CN118632725A - Ingestible device with detachable tissue penetrating member - Google Patents

Abstract

An ingestible device (200) includes: a housing (210, 220) including a stop geometry (228) at an exit hole (224); a tissue penetrating member (230) and an actuator, the actuator including: a push portion (260) configured to move axially from a first position to a second position, the push portion being configured to move the tissue penetrating member from within the housing to a resting position in the tissue, and a retainer portion (270) coupled to the push portion (260) for initial axial movement with the push portion. In the first position, the retainer portion releasably retains the tissue penetrating member (230) in axial retaining engagement. When the push portion (260) moves toward the second position, the tissue penetrating member (230) moves through the exit hole (224) until the retainer portion (270) engages with the stop geometry (228). The push portion (260) moves further to release and advance the tissue penetrating member (230).

Description

Ingestible device with detachable tissue penetrating member

Technical Field

The present invention is directed to an ingestible device adapted to be swallowed into an internal cavity of a patient and having a tissue penetrating member shaped to penetrate tissue of a wall of the internal cavity.

Background Art

In the disclosure of the present invention, reference is mainly made to the treatment of diabetes by delivering insulin, however, this is only an exemplary use of the present invention.

Many people suffer from diseases, such as diabetes, which require them to receive regular and often daily injections of medication. In order to treat the disease, these people need to perform different tasks, which may be considered complex and may be uncomfortable. In addition, they need to carry injection devices, needles and medications with them when they go out. Therefore, if the treatment can be based on oral intake of tablets or capsules, it will be considered a significant improvement in the treatment of such diseases.

However, such solutions are difficult to achieve because protein-based drugs will be degraded and digested rather than absorbed when ingested.

In order to provide an effective solution for delivering insulin into the bloodstream via oral ingestion, the drug must first be delivered into the lumen of the gastrointestinal tract and further into the wall (luminal wall) of the gastrointestinal tract. This presents several challenges, including: (1) The drug must be protected from degradation or digestion by the acid in the stomach. (2) The drug must be released while in the stomach or while in the lower gastrointestinal tract (i.e., after the stomach), which limits the window of opportunity for drug release. (3) The drug must be delivered at the luminal wall to limit the time of exposure to the fluid degradation environment in the stomach and lower gastrointestinal tract. If not released at the wall, the drug may be degraded during its journey from the release point to the wall, or may pass through the lower gastrointestinal tract without being absorbed unless protected from the decomposing fluids.

Prior art references relating to oral administration of active agents and addressing one or more of the above challenges include WO2018/213600 A1 and US2017/156347 A1.

Ingestible capsules have been proposed that include a delivery member formed as a solid from a formulation containing a therapeutic payload, wherein the delivery member is forced from the capsule into the tissue of the lumen wall to deliver the payload. The payload is inserted into the tissue and will dissolve and be absorbed into the patient's body over time. Even though the capsule may be able to be correctly oriented relative to the target site, it is still able to move to another location after the payload is deployed. This carries the risk that the payload will be partially or completely removed from the target site due to the movement of the capsule.

In view of the foregoing, it is an object of the present invention to provide an ingestible device for swallowing into the lumen of the gastrointestinal tract and which is highly effective and reliable in ensuring proper deposition of a delivery member into the tissue.

Summary of the invention

In the disclosure of the present invention, embodiments and aspects will be described that achieve one or more of the above-mentioned objects or that will achieve objects that will be apparent from the following disclosure and description of exemplary embodiments.

Thus, in a first aspect of the present invention, there is provided an ingestible device adapted to be swallowed into a lumen of the gastrointestinal tract of a patient, the lumen having a lumen wall, the ingestible device comprising:

- a housing defining an interior hollow and comprising a stop geometry and an exit orifice arranged within the interior hollow,

a tissue penetrating member disposable in the housing, the tissue penetrating member having a tissue penetrating first end, a second end opposite the first end, and a radially outwardly facing surface between the first and second ends, and

- an actuator arrangement comprising:

a) a push portion configured to move along an axis from a first position to a second position, the push portion being configured to provide a force on the tissue penetrating member to move the tissue penetrating member from an initial position within the housing to a seated position in which at least a portion of the tissue penetrating member is outside of the housing and at least partially seated in tissue of the lumen wall, and

b) a retainer portion coupled to the push portion for initial axial movement therewith, wherein the retainer portion releasably retains the tissue penetrating member in axial retaining engagement when the push portion assumes the first position,

wherein, as the push portion moves toward the second position, the tissue penetrating member is moved into the tissue until the retainer portion engages with the stop geometry of the shell, thereby axially stopping the retainer portion, after which the push portion moves further to release the axial retaining engagement and advance the tissue penetrating member to its placement position.

According to the first aspect, the tissue penetrating member is effectively disengaged from the push portion at a point in time relative to the movement of the tissue penetrating member from an initial position within the housing to a resting position. Thus, the risks associated with the housing of the ingestible device being accidentally moved relative to the target tissue (which could cause the tissue penetrating member to move away from a designated position) are less severe.

Furthermore, for applications in which the tissue penetrating member constitutes part of or comprises a therapeutic payload, the solution according to the first aspect enables a greater percentage of the therapeutic payload to be placed in the tissue and subsequently released into the bloodstream, compared to prior art solutions in which only a portion of the tissue penetrating member is placed in the tissue.

In some embodiments, the stop geometry is formed by the housing shell. In other embodiments, the stop geometry is formed by a component fixedly mounted relative to the housing shell. In various embodiments, the retainer portion can be configured to directly engage the stop geometry of the housing. In other embodiments, the retainer portion engages the stop geometry of the housing through one or more intermediate components.

In some embodiments, when the tissue penetrating member assumes an initial position, the retainer portion assumes a starting position, and wherein the retainer portion is displaced by a driven movement relative to the push portion, moving from the starting position towards the stop geometry.

In some forms, the retainer portion is in frictional engagement with the push portion when assuming a starting position, and wherein the push portion overcomes the frictional engagement when the retainer portion engages the stop geometry.

In a further form, the retainer portion releasably engages the push portion when assuming a starting position, for example by frictional engagement or snap engagement, and wherein the push portion is released from engagement with the retainer portion when the retainer portion engages the stop geometry.

In a further form of the ingestible device, the retainer portion is formed as a sleeve that interconnects the push portion and the tissue penetrating member when the retainer portion is driven relative to the push portion.

