Needleless device for delivery of therapeutic and / or prophylactic agents

Abstract

The present invention relates to needleless devices for delivering therapeutic and / or prophylactic agents, such as solid doses of drugs, including vaccines. Needleless devices disclosed herein include novel structural arrangements as well as actuation and operation modes, bringing improved functionality and benefits to users and / or patients.

Description

[0001] This application is a divisional application of Chinese Patent Application No. 202080094532.X, which is the national phase entry of International Application PCT / GB2020 / 053140 with the invention title of "Improvements in needle-free delivery" and the international filing date of December 8, 2020. Technical Field

[0002] The present disclosure relates to improvements in needle-free devices for delivering therapeutic and / or prophylactic agents (such as solid dosage drugs, including vaccines). Specifically, the needle-free devices disclosed herein include novel structural arrangements and actuation and operation modes, thereby bringing improved functions and benefits to users and / or patients.

[0003] More specifically, the present disclosure and invention relate to a novel needle-free device for delivering solid dosage therapeutic and / or prophylactic agents, which has a reset mechanism with improved reliability, allowing the delivery of at least one therapeutic compound, such as a vaccine (or a preparation containing a vaccine), with improved safety and reliability.

[0004] Also disclosed is a needle-free device for delivering therapeutic and / or prophylactic agents (such as solid drugs, including vaccines), which includes a cartridge release mechanism that further improves safety and user experience when delivering a therapeutic or prophylactic agent.

[0005] The present invention also relates to uses and methods related to needle-free delivery. Background Art

[0006] A common route of administration for therapeutic or prophylactic agents is the parenteral delivery of liquid formulations via needles and syringes. Parenteral delivery is used for therapeutic or prophylactic agents that are generally poorly absorbed via other routes and / or require rapid delivery. Parenteral delivery is also one of the more efficient delivery routes compared to other standard delivery routes such as oral or pulmonary delivery.

[0007] The disadvantages of parenteral delivery via needles are the associated discomfort and pain for patients, as well as the health risks posed by used sharps.

[0008] Most therapeutic or prophylactic agents have poor solubility, often resulting in sub-optimal formulations. In addition, they are generally less stable in aqueous form than in solid dosage forms.

[0009] Potentially, drugs can be administered by accelerating powders to speeds at which they can penetrate the outer layer of the skin. Such systems typically 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 needles.

[0010] The present applicant has successfully developed their own needle-free solid dose delivery technology, which serves as a component for introducing solid dose 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.

[0011] The initial method involved delivering a compound or formulation by penetrating the skin with a pioneer projectile and introducing the therapeutic agent of interest in liquid, semi-liquid, or solid dosage form behind the projectile. However, the device also allows for solid dose delivery without the need for a pioneer projectile.

[0012] These devices suitable for needle-free delivery have been described in detail by the present applicant and in many different iterations and embodiments, such as US 8,574,188 and other disclosures.

[0013] This common type of needle-free device includes a disposable single-use component (also referred to herein as a cartridge) and a reusable actuator. The general mechanism of operation of the device and cartridge designed by the present applicant is briefly described herein, but details can be found in the above-mentioned international patent publication references.

[0014] 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.

[0015] The front end of the housing is operatively connected to 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.

[0016] Actuation can initially be triggered 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 (referred to as a drive pin in this 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 into the patient to the required depth, which is determined in part by the package length and the extent to which it is pushed by the pin.

[0017] Thus, even at low drug delivery speeds, the applicant's device can penetrate the skin with 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 a low speed rather than being launched at a 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 drugs.

[0018] In a user-operated delivery device, it is desirable that the reusable component, i.e., the 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 a needleless drug delivery device.

