Improved injection system for transdermal drug delivery device

Abstract

The present invention relates to a casing, a lower housing of said casing defining a skin contact surface with an orifice for the passage of a transdermal injection cannula, a reservoir containing an active ingredient for administration, a pump system comprising a pump body, a valve piston and a pump piston, each of these two pistons being capable of axial movement within the pump body by a drive system, and a transdermal injection system and an electronic control system for operating the drive systems of the pump system and for releasing the transdermal injection system for the transdermal insertion of said cannula. Abstract figure: Figure 1

Description

Title of the invention: Improved injection system for transdermal drug delivery device. Field of invention

[0001] The present invention relates to the field of external transdermal drug delivery systems, incorporating a pump system and a transdermal administration system. Typically, the system is integrated into a housing whose interior maintains the sterility of the fluidic, self-contained portion which adheres to the abdomen or chest or the like of the patient and delivers the substance to the patient via a cannula which is inserted into the patient subcutaneously,

[0002] The medical treatment of several diseases requires a continuous infusion of medication, by subcutaneous and intravenous injections, particularly for medications that contain large molecules that cannot be digested when administered orally, such as insulin, biological or biosimilar drugs

[0003] Patients with chronic diseases such as immuno-oncology or requiring recurrent post-operative treatment need bolus injections of medications which are generally administered by healthcare personnel. The quantity of injections of these medications can vary from a few milliliters to several tens of milliliters. Since the flow rate is capped to be tolerated by the patient, the injection time increases proportionally with the volume injected and has a direct impact on the occupancy rate of the healthcare personnel.Automatic drug injection pumps have been developed to, on the one hand, free up time for nursing staff when administration via the pump must be supervised by trained personnel, and on the other hand, allow the patient to self-administer the medication safely thanks to an automatic system with simplified operation, allowing them to achieve daily autonomy, drastically reducing the necessary frequency of visits to the hospital.

[0004] Basal and / or bolus volumes must be administered in precise doses according to the individual prescription. Therefore, drug injection pumps must have high reliability, ensuring the patient and caregivers the accuracy and correct monitoring of the administered dose.

[0005] These pumps are also used for the injection of biological drugs, or anticancer active ingredients, requiring shorter injection times, from a few tens of minutes to a few hours, at shorter intervals, weekly or monthly.

[0006] To avoid the problems of resterilization of ambulatory devices intended for home treatments, single-use devices are preferred; the simplicity of the device components is therefore essential to ensure a non-prohibitive selling price.

[0007] Typically, the patient fills the reservoir with the active ingredient, for example from a vial, attaches the needle and delivery tube to the outlet of the reservoir, and then inserts the reservoir into the pump housing. After purging the air from the reservoir, tube, and needle, the patient inserts the needle assembly, penetrating member, and cannula into a selected location on the body and removes the penetrating member. To avoid irritation and infection, the subcutaneous cannula should be replaced and discarded, along with the empty reservoir.

[0008] It also happens that the patient or the healthcare staff uses an additional transfer station so that the contents of the vial are automatically transferred into the internal reservoir of the medical device. To do this, the user must generally successively connect the vial (and the vial adapter if it is not already integrated into the transfer station) on one side and the medical device on the other side, to the transfer station and then start the transfer sequence.

[0009] These devices are equipped with an internal energy source that powers the internal organs during the operation of injecting the drug into the patient. Since these devices can be stored for long periods of time, it is crucial to preserve the energy source during this period and to power the system only at the appropriate time. State of the art

[0010] An example of a micropump developed to be easily integrated into a patch pump is given in EP2992916. This pump is suitable for the continuous delivery of a liquid medication such as insulin for diabetes treatments and comprises two pistons, one of which is a pump piston provided with a rack engaged by a pinion driven by a motor, and is mounted to move back and forth within a pump body which remains stationary. The valve piston comprises a channel configured to fluidly connect the piston chamber with the inlet and / or outlet of the pump body when the torque produced by the motor overcomes the frictional engagement of the valve piston. A disadvantage of this system includes the non-optimal ratio between the pumped volume and the size of the pump.Furthermore, the pumped volume is invariable and defined by the fixed stroke of the piston, so that for certain applications, for which the pumped volume is variable, this solution is not satisfactory.

[0011] Particularly known in the state of the art is European patent EP3354303 of the applicant describing a drug delivery device comprising a transdermal delivery system having a needle actuation mechanism configured for transdermal insertion of a cannula and a needle guide member for guiding axial movement of a needle and a cannula. The needle actuation mechanism comprises a cam member rotatable relative to the needle guide member. The guide member guides a needle attached to a needle holder and a cannula attached to a cannula holder. The needle and cannula holders each comprise an engagement portion, wherein the engagement portion of the needle holder is configured to engage with a first and a second cam surface and the engagement portion of the cannula holder is configured to engage with a locking surface. Disadvantages of the prior art

[0012] In the solution described in patent EP3354303, although the device comprises two electromagnetic actuators, it is not possible to control the needle and cannula actuating mechanism independently of the operation of the pump. Indeed, the mechanism is actuated by a pre-stressed spring, and is locked in position before the first use by the pump piston rod. When the pump is first used, the rod releases the locking of the needle and cannula actuating mechanism, which cannot then be returned to the waiting position.