In some embodiments, the retainer portion may include at least one radially resilient clamping member that provides a radially inwardly directed force on the tissue penetrating member, wherein the radially resilient clamping member cooperates with the stop geometry of the shell to release the radially inwardly directed force when the retainer portion engages the stop geometry.

In some further embodiments, the retainer portion defines a distally facing end surface, and wherein, when the retainer portion retains the tissue penetrating member in axial retaining engagement, the distally facing end surface at least partially surrounds the tissue penetrating member, and the tissue penetrating member extends distally from the distally facing end surface of the retainer portion.

In a further form, the retainer portion includes at least one piercing portion axially projecting from the distally facing end surface of the retainer portion, the at least one piercing portion extending axially beyond the first end of the tissue penetrating member. In various embodiments, when the push portion assumes the first position, the piercing portion projects axially distally beyond the distal end of the tissue penetrating member, for example by projecting further distally than the first end of the tissue penetrating member by a distance in the range of 0.5 mm to 3 mm.

In some embodiments, the push portion and the retainer portion are formed as an integrally formed component formed from a deformable material, and wherein the retainer portion deforms to release the retaining force when engaging the stop geometry.

In a further embodiment, an additional stop feature is associated with the housing, the additional stop feature being configured to block the axial movement of the push portion when the push portion adopts the second position. In some embodiments, the additional stop feature is formed by the housing shell. In other embodiments, the additional stop feature is formed by a component fixedly mounted relative to the housing shell. In different embodiments, the push portion can be configured to directly engage with the additional stop feature of the housing. In other embodiments, the push portion engages with the additional stop feature of the housing through one or more intermediate components.

The shell can be formed to include an outer surface portion surrounding the exit hole, wherein the exit hole allows the tissue penetrating member, the retainer portion and the pushing portion to protrude through the exit hole, and wherein the pushing portion in its second position pushes the first end of the tissue penetrating member a predetermined distance away from the outer surface portion, the predetermined distance being selected from 3 to 7 mm, such as 4 to 6 mm, and such as 4.5 to 5.5 mm.

The shell can be configured such that the outer surface portion surrounds the exit hole, the exit hole allows the tissue penetrating member and the pushing portion to protrude through the exit hole, and wherein the pushing portion in its second position pushes the second end of the tissue penetrating member away from the outer surface portion by a predetermined distance, the predetermined distance being selected from 1 to 5 mm, such as 2 to 4.5 mm, and such as 2.5 to 4 mm.

In some further forms, when the tissue penetrating member assumes an initial position, the tissue penetrating first end is axially separated by a separation distance relative to the outer surface portion surrounding the exit hole, thereby enabling the tissue penetrating member to advance toward the tissue at the target position with an acceleration stroke corresponding to the separation distance, and the separation distance is selected within the range of 0.5 mm to 3 mm, such as within the range of 1 mm to 2.5 mm.

In a further embodiment, the push portion and the retainer portion include a protruding section configured to protrude through the exit hole, and wherein at least a portion of the protruding section is made of a material configured to change shape when exposed to gastric fluid, such as by degrading, softening or swelling.

In some forms, the tissue penetrating member is a solid formed partially or completely from a formulation comprising a therapeutic payload, wherein the tissue penetrating member is made of a dissolvable material that dissolves when inserted into tissue of the lumen wall to deliver at least a portion of the therapeutic payload into the tissue.

In an alternative form, the outer portion of the tissue penetrating member defines a surrounding volume, and the formulation comprising the therapeutically active substance therein forms a liquid, gel or powder contained within the surrounding volume.

In some embodiments, the actuator arrangement includes an energy source configured to power the tissue penetrating member to propel it from the housing to a placement position in the inner cavity wall, and wherein a trigger arrangement is coupled to the actuator arrangement for initiating the release of energy from the energy source to drive the pushing portion from the first position to the second position.

In some embodiments, the actuator arrangement comprises a drive spring, such as a compression spring or a tension spring, which is tensioned or configured to be tensioned to power the movement of the push portion from the first position to the second position.

In some forms, the ingestible device is configured as a self-orienting capsule device, wherein when the self-orienting capsule device is at least partially supported by tissue of the inner cavity wall, the self-orienting capsule device is oriented in a direction that allows the tissue penetrating member to be inserted into the inner cavity wall.

In some further forms, when the tissue penetrating member assumes the initial position, the tissue penetrating first end is axially separated from the exit hole by a separation distance, so that the tissue penetrating member can advance toward the exit hole by an acceleration stroke corresponding to the separation distance. An exemplary separation distance can be set to be greater than 0.5 mm, such as greater than 1 mm, such as greater than 1.5 mm, such as greater than 2 mm, such as greater than 3 mm.

In some forms, the push portion and/or tissue penetrating member is configured to move along an axis. In other forms, the components can move along a non-linear path, such as a curved path.

In some forms, the actuator arrangement includes a hub including at least one pair of latches and a retaining portion configured to retain the hub in a pre-actuation configuration. For each pair of latches and retaining portions, the ingestible device defines a soluble firing member that at least partially dissolves in a fluid, such as a biological fluid, a retaining portion contained by one of the housing and the hub, and a deflectable latch contained by the other of the housing and the hub. The deflectable latch can be configured to move laterally relative to an axis, and the deflectable latch defines a first surface having a blocking portion, and a support surface disposed opposite the first surface and configured to interact with the soluble firing member. In the pre-actuation configuration, the blocking portion of the deflectable latch engages the retaining portion in a latching engagement, and the support surface of the deflectable latch interacts with the soluble firing member to limit the movement of the deflectable latch, thereby preventing release of the latching engagement. In a post-actuation configuration wherein the dissolvable firing member has at least partially dissolved, the deflectable latch is permitted to move, thereby releasing the latch engagement between the blocking portion and the retaining portion of the deflectable latch to allow an energy source to actuate/fire the hub.

With this arrangement, the dissolvable portion does not have a dissolvable member that carries the full power or load of the energy source, but is instead designed to simply block the mechanical activation system. The mechanical activation system can be designed to rely on parts made of a suitable high strength material such as plastic, and not leave any undissolved debris that could clog the mechanical activation system.

In an exemplary embodiment, the deflectable latch is configured to move radially relative to an axis. In some examples, the firing shaft and hub movement are linear. In other exemplary embodiments, the firing shaft may not be linear, for example, the firing trajectory of the hub may be arcuate or curved, or may include an arcuate or curved trajectory. Accordingly, the latch may be configured to move laterally relative to the trajectory of the hub to release the hub.

