, 250), the drive system including a mechanical motion reducer (241, 251), the input end of which is connected to an electric motor (242, 252). The fluid transfer in the inner chamber (208) is made possible by the cooperation of a plurality of ports (211, 212, 213) with an internal channel (209) of the valve piston (202), the internal channel opening at one end to the inner chamber (208) and terminating at its other end by an opening (221). Precise axial positioning of the valve piston (202) enables selective engagement of one of the ports (211, 212, 213) with the pump opening (221).

[0088] exist[ Figure 6 ] In the example shown, port (211) is connected to a reservoir (203) (e.g., a vial) of fluid to be extracted, port (212) is an outlet port and is connected to the injection system, and port (213) is connected to an internal reservoir (215) of the medical device. Ports (211) and (213) may alternatively be used as input or output ports. The pump outlet port is the port from which fluid only flows in order to leave the inner cavity (208) of the pump. In the initial state, the valve piston (202) and the pump piston (205) are in face-to-face contact or only slightly separated, so that the inner cavity (208) has a small amount of air.

[0089] Two injection sequences are preferred without limiting the invention; one using an internal reservoir and the other being direct injection.

[0090] The first injection sequence involves transferring the liquid from the vial to the internal reservoir and then transferring the liquid from the internal reservoir to the injection system. The first pumping sequence consists of the following steps:

[0091] - Synchronously moving the valve piston (202) by means of its respective drive system (240, 250)

[0092] and a pump piston (205) to align the pump port (221) with the port (211) connected to the reservoir (215),

[0093] - moving the pump piston (205) alone by means of the drive system (250) so as to increase the volume of the inner cavity (208) between the valve piston (202) and the pump piston (205), thereby generating a negative pressure which causes the liquid to flow from the reservoir (203) through the internal channel (209)

[0094] is drawn into the inner cavity (208),

[0095] - once the lumen is completely filled, synchronously moving the pistons (202, 205) using their respective drive systems (240, 250) so as to align the pump port (221) with the port (213) connected to the internal reservoir (215),

[0096] - individually translating the pump piston (205) by means of its drive system (250) so as to reduce the volume of the internal cavity (208) and thereby expel all the fluid contained in the internal cavity (208) through the internal channel (209) and towards the internal reservoir (215),

[0097] - Once the liquid is drained, the above steps are repeated continuously until the liquid is contained in the reservoir.

[0098] All of the liquid in (203) or a predetermined amount has been transferred to the internal reservoir (215).

[0099] Once the fluid has been completely transferred into the internal reservoir (215), injection into the patient can begin. Therefore, the first step is to trigger the needle insertion system, as described, for example, in international patent application WO2018141697A1. Once the cannula has been inserted into the subcutaneous tissue, a new pumping sequence occurs in the following steps:

[0100] - Synchronously moving the valve piston (202) by means of its respective drive system (240, 250)

[0101] and a pump piston (205) to align the pump port (221) with the port (213) connected to the internal reservoir (215),

[0102] - moving the pump piston (205) alone by means of the drive system (250) so as to increase the volume of the inner cavity (208) between the valve piston (202) and the pump piston (205), thereby generating a negative pressure which causes liquid to be sucked from the internal reservoir (215) through the internal channel (209) into the inner cavity (208),

[0103] - once the lumen is completely filled, synchronously moving the pistons (202, 205) using their respective drive systems (240, 250) in order to align the pump port (221) with the port (212) connected to the injection system,

[0104] - individually translating the pump piston (205) by means of its drive system (250) so as to reduce the volume of the inner cavity (208) and thereby expel all the fluid contained in the inner cavity (208) through the internal channel (209) and towards the injection system,

[0105] - Once the liquid has been completely expelled, the above steps are continuously repeated until all the liquid contained in the internal reservoir (215) or a predetermined amount has been transferred to the injection system.