[0019] In addition, the component for removing the 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 the need to provide a needleless pharmaceutical device for delivering a therapeutic agent and / or a prophylactic agent and / or a method of operating the device, which is convenient for the drug giver to use and / or self-use. SUMMARY OF THE INVENTION

[0020] The invention disclosed herein includes a needleless device for delivering at least one therapeutic agent and / or prophylactic agent, the needleless device comprising a housing having:

[0021] a rear end including a force generator and a rear piston;

[0022] a front end for receiving a cartridge containing a solid therapeutic agent and / or prophylactic agent for delivery, the housing including a front piston having a central hole defining an axis, the front piston being slidably mounted within the front end;

[0023] 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 end, the mandrel being configured to be laterally movable between a position axially aligned with the central hole and an axially offset position;

[0024] a reset spring seat;

[0025] a reset spring located between the spring seat and the front piston; and

[0026] a mandrel retaining element configured structurally and functionally to exclusively retain the mandrel in the axially offset position.

[0027] Safety and reliability related to the operation of the device are important for ensuring the correct delivery of the dose and the pharmaceutical or prophylactic effect. The applicant has determined that the reset of the device may fail and, in such a case, may prevent the patient / user from further using the device.

[0028] The present invention provides a new solution to this problem. The reconfiguration of the mechanism and the new combination including the features disclosed herein ensure avoiding 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 cartridge.

[0029] The delivery device disclosed herein is capable of reliably displacing the spindle from its central axis and, importantly, always successfully holds in a non-axially aligned or offset position when the current piston is in its most forward position, i.e., when no cartridge is attached.

[0030] First, a reset spring placed between the reset spring seat and the front piston ensures that the piston is in its most forward position when no cartridge is attached, enabling the end of the spindle to rest in a radially outward position offset from the central axis.

[0031] Secondly, in the case where the previous device was used to return the spindle to the offset position, as described above, this arrangement still showed a reset failure. Before the applicant's study and further development of the device structure, the cause of the reset failure was not clear or still undetermined. Without being bound by theory, it has been elucidated that the possible cause of the reset 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 sub-optimal. A different solution is needed to avoid reset failure and improve reliability.

[0032] 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 / essential for the primary actuation of the device), can avoid reset failure. A mechanically independent spindle holding element, which is only used to hold the spindle in the offset position, has been found to successfully achieve this without exception, thus providing an improvement over 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 spindle in the laterally offset position, so that the spindle does not move inadvertently. Through comprehensive testing, it has been determined that the operation of the device of the present invention successfully avoids reset failure events.

[0033] In some embodiments, the end of the mandrel is in an offset or axially misaligned position and abuts or is held against the front piston; in particular, it abuts 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 the rear surface of the piston (until the device is reloaded with a new cartridge, pre-filled and actuated). Thus, this surface can releasably fix the mandrel in the axially misaligned position before actuation and then fix it again after actuation.

[0034] In an embodiment, the mandrel holding element axially offset holds the end of the mandrel by an attractive force laterally spaced from the central axis of the hole.

[0035] The force generator can include a compression or actuating spring.

[0036] In a preferred embodiment, the return spring and the actuating spring are not positioned in series. Prior art mechanisms have used a return spring placed in series with the actuating spring in an attempt to provide the force required for return, so as to keep the mandrel in permanent contact with the rear piston and keep the front piston in its most forward position, such that the mandrel is out of the front piston central hole opening. However, this is undesirable because the length of the device may be affected. Delivery requires a target speed of 6 m / s, which requires a minimum acceleration distance. A portion of the energy delivered by the actuating 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 total length of the device. Therefore, in a preferred embodiment, the return spring and the actuating 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 gets out of the front piston central hole opening and does not engage with the front piston central hole opening, and thus allows the end of the mandrel to return to the 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.

[0037] For example, members that achieve displacement partially by using lateral forces and / or radial attractive forces can be implemented in many different embodiments. Thus, the mandrel holding element can be positioned near the end of the mandrel.

[0038] 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 unipolar radial magnetic ring. The ring can be located inside 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 end of the mandrel. 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 end of the mandrel to disengage from the front piston central hole and be pulled by the magnetic attraction towards the magnetic ring, where it is temporarily held in the axially offset position.

[0039] 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 received within a return spring coil. In particular, one end of the return spring can be coiled in a helical 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 helix is offset from the central axis, thus displacing the end of the mandrel relative to the central axis during return.