[0013] In order to address the drawbacks of the prior art, the present invention relates in its most general acceptance to a transdermal drug delivery device comprising: • a housing, a lower casing of said housing defining a skin connection surface with an orifice; for the passage of a transdermal injection cannula, • a reservoir containing an active ingredient intended to be administered, • a pump system comprising a pump body, a valve piston and a pump piston, each of these two pistons being able to be set in axial movement in the pump body by a drive system, • a transdermal injection system and an electronic control system for operating the drive systems of the pump system and for releasing the transdermal injection system for the transdermal insertion of said cannula, characterized in that said electronic system controls: • over a limited part of the nominal axial stroke of said pump piston or said valve piston, the pumping function or the valve function only, and, • over at least an additional part of said stroke, the axial displacement of said pump piston or said valve piston so as to control an additional function independent of said pumping function or the valve function, said additional function not being activated during the axial displacement of said pump piston or said valve piston over the nominal stroke.

[0014] In particular, said additional function may be the triggering of the transdermal injection system.

[0015] In this case, said transdermal injection system may comprise: • an actuating mechanism of an assembly comprising a needle connected to a needle holder, said cannula connected to a cannula holder, and a guide element configured to guide the axial movement of the needle and the cannula, the actuating mechanism comprising: • a cam element rotatable relative to the needle guide element, the needle holder and the cannula holder each comprising a protrusion cooperating with a rib of the guide element, • a pre-loaded spring for imparting rotational movement to the cam member relative to the needle guide member, for sequentially controlling the needle insertion and needle retraction movement such that the needle and cannula are moved from a retracted position to an extended position upon rotation of the cam member through a first predetermined angle, by cooperation of the protrusions of the needle holder and the cannula holder with the rib of the cam member, and such that the needle is returned to the retracted position upon further rotation of said cam member through a second predetermined angle by cooperation of the protrusion of the needle holder with the rib of the cam member, whereby during rotation through said second predetermined angle, the protrusion of the cannula holder is maintained in the extended position by cooperation with the cam member.

[0016] In a variant, the injection system is provided with a locking device bearing against a wall of the cam element so as to prevent rotation of said cam element subjected to the action of said pre-armed spring.

[0017] In particular, the locking device is provided with a rotation element which can be rotated about an axis and a translation element which can be in translation in a plane orthogonal to the axis, a distal end of the translation element being in contact with the wall of the cam element, the proximal end bearing on a surface of the rotation element, an opposite surface of the rotation element bearing against a surface of a protuberance of the lower casing hindering any translational movement of the translation element, and in that the end of the rod of one of the pistons is movable on said additional stroke to a position where it comes into contact with the rotation element to impart a rotational movement to it, said 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 rotation element.

[0018] In another variant, said additional function is the triggering of a system for perforating a membrane separating the housing of a cartridge containing an active principle from the interior space of said housing.

[0019] "Independent" means that one of the functions does not necessarily drive the other function in a systematic and coordinated manner. The rod can thus control: • pumping only excluding the additional function, during the “nominal stroke”, • triggering of the additional function in the complementary part of the race only. In this additional part of the stroke, the rod can also control pumping, or not, or only over a limited part of the additional stroke.

[0020] Detailed description of a non-limiting example of embodiment

[0021] For a better understanding of the invention, and to show how embodiments thereof may be implemented, reference will now be made, by way of example, to the accompanying drawings in which: 1. [Fig. 1] shows a top view of the locking device of the insertion mechanism in the initial state, 2. [Fig.2] shows a top view of the locking device of the insertion mechanism in the final state, 3. [Fig.3] shows the needle insertion mechanism alone in perspective view and in partial section, 4. [Fig.4] shows a perspective view of the locking mechanism associated with the pump system in partial section and housed in the lower casing of the housing, 5. [Fig.5] shows a side view of the pump system associated with the locking mechanism, 6. [Fig.6] shows a perspective view of the complete fluidic system integrated in the lower casing of the housing, 7. [Fig.7] shows a side sectional view of the pump, 8. [Fig.8] shows a top view of the pump body from which the valve piston, 9. [Fig.9] shows a sectional front view of the pump, 10. [Fig. 10] shows two pump hole shapes for connecting the pipes and the fluid passage sections obtained for different valve piston positions, 11. [Fig. ll], 12. [Fig. 12] and, 13. [Fig. 13] shows a perspective view of the fluidic system compatible with an external bottle for different stages of bottle insertion, [Fig. 11] showing all the elements before assembly, [Fig. 12] showing the bottle positioned in the adapter piece and [Fig. 13] showing the bottle and adapter piece assembly assembled to the receiving piece and in final position, 14. [Fig. 14] shows a side sectional view of the adapter piece and the receiving piece, 15. [Fig.15] shows the reception room in side view, 16. [Fig. 16] and, 17. [Fig. 17] shows top views of the reception part integrated in the lower casing of the housing respectively in the initial and final position of the activation stroke, 18. [Fig. 18] and, 19. [Fig. 19] shows top sectional views of the reception part integrated into the lower casing of the housing respectively in the initial and final position of the activation stroke. Detailed description of the multi-function operation and release of the insertion mechanism controlled by the piston rod

[0022] Figures 1, 2, 3, 4, and 5 illustrate a first embodiment of the needle insertion mechanism locking device according to the invention, [Fig.l] representing the needle insertion mechanism alone, as described in international patent application WO2018141697A1. Figures 2 and 3 present the needle locking and insertion mechanism in a top view, [Fig.2] representing the device in the initial state, which is called "armed", and [Fig.3] presenting the mechanism after triggering and needle insertion. [Fig.4] represents the needle locking and insertion mechanism in a top view perspective and [Fig.5] shows the needle locking and insertion mechanism, without the cam element, in a side view.

