Improved injection system for drug administration device

Abstract

The present invention relates to a device for transdermal drug administration comprising a housing, a lower casing (107) of said housing defining a cutaneous connection surface having an opening (106) for the passage of a transdermal injection canula (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 / or a pump piston (205) which can be axially moved 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(s) (240, 250) of the pump system (200) and for releasing the transdermal injection system (100). The invention is characterised in that said injection system (100) is controlled by a translational element interacting with a connection means (105) inserted between the pump piston (205) or the motorised valve piston (202) on one side and the injection system (100) on the other side, the connection means (105) being movable between a first position which it occupies until the injection system (100) is activated and a second, irreversible position into which it is switched by the triggering of the injection system (100), and in which second position it is retracted so as to no longer have any possible zones of interaction with the piston (202, 205) over the whole stroke of said piston (202, 205).

Description

Improved injection system for drug delivery device. Field of invention

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

[0002] Medical treatment of many diseases requires continuous infusion of medication, through subcutaneous and intravenous injections, particularly for drugs that contain large molecules that cannot be digested when administered orally, such as insulin, biological drugs or biosimilars.

[0003] Patients with chronic illnesses such as immuno-oncology or those requiring recurrent post-operative treatment require bolus injections of medications, which are generally administered by healthcare personnel. The quantity of these medications injected 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 healthcare 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 hospital visits.

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

[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 resterilizing 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 reservoir outlet, 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 element, and cannula into a selected location on the body and removes the penetrating element. 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 caregiver 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 have an internal power source that powers the internal organs while the drug is being injected into the patient. Since these devices can be stored for long periods of time, it is crucial to preserve the power source during this period and only power the system when needed. State of the art

[0010] Known in the prior art is patent application US2019365993 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.

[0011] Also known is patent application US20200108201A1 describing a therapeutic substance delivery device comprising a fluid path having a reservoir needle, a body needle, a body needle injection mechanism, and a pumping assembly (a) configured to pump the substance from the reservoir to the subject, (b) shaped to define a pump chamber, and (c) including a plunger disposed within the pump chamber. The plunger moves back and forth through a plurality of discrete phases of movement. A first phase of movement of the plunger actuates a first operation of a group of operations comprising (a) driving the reservoir needle to enter the reservoir, (b) advancing the body needle into the subject's body, (c) withdrawing the substance from the reservoir, (d) pumping the substance into the subject, and (e) retracting the body needle.A second phase of diver movement actuates a second operation of the operation group.

[0012] Patent application US20210330893A1 describes a manual auto-injector for administering a drug. This auto-injector comprises a body, a syringe holder configured to receive a syringe; a first drive module configured to move the syringe holder relative to the body; and a rigid needle shield removal device comprising a first portion configured to separate a rigid needle shield from the syringe. Disadvantages of the prior art

[0013] In the solution described in patent EP3354303, although the device comprises two electromagnetic actuators, it is not possible to control the needle and cannula actuation 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 used for the first time, the rod releases the locking of the needle and cannula actuation mechanism, which cannot then be returned to the waiting position.

[0014] The solution proposed by patent application US20210330893A1 is not entirely satisfactory. It provides for the actuation by the same motorized element of the pump and the triggering system of an injection needle, by a succession of movements with increasing amplitudes but always limited by the activation position of the first then second triggering of the ejection mechanism. As a result, this solution does not allow the entire motorized stroke to be used, this stroke being limited by the position of the first triggering of the erection of the needle, then of the second triggering of the withdrawal of the needle.The usable stroke for pumping, during the injection phase of the medication via the needle inserted into the patient's body, is therefore reduced and restricted by the needle movement mechanism, and thus requires a greater number of cycles, which increases the electrical consumption of the motor; unless the volume of the pump body is increased, which is however unfavorable because it requires increasing the size of the device.

[0015] Furthermore, to make the most of the available travel, it is necessary to control the movement with great precision, because any error would cause the needle ejection and withdrawal mechanism to be triggered unexpectedly. Solution provided by the invention

[0016] In order to overcome the drawbacks of the prior art, the present invention relates in its most general acceptance to a transdermal drug delivery device having the characteristics of claim 1.