[0040] 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 maintain at least a minimum clearance between the end of the mandrel and the central axis. The profile of the anchoring geometry is configured to temporarily pull the mandrel out of alignment with the bore of the front piston and into an offset position during return.

[0041] In some embodiments, the rear piston abuts the mandrel via a swivel joint. In some examples, the rear piston can 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 can include a ball for improved and reliable rotational movement with the rear piston. A rotatable connector between the rear piston and the mandrel, such as a ball and socket joint, can contribute to increased movement of the mandrel end placement at the forward end of the mandrel. In particular, this connector allows the mandrel to pivot laterally with minimal friction, thus improving the ability of the return to be biased by the displacement mechanism under discussion. For example, the displacement of the mandrel end can be more precise and consistent.

[0042] 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.

[0043] In some embodiments, the rear piston is configured to improve the accuracy during mandrel guidance. Additionally, this can help to minimize the friction between moving parts during device actuation and reduce the actuation force required for the device. In some embodiments, the rear piston can 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.

[0044] The device can also include an alignment mechanism. In this case, alignment is achieved by an alignment sleeve having a ramp with a surface profile. The mandrel can have an enlarged intermediate or central section. During the pre-filling of the device, the intermediate section of the mandrel contacts the alignment sleeve ramp, which axially aligns the mandrel to the central axis and allows the mandrel end to be released through a guide orifice under the force from the actuation spring.

[0045] In a preferred embodiment, the box used with the device contains a drug package, such as a solid formulation containing or containing a therapeutic and / or prophylactic agent. This can particularly include a solid dose vaccine for preventing or treating a disease, or a solid dose immunizing agent for example for treating or preventing allergic symptoms.

[0046] Due to the way the cartridge fits on the front end of the delivery device (via the bayonet arrangement described above), post-actuation disconnection may require handling. Users have noted that the geometry of a spent cartridge makes it challenging to remove in a controlled / precisely timed manner without manual manipulation of the cartridge itself.

[0047] The Applicant has therefore developed another technical solution that enables the cartridge to be removed without actually handling the cartridge itself.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] The present invention also relates to a needleless method for preventing or treating a disease, comprising delivering a solid drug containing a therapeutic or prophylactic agent to a patient in need using the above device. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Aspects of the present invention will now be described by way of example only with reference to the following drawings.

[0055] Figure 1 A cross-sectional view of a needleless device according to the present invention is shown, wherein the device is in a non-actuated position and before the loading cartridge assembly;

[0056] Figure 1a A cartridge assembly for loading into a needleless delivery device containing a therapeutic and / or prophylactic agent is shown;

[0057] Figure 2 Shows Figure 1 A cross-sectional view of the device, wherein 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;

[0058] Figure 3 Shows the arrangement of the device during the pre-injection (pre-actuation) phase Figure 1 ;

[0059] Figure 4 Shows Figure 1 the arrangement of the device just before automatic actuation;

[0060] Figure 5 Shows Figure 1 the arrangement of the device just after actuation;

[0061] Figure 6 Shows the device during reset actuation Figure 1 ;

[0062] Figure 7 Shows an alternative structural arrangement that provides a member for holding the end of the mandrel of the device in an axially offset position;

[0063] Figure 8 Shows another alternative structural arrangement that provides a member for holding the end of the mandrel of the device in an axially offset position; and

[0064] Figure 9a -e shows a combination of a perspective view and a cross-sectional view of another aspect of the present invention, wherein the needleless 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 illustrated in Figures 1 to 8 ; Detailed implementation mode

[0065] In Figure 1 is shown an example of the needleless delivery device of the present invention. The cross-sectional view shows the delivery device (1) in a pre-activated state and before the cartridge is loaded therein.

[0066] The device (1) is adapted to deliver a therapeutic and / or prophylactic agent (117) in solid, semi-solid or liquid form or a formulation comprising a therapeutic / prophylactic agent, 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 pre-puncturing the body. 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.

[0067] In Figure 1a is shown an example of a cartridge assembly "cartridge" for use with the device. In this regard, the cartridge (100) can be pre-packaged for hygiene and opened only when ready to be loaded into the device (1).