[0023] The injection system (100) comprises in particular a needle insertion mechanism composed of a cam element (101), and illustrated in more detail in [Fig.l] with a partial sectional view. Said cam element (101) has a rib (103) whose advantageous profile cooperates with protrusions (111, 112) of a needle support (121) and a cannula support (124) allowing the insertion of the needle (120) and the flexible cannula (122), then the withdrawal of the needle (120) alone, in a rotational movement of less than 360° of the cam element (101). The cannula holder (124) has a conduit for receiving the tube (130) carrying the fluid to be injected through the cannula (122), this conduit being connected to the cannula (122) by an internal cavity (125). The insertion of the needle (120) and the cannula (122) is guided by a through hole (106) of the housing (107).The rotational movement of the cam element (101) is induced by a spiral spring (102), preloaded in the initial state, the cam element (101) being held in position by a locking system (110) described more particularly in Figures 2, 3, 4 and 5. The needle insertion sequence (120) is triggered by a release of the locking system (110), allowing free rotation of the cam element (101) and therefore insertion of the needle (120) thanks to the discharge of the spring (102). It should be noted that this movement sequence is irreversible and that at its completion, the spring (102) is in the discharged state and opposes the movement of the cam (101) in the direction opposite to that traveled for the insertion of the needle (120) and the cannula (122).Thus, the needle (120), once the sequence is completed, is retracted inside the medical device and cannot be deployed again, leaving the device in a state avoiding any risk of injury to the user. The use of a retractable needle (120) housed within a flexible cannula (122) is not limiting of the invention and is especially useful for guaranteeing the sterility of the fluid conduit as long as the needle is located within the cannula. Those skilled in the art could easily imagine other alternatives for producing the fluid interface between the device and the patient.

[0024] More particularly, the locking device comprises a translation element (104) and a rotary element (105) both guided by the lower casing (107) of the housing in respective translation and rotation movements.

[0025] The translation element (104) has an arm (140), the distal end of which rests on a wall (109) of the cam element (101), more visible in [Fig. 5], and the proximal end (140) rests on a surface (150) of the rotation element (105), and an elastic protrusion (142) ensuring that the locking device (110) is held in its final position after triggering, by cooperation with the groove (172) of the lower casing (107) of the housing. Said rotation element (105) has an opposite surface (151) to said surface (150), this opposite surface (151) being supported on a protuberance of the lower casing (107) of the housing. Thus, in the locked position, the cooperation of the translation element (104) and the rotation element (105) makes it possible to transmit the entire preload force of the spiral spring (102), exerted on the cam (101), directly to the lower casing (107) of the housing, thus preventing any possible movement. This also makes it possible to ensure a longer service life of the system during a storage period, the use of a direct recovery of the forces by the housing makes it possible to avoid a risk of fining of the parts.

[0026] The release of the locking device (110) is possible by moving the rotation element (105). Said rotation element (105) has a body (152) provided with a lever arm (153) ensuring rotational guidance of said body (152) around the axis (154). The rotation of the rotation element (105) induces sliding of the surface (150) and of the opposite surface (151) on the facing surfaces (141, 174) belonging respectively to the translation element (104) and to the lower casing (107) of the housing.

[0027] When the rotation of the rotation element (105) is sufficient so that the surface (150) is no longer in contact with the surface (141) of the translation element (104), the locking mechanism (110) is released and the translation element (104) performs a translational movement induced by the preload force of the spiral spring (102). During the translational movement of the translation element (104), the arcuate profile (143) of the elastic protrusion (142) slides along the grooves (171, 172) of the housing (107), causing a displacement of the end of the elastic protrusion orthogonal to the translational movement of the translation element.When the top (144) of the arcuate profile (143) exceeds the separation (175) between the two grooves (171, 172), the translation element (104) is no longer in contact with the cam (101), but the translation movement continues along the groove (172) thanks to the release of the elastic energy accumulated by the elastic protrusion (142) during its movement along the first groove (171), to finally arrive at the stable equilibrium position presented in [Fig.3]. During the translational movement of the translation element (104), the lower surface (145) of the translation element (104) slides on an upper surface (155) of the rotation element (105) so as to impose a movement of said rotation element (105) until it abuts against a protuberance (173) of the lower casing (107) of the housing.The complementary profile of the surfaces (145, 155) advantageously allows the continuity of the translation of the translation element (104) following this stop, while making it possible to block the rotational movement opposite the stop in the final position as presented in [Fig.3].

[0028] Thus, the elastic protrusion makes it possible, after release of the locking device, to ensure a final safety position for which the immobilization of the translation element (104) and of the rotation element (105) is ensured even in the event of sudden movement or impact on the medical device.

[0029] Before the locking device is released, the translation element (104) and the rotation element (105) are held in position by the friction of the surface (150) and the opposite surface (151) respectively on the surfaces (141, 174). The rotation of the rotation element (105) and therefore the release of the locking device is achieved by the end of the pump piston (205) pressing on a circular surface (156) of the lever arm (153). In the embodiment shown, this support is obtained on an extreme part of the movement stroke of the pump piston (205), this advantageously making it possible to perform the pumping function before the locking device is released, making it possible, for example, to transfer the fluid to be injected from an external reservoir to an internal reservoir before the device is placed on the patient.During this operation the stroke of the pump piston can easily be limited by software.