[0017] The system 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 / or a pump piston capable of being set in axial movement in the pump body by at least one drive system,a transdermal injection system and an electronic control system for operating the drive system(s) of the pump system and for releasing the transdermal injection system,characterized in thatsaid injection system is controlled by a translation element interacting with a connecting means interposed between the pump piston or the motorized valve piston on the one hand, and the injection system on the other hand,said connecting means being movable between a first position which it occupies until the activation of said injection system, and a second, irreversible position, into which it is tilted by the triggering of said injection system, and in which second position it is retracted so as to no longer present any possible zone of interaction with the piston, over the entire stroke of said piston.

[0018] Furthermore, said electronic system can control: 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 movement 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 movement of said pump piston or said valve piston over the nominal stroke.

[0019] In particular, said additional function may be the triggering of the transdermal injection system.

[0020] In this case, said transdermal injection system may comprise: 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 the axial movement of the needle and the cannula,

[0021] the actuating mechanism comprising:a cam member rotatable relative to the needle guide member, the needle holder and the cannula holder each comprising a protrusion cooperating with a rib of the guide member,a pre-loaded spring for imparting rotational movement to the cam member relative to the needle guide member, for sequentially controlling 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.,

[0022] In one 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-loaded spring.

[0023] In particular, the locking device is provided with a connecting means which can be rotated about an axis and a translation element which can be translated 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 connecting means, an opposite surface of the connecting means 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 over said additional stroke to a position where it comes into contact with the connecting means to impart a rotational movement thereto, 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 connecting means.

[0024] 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 ingredient from the interior space of said housing.

[0025] "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, to the exclusion of the additional function, during the "nominal stroke", triggering of the additional function in the complementary part of the stroke only. In this complementary part of the stroke, the rod can also control pumping, or not, or only over a limited part of the complementary stroke.

[0026] Detailed description of a non-limiting example of embodiment

[0027] 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:Theshows a top view of the locking device of the insertion mechanism in the initial state,theshows a top view of the locking device of the insertion mechanism in the final state,theshows the needle insertion mechanism alone in perspective and partial sectional view,theshows a perspective view of the locking mechanism associated with the pump system in partial sectional view and housed in the lower casing of the housing,theshows a side view of the pump system associated with the locking mechanism,theshows a perspective view of the complete fluidic system integrated in the lower casing of the housing,theshows a side sectional view of the pump,theshows a top view of the pump body from which the valve piston protrudes,lapresents a front sectional view of the pump,lapresents two pump hole shapes for connecting the tubing and the fluid passage sections obtained for different valve piston positions,la,laand,lapresents a perspective view of the fluid system compatible with an external bottle for different stages of bottle insertion, lashowing all the elements before assembly, lashowing the bottle positioned in the adapter piece and lashowing the bottle and adapter piece assembly assembled to the docking piece and in the final position,lapresents a side sectional view of the adapter piece and the docking piece,lapresents the docking piece in a side view,laand,lapresents top views of the docking piece integrated in the lower casing of the housing respectively in the initial and final position of the activation stroke,laand,show top sectional views of the reception part integrated in the lower casing of the housing respectively in the initial and final position of the activation stroke. General principle of triggering the injection system,

[0028] First, a preferred embodiment of the invention relates to a solution using a cannula and a needle. The injection mechanism then operates with several steps:

[0029] Insertion of the needle surrounded by the cannula, Withdrawal of the needle alone, the cannula remaining implanted in the patient's body, as soon as the cannula-needle assembly has reached its position in the patient's body Transfer of the medication through the cannula, the needle remaining locked in the withdrawn position and the cannula locked in the insertion position, for the duration of the treatment, After the end of the treatment, removal of the cannula by removing the device.

[0030] However, the present invention is not limited to this preferred embodiment, and may also provide a more rudimentary mechanism as proposed by patent application US20210330893A1, consisting of simply moving a hollow needle which remains implanted in the patient's body.

[0031] The invention is based on the interposition of a connecting means (105), interposed between the motorized pump piston (205) or valve piston (202) on the one hand, and the injection system (100) on the other hand.

[0032] This connecting means (105) is movable between a first position which it occupies until the erection of the needle or the needle-cannula assembly is commanded, and a second, irreversible position, into which it is tilted by the triggering of the injection system (100), and in which it is held definitively and irreversibly.

