Improvements in needleless delivery

Abstract

The present invention relates to improvements in needleless devices for delivering therapeutic and / or prophylactic agents, such as solid dose pharmaceuticals, including vaccines. The needleless devices disclosed herein include novel structural arrangements and actuation and operation modes, thereby providing improved functionality and benefits to the user and / or patient.

Description

Technical Field

[0001] The present disclosure relates to improvements to needleless devices for delivering therapeutic and / or prophylactic agents (e.g., solid dosage drugs, including vaccines). Specifically, the needleless devices disclosed herein include novel structural arrangements and actuation and operation modes, thereby providing improved functions and benefits to users and / or patients.

[0002] More specifically, the present disclosure and invention relate to a novel needleless device for delivering solid dosage therapeutic and / or prophylactic agents, which has a reset mechanism with improved reliability, allowing for the delivery of at least one therapeutic compound, such as a vaccine (or a preparation containing a vaccine), with improved safety and reliability.

[0003] Also disclosed is a needleless device for delivering therapeutic and / or prophylactic agents (e.g., solid drugs, including vaccines), which includes a cartridge release mechanism that further improves safety and the user experience when delivering a therapeutic or prophylactic agent.

[0004] The present invention also relates to uses and methods related to needleless delivery. Background Art

[0005] Common routes of administration for therapeutic or prophylactic agents are the parenteral delivery of liquid formulations using needles and syringes. Parenteral delivery is used for therapeutic or prophylactic agents that are generally poorly absorbed by other routes and / or require rapid delivery. Compared with other standard delivery routes such as oral or pulmonary delivery, parenteral delivery is also one of the more efficient delivery routes.

[0006] The disadvantages of parenteral delivery via needles are the associated discomfort and pain to the patient, as well as the health risks posed by used sharps.

[0007] Most therapeutic or prophylactic agents have poor solubility, often resulting in the production of suboptimal formulations. In addition, they are generally less stable in aqueous form than in solid dosage forms.

[0008] Potentially, drugs can be administered by accelerating powders to a speed at which they can penetrate the outer layer of the skin. Such systems generally require speeds of several hundred meters per second to penetrate human tissue. Other systems use solid rods or fragments of therapeutic compounds, which can be pushed into the skin at relatively low speeds without the need for a needle.

[0009] The present applicant has successfully developed their own needleless solid dosage delivery technology, which is used as a component for introducing solid dosage therapeutic agents (including proteins and vaccines). The development of this technology is described at least in International Applications WO2003 / 023773, WO2004 / 014468, WO2006 / 082439, WO 2006 / 082439, and WO2017 / 068351.

[0010] The initial method involved delivering a compound or formulation by penetrating the skin with a pioneer projectile and introducing, behind the projectile, a therapeutic agent of interest in liquid, semi-liquid or solid dosage form. However, the device also allows for solid dose delivery without the need for a pioneer projectile.

[0011] These devices suitable for needleless delivery have been described in detail by the present applicant and are described in many different iterations and embodiments, such as US 8,574,188 and other disclosures.

[0012] This common type of needleless device includes a disposable single-use component (also referred to herein as a cartridge) and a reusable actuator. The general mechanism by which the devices and cartridges designed by the present applicant operate is briefly described herein, but details can be found in the above-mentioned international patent publication references.

[0013] The disposable cartridge includes a central bore in which an ejector or drive pin is mounted behind a drug package or injectate that contains the therapeutic agent and / or formulation. The disposable component that houses the drug package can be loaded into the actuator by positioning it, for example, by screwing it into the interior of the housing end of the actuator device.

[0014] The front end of the housing is in operative communication with the cartridge such that when assembled with the cartridge and the device is operated, the actuation mechanism of the device generates a force sufficient to eject the drug package from the cartridge.

[0015] Actuation can initially be triggered either by a button or by pushing the disposable cartridge (already loaded into the actuator device) against the skin. Under the action of a spring force in the rear end of the device, a firing pin (such as a hammer or a mandrel) travels along a guide within the housing and contacts the pin. The pin (a drive pin in the present disclosure) includes a flat head and an elongated body and is positioned such that when it is contacted, the drug package is pushed along the central bore and ejected from the cartridge jaws. The energy generated is sufficient to cause the drug package to pierce the skin. The pin continues to push the drug package to the depth required within the patient, which depth is determined in part by the package length and the extent to which it is pushed by the pin.

[0016] Then even at low dosing speeds, the applicant's device can cause the skin to be penetrated by the drug package. Low speed is generally defined herein as less than 100 meters per second, but preferably, the speed is less than 10 meters per second. Since the drug is pushed at low speed rather than being launched at high speed, it can be ensured that the dose is always delivered to the correct (and the same) depth under the skin. This means that the system can be used for different skin types and skin locations and the dose will still be delivered to the same depth. However, there are still some challenges in the needleless delivery of solid dose medications.

[0017] In a user-operated delivery device, it is desirable that a reusable component, namely an actuator device, can be easily and reliably reset after actuation. Thus, in one aspect, the present invention stems from the desire to improve the reliability of needle-free drug delivery devices.