[0030] Of course, once the locking device (110) is triggered by a first movement of the pump piston (205) on the extreme part of its stroke, the pump piston (205) can benefit from the entire stroke for the pumping function and thus increase, for each pump cycle, the volume transferred from the internal reservoir to the patient.

[0031] Note that the pump piston (205) only ensures the rotational movement of the rotation element (105) until the locking mechanism (110) is released, as described above. In order to ensure the free movement of the piston over this extreme stroke, it is necessary, after release of the locking device (110), to maintain the rotation element (105) in the safety position as permitted here by its cooperation with the translation element (104).

[0032] Detailed description of the pump body with oblong holes

[0033] An embodiment of the pump system (200) is to be appreciated with regard to figures 6 to 10. [Fig. 6] represents the pump system (200) integrated in the lower casing (107), connected to the reservoir (203) of fluid to be extracted and to the internal reservoir (215). [Fig. 7] presents the pump system (200) in a side sectional view showing the fluid circuit. [Fig. 8] represents the pump body (201) seen from the side from which the valve piston (202) emerges. [Fig. 9] presents the pump system (200) in radial section, the pump body (201) being cut along two axially offset planes to show the ports (212 and 213) simultaneously. Figures 10a to 10d highlight the geometry of the three ports (21, 212, 213) of the body pump (201) and their advantage over those used in international patent application WO2018141697A1.

[0034] More particularly, and as shown in Figures 6 and 7, the pump is composed of a pump body (201) and two pistons, a pump piston (205) and a valve piston (202), defining between them an internal cavity (208) of variable volume. These two pistons are respectively secured to a rack (248, 258) which can be set in axial movement by a drive system (240, 250) composed of a mechanical movement reducer (241, 251), the input of which is coupled to an electric motor (242, 252). The transfer of fluid within the internal cavity (208) is possible by the cooperation of multiple ports (211, 212, 213) with an internal channel (209) of the valve piston (202) opening at one end into the internal cavity (208) and terminated by an orifice (221) at its other end. The precise axial positioning of the valve piston (202) makes it possible to selectively bring into cooperation one of the ports (211, 212, 213) with the orifice (221) of the pump.

[0035] In the example of [Fig.6], the port (211) is connected to the reservoir (203) of fluid to be extracted, for example a bottle, the port (212) is an outlet port and is connected to the injection system, the port (213) is connected to the internal reservoir (215) of the medical device. The port (211) and the port (213) can serve alternately as an inlet port or an outlet port. By outlet port of the pump, we mean a port from which the fluid circulates exclusively so as to leave the internal cavity (208) of the pump. In the initial state, the valve piston (202) and the pump piston (205) are in frontal contact or have a small distance apart, so that the internal cavity (208) has a small volume of air.

[0036] Two injection sequences are preferred without being limiting of the invention. Either with use of the internal reservoir or by direct injection.

[0037] The first injection sequence consists of transferring the liquid from the bottle to the internal reservoir, then transferring the liquid from the internal reservoir to the injection system. The first pumping sequence is then broken down into the following steps: • synchronously moving the valve piston (202) and the pump piston (205), by their respective drive system (240, 250) to match the orifice (221) of the pump with the port (211) connected to the reservoir (215), • move the pump piston (205) alone, using the drive system (250), so as to increase the volume of the internal cavity (208) located between the valve piston (202) and the pump piston (205), this creating a depression leading to the liquid being sucked from the reservoir (203) towards the internal cavity (208) through the internal channel (209), • once the internal cavity is completely filled, move the pistons (202, 205) in a synchronized manner, using their respective drive system (240, 250) so as to match the orifice (221) of the pump with the port (213) connected to the internal reservoir (215), • translate the pump piston (205), alone, by its drive system (250), so as to reduce the volume of the internal cavity (208) in order to expel all of the fluid contained in the internal cavity (208) through the internal channel (209) and towards the internal reservoir (215), • once the expulsion of the liquid is complete, repeat the previous steps successively until all of the liquid contained in the reservoir (203), or a predetermined quantity, is transferred into the internal reservoir (215).

[0038] Once the fluid has been fully transferred into the internal reservoir (215), injection into the patient can begin. The first step therefore consists of triggering the needle insertion system, as for example described in international patent application WO2018141697A1. Once the cannula has been inserted into the subcutaneous tissues, a new pumping sequence takes place according to the following steps: • synchronously moving the valve piston (202) and the pump piston (205), by their respective drive system (240, 250) to match the orifice (221) of the pump with the port (213) connected to the internal reservoir (215), • move the pump piston (205) alone, using the drive system (250), so as to increase the volume of the internal cavity (208) located between the valve piston (202) and the pump piston (205), this creating a depression leading to the liquid being sucked from the internal reservoir (215) towards the internal cavity (208) through the internal channel (209), • once the internal cavity is completely filled, move the pistons (202, 205) in a synchronized manner, using their respective drive system (240, 250) so as to match the orifice (221) of the pump with the port (212) connected to the injection system, • translate the pump piston (205), alone, by its drive system (250), so as to reduce the volume of the internal cavity (208) in order to expel all of the fluid contained in the internal cavity (208) through the internal channel (209) and towards the injection system. • once the liquid has been expelled, repeat the previous steps successively until all of the liquid contained in the internal reservoir (215), or a predetermined quantity, is transferred into the patient.