In an exemplary embodiment, multiple pairs of latching and retaining portions are provided, such as two, three, four, five or more pairs of latching and retaining portions, and these pairs of latching and retaining portions are evenly arranged around the axis.

In some embodiments, the dissolvable firing member is common to all latch and retaining portion pairs.

In a further embodiment, the dissolvable firing member is arranged along an axis, wherein at least one pair of latch and retaining portions are arranged radially outside of the dissolvable firing member.

In other variations, one or more dissolvable firing members are arranged in an annular configuration about an axis, for example, wherein the one or more dissolvable firing members surround at least one pair of latch and retaining portions.

The capsule may include one or more openings to allow biological fluids, such as gastric fluids, to enter the capsule for dissolving the dissolvable firing member.

In some embodiments, the energy source is or includes at least one spring configured as a drive spring. Exemplary springs include compression springs, torsion springs, leaf springs, or constant force springs. The spring can be tensioned or configured to be tensioned to provide power to the hub. Other non-limiting exemplary types of energy sources for actuators include compressed gas actuators or gas generators. In some embodiments, in a pre-actuation configuration, the energy source applies a load to the hub, thereby biasing the hub along an axis. In other embodiments, the energy source is configured to apply a load to the hub only when a trigger member or mechanism of the ingestible device is triggered.

In an exemplary embodiment, the ingestible device is configured to be swallowed by a patient and travel into the lumen of the patient's gastrointestinal tract, such as the stomach, small intestine, or large intestine. The capsule of the device may have a certain shape and size to allow it to be swallowed by a subject, such as a human.

In further exemplary embodiments, the ingestible device is configured as a self-righting capsule, wherein when the self-righting capsule is at least partially supported by tissue of the lumen wall, the self-righting capsule is oriented in a direction that allows the delivery member to be inserted into the lumen wall to deliver at least a portion of the therapeutic payload into the tissue. In certain embodiments, the ingestible device can be configured as a self-righting capsule device having a geometric center and a center of mass offset from the geometric center along an axis, wherein when the capsule device is supported by tissue of the lumen wall while being oriented such that the center of mass is laterally offset from the geometric center, the capsule device is subjected to an externally applied torque due to gravity to orient the capsule device such that the axis is oriented in the direction of gravity, thereby enabling the delivery member to interact with the lumen wall at the target location.

In certain embodiments, the self-righting capsule may be configured to define a monostatic body, such as or The body has a shaped body that will tend to reorient itself to its single stable orientation when placed on a surface in any orientation other than the single stable orientation of the body. In a typical embodiment, the single stable orientation of the body aligns the exit aperture so that the exit aperture faces vertically downward toward the supporting tissue at the target location.

In some embodiments, actuation of the actuator arrangement is controlled by a mechanism that is sensitive to the environment of the gastrointestinal tract.

The gastrointestinal environment-sensitive mechanism may include a trigger member, wherein the trigger member is characterized by at least one of the following:

a) the trigger member comprises a material that degrades, corrodes and/or dissolves due to pH changes in the gastrointestinal tract;

b) the trigger member comprises a material that degrades, corrodes and/or dissolves due to the pH in the gastrointestinal tract;

c) the trigger member comprises a material that degrades, corrodes and/or dissolves due to the presence of enzymes in the gastrointestinal tract; and

d) The trigger member comprises a material that degrades, corrodes and/or dissolves due to changes in enzyme concentrations in the gastrointestinal tract.

In an alternative form, the trigger arrangement may also be or include an electronic trigger.

In a second aspect of the present invention, there is provided an ingestible device adapted to be swallowed into a lumen of a patient's gastrointestinal tract, the lumen having a lumen wall, the ingestible device comprising:

- a housing defining an interior hollow and comprising a stop geometry arranged within the interior hollow,

a tissue penetrating member disposable in the housing, the tissue penetrating member having a tissue penetrating first end, a second end opposite the first end, and a radially outwardly facing surface between the first and second ends, and

- an actuator arrangement comprising:

a) an urging portion configured to move from a first position to a second position, the urging portion being configured to provide a force on the tissue penetrating member to move the tissue penetrating member from an initial position within the housing to a seated position in which at least a portion of the tissue penetrating member is outside of the housing and at least partially seated in tissue of the lumen wall, and

b) a retainer portion which, when the push portion adopts the first position, releasably retains the tissue penetrating member, for example by exerting a retaining force on a radially outwardly facing surface of the tissue penetrating member,

Wherein, when the push portion moves toward the second position, the retainer portion engages with the stop geometry of the housing to initiate release of the retaining force, after which the push portion moves further toward the second position until the tissue penetrating member assumes its resting position.

In alternative embodiments, any features defined in relation to the first aspect may be combined with the second embodiment.

By the above arrangement, the orally administered drug substance can be safely and reliably delivered to the stomach wall or intestinal wall of a living mammalian subject. The drug substance can be in the form of, for example, a solid, encapsulated solid, liquid, gel or powder, or any combination thereof.

As used herein, the terms "drug", "drug substance" or "payload" are intended to encompass any drug formulation that can be delivered into or onto a designated target site. The drug can be a single drug compound or a premixed or co-formulated multi-drug compound. Representative drugs include agents such as peptides (e.g., insulin, drugs containing insulin, drugs containing GLP-1 and derivatives thereof), proteins and hormones, biologically derived agents or active agents, hormones and gene-based agents, nutritional formulas and other substances in solid, powder or liquid form. Specifically, the drug can be insulin or a drug containing GLP-1, including analogs thereof and combinations with one or more other drugs.

BRIEF DESCRIPTION OF THE DRAWINGS

The embodiments of the present invention will be described below with reference to the accompanying drawings, in which

1a and 1b show cross-sectional views of a prior art capsule device 100 in a pre-actuation configuration and a post-actuation configuration, respectively.

2a and 2b each show a cross-sectional front view of a capsule device 200 according to a first embodiment of the present invention, the device being in a pre-actuation configuration and a post-actuation configuration, respectively.

FIG. 2 c shows a detailed view of a subassembly of the first embodiment capsule device 200 providing a push rod 260 , a retainer sleeve 270 and a payload portion 230 ,

3a and 3b each show a cross-sectional front view of a capsule device 300 according to a second embodiment of the present invention, the device being in a pre-actuation configuration and a post-actuation configuration, respectively.