[0018] In addition, a component for removing a disposable cartridge from the device after actuation is important, and although there is no risk of needle stick injury, minimal contact with the just-injected end is desirable in order to improve the comfort and compliance of the drug giver. Thus, the present invention stems from a need to provide a needle-free medicament device for delivering a therapeutic and / or prophylactic agent and / or a method of operating such a device that is user-friendly and / or self-administerable for the drug giver. SUMMARY OF THE INVENTION

[0019] The invention disclosed herein includes a needle-free device for delivering at least one therapeutic and / or prophylactic agent, the needle-free device comprising a housing having:

[0020] a rear end including a force generator and a rear piston;

[0021] a front end for receiving a cartridge containing a solid therapeutic and / or prophylactic agent for delivery, the housing including a front piston having a central hole defining an axis, the piston being slidably mounted within the front end;

[0022] a mandrel located between the front end and the rear end and operatively connecting the rear piston to the front end of the device, the mandrel having a mandrel tip, the mandrel being configured to be laterally movable between a position axially aligned with the central hole and an axially offset position;

[0023] a reset spring seat;

[0024] a reset spring located between the spring seat and the front piston; and

[0025] a mandrel retaining element configured structurally and functionally to exclusively retain the mandrel in the axially offset position.

[0026] Safety and reliability related to the operation of the device are very important for ensuring the correct delivery of the dose and the medicinal or prophylactic effect. The applicant has determined that the reset of the device may fail, and in such a case, it may prevent further use of the device by the patient / user.

[0027] The present invention provides a new solution to this problem. The reconfiguration of the mechanism and the new combination of features included herein ensure avoidance of the risk of failure of the reset mechanism and reliably enable the patient or clinician to reuse the delivery device for each new therapeutic and / or prophylactic agent cartridge.

[0028] The delivery device disclosed herein enables the mandrel to reliably deviate from its central axis, and importantly, when the current piston is in its most forward position, i.e., when no cassette is attached, it is always successfully held in an unaxially aligned or offset position.

[0029] First, a return spring placed between the return spring seat and the front piston ensures that the piston is in its most forward position when no cassette is attached, such that the end of the mandrel can rest in a radially outward position offset from the central axis.

[0030] Second, in the case of the previous device for returning the mandrel to the offset position, as described above, this arrangement still showed a return failure. Before the present applicant's study and further development of the device structure, the reason for the return failure was not clear or still undetermined. Without being bound by theory, it has been clarified that the possible reason for the return failure stems from the existing features (already present in the device) inherently being used for multiple functions. In other words, the existing features provide additional functions beyond their primary mechanical role in device actuation, but this function may be suboptimal. Different solutions are needed to avoid return failure and improve reliability.

[0031] Helpfully, the applicant has found that the new configuration of the device of the present invention, including the introduction of new separate elements that are mechanically independent (i.e., not already existing / vital for the primary actuation of the device), can avoid return failure. A mechanically independent mandrel holding element, solely for holding the mandrel in the offset position, has been found to successfully achieve this without exception, thus providing an improvement over the prior art devices. Helpfully, the new configuration and combination of features, including the independent structural features of the holding element, provide sufficient additional force required to hold the end of the mandrel in the laterally offset position, such that the mandrel does not move inadvertently. Through comprehensive testing, it has been determined that the operation of the device of the present invention successfully avoids return failure events.

[0032] In some embodiments, the end of the mandrel is in an offset or unaxially aligned position, with the end abutting against or being held against the front piston; in particular, it abuts against the rear surface of the front piston, while in the axially aligned position, the end of the mandrel is aligned with the axis of the central hole in the front piston. For example, the rear-facing surface of the front piston temporarily abuts against the rear surface of the piston (until the device is reloaded with a new cassette, pre-filled, and actuated). Thus, this surface can releasably fix the mandrel in the unaxially aligned position before actuation and then fix it again after actuation.

[0033] In an embodiment, the mandrel holding element axially offset and holds the end of the mandrel by an attractive force laterally spaced from the central axis of the hole.

[0034] The force generator can include a compression or actuation spring.

[0035] In a preferred embodiment, the return spring and the actuation spring are not positioned in series. Prior art mechanisms have used a return spring placed in series with the actuation spring in an effort to provide the force required for return, thus maintaining permanent contact of the mandrel with the rear piston and keeping the front piston in its most forward position such that the mandrel is out of the front piston central orifice. However, this is undesirable as the length of the device may be affected. Delivery requires a target velocity of 6 m / s, which requires a minimum acceleration distance. A portion of the energy delivered by the actuation spring is absorbed by the return spring, and thus an additional acceleration distance is required to compensate for this energy absorption, resulting in an increase in the overall length of the device. Accordingly, in the preferred embodiment, the return spring and the actuation spring are arranged in parallel. This arrangement is useful because the return mechanism of the present invention involves the front piston moving forward to a position where the end of the mandrel is out of and not engaged with the front piston central orifice, and thus allows the end of the mandrel to return to an axially offset position until the trigger point is reached, but does not result in a need for a greater acceleration distance. Advantageously, this allows for a shorter and thus more compact device.