[0039] The second injection sequence does away with the transfer of fluid into the internal reservoir. The first step therefore consists of triggering the needle insertion system, as for example described in international patent application WO2018141697A1. Once the cannula is inserted into the subcutaneous tissues, a pumping sequence takes place according to the following steps: • synchronously moving the valve piston (202) and the pump piston (205), by their respective drive system (240, 250) to match the orifice (221) of the pump with the port (211) connected to the reservoir (203), • move the pump piston (205) alone, using the drive system (250), so as to increase the volume of the internal cavity (208) located between the valve piston (202) and the pump piston (205), this creating a depression leading to the liquid being sucked from the reservoir (203) towards the internal cavity (208) through the internal channel (209), • once the internal cavity is completely filled, move the pistons (202, 205) in a synchronized manner, using their respective drive system (240, 250) so as to match the orifice (221) of the pump with the port (212) connected to the injection system, • translate the pump piston (205), alone, by its drive system (250), so as to reduce the volume of the internal cavity (208) in order to expel all of the fluid contained in the internal cavity (208) through the internal channel (209) and towards the injection system. • once the expulsion of the liquid is complete, repeat the preceding steps successively until the entirety of the liquid contained in the reservoir (203), or a predetermined quantity, is transferred into the patient.

[0040] These two injection sequences are not limiting of the invention and other alternatives can be envisaged. The pump system (200) can in particular be used for drug reconstitution functions, for example to reconstitute a lyophilized drug and a diluent. The internal reservoir (215) could then be a cartridge pre-filled with a diluent, and a pump sequence could be carried out to transfer this diluent to a reservoir (203) containing a lyophilized drug in order to dissolve it. Once the lyophilized drug is dissolved, the reverse transfer, i.e. from the reservoir (203) to the internal reservoir (215), is carried out in order to inject it into the patient subsequently.It is also conceivable to carry out several successive transfers, partial or total, between the reservoir (203) and the internal reservoir, this being able to facilitate the dissolution of the lyophilized drug in the diluent.

[0041] An alternative would consist of completely dispensing with the external reservoir (203), the internal reservoir (215) being a cartridge pre-filled with the fluid to be injected. In . In this case, the fluid is transferred from the internal reservoir (215) to the internal cavity and then to the injection system. This sequence of steps is repeated as many times as necessary.

[0042] As more particularly visible in [Fig.8], the ports (211, 212, 213) are arranged in a staggered manner, the ports (211 and 213) being in the same longitudinal plane, the port (212) being radially offset and being located axially between the two ports (211 and 213). This staggered configuration is particularly advantageous for limiting the stroke required by the valve piston (202) to select one of the ports (211, 212, 213), this procedure having to be repeated several times during an injection cycle, the axial approximation of the ports (211, 212, 213) has a direct influence on the durability of the battery (260) and therefore affects the overall efficiency of the device. The counterpart is that the axial dimension of the ports is limited and therefore the axial positioning of the valve piston (202) must be more precise, poor positioning resulting in a reduction in the fluid passage section.Depending on the viscosity of the fluid, this can lead to significant pressure losses and therefore a reduction in fluid flow.

[0043] It is retained from this principle that the positioning of the orifice of the pump valve piston opposite one of the ports is a critical point of the current state of the art, as achieved in international patent application WO2018141697A1. Ensuring a minimum fluid passage section in the event of axial “poor positioning” of the piston has the advantage of making the system more stable, robust and of limiting pressure losses, thus guaranteeing the accuracy of the flow rate, the quantity of medication injected into the patient, as well as the injection time. The invention proposes to overcome this problem by suggesting two improvements that can be used independently or in combination.

[0044] Figures 8 and 9 highlight one of these improvements. The staggered arrangement of the ports (211, 212, 213) results in a tangential misalignment of these holes relative to the orifice (221) of the valve piston (202). Thus, in order not to reduce the flow rate of the pump, the orifice (211) of the valve piston (202) has on either side a tangential flare (223, 224) of its radial end opposite the ports (211, 212, 213). These flares are delimited by tangential beads (225, 226) and axial beads (227, 228) made of a flexible and deformable material, such as silicone or a flexible thermoplastic, in order to fit the cylindrical interior surface of the pump body (201) and ensure sealing.For this purpose, the valve piston has a hard core (230), in which the internal conduit (209) connected to the orifice (221) is made, this hard core (230) being overmolded by an elastomer (229) to form the tangential flares (223, 224). [Fig.9] shows the valve body in radial section, this section not being made in the same axial plane for the . left and right halves, but according to two half-planes located respectively at the level of the middle of the port (212) and the port (213). This section makes it possible to visualize the good correspondence between the tangential flares (223, 224) and the ports (212, 213) offset tangentially with respect to the orifice (221) of the valve piston (202).