[0106] The second injection sequence eliminates the need to transfer fluid to an internal reservoir. Therefore, the first step is to trigger the needle insertion system, as described, for example, in international patent application WO2018141697A1. Once the cannula has been inserted into the subcutaneous tissue, the pumping sequence occurs in the following steps:

[0107] - Synchronously moving the valve piston (202) by means of its respective drive system (240, 250)

[0108] and a pump piston (205) to align the pump port (221) with the port (211) connected to the reservoir (203),

[0109] - moving the pump piston (205) alone by means of the drive system (250) so as to increase the volume of the inner cavity (208) between the valve piston (202) and the pump piston (205), thereby generating a negative pressure which causes the liquid to flow from the reservoir (203) through the internal channel (209)

[0110] is drawn into the inner cavity (208),

[0111] - once the lumen is completely filled, synchronously moving the pistons (202, 205) using their respective drive systems (240, 250) in order to align the pump port (221) with the port (212) connected to the injection system,

[0112] - individually translating the pump piston (205) by means of its drive system (250) so as to reduce the volume of the inner cavity (208) and thereby expel all the fluid contained in the inner cavity (208) through the internal channel (209) and towards the injection system,

[0113] - Once the liquid has been completely expelled, the above steps are continuously repeated until all the liquid contained in the reservoir (203) or a predetermined amount has been transferred to the injection system.

[0114] These two injection sequences do not limit the present invention, and other alternatives are conceivable. In particular, the pump system (200) can be used for drug reconstitution functions, such as for reconstructing lyophilized drugs and diluents. Then, the internal reservoir (215) can be a cartridge pre-filled with a diluent, and a pump sequence can be performed to transfer the diluent to the reservoir (203) containing the lyophilized drug in order to dissolve it. Once the lyophilized drug has dissolved, the transfer from the reservoir (203) to the internal reservoir (215) is performed in the opposite manner for subsequent injection into the patient. It is also conceivable to perform multiple continuous (partial or complete) transfers between the reservoir (203) and the internal reservoir, as this can cause the lyophilized drug to dissolve in the diluent.

[0115] Alternatively, the external reservoir (203) may be omitted entirely and the internal reservoir (215) may be a cartridge pre-filled with the fluid to be injected. In this case, the fluid is transferred from the internal reservoir (215) to the lumen and then to the injection system. This sequence of steps is repeated as many times as desired.

[0116] like[ Figure 8], the ports (211, 212, 213) are staggered, the ports (211 and 213) are located in the same longitudinal plane, the port (212) is radially offset and axially located between the two ports (211 and 213). This staggered configuration is particularly advantageous for limiting the stroke required for the valve piston (202) to select one of the ports (211, 212, 213), as this process must be repeated many times during an injection cycle. The axial proximity of the ports (211, 212, 213) has a direct impact on the durability of the battery (260) and therefore on the overall efficiency of the device. Disadvantageously, the axial size of the ports is limited, so the axial positioning of the valve piston (202) must be more precise, as incorrect positioning will result in a reduced cross-section for fluid flow. Depending on the viscosity of the fluid, this may result in significant pressure losses and therefore a reduction in fluid flow.

[0117] The assumption according to this principle that the valve piston opening of the pump is positioned opposite one of the ports is a key point in the current prior art, as embodied in the international patent application WO2018141697A1. Ensuring a minimum fluid flow cross section in the event of an axial piston "mispositioning" has the advantages of making the system more stable and robust and limiting pressure losses, thus guaranteeing an accurate flow, amount of drug injected into the patient and injection time. The present invention proposes to overcome this problem by suggesting two improvements, which can be used independently or in combination.

[0118] Figure 8 and Fig. 9 One of these improvements is highlighted. The staggered arrangement of the ports (211, 212, 213) results in a tangential misalignment of these holes relative to the opening (221) of the valve piston (202). In order not to reduce the pump flow, the opening (211) of the valve piston (202) has tangential expansion sections (223, 224) on either side of its radial ends facing the ports (211, 212, 213). These expansion sections are defined by tangential flanges (225, 226) and axial flanges (227, 228) to match the cylindrical inner surface of the pump body (201) and ensure sealing, and the tangential flanges and axial flanges are made of flexible, deformable materials such as silicone or soft thermoplastic materials. To this end, the valve piston has a hard core (230) in which an internal conduit (209) connected to the opening (221) is formed, the hard core (230) being overmolded by an elastomer (229) to form tangentially diverging sections (223, 224). [ Fig. 9] shows a radial cross section of a valve body, wherein the left and right half valves of the valve are not in the same axial plane, but in two half planes at the middle port (212) and the middle port (213), respectively. The cross section shows the correct correspondence between the tangential expansion sections (223, 224) and the ports (212, 213) tangentially offset from the opening (221) of the valve piston (202).