[0036] For example, a member that effects displacement in part by using lateral forces and / or radial attraction can be implemented in many different embodiments. Thus, the mandrel retaining element can be positioned near the end of the mandrel.

[0037] In one embodiment, the attracting element is a magnetic ring and at least a portion of the mandrel or the end of the mandrel includes metal. In a preferred embodiment, the ring is a monopole radial magnetic ring. The ring can be located within the rear end of the front piston, which can be open. In such an embodiment, the magnetic field generated by the ring attracts the metal mandrel end. For example, during the return phase, due to the reaction force exerted by the return spring, the front piston moves forward, allowing the mandrel and the mandrel end to disengage from the front piston central orifice and be pulled by magnetic attraction towards the magnetic ring, where it is temporarily held in an axially offset position.

[0038] In other embodiments, the mandrel retaining element is configured to bias the position of the mandrel. The mandrel retaining element can include a secondary coil housed within the coils of the return spring. In particular, one end of the return spring can be coiled in a spiral pattern. The inner diameter of the inner portion of the coil can be slightly larger than the diameter of the front end of the mandrel. However, the final coil formed by the spiral is offset from the central axis and thus displaces the end of the mandrel relative to the central axis during return.

[0039] In some embodiments, the mandrel retaining element includes a spring wire having an anchoring geometry and attached to the front piston. The anchoring geometry includes a double pitch coil that serves to keep the end of the mandrel at least a minimum clearance from the central axis. The profile of the anchoring geometry is configured to temporarily pull the mandrel out of alignment with the front piston orifice and into an offset position during return.

[0040] In some embodiments, the rear piston abuts the mandrel via a rotary joint. In some examples, the rear piston may include a female connector or socket located at the rearward end of the mandrel for receiving a corresponding male connector. The male connector of the mandrel may include a ball for improved and reliable rotational movement with the rear piston. The rotatable connection between the rear piston and the mandrel, such as a ball-and-socket joint, can contribute to increased movement of the mandrel tip placement at the forward end of the mandrel. In particular, this connection allows the mandrel to pivot laterally with minimal friction, thereby improving the ability to reset the bias of the displacement mechanism under discussion. For example, the displacement of the mandrel tip can be more precise and consistent.

[0041] In a further embodiment, the ball-and-socket can be clamped onto the mandrel. Structurally, this can allow the return spring to be placed in a parallel arrangement as there is no longer a need to hold the mandrel in place.

[0042] In some embodiments, the rear piston is configured to improve the accuracy during mandrel guidance. Additionally, this can help minimize friction between moving parts during device actuation and reduce the actuation force required for the device. In some embodiments, the rear piston may include a front shoulder or alternatively an extended rearward end to improve the engagement within the rear end of the housing and its guide post.

[0043] The device may also include an alignment mechanism. In this case, alignment is achieved by an alignment sleeve having a ramp with a surface profile. The mandrel may have an enlarged intermediate or central section. During the pre-injection process of the device, the intermediate section of the mandrel contacts the alignment sleeve ramp, which centers the mandrel to the central axis, axially aligns the mandrel, and allows the mandrel tip to be released through the guide orifice under the force from the actuation spring.

[0044] In a preferred embodiment, the cartridge used with the device houses a pharmaceutical package, such as a solid preparation containing or accommodating a therapeutic and / or prophylactic agent. This may particularly include a solid dose vaccine for preventing or treating a disease, or a solid dose immunizing agent for treating or preventing allergic symptoms, for example.

[0045] Due to the way the cartridge is assembled at the front end of the delivery device (via the bayonet arrangement described above), handling of the disconnection after actuation may be required. Users have pointed out that the geometry of the used cartridge poses challenges for removal in a controlled / precise timing manner without manual manipulation of the cartridge itself.

[0046] Therefore, the applicant has developed another technical solution that enables the removal of the cartridge without actually handling the cartridge itself.

[0047] The device as previously described may also include a cartridge release and automatic ejection mechanism, wherein the front and rear ends may be axially rotatable relative to each other, wherein external axial rotation of the front end relative to the rear end releases the cartridge from an internal structural restraint within the front end, such that the return spring force acting on the front piston causes the cartridge to be automatically ejected from the device.

[0048] Thus, the present invention extends to a needle-free device for delivering therapeutic and / or prophylactic agents, comprising: a rear end, the rear end including a force generator, the force generator being used to push a solid drug containing the therapeutic and / or prophylactic agent from the device; a front end, the front end being used to receive a box containing the drug, the front end including a front piston slidably mounted therein; and a box release and automatic ejection mechanism, wherein the front end and the rear end are axially rotatable relative to each other, and the external axial rotation of the front end relative to the rear end releases the internal structural restraint used to retain the box within the front end, so that the force acting on the front piston can cause the box to be automatically ejected from the device.

[0049] This novel arrangement of the device facilitates semi-automatic disconnection (manual twist to release, then automatic ejection) through a simple and easily recognizable user movement for rapid but controlled disposal of the spent cartridge from the device. This further reduces the risk of contamination in needle-free delivery and allows the device to be efficiently reused (unloaded and reloaded with drug consumables), which may be particularly helpful in a field-based environment.