[0045] The second improvement to improve the tolerance to the positioning of the valve piston is shown in Figures 7, 8 and 10. In particular, the ports (211, 212, 213) of the pump body (205) are extended by conical clearances (231, 232, 233) allowing coupling with the cylindrical flexible tubes (261, 262, 263), visible in [Fig. 4], connecting elements of the fluidic system while ensuring a radial stop of these tubes thanks to a shoulder (220, 222). Consequently, the diameter of the ports (211, 212, 213) must be less than the outside diameter of the flexible tubes and ideally greater than the inside diameter of the flexible tube so as not to limit the flow rate. Although the shoulder helps secure the mechanical assembly, it is not necessary for it to be present around the entire circular periphery of the flexible tubing.Thus the ports (211, 212, 213) can advantageously have an oblong periphery to increase the cross-section opposite the orifice of the valve piston (202) while providing a mechanical stop for the flexible tubing.

[0046] By oblong periphery is meant that the section of the ports (211, 212, 213), as shown in [Fig. 8], is not disc-shaped but has a different length in the axial and tangential directions. In the example of figures 8, and sub-figures c and d of [Fig. 10], the section is a groove in the tangential direction, terminated by two half-cylinders. Nevertheless, the invention is not limited to this type of shape, but includes any type of elongated section, such as a rectangle or an ellipse. Also, the long length is not limited to the tangential direction, but can also be made in the radial direction and will be chosen according to the arrangement of the ports (211, 212, 213).

[0047] Figure 10 illustrates different positioning scenarios of the valve piston (202), sub-figures a and b representing the case of an orifice (221) and a port (211) both with a disc section, as produced in patent application WO2018141697A1. Sub-figure a represents a cylindrical port (211) having a section of 0.196 mm2 for a diameter of 0.5 mm and being perfectly aligned with an identical orifice (221), the fluid passage section is represented by hatching. Sub-figure figure b represents the evolution of the hatched passage section when there is an axial misalignment between the orifice (221) and the port (211), it can be noted that an offset of 0.1 mm results in a remaining passage section of 0.122 mm2, i.e. a reduction of more than 35%. The oblong shape of the port (211) according to the invention is presented in sub-figures c and d, it makes it possible to offer a passage section of the fluid of 0.321 mm2 in the same axial size when combined with an identical orifice or a disc orifice having a tangential flare as shown. Sub-figure d represents the evolution of the hatched passage section during incorrect axial positioning of the pump. It will be noted that for an offset of 0.1 mm, the section then decreases to leave a passage of 0.268 mm2. It will also be noted that up to an axial offset of 0.2 mm, i.e. a passage section of 0.198 mm2, the passage section remains greater than or equal to that obtained for a disc section port of the same axial size. This means that even with an offset of 0.2 mm, corresponding to a limit tolerance, the shape of the present invention makes it possible to ensure a fluid passage section equivalent to the cylindrical shape of a tube at 0.5 mm as produced in the prior art.The shape of the present invention therefore makes it possible to have precise positioning to ± 0.2 mm without having an impact on the pressure losses in said system.

[0048] It should be noted that the invention is not limited to an oblong shape, but can be extended to any shape making it possible to increase the fluid passage section while ensuring the radial stop of the tubes connected to the pump body.

[0049] Detailed description of activation by insertion of the vial

[0050] The medical device according to a variant of the invention, to be appreciated through Figures 11 to 20, is capable of interfacing with an external reservoir (203), such as a bottle. To simplify the use of the device and its reliability, the bottle must be coupled to an adapter part (311) intended to be inserted into a receiving part (308) of the medical device, having complementary shapes. In the example of [Fig. 5], the adapter part (311) has a hollow needle (315) intended to pierce the septum of the bottle (312) and collect the fluid contained therein, the hollow needle (315) being connected to a central channel of the adapter part (311).This operation is carried out before activation of the medical device and the configuration of the septum and the needle are such that only the flow of fluid through the internal channel is possible, this making it possible to prevent air from entering the bottle (312) and therefore preventing the spontaneous flow of the fluid contained in the bottle. The activation of the medical device is obtained by inserting said adapter part (311) into the receiving part (308). For this purpose, the adapter part (311) and the receiving part (308) can be screwed into each other so as to make central tubes (320, 321) complementary to each of the parts cooperate so as to provide a sealed flow channel for conveying the fluid between the bottle and the medical device.In the example presented, the central tubes (320, 321) cooperate by conical fitting and produce a luer type connection, but the invention extends to any type of connection compatible with medical applications. When screwing the adapter part (311) into the receiving part (308), . the torque exerted by the adapter part (311) on the receiving part (308) causes the latter to rotate in order to activate the electronic system (310) and to authorize the transfer of the medication to the internal reservoir as described in international patent application WO2018141697A1. Once the medication has been transferred, the user can disconnect the adapter part (311) by unscrewing it, this movement then causing the receiving part (308) to return to its initial position and simultaneously deactivating the electronic system (310). During the activation and deactivation sequence of the system by the means described, the user can be informed about the state of the medical device by haptic or visual signals, such as vibrations or the powering of LEDs. The triggering of said signals can be directly activated by the user's actions on the device.