[0033] In the second position, this connecting means (105) is removed so as to no longer present any possible interaction zone with the piston (202, 205), over the entire stroke of the piston. Said entire stroke comprises a nominal stroke and a trigger stroke. Unlike the solution proposed by US20210330893A1 where an interaction zone imperatively remains, to allow triggering of the withdrawal of the needle, after removal of the connecting means (105), the entire stroke of the piston (202, 205) can be used for throttling or pumping purposes.

[0034] In the example described illustrating an exemplary embodiment of this connecting means (105), it has the form of a rotating element 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 means (105), it causes it to tilt around the axis (154), which releases the movement of the translation element which releases the operation of the injection system (100), and moves the connecting means (105) into its second position where it is permanently held. This holding is ensured for example by a rib (171, 172) which leads this part into its second position where it is held by an elastic return means.In this second position, the connecting means (105) is permanently retracted to allow movement of the piston over its entire stroke, to ensure pumping, without any new direct or indirect interaction with the injection system (100).

[0035] It should be noted that the invention is not limited to a drug delivery device implementing this triggering mode of the injection system, and includes other inventive technical choices which are associated in an exemplary embodiment of this triggering mode, but can also be exploited without this triggering mode.

[0036] Detailed description of the multi-function operation and release of the insertion mechanism controlled by the piston rod

[0037] Figures 1, 2, 3, 4, and 5 illustrate a first embodiment of the needle insertion mechanism locking device according to the invention, lrepresenting the needle insertion mechanism alone, as described in international patent application WO2018141697A1. Figures 2 and 3 show the needle locking and insertion mechanism in a top view, lrepresenting the device in the initial, so-called "cocked" state, and lrepresenting the mechanism after triggering and needle insertion. Lrepresents the needle locking and insertion mechanism in a perspective view and lrepresents the needle locking and insertion mechanism, without the cam element, in a side view.

[0038] The injection system (100) comprises in particular a needle insertion mechanism composed of a cam element (101), and illustrated in more detail 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 support (124) has a conduit for receiving the tube (130) conveying 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.

[0039] More particularly, the locking device comprises a translation element (104) and a connecting means (105), having a degree of freedom in rotation, both guided by the lower casing (107) of the housing in respective translation and rotation movements.

[0040] 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 on the, and the proximal end (140) rests on a surface (150) of the connecting means (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 connecting means (105) has a surface (151) opposite said surface (150), this opposite surface (151) resting 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 connecting means (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 ensures a longer life of the system during a storage period, the use of direct load absorption by the housing avoids the risk of creep of the parts.

[0041] The release of the locking device (110) is possible by moving the connecting means (105). Said connecting means (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 connecting means (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.

[0042] When the rotation of the connecting means (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 shown in. 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 connecting means (105) so as to impose a movement of said connecting means (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.

[0043] 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 the connecting means (105) is ensured even in the event of sudden movement or impact on the medical device.

[0044] Before the locking device is released, the translation element (104) and the connecting means (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 connecting means (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 presented, 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 placing the device on the patient.During this operation the stroke of the pump piston can easily be limited by software.

[0045] 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.

[0046] It should be noted that the pump piston (205) only ensures the rotational movement of the connecting means (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 connecting means (105) in the safety position as permitted here by its cooperation with the translation element (104).

[0047] Detailed description of the oblong hole pump body

[0048] An embodiment of the pump system (200) is to be appreciated with regard to figures 6 to 10. Lrepresents 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). Lrepresents the pump system (200) in side sectional view showing the fluid circuit. Lrepresents the pump body (201) seen from the side from which the valve piston (202) emerges. Lrepresents 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 pump body (201) and their advantage over those used in international patent application WO2018141697A1.

[0049] 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.

[0050] In the example of the, 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. An outlet port of the pump is understood to 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 air volume.

[0051] Two injection sequences are preferred without being limiting of the invention. Either with use of the internal reservoir or by direct injection.