[0068] 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 located in the appropriate positions within the cartridge body. The carrier is releasably fixed within the cartridge body and is held in place by pre-release legs (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.

[0069] 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 one or more corresponding grooves in the pin.

[0070] The cartridge (100) also includes a bayonet peg (112) which is used to assist in connecting the cartridge and releasing the cartridge from the actuator.

[0071] 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 internally to each other and, in an embodiment, are arranged such that two parts of the outer housing rotate relative to each other.

[0072] The rear-end component (212b) houses a force-generating member, shown here as a compression or actuating spring (214) and a rear piston (215). The force generated is about 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.

[0073] 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, pushing the proximal end of the device causes the front surface of the cartridge to engage the body surface, and then the cartridge and the front piston slide upward within the front-end component to pre-charge and ultimately actuate the device. The front piston also defines a central axis (X) and a central hole (250) therein. A return spring (244) is located at the front and is between the front piston (218) and the alignment sleeve return spring seat (209).

[0074] The front and rear housing components (212a; 212b) are operatively connected by a mandrel (210). The mandrel (210) includes a mandrel end (211) that is ultimately adapted to connect with 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 hole (250) during actuation.

[0075] In this example, the proximal end of the mandrel (proximal is defined as the end of the mandrel closest to the patient's skin where the device is pressed) includes a mandrel tip (211) made of a material that is pulled into and can be connected to a magnetic ring (205). Thus, the magnetic ring independently acts as a mandrel retention 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 displacing 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 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.

[0076] In the figure shown, 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) that is connected to the rear piston via a socket (225) of the rear piston. The ball and socket connection serves to control the axial position of the mandrel tip (211) as the mandrel laterally moves between being axially aligned and not axially aligned with the hole in the front piston. This type of connection allows the mandrel to pivot with minimal friction, improving the ability to reset the bias of the displaced mechanism and being more precise and consistent.

[0077] The front piston and the rear piston communicate via a rear hole (243) and the mandrel (210), the distal end of the mandrel passing through the hole (243) where it contacts a spring follower of the piston (215).

[0078] In this example, as shown, the mandrel is also adapted with an intermediate region (231) and a shaped shoulder (231a). This feature is designed to connect to and follow the profile of an alignment sleeve (260). This allows for automatic actuation: the mandrel needs to be pulled from being misaligned with the central hole (250) to being axially aligned with the central hole (250) such that when it is fully pre-charged, the device is automatically actuated.

[0079] Thus, the inner surface (260 / 232) of the alignment sleeve is shaped to generally guide the mandrel, the shoulder region (231a) of the intermediate section (231) of the mandrel, and to force the mandrel end to move radially inward from the offset idle position towards the central axis (X). Eventually, when the device is fully pre-filled, the mandrel end will be perfectly aligned with the central hole (250) in the front piston (218) such that it will be driven in a straight line by the actuation spring (214) and pass through the central hole (250), where it contacts the drive pin (105).

[0080] Cartridge connection:

[0081] Figure 2 Illustrated is how the cartridge is aligned with and loaded into the device. Further usefully, the connection of 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.

[0082] 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.

[0083] In the present case, when the operation is about to start, the user aligns the cartridge bayonet stud (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 stud (112) and the connection indicators I / II (151, 251), can be seen more clearly in Figure 9a and 9e .

[0084] Figure 2 Illustrated is a partially loaded cartridge by pushing the cartridge in the direction Y. With the use of 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 before 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 part thereof for alignment and insertion of the cartridge with the actuator.

[0085] When the packaging is opened, it can additionally be used to hold the cartridge, or a separate auxiliary device can already be mounted on the cartridge and be used to first align and insert the cartridge into the delivery device without directly contacting it.

[0086] By inserting the front end of the cartridge insertion 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).

[0087] Once the cartridge (100) is inserted into the actuator, contact is made between the cartridge surface (116) and the front piston.

[0088] 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 device interior via a cam mechanism, which is produced, for example, 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.