[0051] Figures 11 to 13 represent the isolated fluidic system (300) of an exemplary embodiment according to the invention. Figures 11 and 13 are perspective views showing the different steps of connecting an external reservoir (203), [Fig. 11] showing an exploded view of the different unconnected elements, [Fig. 12] showing the connection of the reservoir (203) to the adapter piece (311) and [Fig. 13] showing the connection of the reservoir (203) and adapter piece (311) assembly to the receiving piece (308). These different figures also show the other components of the fluidic system, namely the fluidic part of the pump system (200), the internal reservoir (215) and the needle support (121) of the injection system, these different elements being connected by flexible tubes, one end of which is inserted into clearances (231, 233) of the pump body (201).The fluid is directed towards one or other of the elements thanks to the movements of the valve piston (202) and the pump piston (205) described in this application. [Fig.l 1] shows in particular the presence of a hollow needle (315), intended to pierce the septum of the external reservoir to create a sealed connection between said external reservoir (203) and the piping of the fluidic system (300). The assembly shown in [Fig.13] is obtained, from [Fig.12], following the screwing of the adapter part (311) and the receiving part (308) by cooperation of a thread (331) and a tapping (330).

[0052] [Fig. 14] shows a sectional view of the adapter part (311) and the receiving part (308) before assembly, in order to better visualize the fluid connection between these parts and their connection. In particular, the complementary central tubes (320, 321) belonging respectively to the adapter part (311) and to the receiving part (308) make it possible to ensure the connection of the fluid outlet port (313) of the adapter part (311) to the inlet port (387) of the receiving part (308). The hollow needle (315) of the adapter part (311) has an internal channel terminated by the outlet port (313) opening into the central tube (320). The receiving part (308) is formed of a cylindrical body (341) having a cavity opening axially in which the central tubing (321) extends, the internal cylindrical surface of the cavity having the thread (330) cooperating with the thread (331) of the adapter part (311). At its other axial end, the receiving part (308) has a hollow axial protuberance (386) with a slightly conical periphery so as to be able to easily fit into a flexible tubing, to ensure the transfer of the fluid to the pump body. The receiving part is thus axially crossed by a conduit opening on the one hand, onto the inlet port (387) at an axial end of the central tubing (321), and on the other hand, onto an outlet port (388) located at the end of the axial protuberance (386).

[0053] The central tubes (320, 321) have an advantageously conical shape, known as a "luer taper", allowing a sealed coupling, in compliance with the ISO 80369 standard, when a sufficient contact force is ensured. The fitting of the complementary central tubes (320, 321) and the application of force necessary for sealing are ensured thanks to the cooperation of a thread (331) complementary to a tapping (330), respectively made in the hollow cylindrical protuberance (340) of the adapter part (311) and in the cylindrical body (341) of the receiving part (308), surrounding the central tubes (320, 321). Thus, once the adapter piece (311) and the receiving piece (308) are assembled, any fluid entering through the hollow needle (315) is conducted to the outlet port (388) without further leakage.

[0054] It should be noted that the arrangement of this connection is not limiting of the invention, the person skilled in the art being able to easily imagine alternatives for pipes of two complementary parts in a sealed manner by a screwing method.

[0055] [Fig. 15] allows the reception part (308) shown in Figures 11 to 14 to be appreciated in more detail. In the upper part of this figure, the central tube (321) emerging from the hollow cylindrical body (341) having the thread allowing screwing with the adapter part is notably visible. The cylindrical body (341) intended to guide the rotation of the reception part (308) by cooperation with an annular protrusion of the lower casing (107) of the housing is also shown.Finally, in order to ensure that rotation stops once the adapter part has been completely screwed into the receiving part (308) by the user, two cylindrical axial protrusions (381, 382) extend from the cylindrical body (341), these axial protrusions (381, 382) are located radially on either side of the axial protrusion (386) and are intended to extend into the lower casing (107) of the housing, so as to cooperate with an elastically deformable part, to ensure that the final angular position of the receiving part is maintained. Said final angular position is obtained by the stop of a radial protrusion (383), extending radially from the lower axial end of the cylindrical body (341), against . a complementary stop of the lower casing of the housing. Finally, it may be noted the presence of a partial annular protuberance (384) axially extending the cylindrical body (341) over a limited angular portion. This partial annular protuberance (384) is called the activation arm and makes it possible to engage or release the activation switch of the medical device depending on the angular position of the receiving part (308). The partial annular protuberance (384) also has a concentric cylindrical inner surface of a cylindrical protrusion of the lower casing of the housing, in order to ensure a return to guiding in rotation of the receiving part (308).

[0056] Figures 16 and 18 show the receiving part (308) installed in the lower casing (9) of the housing in its initial state, that is to say before the insertion of the bottle fitted with its adapter part. [Fig. 16] showing an axial incidence view and [Fig. 18] showing a sectional view, at the level of the axial protuberances (381, 382), according to the same incidence. During screwing, the adapter part is inserted axially into the receiving part (308), the receiving part remaining fixed, until the central tubes are in coaxial contact so as to generate a jamming. Therefore, if an additional torque is applied to the adapter part, this torque is transmitted to the receiving part (308) whose rotation is stopped by the axial protuberances (381, 382) pressing against the flanges (912, 913) of the lower casing (107) of the housing.Said beads (912, 913) are protrusions located in flexible beams (922, 923) which can be elastically deformed by the axial protuberances (381, 382), as soon as a threshold torque is applied, allowing the receiving part to rotate until the radial protuberance (383) comes into abutment, together with the partial annular protuberance (384) against complementary stops (915, 916) of the lower casing (107) of the housing. This final position is represented by figures 17 and 19 corresponding respectively to figures 16 and 18. It can be noted that the axial protuberances (381, 382) can deform as an alternative or in addition to the flexible beams (922, 923) to allow rotation of the receiving part (308) when a torque greater than the threshold torque is applied to the latter.