[0050] While this arrangement constitutes its own inventive concept by providing a combination and arrangement of features for solving the technical problem of contamination in the process, in a particularly preferred embodiment the present invention can be used with the aforementioned device. This combination can be combined with the device to provide further advantages in the field of needle-free delivery.

[0051] This unique combination of these two aspects of the invention together provides further advantages in the field of needle-free delivery of drugs and vaccines.

[0052] The present invention also relates to a needle-free method for preventing or treating a disease, comprising using the above device to deliver a solid drug containing a therapeutic agent or a preventive agent to a patient in need. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Various aspects of the invention will now be described, by way of example only, with reference to the following drawings.

[0054] Figure 1 shows a cross-sectional view of a needle-free device according to the present invention, wherein the device is in an inactive position and prior to loading a cartridge assembly;

[0055] Figure 1a A cartridge assembly for loading into a needle-free delivery device containing a therapeutic and / or prophylactic agent is shown;

[0056] Figure 2 shows Figure 1 a cross-sectional view of an apparatus in which a cartridge package containing a therapeutic and / or prophylactic agent has been inserted into the front end, rotationally engaged therewith and firmly connected, ready for use;

[0057] Figure 3 shows the arrangement of the apparatus during the pre-injection (pre-actuation) phase Figure 1 of the apparatus;

[0058] Figure 4 shows Figure 1 the arrangement of the apparatus just prior to automatic actuation;

[0059] Figure 5 shows Figure 1 the arrangement of the apparatus just after actuation;

[0060] Figure 6 shows the apparatus during reset actuation Figure 1 of the apparatus;

[0061] Figure 7 shows an alternative structural arrangement that provides a member for holding the spindle end of the apparatus in an axially offset position;

[0062] Figure 8 shows another alternative structural arrangement that provides a member for holding the spindle end of the apparatus in an axially offset position; and

[0063] Figure 9a -e shows a combination of perspective and cross-sectional views of another aspect of the present invention, in which the needle-free device includes a novel hands-free cartridge ejection mechanism. According to an example, this aspect of the present invention can also be combined with the device invention according to any of the foregoing embodiments and is related to any of the features exemplified Figures 1 to 8 therein. Detailed Description

[0064] In Figure 1 , an example of the needle-free delivery device of the present invention is shown. The cross-sectional view shows the delivery device (1) in a pre-actuated state and before the cartridge is loaded therein.

[0065] The device (1) is adapted to deliver a therapeutic and / or prophylactic agent (117) or a formulation containing a therapeutic / prophylactic agent in solid, semi-solid or liquid form, such as a pharmaceutical or a vaccine. Delivery is achieved by effectively pushing the agent or formulation (117) initially contained within the cartridge assembly (100) from the cartridge into a human or animal body without the device itself piercing the body beforehand. The agent for delivery can be formulated as a tablet or microtablet, a fragment or other solid of a size suitable for the cartridge. Typically, "solid dose formulation" will be referred to throughout the specification.

[0066] In Figure 1a an example of a cartridge assembly “cartridge” for use with the device is shown. In this regard, the cartridge (100) may be pre-packaged for hygiene and opened only when ready to be loaded into the device (1).

[0067] The cartridge (100) includes a cartridge body (103) and a carrier (107), which in turn houses a centrally located cartridge pin (105) and a solid dose formulation (117). These components are initially fixedly positioned within the cartridge body. The carrier is releasably fixed within the cartridge body and is held in place by a pre-release leg (not shown) prior to actuation. The cartridge body also includes an opening cone (111) located at the foremost or proximal position of the cartridge body.

[0068] The carrier includes two jaws (109) located at the front end of the carrier (107). The solid dose formulation (117) is held by compression acting on its outer surface. In particular, during storage of the cartridge and during general movement or transportation, the lateral compression force of the jaws creates sufficient friction to hold the solid dose (117) in this position within the carrier (107) until the point of loading and actuating the delivery device. The cartridge pin (105) is positioned behind the solid dose formulation (117) and abuts its rearward-facing end. The cartridge pin is initially held in place within the carrier (107) by a set of pin release clips (115). During the assembly of the cartridge (100), the pin release clips are latched onto corresponding one or more grooves in the pin.

[0069] The cartridge (100) also includes a bayonet peg (112) that is used to assist in connecting the cartridge and releasing the cartridge from the actuator.

[0070] Returning to reference Figure 1 , the needle-free delivery device (1) itself includes a housing (212) having a front end component / section (212a) and a rear end component / section (212b). These sections are operatively connected to each other internally and are arranged in an embodiment such that the two parts of the outer housing rotate relative to each other.

[0071] The rear end component (212b) houses a force generating member, shown here as a compression or actuation spring (214) and a rear piston (215). The force generated is approximately 10 - 40 N, more preferably 15 - 35 N, and most preferably 18 - 31 N. Behind the spring is a compression rod (234) that provides a contact surface against which the spring can act.