[0119] The second improvement in valve piston position tolerance is Figure 7 , Figure 8 and Fig.10 In particular, the ports (211, 212, 213) of the pump body (205) extend through the tapered cavities (231, 232, 233) for use with the pump body (205) in the embodiment of the present invention. Figure 4 ], the cylindrical flexible pipes (261, 262, 263) visible in the figure, are connected to the connecting elements of the fluid system, while benefiting from the shoulders (220, 222) to ensure radial stops of these pipes. Therefore, the diameter of the ports (211, 212, 213) must be smaller than the outer diameter of the flexible pipe and ideally larger than the inner diameter of the flexible pipe so as not to restrict the flow. Although the shoulder secures the mechanical connection, it does not have to exist around the entire circular periphery of the flexible pipe. In this way, the ports (211, 212, 213) can advantageously have a rectangular periphery to increase the cross-section relative to the opening of the valve piston (202) while providing a mechanical stop for the flexible pipe.

[0120] like[ Figure 8 ], the term "rectangular perimeter" means that the cross-section of the ports (211, 212, 213) is not disc-shaped, but has different lengths in the axial and tangential directions. Figure 8 In the examples shown, and in [ Fig.10 ] In sub-figures c and d of FIG, the cross section is a groove in the tangential direction, terminating in two semi-cylinders. However, the present invention is not limited to this type of shape, but includes any type of elongated cross-section, such as rectangular or elliptical. In addition, the longer length is not limited to the tangential direction, but can also be achieved in the radial direction and will be selected according to the arrangement of the ports (211, 212, 213).

[0121] Fig.10 Different scenarios for positioning the valve piston (202) are shown, with sub-figures a and b representing the case where both the port (221) and the port (211) have a disc-shaped cross section, as implemented in patent application WO2018141697A1. Sub-figure a shows a 0.5 mm diameter with a 0.196 mm 2The cross-sectional cylindrical port (211) is perfectly aligned with the same port (221), and the fluid flow cross section is indicated by cross-hatching. Sub-figure b shows the progression of the channel cross section shown by hatching when there is an axial misalignment between the opening (221) and the port (211). It can be noted that a deviation of 0.1 mm results in a 0.122 mm 2 The remaining cross-sectional area of ​​the port (211) according to the present invention is shown in sub-figures c and d, and when combined with the same opening or disc-shaped opening with a tangential expansion section as shown, provides 0.321 mm in the same axial space. 2 Subfigure d shows the evolution of the channel cross section in hatched form in the case of incorrect axial positioning of the pump. Note that for a 0.1 mm offset, the cross section decreases to leave 0.268 mm 2 Also note that until the axial offset reaches 0.2 mm, that is, the channel cross section is 0.198 mm 2 , the channel cross section is still greater than or equal to the channel cross section obtained for a disc-shaped cross-section port of the same axial size. This means that even with a 0.2 mm offset, corresponding to the extreme tolerance, the shape of the present invention ensures that the fluid flow cross section is equivalent to The cylindrical shape of the inventive form thus achieves accurate positioning of ±0.2 mm without affecting the pressure loss in the system.

[0122] It should be noted that the invention is not limited to a rectangular shape but can be extended to any shape that increases the cross-sectional area for the fluid flow while ensuring radial closure of the conduits connected to the pump body.