[0089] 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 within the front piston. As the front piston moves sharply forward, this descent creates an internal shock, generating a slight vibration to obtain tactile feedback. At this point, the cartridge is firmly connected within the actuator.

[0090] 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 axially misaligned position during pre-injection via a physical surface connection between the end of the mandrel (211) and the back surface of the front piston.

[0091] The pin release clips (115) of the cartridge cannot extend because they are restricted 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 before the user intentionally actuates the device in the following manner.

[0092] As Figure 3 shown, from this point on, the device is ready for use.

[0093] Actuation:

[0094] 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 already started.

[0095] When it does so, the mandrel slides through the rear hole (243), and the rear end (221) of the mandrel presses against the spring follower (215), causing the actuating 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 aligns the mandrel end (211) towards the central axis (X), enabling the mandrel to be released 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 contacting the leading edge of the alignment sleeve, releasing the carriage (107) from the cartridge (103).

[0096] At Figure 4 the point shown, the formed shoulder region (231a) has been pulled into the foremost formed surface (232), and the action of the return spring (244) is resisted, so the actuating spring (244) is fully charged, and once the mandrel end is axially aligned with the central hole (250), the device will automatically actuate.

[0097] When doing so, as Figure 5 shown, the actuating spring (244) forces the mandrel end (211) 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 should be noted that the longitudinal axis of the mandrel cannot be aligned with the hole (250) until the required actuating 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), thereby providing a safety mechanism to prevent accidental actuation.

[0098] The mandrel drives the carriage (107), the drive pin (105), and the drug or solid dose (117) forward. The carriage retaining jaws (109) strike the opening cone (111) in the cartridge and stop, and the solid dose or drug (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. The mandrel only moves a short distance before striking the drive pin. 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.

[0099] Reset

[0100] Since the device is reusable, it is desirable for the cartridge to be disconnected and removed from the actuator and discarded in a safe manner so that the device can be used with a new cartridge and drug for delivery. Other specific methods and features involved in disconnecting the cartridge will be described in full below.

[0101] Figure 6 Shows the device just after reset, with its central axis (210) in the idle position and spring - reset.

[0102] The reset action requires the front piston (218) to move forward to a position where the end of the mandrel no longer engages or rests near the central bore (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.

[0103] In this example, the reset spring (244) does not pull the mandrel (210) from alignment with the bore (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 of the axis.

[0104] In this example, reset is only possible through a mandrel - holding element that specifically and independently helps the mandrel to enter a 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 an axially offset position until the pre - filling and actuation mechanism overrides the bias of this position.

[0105] 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.

[0106] 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 bore (250) and be pulled towards the magnetic ring (205).

[0107] Figure 7 and Figure 8 The following further examples shown in

[0108] such as Figure 7As shown, one end of the return 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 off-axis relative to the hole (250) when the end of the mandrel abuts and articulates against the ball-and-socket joint (225 / 221). The ball-and-socket joint enables the mandrel to rotate in any plane. Alternatively, in 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 double-pitch coils that keep the end of the mandrel (211) off-center relative to the hole (250) by applying a lateral force that causes the end of the mandrel (211) to be off-axis when the mandrel (211) abuts and articulates against the ball-and-socket joint (225 / 221).

[0109] Releasing and ejecting the cartridge from the device

[0110] 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.

[0111] In a particularly preferred embodiment, including Figures 9a to 9e the example shown, the features of the needle-free device for hands-free cartridge ejection are used in conjunction with the examples of the needle-free devices for delivering therapeutic or prophylactic agents described above.

[0112] The cartridge used with the device herein is a single-use disposable item and, when the device actuation is complete and the drug has been delivered therefrom, the cartridge is empty and must be removed from the device and discarded.

[0113] 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 cannula (212a) approximately 90 degrees about the main axis (X) of the device relative to the rear cannula (212b). Figure 9b shows the start of the "twist-release" movement as the action begins, where the device is provided in cross-section.