[0072] The front-end component (212a) includes a front piston (218). The front piston (218) is slidably mounted within the device such that when the cartridge is loaded, proximal actuation of the device causes the front surface of the cartridge to engage the body surface, and then the cartridge and the front piston slide upwardly within the front-end component to pre-fill and ultimately actuate the device. The front piston also defines a central axis (X) and a central bore (250) therein. A return spring (244) is located at the front end and is between the front piston (218) and the alignment sleeve return spring seat (209).

[0073] The front and rear housing components (212a; 212b) are operatively connected by a mandrel (210). The mandrel (210) includes a mandrel tip (211) that is ultimately adapted to connect to the drive pin (105) of the cartridge (when loaded) to push a therapeutic and / or prophylactic agent (117) from the cartridge (100) into a human or animal body when the mandrel is aligned with the central axis (X), and thus is adapted to pass through the central bore (250) during actuation.

[0074] In this example, the proximal end of the mandrel (proximal is defined as the end of the mandrel closest to the patient's skin site where the device is pushed) includes the mandrel tip (211) which is made of a material that is pulled to a magnetic ring (205) (and can be connected to the magnetic ring). Thus, the magnetic ring independently acts as a mandrel holding element within the structural arrangement of the device and is configured to reliably hold the mandrel tip in an axially offset position. The magnetic ring will continue to do so until the device is actuated. However, the feature of the magnetic ring (205) can equally well be an alternative structure; an alternative structure for laterally shifting and holding the mandrel and / or its tip. This feature is mentioned elsewhere and is explicitly disclosed in combination with the other features provided in this example of the present invention, regardless of the specific form, as long as the independent function is satisfied (i.e., the structure is provided and arranged separately to perform this function without other functions). For example, structural features that already exist in the prior art and thus have a primary function in the disclosure of this mechanism will not meet this basic requirement because they will be susceptible to the same problem of reset failure and thus cannot reasonably solve the technical problem.

[0075] In the illustrated figure, the rear piston 215 abuts the mandrel (210) via a rotary joint (225 / 221). The rear end of the mandrel (210) is provided as a ball joint (221) which is connected to the rear piston via a socket (225) of the rear piston. The ball-and-socket connection is used to control the axial position of the mandrel tip (211) when the mandrel laterally moves between being axially aligned and not axially aligned with the bore in the front piston. This type of connection allows the mandrel to pivot with minimal friction, improves the ability to reset the displaced mechanism, and is more precise and consistent.

[0076] The front piston and the rear piston communicate via the rear bore (243) and the mandrel (210), the distal end of the mandrel passing through the bore (243) where it contacts the spring follower of the piston (215).

[0077] In this example, as shown, the mandrel is also adapted with an intermediate region (231) and a formed shoulder (231a). This feature is designed to connect with and follow the profile of the alignment sleeve (260). This allows for automatic actuation: the mandrel needs to be pulled from misalignment with the central bore (250) to axial alignment with the central bore (250) such that when it is fully pre-charged, the device is automatically actuated.

[0078] Thus, the inner surface of the alignment sleeve (260 / 232) is shaped to generally guide the mandrel (the shoulder region (231a) of the intermediate section (231) of the mandrel) and force the end of the mandrel to move radially inward from the offset idle position towards the central axis (X). Finally, when the device is fully pre-charged, the end of the mandrel will be fully aligned with the central bore (250) in the front piston (218) such that it will be driven in a linear direction by the actuation spring (214) and pass through the central bore (250) where it contacts the drive pin (105).

[0079] Cartridge connection:

[0080] Figure 2 Illustrated is how the cartridge is aligned with and loaded into the device. Further usefully, the connection between the cartridge and the device provides positive feedback to the user. Thus, a bayonet-type connection that provides sufficient visual or other feedback to indicate that the cartridge is securely connected is preferred.

[0081] Thus, the present device additionally provides embodiments and examples where the connection feedback mechanism provides tactile information in addition to visual feedback, i.e., that the cartridge is securely connected and ready to be actuated.

[0082] In the present case, when the operation is about to start, the user aligns the cartridge bayonet peg (112) of the cartridge (100) with the bayonet opening (315) in the front end (212a) of the device (1) via the bayonet connection ring (314), which includes the opening (315) and a dead stop. The user can be further assisted with the help of connection indicators I and II (151, 251) respectively provided on the cartridge body and the proximal end of the front end. Some of these individual features, such as the peg (112) and the connection indicators I / II (151, 251), can be seen more clearly in Figure 9a and 9e where some of these individual features, such as the peg (112) and the connection indicators I / II (151, 251), can be seen more clearly.

[0083] Figure 2Shown is a cartridge partially loaded by pushing the cartridge in the direction Y. By using an applicator or an assembly aid, the cartridge can be aligned with the front end component without touching the cartridge. The assembly aid (not shown) can be inherently formed by the packaging in which the sterile cartridge is stored prior to use, or the sterile cartridge can be a separate component stored within the packaging and attached to the packaging as part of a kit. The assembly aid is shaped to easily and temporarily enclose the cartridge or a portion thereof for alignment and insertion of the cartridge with the actuator.