FIG. 3 c shows a detailed view of selected components of the second embodiment capsule device 300 in a state immediately prior to post-actuation deployment,

4a and 4b are cross-sectional front views of a capsule device 400 according to a third embodiment of the present invention, the device being in a pre-actuation configuration and a post-actuation configuration, respectively.

FIG. 4c is a perspective view of the upper capsule portion 410 of the capsule device 400 of FIGS. 4a and 4b ,

FIG. 4d is a perspective view of the upper portion 451 of the actuator hub of the capsule device 400 of FIGS. 4a and 4b ,

5a and 5b show detailed perspective views of a subassembly of a fourth embodiment of a capsule device, the subassembly consisting of a push rod 560, a retainer sleeve 570 and a payload portion 530, wherein FIG. 5a shows a pre-actuation configuration and FIG. 5b shows a post-actuation configuration.

FIG5c is three cross-sectional side views corresponding to FIG5a of the fourth embodiment subassembly in a pre-actuation configuration,

FIG5d is three cross-sectional side views corresponding to FIG5b of the fourth embodiment subassembly in an actuated configuration,

6a and 6b show detailed perspective views of a subassembly of a capsule device of a fifth embodiment, the subassembly consisting of a push rod 660, a retainer sleeve 670 and a payload portion 630, wherein FIG. 6a shows a pre-actuation configuration and FIG. 6b shows a post-actuation configuration,

FIG. 6c is two side views corresponding to FIG. 6a of the fifth embodiment subassembly in a pre-actuation configuration, and

FIG. 6d is two side views corresponding to FIG. 6b of the fifth embodiment subassembly in an actuated configuration.

In the drawings, similar structures are mainly denoted by similar reference numerals.

DETAILED DESCRIPTION

When terms such as "upper" and "lower", "right" and "left", "horizontal" and "vertical" or similar relative expressions are used below, these terms refer only to the drawings and do not necessarily refer to actual usage. The figures shown are schematic representations and therefore the construction of the different structures as well as their relative sizes are intended for illustrative purposes only. When the term member or element is used for a given component, it generally means that the component is a single component in the described embodiment, however, the same member or element may alternatively include multiple sub-components, just as two or more of the described components may be provided as a single component, for example manufactured as a single injection molded part. The terms "assembly" and "subassembly" do not mean that the components described must be able to be assembled during a given assembly process to provide a single or functional component or subassembly, but are merely used to describe components grouped together as being more closely related in function.

Referring to Figures 1a and 1b, an exemplary prior art drug delivery device 100 is shown, which is disclosed in WO2020/245448A1 and has a specific actuation principle for deploying a solid dose from a solid dose capsule device. The prior art capsule device 100 shown is intended to be ingested by a patient to allow the capsule device to enter the gastric cavity, then be oriented relative to the stomach wall, and finally deploy a solid dose payload for insertion at a target location in the gastric wall tissue. For the capsule device 100, the general principle for orienting the capsule relative to the stomach can utilize the principles disclosed in WO 2018/213600 A1.

The ingestible self-righting capsule device 100 includes a first portion 100A having an average density, and a second portion 100B having an average density different from the average density of the first portion 100A. The capsule device 100 contains a payload portion 130, which is used to carry a drug for release in the body of a subject who ingests the article. In the illustrated device, the average density of the capsule device before deployment is greater than the average density of gastrointestinal fluid, so that the capsule device can sink to the bottom of the stomach cavity. The outer shape of the self-righting article is Shape, that is A shape that, when placed on a surface in any orientation other than a single stable orientation of the shape, will tend to reorient itself to its single stable orientation.

The capsule device shown comprises the upper (proximal) capsule part 110 that cooperates and is attached to the lower (distal) capsule part 120. The upper capsule part 110 and the lower capsule part 120 together constitute the capsule of the device. The capsule defines the inner hollow that holds the effective load part 130, keeps and drives the hub 150 of the effective load part 130 forward, and comprises the firing and propulsion mechanism of the actuator, and the actuator is configured to actuate and drive the hub with effective load forward for drug delivery. The effective load part 130 is oriented along the firing axis and is configured to move along the firing axis. In the device shown, the upper capsule part 110 and the lower capsule part 120 form the rotationally symmetrical part symmetrical around the firing axis. In the accompanying drawings, the device is oriented to the firing axis vertically pointing, wherein the effective load part 130 vertically points downward to the outlet hole 124 that is centrally arranged in the lower capsule part 120, and the outlet hole allows the effective load part 130 to be transported and shift out of the capsule device 100 by the outlet hole. The lower portion 120 includes a tissue engaging surface 123 formed as a substantially planar lower outer surface surrounding an exit aperture 124 .

With regard to materials suitable for the capsule portion of the device shown in Figures 1a and 1b, the upper portion 110 may suitably be made of a low density material such as polycaprolactone (PCL), while the lower portion 120 may suitably be made of a high density material such as 316L stainless steel.

In the illustrated prior art device, due to the density distribution of the entire capsule device 100, and due to the external shape of the device, the capsule device 100 will tend to orient itself in a manner such that the firing axis is substantially perpendicular to a surface (e.g., a surface substantially orthogonal to gravity, a tissue surface, such as the wall of the gastrointestinal tract). Thus, the capsule device tends to orient relative to the direction of gravity so that the tissue engaging surface 123 is facing vertically downward.

The interior of the upper capsule part 110 includes a sleeve-shaped hub guide structure 115, which extends from the upper part of the upper capsule part 110 to the hub stop surface 128 concentrically with the firing axis, and the hub stop surface 128 is defined by the inner bottom surface (i.e., the stop surface facing the proximal side) formed in the lower capsule part 120. In addition, in the illustrated device, the second sleeve-shaped structure 114 is concentric with the firing axis and extends radially and downward along the firing axis from the upper capsule part 110 inside the hub guide structure 115. The second sleeve-shaped structure 114 acts as a retaining structure for resisting the driving force from the tensioning drive spring 140 arranged in the capsule to retain the hub 150, that is, the drive spring acts as an actuator for driving the hub forward from the first position to the second position. In the illustrated device, the retaining structure has a radially inwardly protruding retaining portion 113 arranged at the lower end of the retaining structure. In the illustrated device, the retaining portion 113 is provided as two opposite radially inwardly protruding arc-shaped protrusions.