[0057] When the receiving part (308) rotates, the partial annular protrusion (384) will press against the lever of the switch (390) for activating the medical device arranged on the electronic system (310). At the end of the movement, the radial protrusion (383) and the partial annular protrusion (384) when they are in respective contact with the complementary stops (915, 916), make it possible to absorb excess torque supplied by the user to the receiving part (308) making it possible to prevent this excess torque from being passed on to the axial protrusions (381, 382) thus avoiding damaging them.

[0058] Note that the deformation torque required to rotate the receiving part (308) is greater than the torque required to ensure the tightness of the connection according to the ISO 80369 standard. This deformation serves as haptic feedback to the user to indicate the successful completion of the installation of the bottle and the activation of the medical device.

[0059] It should also be noted that the final angular position is not irreversible. If the user applies a torque of identical amplitude to that deployed for activation of the device, but in the opposite direction, the flexible beams (922, 923) can again be elastically deformed by the axial protrusions (381, 382), allowing the receiving part to perform a reverse rotation to return to the initial state shown in [Fig. 16] and 18. This operation is accompanied by the disarming of the switch (390) signaling to the medical device that the bottle is no longer engaged. The user has the option of continuing to unscrew the adapter part (308) to remove the bottle (312).

[0060] This activation system thus offers a function guaranteeing the user monitored and secure insertion of the bottle to limit any risk of misuse.

Claims

1. Claims Transdermal drug delivery device comprising • a housing, a lower casing (107) of said housing defining a skin connection surface with an orifice (106) for the passage of a transdermal injection cannula (122), • a reservoir (203, 215) containing an active ingredient intended to be administered, • a pump system (200) comprising a pump body (201), a valve piston (202) and a pump piston (205), each of these two pistons being able to be set in axial movement in the pump body (200) by a 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) for transdermal insertion of said cannula (122), characterized in that said electronic system controls • over a limited part of the nominal axial stroke of said pump piston or said valve piston, the pumping function or the valve function only, and, • over at least an additional part of said stroke, the axial displacement of said pump piston or said valve piston so as to control an additional function independent of said pumping function or of the valve function, said additional function not being activated during the axial displacement of said pump piston or said valve piston over the nominal stroke and in that - said injection system (100) is provided with a locking device (110) bearing against a wall (109) of the cam element (101) so as to prevent rotation of a cam element (101) subjected to the action of a pre-armed spring (102) - said locking device being provided with a rotation element (103) rotatable about an axis (154) and a translation element (104) translational in a plane orthogonal to the axis (154), a distal end of the translation element (104) being in contact with the wall (109) of the cam element (101), the proximal end (140) bearing on a surface (150) of the rotation element (103), an opposite surface (151) of the rotation element (103) bearing against a surface (174) of a protuberance of the lower casing (107) hindering any translational movement of the translation element, and in that the end of the rod of one of the pistons (202, 205) is movable over said additional stroke to a position where it comes into contact with the rotation element (103) to give it a rotational movement,said rotational movement causing the release of the locking device (110) by releasing the contact between the proximal end (140) of the translation element (104) and the surface (150) of the rotation element (103).,

2. Transdermal drug delivery device according to claim 1 characterized in that said additional function is the triggering of the transdermal injection system (100).

3. Transdermal drug delivery device according to the preceding claim, characterized in that said transdermal injection system (100) comprises: • an actuating mechanism of an assembly comprising a needle (120) connected to a needle holder (121), said cannula (122) connected to a cannula holder (124), and a guide element (125) configured to guide the axial movement of the needle and the cannula, the actuating mechanism comprising: • a cam element (101) rotatable relative to the needle guide element (125), the needle holder

4. (121) and the cannula holder (124) each comprising a protuberance (111, 112) cooperating with a rib (103) of the guide element (101), • a spring (102) pre-loaded to impart a rotational movement to the cam member (101) relative to the needle guide member (125), to sequentially control the movement of insertion of the needle (120) and retraction of the needle (120) so that the needle (120) and the cannula (122) are moved from a retracted position to an extended position upon rotation of the cam member (101) by a first predetermined angle, by cooperation of the protrusions (111, 112) of the needle holder (121) and of the cannula holder (124) with the rib (103) of the cam member (101), and such that the needle (120) is returned to the retracted position upon further rotation of said cam member (101) by a second predetermined angle by cooperation of the protrusion (111) of the needle holder (121) with the rib (103) of the cam element (101), whereby during rotation through said second predetermined angle,the protrusion (112) of the cannula holder (124) is held in the extended position by cooperation with the cam element (101)., Transdermal drug delivery device according to claim 1 characterized in that said electronic system (310) controls: - over a limited part of the nominal axial stroke of said pump piston (205) or said valve piston (202), the pumping function or the valve function only, and, over at least an additional part of said stroke, the axial displacement of said pump piston (205) or said valve piston (202) so as to control an additional function independent of said pumping function or the valve function, said additional function not being activated during the axial displacement of said pump piston (205) or said valve piston (202) over the nominal stroke. 23

5. Transdermal drug delivery device according to claim 1 characterized in that said additional function is the triggering of a system for perforating a membrane separating the housing of a cartridge containing an active ingredient from the interior space of said housing.

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