[0084] When the packaging is opened, it can additionally be used to hold the cartridge, or a separate aid can already be mounted on the cartridge and used to first align the cartridge with the actuator and insert the cartridge into the delivery device without directly contacting it.

[0085] By inserting the front end of the cartridge into the device in this direction, the return spring (244) is compressed and contact is made between the mandrel (210) and the back surface (278a) of the pre-release clip (278) until the cartridge bayonet peg (112) contacts the dead stop of the bayonet connection ring (314).

[0086] Once the cartridge (100) is inserted into the actuator, contact is made between the cartridge surface (116) and the front piston.

[0087] At this point, the cartridge (100), still held by the assembly aid, can be easily rotated clockwise, which further pushes the front piston into the interior of the device via a cam mechanism, such as that created by a cartridge tactile ramp (not shown) and an inner ramp within the front piston. When the axial rotation of the cartridge is locked, the front piston moves backward.

[0088] When the cartridge (100) rotates until it reaches the rotational dead stop, the cartridge tactile ramp leaves the inner ramp of the front piston due to the descent of the inner ramp profile of the front piston. This descent creates an internal shock as the front piston moves sharply forward, generating a slight vibration for tactile feedback. At this point, the cartridge is firmly connected within the actuator.

[0089] The cartridge peg (112) is now held in the track, so the cartridge (100) cannot move forward, and the mandrel (210) contacts the back surface of the front piston pre-release clip (278a). The front piston (218) also helps to releasably fix the mandrel (210) in an unaxially aligned position during pre-injection through a physical surface connection between the end of the mandrel (211) and the back surface of the front piston.

[0090] The pin release clips (115) of the cartridge cannot extend because they are limited by the inner diameter size of the cartridge body (103). The pin release clips are in a "V" shape to control the axial position of the cartridge pins (105) within the carriage (107). Thus, the pins are made more secure, and this movement control feature ensures that no unintentional forward movement relative to the carriage (107) is transmitted to the solid dose until the user intentionally actuates the device in the following manner.

[0091] As Figure 3 shown, from this point onwards, the device is ready for use.

[0092] Actuation:

[0093] In practice, the user holds the device around the device housing and presses firmly against the patient's skin. This first causes the skin to be tensed, and then any pressure applied to the cartridge will compress both the return spring (244) and the actuation spring (214) via the relative contact of the mandrel (210). Figure 4 A diagram of the device is shown where compression against the skin has started.

[0094] When it does so, the mandrel slides through the rear hole (243), and the rear end (221) of the mandrel pushes against the spring follower (215), causing the actuation spring (214) to be compressed, thereby charging the device with potential energy. The middle section (231) of the mandrel contacts the alignment sleeve ramp, which causes the end (211) of the mandrel to be oriented towards the central axis (X), which will enable the release of the mandrel through the central hole (250) of the front piston. At the same time, the pre-release clip (278) in the front piston (218) deflects when it contacts the leading edge of the alignment sleeve, releasing the carriage (107) from the cartridge body (103).

[0095] At Figure 4 the point shown, the formed shoulder region (231a) has been pulled into the formed frontmost surface (232), and the action of the return spring (244) is resisted, so the actuation spring (244) is fully charged, and once the end of the mandrel is axially aligned with the central hole (250), the device will automatically actuate.

[0096] When doing so, as Figure 5 shown, the actuation spring (244) forces the end (211) of the mandrel and the mandrel (210) through the hole (250), causing it to push the drive pin (105), which in turn causes the therapeutic and / or prophylactic agent (117) to be dispensed into the human or animal body. It is noted that the longitudinal axis of the mandrel cannot be aligned with the hole (250) until the required actuation force is reached, which is set to coincide with the point at which the formed shoulder region (231a) moves in the general area of the recessed surface (232), thus providing a safety mechanism against accidental actuation.

[0097] The mandrel drives the carriage (107) forward, the drive pin (105), and the pharmaceutical or solid dose (117). The carriage holding jaws (109) strike the opening cone (111) in the cartridge and stop, and the solid dose or pharmaceutical (117) continues to move forward under the force from the drive pin (105) and is released from the carriage and the cartridge into the human or animal body without the need for a separate needle to penetrate the skin. Before striking the drive pin, the mandrel moves only a short distance. Therefore, the available potential energy is important because to pierce the skin, the solid dose needs to strike the skin at a given distance. The drive pin, the carriage, and the solid dose move together until the carriage strikes the opening cone, whereby 12 mm is the approximate given distance between the solid dose and the skin.

[0098] Reset

[0099] Since the device is reusable, it is desirable that the cartridge can be disconnected from the actuator and removed, and discarded in a safe manner so that the device can be used with a new cartridge and pharmaceutical for delivery. Other specific methods and features involved in disconnecting the cartridge will be described in detail below.

[0100] Figure 6 The device just after reset is shown, in which the mandrel (210) is in the idle position and spring - reset.