[0114] In doing so, the release indicator I (351) provided at the distal end of the front cannula moves in the rotational direction towards the release indicator II (352) on the proximal end of the rear cannula, such that the two release indicators I and II are aligned and reach a dead stop. In this example, the 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.

[0115] The position after fully twisting the front housing cannula is additionally shown in Figure 9e wherein the release indicators I, II (351, 352) are aligned.

[0116] When the movement occurs, the front end is axially and rotationally internally connected via 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 peg (112) of the cartridge (100). When the cartridge is connected, the release finger feature (353) laterally contacts the cartridge bayonet peg (112). The structural link between these features means that when the front cannula (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 peg (112) until the peg reaches the bayonet opening (315) in the bayonet connection ring (314). In other words, the twisting mechanism of the outer cannula allows the cartridge to be released from the internal structure that previously held the cartridge firmly constrained or retained 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 which there is no cartridge.

[0117] As previously described, the cartridge (100) contacts the front piston (218). Since the return spring (244) exerts a reaction force on the front piston (218) at this time, when the bayonet peg (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.

[0118] The ejection force is sufficient to enable the cartridge to be directly discarded into a suitable unit / container / bin 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.

[0119] After ejection, the user can stop applying a torsional force on the front cannula (212a) relative to the rear cannula (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 the needle-free operating mode.

Claims

1. A needleless device for delivering a therapeutic and / or prophylactic agent, comprising a housing, the housing including: A rear end section including a force generator for pushing a solid medicament containing a therapeutic and / or prophylactic agent from the needleless device; A front end section for receiving a cartridge containing the solid medicament, the front end section further including a front piston slidably mounted in the front end section and in contact with the cartridge, a return spring arranged to exert a reaction force on the front piston, and an internal structural restraint for holding the cartridge within the front end section; And A cartridge release and automatic ejection mechanism, wherein a first sleeve enclosing the front end section is axially rotatable relative to a second sleeve enclosing the rear end section, and by twisting the first sleeve and the second sleeve relative to each other, the internal structural restraint is released, such that the front piston can move forward under the force of the return spring and the cartridge can be automatically ejected from the needleless device.

2. The needleless device according to claim 1, wherein, The first sleeve is axially rotatable relative to the second sleeve by approximately 90 degrees.

3. The needleless device according to claim 1 or 2, wherein, The first sleeve includes a first release indicator (I) at its distal end, and the second sleeve includes a second release indicator (II) at its proximal end, such that axial rotation of the first sleeve relative to the second sleeve causes the first release indicator (I) to move in the direction of rotation towards the second release indicator (II) until both the first release indicator (I) and the second release indicator (II) are aligned and reach a dead stop.

4. The needleless device according to claim 3, wherein, The first sleeve includes a direction indicator indicating the direction of rotation for aligning the first release indicator and the second release indicator.

5. The needleless device according to claim 1, wherein, The internal structural restraint is defined by at least a cartridge bayonet peg and a bayonet connection ring in the front end section of the needleless device, the bayonet connection ring being configured to hold the cartridge bayonet peg.

6. The needleless device according to claim 5, wherein, The cartridge release and automatic ejection mechanism further includes a torsion release ring and a release finger allowed to axially rotate in a dedicated track within the bayonet connection ring in the front end section.

7. The needleless device according to claim 6, wherein, When the cartridge is connected to the needleless device, the release finger is in lateral contact with the cartridge bayonet peg, and by twisting the first sleeve and the second sleeve relative to each other, the torsion release ring is rotated, causing the release finger to rotationally engage the cartridge through the cartridge bayonet peg until the cartridge bayonet peg reaches a bayonet opening in the bayonet connection ring, such that the force acting on the front piston can cause the front piston to move forward and eject the cartridge from the needleless device.

8. The needleless device according to claim 1 or 2, wherein, The cartridge release and automatic ejection mechanism further includes an internal torsion spring configured to automatically return the first sleeve enclosing the front end section to its initial position.

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

10. The needleless device according to claim 9, wherein, The at least one therapeutic agent and / or prophylactic agent includes a solid dose vaccine or a solid dose immunizing agent for preventing or treating a disease.

Images