In the prior art device shown in Fig. 1a and Fig. 1b, the effective load portion 130 defines a solid delivery member formed entirely or in part by a preparation containing a therapeutic effective load. In the device shown, the solid delivery member is formed as a thin cylindrical rod shaped to penetrate the tissue of the lumen wall, and the cylindrical rod has a tissue penetration end and a tail end opposite to the tissue penetration end. The tissue penetration end of the rod is pointed so as to be easily inserted into the tissue of the lumen wall, and in the device shown, the tail end defines a truncated cylinder cut off by 90 degree cutting. A non-limiting example of a drug suitable for delivery by the capsule device 100 is a dry compressed API, such as insulin.

The hub 150 includes an upper retaining portion 151 and a lower interface portion 155 configured to hold the trailing end of the payload portion 130 in place. In the illustrated arrangement, the interface portion includes a downwardly facing opening that receives the trailing end of the payload portion 130 in a manner such that the payload portion 130 is securely attached within the opening. The lower interface portion 155 further defines an annular outer flange having a diameter slightly smaller than the diameter of the hub guide structure 115. In the illustrated arrangement, the hub 150 is movable while being guided by the hub guide structure 115 for axial movement from the pre-actuation configuration shown in FIG. 1a to the post-actuation configuration shown in FIG. 1b.

About the drive spring 140 mentioned above, in capsule device 100, the spiral compression spring is arranged coaxially with the firing shaft. The proximal end of the drive spring 140 is seated against the spring seat of the upper capsule part 110, i.e., radially located between the hub guide structure 115 and the retaining structure. The distal end of the drive spring 140 is seated against the spring seat formed by the proximal surface of the flange defined by the lower interface part 155 of the hub 150. As a part of assembling capsule device 100, the drive spring 140 has been energized by axially compressing the drive spring 140 between two spring seats. Therefore, the hub initially bears the load from the drive spring, such as about 10-30N. As an alternative to using a compression spring to generate a driving force, other spring configurations can be used to energize the capsule device 100, such as a torsion spring, a leaf spring, a constant force spring or a similar spring. In a further alternative, a gas spring or a gas generator can be used.

The upper retaining portion 151 of the hub 150 includes a deflectable latch provided in the form of two deflectable arms 152 extending in a distal direction from the upper end of the hub toward the outlet opening 124, each arm being resiliently deflectable in a radially inward direction. The end of each deflectable arm 152 includes a blocking portion 153 protruding radially outward from the resilient arm. In the pre-actuation configuration shown in FIG. 1 a, the distal surface of each blocking portion 153 engages with the proximal surface of a corresponding one of the retaining portions 113. Since the blocking portion 153 is initially located proximal to the retaining portion 113, the hub 150 cannot move distally past the retaining portion 113 unless the deflectable arm 152 is sufficiently deflected in a radially inward direction.

In the pre-actuation configuration, the dissolvable pellet 195 is arranged between the two deflectable arms 152 so that the radially opposite surfaces of the pellet 195 engage the radially inwardly facing support surfaces of the two deflectable arms 152. In the illustrated device, the pellet 195 is arranged in a compartment inside the upper capsule portion 110, and the upper opening disposed proximally in the upper capsule portion 110 facilitates exposure of the fluid to the dissolvable pellet when the capsule device is immersed in the fluid. In the pre-actuation configuration shown in FIG. 1a, since the dissolvable pellet 195 assumes an incompressible state, the pellet prevents the two deflectable arms from bending inwardly. However, once exposed to the fluid, such as the gastric fluid present in the patient's stomach, the dissolvable pellet begins to dissolve. The pellet 195 is designed to dissolve gradually so that after a predetermined activation time, the pellet dissolves to a certain extent so that the two deflectable arms 152 are fully deflected inwardly, thereby enabling the blocking portion 153 of the hub 150 to move distally past the retaining portion 113. In this state, i.e., the post-actuation configuration, the hub 150 has been actuated and the load of the drive spring 140 is pressing the hub 150 distally toward the exit orifice 124. The hub 150 drives the payload portion 130 distally, with the payload tip initially protruding from the capsule and gradually pressing out the remaining payload portion 130. When the hub 150 bottoms out in the lower capsule portion 120, the forward movement of the payload portion 130 stops. This situation is depicted in FIG. 1 b.

In the illustrated device, the interface between the retaining portion 113 and the blocking portion 153 is inclined at approximately 30° so that the deflectable arms will slide inwardly as the dissolvable pellet dissolves. This angle determines the shear force on the pellet and to what extent the deflectable arms will tend to slide inwardly when subjected to a load force. With respect to the acceleration length of the hub when fired, the optimal angle is 0°, but much higher spring forces are required to activate such a configuration. For the inclined portion, in other devices, angles other than 30° may be used.

FIG. 1 b reveals that in the illustrated prior art device, the hub 150 and the payload portion 130 can be brought into a slightly tilted orientation relative to the firing axis. This effect is obtained by a tilting mechanism that tilts the hub 150 when the hub reaches its final destination (i.e., the end-of-stroke position). However, the situation schematically illustrated in FIG. 1 b is somewhat hypothetical, as it only represents the capsule device being fired into an opening, or the payload portion being fired into a fluid.

In the case of intended use, the payload portion 130 is inserted into the tissue of the lumen wall, where it will be anchored generally in the direction along the firing axis. However, at the end of the drive stroke, due to the tilting action of the hub 150, a bending torque is applied to the payload portion 130, tending to break or otherwise release the connection between the payload 130 and the hub 150. This effect is introduced to enable the payload portion 130 to be forcibly separated from the hub 150 to prevent the payload portion 130 from withdrawing from the tissue after being properly placed in the tissue.

At this point, the capsule device 100 has delivered the intended dose and will release relative to the deposited payload portion 130 located within the tissue wall. The remainder of the capsule device will then travel through the user's digestive system to be excreted and disposed of.

If the payload 130 remains fixedly connected to the hub 150, and therefore also fixedly connected to the remainder of the capsule device 100, there is a high probability that the payload portion will be retracted from the tissue due to movement of the capsule device relative to the target site.

In the illustrated prior art device, the tilting motion of the hub 150 upon reaching the final destination is achieved by forming an eccentrically arranged protrusion 158 on the distally facing surface of the interface portion 155 of the hub 150. Since the proximally facing hub stop surface 128 defined by the inner bottom surface formed in the lower capsule portion 120 is flat and oriented orthogonally to the firing axis, the tilting effect is achieved when the hub 150 meets the hub stop surface 128.