[0101] The reset action requires the front piston (218) to move forward to a position where the end of the mandrel no longer engages with or rests near the center hole (250) of the front piston. As will be further described below, the reset spring (244) also helps to push the front piston (218) and, indirectly, the used cartridge so that the cartridge can be ejected from the device when the cartridge is released, as will be described in further detail below.

[0102] In this example, the reset spring (244) does not pull the mandrel (210) from alignment with the hole (250); it does not provide any lateral force to pull the mandrel off - center. As mentioned above, the end of the mandrel must be reliably held off - center.

[0103] In this example, reset is possible only through the mandrel holding element, which specifically and independently helps the mandrel to enter the lateral / radial offset position after actuation. For example, a magnetic ring (205) that attracts the end of the mandrel (211) towards it, as Figure 6 shown. Thus, this feature serves as an active shifting member and is configured to hold the end of the mandrel in the axial offset position until the pre - injection and actuation mechanism overrides the bias of this position.

[0104] The structural examples used here are not restrictive, and any embodiment sufficient to provide axial reset by laterally shifting the mandrel is within the scope of the present invention.

[0105] A unipolar radial magnetic ring within the rear open end of the front piston applies a magnetic field that attracts the metal mandrel (10) articulated at the ball-and-socket joint (225 / 221). During the reset phase, due to the reaction force applied by the reset spring (244), the front piston (212a) moves forward, allowing the mandrel to disengage from the piston central hole (250) and be pulled towards the magnetic ring (205).

[0106] Figure 7 and Figure 8 The following further examples as shown in can be used as an alternative solution to the magnetic ring shown in the previous figures to keep the end of the mandrel offset from the central axis of the hole (250). In each case, additional components or structural elements in addition to the normal spring (which forms part of the reset) are present in the device. Thus, this feature structurally and functionally meets the requirement that it is uniquely configured to hold the mandrel in an axially offset position.

[0107] As Figure 7 shown, one end of the reset spring (244) includes an additional feature of a secondary spring coiled in a spiral pattern. The inner diameter of the inner part of the coil is slightly larger than the diameter of the front end of the mandrel (211). The last coil formed by the spiral is off-center, applying a lateral force that keeps the end of the mandrel offset from the axis relative to the hole (250) when the end of the mandrel abuts the ball-and-socket connection (225 / 221) for articulation. The ball-and-socket joint enables the mandrel to rotate in any plane. Alternatively, in Figure 8 Figure 8 the spring wire is formed with an anchoring geometry to allow it to be attached to the front piston (20). The spring is formed by a double-pitch coil that keeps the end of the mandrel (211) offset from the center relative to the hole (250) by applying a lateral force that causes the end of the mandrel (211) to be offset from the axis when the mandrel (211) abuts the ball-and-socket connection (225 / 221) for articulation.

[0108] Releasing and ejecting the cartridge from the device

[0109] Series Figure 9a 、 Figure 9b 、 Figure 9c 、 Figure 9d and Figure 9e show how, after a solid dose injection, the disposable cartridge can be removed "hands-free" by a twist-release mechanical arrangement. This arrangement is structurally defined within the housing section and utilizes some of the existing structures of both the cartridge and the device to provide additional functionality to the needle-free device. This arrangement is not limited to but can also be of the type of needle-free device described above herein.

[0110] In a particularly preferred embodiment, including Figures 9a to 9eThe example shown, for a needle-free device for hands-free cartridge ejection, is used in conjunction with the foregoing examples of needle-free devices for delivering therapeutic or prophylactic agents.

[0111] The cartridge used with the device herein is a single-use disposable item, and when actuation of the device is complete and the drug has been delivered therefrom, the cartridge is empty and must be removed from the device and discarded.

[0112] As Figure 9a shown, to enable improved release and ejection of the cartridge (100) from the device, the user can rotate or twist the front end sleeve (212a) approximately 90 degrees about the main axis (X) of the device relative to the rear end sleeve (212b). Figure 9b The start of a "twist-release" movement, which is the start of the action, is shown, where the device is provided in cross-section.

[0113] In so doing, the release indicator I (351) provided at the distal end of the front end sleeve moves in the direction of rotation towards the release indicator II (352) on the proximal end of the rear end sleeve, such that the two release indicators I and II are aligned and reach a dead stop. In this example, a visual guide (340), shown here as multiple chevrons, can assist the user by clearly indicating the direction of travel that the front end must take in order to correctly align the two release indicators.

[0114] The position after complete twisting of the front end housing sleeve is additionally shown in Figure 9e where the release indicators I, II (351, 352) are aligned.