[0052] 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 is then broken down into the following steps:moving the valve piston (202) and the pump piston (205) in a synchronized manner, by their respective drive system (240, 250) to match the orifice (221) of the pump with the port (211) connected to the reservoir (215),moving the pump piston (205) alone, thanks to 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 suction of the liquid from the reservoir (203) towards the internal cavity (208) through the internal channel (209),once the internal cavity is completely filled, moving 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).,

[0053] Once the fluid has been fully transferred into the internal reservoir (215), the injection into the patient can begin. The first step is therefore to trigger the needle insertion system, as for example described in international patent application WO2018141697A1. Once the cannula is inserted into the subcutaneous tissues, a new pumping sequence takes place according to the following steps:move the valve piston (202) and the pump piston (205) in a synchronized manner, 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, thanks to 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 suction of the liquid from the internal reservoir (215) towards the internal cavity (208) through the internal channel (209), once the internal cavity is completely filled, moving 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, translating 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 previous steps successively until all of the liquid contained in the internal reservoir (215), or a predetermined quantity, is transferred in the patient.,

[0054] 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 described for example in international patent application WO2018141697A1. Once the cannula is inserted into the subcutaneous tissues, a pumping sequence is performed according to the following steps:moving the valve piston (202) and the pump piston (205) in a synchronized manner, by their respective drive system (240, 250) to match the orifice (221) of the pump with the port (211) connected to the reservoir (203),moving the pump piston (205) alone, thanks to 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 suction of the liquid from the reservoir (203) towards the internal cavity (208) through the internal channel (209),once the internal cavity is completely filled, moving 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, translating 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, repeating the previous steps successively until all of the liquid contained in the reservoir (203), or a predetermined quantity, is transferred into the patient.,

[0055] 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.

[0056] An alternative would be to completely dispense with the external reservoir (203), the internal reservoir (215) being a cartridge pre-filled with the fluid to be injected. 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.

[0057] As more particularly visible in the, 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 of 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.

[0058] 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 the 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 to 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.

[0059] 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 a silicone or a flexible thermoplastic, in order to fit the cylindrical inner 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).The valve body is shown 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 middle of the port (212) and the port (213). This section makes it possible to visualize the correct 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).

[0060] 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 tapered clearances (231, 232, 233) allowing coupling with the cylindrical flexible tubes (261, 262, 263), visible in, 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. If the shoulder makes it possible to secure the mechanical assembly, it is nevertheless not necessary for it to be present over the entire circular periphery of the flexible tube.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.

[0061] By oblong periphery is meant that the section of the ports (211, 212, 213), as presented in the, is not disc-shaped but has a different length according to the axial and tangential directions. In the example of figures 8, and sub-figures c and d of the, the section is a groove according to the tangential direction, terminated by two half-cylinders. Nevertheless, the invention is not limited to this type of shape, but includes any type of section of elongated shape, such as a rectangle or an ellipse. Also, the great length is not limited to the tangential direction, but can also be produced according to the radial direction and will be chosen according to the arrangement of the ports (211, 212, 213).

[0062] Figure 10 illustrates different positioning scenarios of the valve piston (202), subfigures a and b representing the case of an orifice (221) and a port (211) both with a disc section, as realized in the patent application WO2018141697A1. Subfigure a represents a cylindrical port (211) having a section of for a diameter of and being perfectly aligned on an identical orifice (221), the fluid passage section is represented by hatching. The 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 results in a remaining passage section of , a reduction of more than 35%. The oblong shape of the port (211) according to the invention is shown in sub-figures c and d, it makes it possible to provide a fluid passage section of in the same axial space when combined with an identical orifice or a disc orifice with a tangential flare as shown. Sub-figure d represents the evolution of the hatched passage section during incorrect axial positioning of the pump. It should be noted that for an offset of , the section then decreases to leave a passage of . It should also be noted that up to an axial offset of , or a passage section of 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 , 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 with Ø as implemented in the prior art. The form of the present invention therefore allows for precise positioning at without having an impact on the pressure losses in said system.

[0063] 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 pipes connected to the pump body.

[0064] Detailed description of activation by insertion of the bottle

[0065] 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 the, 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 make 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 described means, the user may 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 may be directly activated by the user's actions on the device.

[0066] 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), showing an exploded view of the different unconnected elements, showing the connection of the reservoir (203) to the adapter part (311) and showing the connection of the reservoir (203) and adapter part (311) assembly to the receiving part (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 the other of the elements thanks to the movements of the valve piston (202) and the pump piston (205) described in this application. The shows in particular the presence of a hollow needle (315), intended to pierce the septum of the external reservoir to make a sealed connection between said external reservoir (203) and the piping of the fluidic system (300). The assembly shown is obtained, from the, following the screwing of the adapter part (311) and the receiving part (308) by cooperation of a thread (331) and a tapping (330).