For the dissolvable member discussed above, i.e., the dissolvable pellet 195 that forms the dissolvable firing member, different forms and compositions can be used. Non-limiting examples include injection molded Isomalt pellets, compressed granular Isomalt pellets, compressed pellets made from a granular composition of citrate/NaHCO ₃ , or compressed pellets made from a granular composition of Isomalt/citrate/NaHCO _3. Non-limiting exemplary sizes of the dissolvable pellets are 1.5 to 2.5 cm in size when manufactured. 3mm pellets.

In the prior art example of the hub 150 shown, the upper retaining portion 151 is formed as a chamber in which the dissolvable pellet 195 is received in a close fit. In the device shown, the central upper portion of the capsule device 100 includes an opening for introducing gastric fluid into the capsule. In other devices, the capsule may include fluid inlet openings of other designs, such as multiple openings distributed around the capsule. In some designs, the payload portion 130 is contained in a chamber that is fluid-tightly sealed with the chamber of the dissolvable pellet. In addition, the outlet hole 124 may include a seal to prevent moisture from entering the payload portion chamber before the capsule device 100 is fired.

Turning now to Figures 2a to 2c, a first embodiment of a drug delivery device according to the present invention is schematically shown and will be described. The first embodiment capsule device 200 is configured as an ingestible self-righting capsule device, which includes a first upper portion having a first density, and a second lower portion having a second density different from the first density of the upper portion. The capsule device 200 accommodates a payload portion 230, forming a tissue penetrating member for carrying a drug for release in a subject user who ingests the article. In the illustrated device, at least in the state before deployment, the density of the capsule device is greater than the density of the gastrointestinal fluid, so that the capsule device can sink to the bottom of the gastric cavity. In the illustrated embodiment, the capsule device defines a single static body. The outer shape of the self-righting article is Shape, that is The capsule device 200 is a shaped body that will tend to reorient itself to its single stable orientation when placed on a surface in any orientation other than a single stable orientation of the shape. The first upper portion and the second lower portion are provided with a density distribution such that the capsule device 200 quickly seeks to enter a stable orientation in which the central longitudinal axis of the capsule body is oriented vertically or approximately vertically so that the tissue penetrating member 230 aligned with the trigger axis (coaxial with the longitudinal axis) assumes an orientation approximately perpendicular to the tissue wall portion supporting the lower portion of the capsule.

Accordingly, the first embodiment capsule device 200 includes an upper (proximal) capsule portion 210 that is matched and attached to a lower (distal) capsule portion 220. The two portions 210 and 220 are connected to each other by snap-fit connection. In other embodiments, the two portions 210 and 220 are connected by other mounting methods, such as by threaded connection or bayonet connection. The upper capsule portion 210 and the lower capsule portion 220 together constitute the outer shell portion of the capsule device 200, i.e., the outer portion of the capsule shell. The capsule defines an internal hollow that accommodates the payload portion 230, an assembly of components of a push member/hub 250 that is combined to form a push member/hub 250 that holds and drives the payload portion 230 forward, and an actuation arrangement that is configured to actuate and drive the push member/hub 250 with the payload portion 230 forward for drug delivery. The payload portion 230 is initially arranged in a sealed payload chamber and oriented along the trigger axis. The payload portion 230 is configured to move along the trigger axis when the capsule device is triggered. In the illustrated device, the outer portions of the upper capsule portion 210 and the lower capsule portion 220 form a generally rotationally symmetrical portion whose axis of symmetry is arranged coaxially with the trigger axis. In the drawings, the device is oriented with the trigger axis pointing vertically, wherein the payload portion 230 is pointing vertically downward toward an exit hole 224 centrally arranged in the lower capsule portion 220, which allows the payload portion 230 to be transported through the exit hole and removed from the capsule device 200. As shown, the lower portion 220 includes a tissue engaging surface 223 formed as a substantially flat lower outer surface surrounding the exit hole 224.

For the capsule device 200 in the pre-actuation configuration, the payload portion 230 takes the position shown in FIG. 1a in the sealed payload chamber, so that the distal surface of the payload portion is axially separated from the distal surface surrounding the outlet opening, that is, separated by a separation distance, so that the payload portion can be accelerated toward the outlet opening and further toward the tissue surface by an acceleration stroke corresponding to the separation distance. In this embodiment, the separation distance is selected from about 2-3 mm.

Regarding exemplary materials for the capsule components of capsule device 200, upper portion 210 may be suitably made of a low-density material such as polycaprolactone (PCL) or polyetheretherketone (PEEK), while lower portion 220 may be suitably made of a high-density material such as 316L stainless steel.

The interior of the upper capsule part 210 includes a first sleeve-shaped structure 215, which extends concentrically with the trigger axis and provides a radially inwardly facing cylindrical hub guide structure, which extends concentrically with the trigger axis from the upper part of the upper capsule part 210 toward the lower capsule part 220. In addition, in the first embodiment, a second sleeve-shaped structure 214 extends concentrically with the trigger axis and radially inside the hub guide structure from the upper capsule part 210 and downward along the trigger axis. The second sleeve-shaped structure acts as a retaining structure and includes a retaining portion 213 for retaining the hub 250 against the driving force from the tensioning compression drive spring 240 arranged in the capsule, that is, the drive spring acts as an energy source for driving the hub forward from the first position to the second position.

The upper retaining portion 251 of the hub 250 includes a deflectable latch provided in the form of two deflectable arms 252 extending in the distal direction from the upper end of the hub, each arm being resiliently deflectable in the radially inward direction. The end of each deflectable arm 252 includes a blocking portion 253 protruding radially outward from the resilient arm. In the pre-actuation configuration shown in FIG. 1 a, the distally facing surface of each blocking portion 253 engages with the proximally facing surface of a corresponding one of the retaining portions 213. Since the blocking portion 253 is initially located proximal to the retaining portion 213, the hub 250 cannot move distally past the retaining portion 213 unless the deflectable arm 252 is sufficiently deflected in the radially inward direction.