[0115] When the movement occurs, the front end is axially rotationally internally connected by a set of interacting ribs by a twist-release ring (357). The twist-release ring (357) includes release fingers (353) that can axially rotate in a dedicated track in the aforementioned bayonet connection ring (314). This track is also aligned with the axial position of the cartridge bayonet pin (112) of the cartridge (100). When the cartridge is connected, the release finger feature (353) laterally contacts the cartridge bayonet pin (112). The structural link between these features means that when the front end sleeve (212a) rotates as described, the twist-release ring (357) rotates and the release fingers (353) rotationally engage the cartridge via their contact with the cartridge bayonet pin (112) until the pin reaches the bayonet opening (315) in the bayonet connection ring (314). In other words, the twisting mechanism of the outer sleeve allows the cartridge to be released from the internal structure that previously firmly constrained or held the cartridge within the front end of the device. The features of the twist-release ring (357) and the release fingers (353) can be more easily seen in Figure 9d a cross-sectional view of

[0116] As previously described, the cartridge (100) contacts the front piston (218). Since the return spring (244) applies a reaction force on the front piston (218) at this time, when the bayonet pin (112) reaches the opening (315) in the bayonet connection ring (314), the front piston moves forward under the force of the spring. Any potential frictional force that may hold the cartridge in the device is overcome by this force. As Figure 9d and 9e shown, the rapid release of energy ensures that the cartridge (100) is fully ejected from the front end (212a) and exits the device in the direction Y.

[0117] The ejection force is sufficient for the cartridge to be directly discarded into a suitable unit / container / case or the like without further assistance. There is no need to manually handle the cartridge to remove and / or transport the cartridge to the disposal site after removal.

[0118] After ejection, the user can stop applying the torsional force on the front sleeve (212a) relative to the rear sleeve (212b), which allows the front end to automatically return to its initial position via an internal torsion spring (not shown). Then, the device is reset and ready to insert a new cartridge and connect the new cartridge to the device, and the device is used again to deliver a new therapeutic or prophylactic agent via a needle-free operation mode.

Claims

1. A needleless device for delivering at least one therapeutic and / or prophylactic agent, comprising a housing having: a rear end including a force generator and a rear piston; a front end for receiving a cartridge containing a solid therapeutic and / or prophylactic agent for delivery, the housing including a front piston having a central bore defining an axis, the front piston being slidably mounted within the front end; a mandrel located between the front end and the rear end and operatively connecting the rear piston to the front end, the mandrel having a mandrel tip, the mandrel being configured to be laterally movable between a position axially aligned with the central bore and an axially offset position; a return spring seat; a return spring located between the return spring seat and the front piston; and a mechanically independent mandrel retaining element configured structurally and functionally only to specifically retain the mandrel in the axially offset position, i.e., the mandrel retaining element is not multifunctional, does not provide additional functions, and is only used to retain the mandrel in the axially offset position. In other words, the mandrel retaining element is provided and arranged separately to perform the function of retaining the mandrel in the axially offset position without performing other functions, wherein the mandrel retaining element is a separate element from the return spring.

2. The needleless device according to claim 1, wherein, The mandrel retaining element is located proximal and / or near the mandrel tip.

3. The needleless device according to claim 1 or 2, wherein The mandrel retaining element holds the mandrel tip in the axially offset position by an attractive force.

4. The needleless device according to claim 1 or 2, wherein, The mandrel retaining element is magnetic.

5. The needleless device according to claim 1 or 2, wherein, The mandrel includes a material attracted to the mandrel retaining element.

6. The needleless device according to claim 1, wherein, The mandrel retaining element is configured to physically bias the mandrel to the axially offset position.

7. The needleless device according to claim 6, wherein, The mandrel retaining element includes a coil housed within the return spring, wherein the apex of the coil is axially offset.

8. The needleless device according to claim 1, wherein, The mandrel retaining element includes a spring wire suitable for anchoring the mandrel in the axially offset position.

9. The needleless device according to claim 1 or 2, further comprising a mandrel alignment mechanism.

10. The needleless device according to claim 9, wherein, The mandrel alignment mechanism includes an alignment sleeve having a ramp suitable for guiding an intermediate section of the mandrel so that the mandrel tip is laterally moved towards the axially aligned position.

11. The needleless device according to claim 1 or 2, wherein The force generator includes an actuation spring.

12. The needleless device according to claim 11, wherein, The return spring and the actuation spring are arranged in parallel.

13. The needleless device according to claim 1 or 2, wherein, The rear piston abuts the mandrel through a rotary joint.

14. The needleless device according to claim 13, wherein, The rotary joint includes a female connector or socket for receiving a corresponding male connector located at the rearward end of the mandrel.

15. The needleless device according to claim 1 or 2, in combination with a cartridge for the needleless device, the cartridge containing tablets, microtablets or fragments comprising at least one therapeutic and / or prophylactic agent.

16. The needleless device according to claim 1 or 2, wherein The needleless device further includes a connection feedback mechanism that provides a tactile signal to the user in addition to visual feedback, indicating that the cartridge is firmly connected and the needleless device is ready to be actuated.

17. The needleless device according to claim 16, wherein the haptic signal is vibration.

18. The needleless device according to claim 1 or 2, further comprising a cartridge release and automatic ejection mechanism, wherein the front outer sleeve and the rear outer sleeve are axially rotatable relative to each other, and twisting both the front outer sleeve and the rear outer sleeve releases the cartridge from the internal structural restraint within the front end such that the force of the return spring acting on the front piston causes the cartridge to be automatically ejected from the needleless device.

19. The needleless device according to claim 4, wherein, The mandrel holding element is a magnetic ring.

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