[0067] The 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 into which the central tube (321) extends, the internal cylindrical surface of the cavity having the tapping (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 tube, 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 tube (321), and on the other hand, onto an outlet port (388) located at the end of the axial protuberance (386).

[0068] 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 possible leakage.

[0069] 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.

[0070] This 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 rotational stopping 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 maintenance of the final angular position of the receiving part. 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 protrusion (384) is called the activation arm and allows the activation switch of the medical device to be engaged or released depending on the angular position of the receiving part (308). The partial annular protrusion (384) also has a cylindrical inner surface concentric with a cylindrical protrusion of the lower casing of the housing, in order to ensure a return to rotational guidance of the receiving part (308).

[0071] 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. Lshowing a view in axial incidence and lshowing 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 protrusions (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.

[0072] 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.

[0073] Note that the deformation torque required to rotate the receiving part (308) is greater than the torque required to ensure the connection is watertight according to the ISO 80369 standard. This deformation serves as haptic feedback to the user to indicate that the bottle has been installed successfully and the medical device has been activated.

[0074] 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 presented in 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).

[0075] This activation system thus offers a function guaranteeing the user monitored and secure bottle insertion to limit any risk of misuse.

Claims

Transdermal drug delivery device comprising a housing, a lower casing (107) of said housing defining a skin contact surface with an orifice (106) for the passage of a transdermal injection cannula (122), a reservoir (203, 215) containing an active ingredient intended for administration, a pump system (200) comprising a pump body (201), a valve piston (202) and / or a pump piston (205) capable of axial movement within 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(s) (240, 250) of the pump system (200) and for releasing the transdermal injection system (100),characterized in that said injection system (100) is controlled by a translational element interacting with a linkage means (105) interposed between the motorized pump piston (205) or valve piston (202) on the one hand, and the injection system (100) on the other hand, said linkage means (105) being movable between a first position which it occupies until the activation of said injection system (100), and a second, irreversible position, into which it is tilted by the triggering of said injection system (100), and in which second position it is removed so as not to present any area of ​​possible interaction with the piston (202, 205), over the entire stroke of said piston (202, 205). Transdermal drug delivery device according to claim 1 characterized in that said electronic system (310) controls: on 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, on 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 valve function, said additional function not being activated during the axial displacement of said pump piston (205) or said valve piston (202) on the nominal stroke. Transdermal drug delivery device according to claim 1 characterized in that said additional function is the triggering of the transdermal injection system (100). A transdermal drug delivery device according to the preceding claim, characterized in that said transdermal injection system (100) comprises: an actuation mechanism of an assembly including 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 cannula; the actuation mechanism comprising: a cam element (101) capable of rotating relative to the 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 spring (102) pre-wound to impart a rotational movement to the cam element (101) relative to the needle guide element (125).to sequentially control the insertion and retraction of the needle (120) such that the needle (120) and the cannula (122) are moved from a retracted position to an extended position during the rotation of the cam element (101) through a first predetermined angle, by cooperation of the protrusions (111, 112) of the needle holder (121) and the cannula holder (124) with the rib (103) of the cam element (101), and such that the needle (120) is returned to the retracted position during a further rotation of said cam element (101) through 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 the rotation through said second predetermined angle, the protrusion (112) of the cannula support (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 the 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 said cam element (101) subjected to the action of said pre-armed spring (102). A transdermal drug delivery device according to the preceding claim, characterized in that the locking device is provided with a connecting means (105) that can be rotated about an axis (154) and a translational element (104) that can be translated in a plane orthogonal to the axis (154), a distal end of the translational element (104) being in contact with the wall (109) of the cam element (101), the proximal end (140) bearing against a surface (150) of the connecting means (105), an opposite surface (151) of the connecting means (105) bearing against a surface (174) of a protrusion of the lower housing (107) hindering any translational movement of the translational element, and in that the end of the rod of one of the pistons (202, 205) is movable over said additional stroke until it reaches a position where it in contact with the connecting means (105) to impart a rotational movement to it,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 connecting means (105). Transdermal drug delivery device according to claim 1 characterized in that said additional function is the triggering of a perforation system of a membrane separating the housing of a cartridge containing an active ingredient from the internal space of said housing.

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