[0123] Detailed description of activation via vial insertion

[0124] Will pass Figure 11 to Figure 2 The medical device according to the variant of the present invention as understood in the present invention is suitable for docking with an external reservoir (203) such as a vial. In order to simplify the use of the device and its reliability, the vial must be connected to an adapter (311) designed to fit into the docking piece (308) of the medical device, having a complementary shape. Fig.11] In the example shown, the adapter (311) has a hollow needle (315) for piercing the septum of the vial (312) and extracting the fluid contained therein, the hollow needle (315) being connected to the central channel of the adapter (311). This operation is performed before the medical device is activated, and the configuration of the septum and the needle makes it possible for the fluid to flow only through the internal channel, thus preventing air from entering the vial (312) and thus preventing the fluid contained in the vial from flowing spontaneously. The medical device is activated by inserting the adapter (311) into the docking piece (308). To this end, the adapter (311) and the docking piece (308) can be screwed into each other so that the complementary central conduits (320, 321) on the two parts cooperate to provide a sealed flow channel for conveying fluid between the vial and the medical device. In the example shown, the central conduits (320, 321) cooperate with the aid of a tapered fitting to form a Luer connection, but the invention extends to any type of connection compatible with medical applications. When the adapter (311) is screwed into the receiving member (308), the torque applied by the adapter (311) on the receiving member (308) drives the latter to rotate so as to activate the electronic system (310) and permit the transfer of the drug to the internal reservoir, as described in international patent application WO2018141697A1. Once the drug has been transferred, the user can disconnect it by unscrewing the adapter (311), which movement then returns the docking member (308) to its initial position and simultaneously deactivates the electronic system (310). During the sequence of activating and deactivating the system by the described components, the user can be informed of the status of the medical device by a tactile or visual signal (such as vibration or power-on of an LED). The triggering of the signal can be directly activated by the user's action on the device.

[0125] Figures 11 to 13 An isolation fluid system (300) according to one embodiment of the present invention is shown. Fig.11 and Fig.13 is a perspective view showing various steps of connecting the external reservoir (203), [ Fig.11 ] shows an exploded view of each unconnected component, [ Fig.12 ] shows the reservoir (203) connected to the adapter (311), [ Fig.13 ] shows the reservoir (203) and adapter (311) assembly connected to a docking piece (308). These various figures also show other components of the fluid system, namely, the fluid portion of the pump system (200), the internal reservoir (215), and the needle holder (121) of the injection system, these various elements being connected by a flexible conduit, one end of which is inserted into a cavity (231, 233) in the pump body (201). The fluid is directed to either element by the movement of the valve piston (202) and the pump piston (205) described in the present application. In particular, [ Fig.11 ] shows the presence of a hollow needle (315) designed to pierce the septum of the external reservoir to form a sealed connection between the external reservoir (203) and the fluid system line (300). According to [ Fig.12 ], obtained by screwing the adapter (311) and the docking piece (308) together via the thread (331) and the internal thread (330) [ Fig.13 ] shown in the components.

[0126] [ Fig.14 ] shows a cross-sectional view of the adapter (311) and the docking piece (308) before assembly to better observe the fluid connection between these parts and how they are connected. In particular, complementary central manifolds (320, 321) belonging to the adapter (311) and the docking piece (308), respectively, ensure that the fluid outlet port (313) of the adapter (311) is connected to the inlet port (387) of the docking piece (308). The hollow needle (315) of the adapter (311) has an internal channel terminating in the outlet port (313) which leads to the central conduit (320). The docking piece (308) is formed by a cylinder (341) having an axial open cavity in which the central conduit (321) extends, the inner cylindrical surface of which has a thread (330) that cooperates with the thread (331) of the adapter (311). At its other axial end, the abutment (308) has a hollow axial projection (386) with a slightly tapered periphery, allowing it to be easily inserted into a flexible pipe to ensure that the fluid is transferred to the pump body. In this way, a conduit passes axially through the abutment, on the one hand leading to an inlet port (387) at one axial end of the central pipe (321), and on the other hand leading to an outlet port (388) located at the end of the axial projection (386).

[0127] The central conduits (320, 321) are advantageously of conical shape, known as "Luer taper", which enables tight coupling according to ISO 80369, while ensuring sufficient contact force. The interlocking of the complementary central conduits (320, 321) and the application of the forces required for sealing are ensured by the cooperation of a thread (331) complementary to the female thread (330), which is formed in the hollow cylindrical protrusion (340) of the adapter (311) and in the cylindrical body (341) of the abutment (308), respectively, around the central conduits (320, 321). Thus, once the adapter (311) and the abutment (308) are assembled, any fluid entering through the hollow needle (315) is directed to the outlet port (388) without further leakage.