In the pre-actuation configuration, the dissolvable pellet acts as a dissolvable latch support 295, which is arranged between the two deflectable arms 252, so that the radially opposite surfaces of the dissolvable latch support 295 engage with the radially inwardly facing support surfaces of the two deflectable arms 252. In the illustrated device, the dissolvable latch support 295 is arranged in a compartment inside the upper capsule portion 210, and the upper opening disposed proximally in the upper capsule portion 210 facilitates exposure of the fluid to the dissolvable latch support when the capsule device is immersed in the fluid. In the pre-actuation configuration shown in FIG. 1a, since the dissolvable latch support 295 assumes an incompressible state, the pellet prevents the two deflectable arms from bending inwardly. However, once exposed to a fluid, such as gastric fluid present in the patient's stomach, the dissolvable latch support begins to dissolve. The dissolvable latch support 295 is designed to dissolve gradually so that after a predetermined activation time, the pellet dissolves to a degree that the two deflectable arms 252 are sufficiently deflected inwardly to allow the blocking portion 253 of the hub 250 to move distally past the retaining portion 213. In this state, i.e., the in-activation configuration, the hub 250 has been actuated and the load of the drive spring 240 is pressing the hub 250 distally toward the exit orifice 224. The hub 250 drives the payload portion 230 distally, initially protruding from the capsule, and gradually pressing the payload portion 230 deeper into the supporting tissue. When the hub 250 bottoms out relative to the lower capsule portion 220, the forward movement of the payload portion 230 stops. This situation is depicted in Figure 1b.

In the illustrated device, the interface between the retaining portion 213 and the blocking portion 253 is inclined at approximately 30° so that the deflectable arms will slide inwardly as the dissolvable pellet dissolves. This angle determines the shear forces on the pellet and to what extent the deflectable arms will tend to slide inwardly when subjected to load forces. With respect to the acceleration length of the hub when fired, the optimal angle is 0°, but much higher spring forces are required to activate such a configuration. For the inclined portion, in other devices, angles other than 30° may be used.

The first embodiment capsule device 200 further includes a pair of sealing elements 280, 290 for maintaining the payload portion 230 in fluid isolation from the environment outside the capsule device 200 prior to actuation. In the illustrated embodiment, the upper sealing element 290 formed as a ring of a soft, pliable material such as an elastomeric material is inserted between the lowermost annular surface of the second sleeve-shaped structure 214 and the proximally facing annular flange surface of the hub 250.

Another sealing element, the lower sealing element 280, is formed as a fluid gate, which is configured to keep the outlet hole 224 fluid blocked before actuation. In the illustrated embodiment, the sealing element 280 includes an elastomeric sealing member having a generally disc-shaped form. The outer periphery of the sealing element 280 is mounted below the lowermost annular surface of the hub guide structure 215 and clamped above the proximal-facing annular surface of the lower capsule portion 220. As disclosed in US2020/0129441 A1, the central region of the sealing element 280 may include a fluid gate formed to provide a self-sealing valve, such as formed by one or more thin cuts (e.g., one or more thin slits) extending partially or completely through the thickness of the fluid gate.

Thus, the sealing elements 280 and 290 cooperate to form a compartment inside the capsule device 200 that is used to keep the payload portion 230 fluidly isolated from the biological fluid outside the capsule device 200 prior to actuation, but allows the payload portion to easily pass through the sealing element 280 when actuated for delivery of the payload into tissue.

In the illustrated embodiment, the hub 250 includes an upper retaining portion 251 and a lower interface portion 255. The lower interface portion 255 defines an annular outer flange having a diameter slightly smaller than the diameter of the hub guide structure 215. The distally facing end surface of the lower interface portion 255 includes a hole extending proximally at the center of the lower interface portion 255. A proximally facing hole 256 is formed in the distally facing surface of the lower interface portion 255. The hole 256 is configured to fixedly receive a proximal portion of a push rod 260 that is used to transmit distal forces from the hub 250 to the payload portion 230.

In this embodiment, the payload portion 230 is formed as a small cylindrical piece having outer dimensions of approximately 0.82 mm high. Other sizes and different shapes of payload portions may be used in alternative embodiments. For example, the distal-facing surface of the payload portion 230 shown may be formed in a different manner, for example, with a sharp distal spike portion pointing toward the center of the exit hole 224.

Referring primarily to FIG. 2c, in the illustrated embodiment, the payload portion 230 is not directly attached to the push rod 260, but rather abuts the push rod 260 from the outset or will engage the push rod 260 during a portion of the displacement that the push rod 260 undergoes during actuation. A retainer portion provided in the form of a retainer sleeve 270 is not directly retained by the push rod 260, but rather surrounds both the push rod 260 and the proximal portion of the payload and, in the pre-actuation configuration, is attached to both the push rod 260 and the payload portion 230. The retainer sleeve 270 is formed with a distal portion 271 formed as a generally cylindrical sleeve having an inner diameter that generally corresponds to the outer diameter of the distal portion 263 of the push rod 260. The inner diameter of the cylindrical sleeve also generally corresponds to the outer diameter of the payload portion 230. The retainer sleeve 270 is also formed such that at the proximal end of the cylindrical sleeve, a circular flange 277 extends radially outwardly from the outer wall of the cylindrical sleeve. The circular flange 277 of the retainer sleeve 270 defines a distally facing stop surface 278 and a proximally facing surface 279, wherein the distally facing stop surface 278 is configured to cooperate with the hub stop surface 228 through the sealing element 280, and the proximally facing surface 279 is configured to cooperate with the lower interface portion 255 of the hub 250.

In the illustrated embodiment, the dimensions of the inner surface of the cylindrical sleeve of the retainer sleeve 270 are selected so as to provide a friction fit between the distal end 272 of the retainer sleeve 270 and the payload portion 230. In addition, in the illustrated embodiment, a cooperating releasable snap geometry is formed between the push rod 260 and the retainer sleeve 270. In FIG. 2 c , the snap geometry can be shown as an inner snap geometry 274 formed on the retainer sleeve 270 and an outer snap geometry 264 formed on the push rod 260. In the illustrated embodiment, the dimensions of the retainer sleeve 270 are such that the retainer sleeve distal portion 272 axially overlaps the payload portion 230 in a manner such that approximately half of the axial height of the payload portion is gripped by the retainer sleeve distal portion 272, i.e., a distance indicated as “d” in FIG. 2 c .

Non-limiting exemplary materials for retainer sleeve 270 and push rod 260 may be selected to be relatively resilient polymeric materials, such as materials formed of PEEK. Alternative materials for retainer sleeve 270 may be formed of an elastomeric material, such as silicone rubber.

Referring again to FIG. 2a , it can be seen that the push rod 260 is suspended from the lower interface portion 255 of the hub 250. Although in the illustrated embodiment, the two components are formed as two separate parts that are connected during assembly, alternative embodiments may provide corresponding features through a single component. In this embodiment, the system is designed so that in the pre-actuation configuration, the distal surface of the payload portion 230 is arranged approximately 2 mm from the tissue engagement surface 223, which means that before the payload portion engages the adjacent tissue below the exit hole 224, the assembly formed by the hub 250, the push rod 260, the retainer sleeve 270 and the payload portion 230 moves together for an acceleration stroke of approximately 2 mm.