[0128] It should be noted that this arrangement of connection does not limit the invention, since a person skilled in the art can easily conceive of alternative solutions for conduits of two complementary parts in a watertight manner by means of screw joining methods.

[0129] [ Fig.15 ] gives Figures 11 to 14 A more detailed view of the docking piece (308) shown in the figure. The upper part of the figure shows a central tube (321) emerging from a hollow cylinder (341) having threads for screwing onto the adapter. Also shown is a cylinder (341) for guiding the rotation of the docking piece (308) by cooperating with an annular protrusion of the lower shell (107) of the housing. Finally, in order to ensure that the rotation stops once the adapter is fully screwed into the docking piece (308) by the user, two cylindrical axial protrusions (381, 382) extend from the cylinder (341), which are radially positioned on either side of the axial protrusion (386) and are designed to extend into the lower shell (107) of the housing so as to cooperate with the elastically deformable portion to ensure that the final angular position of the docking piece is maintained. The final angular position is obtained by a radial protrusion (383) extending radially from the lower axial end of the cylinder (341) abutting against a complementary abutment of the lower shell of the housing. Finally, it can be noted that there is a partial annular protrusion (384) which extends axially the cylinder (341) over a limited angular portion. This partial annular protrusion (384) is called an activation arm and enables the medical device activation switch to be engaged or released depending on the angular position of the docking piece (308). The partial annular protrusion (384) also has a cylindrical inner surface concentric with the cylindrical protrusion of the lower shell of the housing in order to ensure the rotational guidance of the docking piece (308).

[0130] Fig.16 and Fig.18 The docking piece (308) is shown mounted in the lower housing (9) of the housing in its initial state, i.e. before insertion of a vial fitted with its adapter. [ Fig.16 ] shows a view from an axial perspective, and [ Fig.18] shows a cross-sectional view at the level of the axial protrusions (381, 382) from the same angle. When screwed in, the adapter is inserted axially into the abutment (308), wherein the abutment remains stationary until the center pipe is coaxially in contact so as to produce a wedging. Therefore, if an additional torque is applied to the adapter, this torque is transmitted to the abutment (308), the rotation of which is stopped by the axial protrusions (381, 382) that abut against the flanges (912, 913) of the lower shell (107) of the housing. The flanges (912, 913) are protrusions located in the flexible beams (922, 923), which can be elastically deformed by the axial protrusions (381, 382) when a threshold torque is applied, so that the abutment can rotate until the radial protrusions (383) abut together with the local annular protrusions (384) against complementary stops (915, 916) on the lower shell (107) of the housing. The final position is Fig.17 and Fig.19 As shown in the figure, they correspond to Fig.16 and Fig.18 It may be noted that, instead of or in addition to the flexible beams (922, 923), the axial protrusions (381, 382) may be deformable to allow the docking member (308) to rotate when a torque greater than a threshold torque is applied thereto.

[0131] As the docking member (308) rotates, the partial annular protrusion (384) presses against the lever of the medical device activation switch (390) on the electronic system (310). At the end of the movement, when it contacts the corresponding complementary stop members (915, 916), the radial protrusion (383) and the partial annular protrusion (384) absorb any excess torque applied by the user to the docking member (308), preventing the excess torque from being reflected on the axial protrusions (381, 382), thereby avoiding damage thereto.

[0132] It should be noted that the deformation torque required to rotate the dock (308) is greater than the torque required to ensure tightness of the connection according to ISO 80369. This deformation serves as tactile feedback to the user to indicate successful vial installation and activation of the medical device.

[0133] It should also be noted that the final angular position is not irreversible. If the user applies a torque in the opposite direction with the same torque amplitude as that deployed to activate the device, the axial protrusions (381, 382) can again elastically deform the flexible beams (922, 923), thereby allowing the docking member to rotate in the opposite direction to [ Fig.16 ]and[ Fig.18 ] is shown in the initial state. This operation is accompanied by the release of switch (390), thereby indicating to the medical device that the vial is no longer engaged. The user can continue to unscrew the adapter (308) to remove the vial (312).

[0134] The activation system provides a function that ensures user monitoring and safe vial insertion, limiting any risk of misuse.

Claims

1. A device for transdermal drug administration, the device comprising a housing, the lower shell (107) of which defines a skin connection surface having an opening (106) for the passage of a percutaneous injection cannula (122), a reservoir (203, 215) containing the active ingredient to be administered, a pump system (200), comprising a pump body (201), a valve piston (202) and / or a pump piston (205), the pump piston being axially movable in the pump body (200) by means of at least one drive system (240, 250), a transdermal injection system (100) and an electronic control system (310) for operating the drive system (240, 250) of the pump system (200) and for releasing the transdermal injection system (100), It is characterized in that The injection system (100) is controlled by a translation element which interacts with a connecting member (105) inserted between the pump piston (205) or the motor valve piston (202) on one side and the injection system (100) on the other side, the connecting member (105) being movable between a first position and a second, irreversible position, the connecting member occupying the first position until the injection system (100) is activated, the connecting member being switched into the second, irreversible position by triggering the injection system (100), and in the second position the connecting member retracts so that there is no longer any zone with which the piston (202, 205) could interact over the entire stroke of the piston (202, 205).

2. The device for transdermal drug administration according to claim 1, characterized in that The electronic system (310): only controlling the pumping function or the valve function over a limited portion of the nominal axial stroke of the pump piston (205) or the valve piston (202), and controlling the axial displacement of the pump piston (205) or the valve piston (202) over at least an additional portion of the stroke in order to drive an additional function independent of the pumping function or the valve function, the additional function not being activated during the axial displacement of the pump piston (205) or the valve piston (202) over the nominal stroke.

3. The device for transdermal drug administration according to claim 1, characterized in that The additional function is to trigger the transdermal injection system (100).

4. A device for transdermal drug administration according to the preceding claims, characterized in that The transdermal injection system (100) controls: A mechanism for actuating an assembly comprising a needle (120) connected to a needle holder (121), the cannula (122) connected to a cannula holder (124), and a guide element (125) configured to guide axial displacement of the needle and the cannula, the actuation mechanism comprising: a cam element (101) rotatable relative to a needle guide element (125), the needle holder (121) and the cannula holder (124) each comprising a protrusion (111, 112) cooperating with a rib (103) of the guide element (101), a preload spring (102) for imparting a rotational movement relative to the needle guide element (125) to the cam element (101) for sequentially controlling the needle insertion (120) and the needle retraction movement (120) so that the needle (120) and the cannula (122) pass through the protrusions (111, 112) of the needle holder (121) and the cannula holder (124) and the ribs of the cam element (101) when the cam element (101) rotates through a first predetermined angle (103) moves from the retracted position to the extended position, and the needle (120) returns to the retracted position through the cooperation between the protrusion (111) of the needle holder (121) and the rib (103) of the cam element (101) when the cam element (101) further rotates through a second predetermined angle, thereby keeping the protrusion (112) of the cannula holder (124) in the extended position by cooperating with the cam element (101) during the rotation through the second predetermined angle.

5. The device for transdermal drug administration according to claim 1, characterized in that: The injection system (100) is provided with a locking device (110) which abuts against a wall (109) of the cam element (101) in order to prevent the cam element (101) from rotating under the action of the preload spring (102).

6. Device for transdermal drug administration according to the preceding claims, characterized in that The locking device is provided with a connecting member (105) capable of rotating about an axis (154) and a translation element (104) capable of translating in a plane orthogonal to the axis (154), wherein the distal end of the translation element (104) contacts the wall (109) of the cam element (101), the proximal end (140) rests on the surface (150) of the connecting member (105), and the opposite surface (151) of the connecting member (105) rests on the raised surface (174) of the lower housing (107). ) on the translatory element (104), thereby preventing any translational movement of the translatory element, and is characterized in that the end of the rod of one of the pistons (202, 205) can be moved by the additional stroke to a position where the end contacts the connecting member (105) to impart a rotational movement to the connecting member, and the rotational movement causes the release of the locking device (110) by releasing the contact between the proximal end (140) of the translatory element (104) and the surface (150) of the connecting member (105).

7. The device for transdermal drug administration according to claim 1, characterized in that The additional function is to trigger a system for perforating a membrane which separates a recess for a cartridge containing the active ingredient from the inner space of the housing.

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