In the illustrated embodiment, the push rod 260 is further sized such that the insertion depth of the distal portion of the payload portion 230 is approximately 4 mm relative to the tissue engaging surface 223. In the illustrated embodiment, the lower interface portion 255 of the hub 250 forms a distally facing blocking surface that is configured to abut against a proximally facing surface 279 of the retainer sleeve 270. The distally facing surface 278 of the retainer sleeve 270 is configured to abut against a proximally facing surface of the sealing element 280.

Turning now to the operation of the first embodiment capsule device 200, first refer to FIG. 2a, which shows a capsule in an initial state, which represents the state that the capsule device assumes during storage or just after ingestion. In this state, the hub 250 assumes a pre-actuation configuration, wherein the two deflectable arms 252 are held in the illustrated position by engaging with the radially outwardly facing surface of the dissolvable latch support 295, which engages the radially outwardly facing surface 252a of the deflectable arms 252. As a result, the blocking portion 253 engages the proximal surface of a corresponding one of the retaining portions 213, thereby preventing the deflectable arms from sliding relative to the retaining portion. Since the deflectable arms 252 are confined to the proximal side of the retaining portion 213, the hub 250 cannot move distally even if the drive spring 240 applies its full compressive load to the hub 250.

The upper sealing element 290 engages the lowermost annular surface of the second sleeve-shaped structure 214 and the proximally facing annular flange surface of the hub 250 to maintain the interface as a fluid-tight seal. In addition, the lower sealing element 280 maintains the outlet hole 224 as a fluid-tight seal.

After the capsule device 200 is ingested, the capsule device sinks rapidly to the bottom of the stomach. When supported by the stomach wall, due to the self-righting ability of the capsule device, the capsule device will quickly reorient so that its tissue engagement surface 223 engages the tissue stomach wall, wherein the trigger axis of the capsule device is oriented almost vertically, that is, the payload portion 230 and the push rod 260 point downward. Due to exposure to gastric fluid, the soluble latch support 295 has begun to dissolve. This is shown in Figure 1b in relation to the reference 295. The support of the soluble latch support 295 against the deflectable arm 252 will stop at a specific time after swallowing. The load of the drive spring 240 will cause the deflectable arm 252 to gradually deflect radially inward, thereby allowing the arm to slide out of engagement with the retaining portion 113. At a certain point in time, the deflectable arm 252 will reach its radially collapsed position, after which the hub 250, the push rod 260, the retainer sleeve 270 and the payload portion 230 with the payload will be released from the capsule shell. This state corresponds to the actuated configuration (not shown).

When the drive spring 240 applies a load to the hub 250, the push rod 260, the retainer sleeve 270 and the effective load portion 230 are caused to move unimpeded toward the outlet hole 224 as the hub 250 follows, wherein the effective load portion penetrates the lower sealing element 280 and further enters the mucosal tissue at the target position. During the distal movement of the components, the distally facing stop surface 278 of the retainer sleeve will engage with the lower sealing element 280 and will be prevented from moving further distally. However, in this state, the residual load of the drive spring 240 will still further push the push rod 260 distally. Since the snap-fit engagement 264/274 defines a relatively weak force transmission, the snap-fit engagement will be released, thereby causing the push rod 260 to move further distally with the effective load portion 230 so as to perform a distal sliding movement relative to the retainer sleeve 270. Shortly thereafter, the payload portion will be pushed by the push rod 260 to the target depth in the tissue, which occurs when the distally facing blocking surface of the lower interface portion 255 of the hub 250 engages the proximally facing surface 279 of the retainer sleeve 270 in abutting contact. This prevents the hub 250 from moving further distally. FIG2 b depicts this state, but it should be noted that the spring is only schematically shown in the expanded state. In a real life scenario, the spring will expand between the proximal spring seat and the lower interface portion 255.

In the illustrated embodiment, the target insertion depth of the distal face of the payload portion is designed to be about 4 mm into the mucosal tissue. For stomach wall deployment, further exemplary insertion depths may be selected from 3 to 7 mm, such as 4 to 6 mm, or such as 4.5 mm to 5.5 mm.

In the case of intended use, the payload portion 230 is inserted into the tissue of the lumen wall, where it will be anchored generally in the direction along the actuation axis. As described in the present disclosure, depending on the specific design of the capsule device, the payload portion 230 will be actively released from the remainder of the capsule at the end of the insertion stroke. When the capsule device 200 has delivered the intended dose, the capsule will be released relative to the deposited payload portion 230 retained in the tissue wall to release the therapeutic agent into the subject's bloodstream.

Next, turn to the second embodiment 300 of the capsule, see Figures 3a to 3c. The capsule device 300 has many common construction features with the corresponding features of the first embodiment capsule device 200 described above, and the overall operating principle is the same. However, the payload holding portion and the release function have been modified. Parts of the actuation mechanism including the trigger release design have also been modified.

As with the first embodiment, in which the payload retention portion and release functionality is provided by three components, namely the hub 250, the push rod 260 and the retainer sleeve 270, which include a specified relative movement for releasing the payload 230, the second embodiment includes similar functionality in a single, integral component, namely the hub 350. To provide this, the hub 350 is formed of a primarily resilient material that releasably grips the payload portion 330 at the interface surface 356a until the hub 350 is deformed to release the grip, the release being caused by the interaction between the hub and the lower interior surface of the capsule housing.

Referring to FIG. 3 a, which shows a capsule 300 in a pre-actuation configuration, the overall design of the actuation mechanism of the second embodiment device 300 is slightly modified compared to the first embodiment device 200, i.e., the dissolvable latch support 395 is formed as a tapered element to support the resilient arm provided in a V-shaped configuration. The hub 350 includes an upper retaining portion and a lower interface portion 355 of the hub 350, the upper retaining portion being configured to releasably retain the hub relative to the retaining structure 313 of the capsule housing, and the lower interface portion 355 being configured to hold the tail end of the payload portion 330 in place. In the illustrated embodiment, the lower interface portion 355 includes a downward opening 356, which receives the tail end of the payload portion 330 in a manner such that the payload portion 130 is initially firmly retained within the hole. The lower interface portion 355 further defines an annular spring seat for the drive spring 340. In addition, the distally facing end surface of the lower interface portion 355 includes a set of inclined surfaces 355a, which will be discussed further below.

Each resilient arm, i.e., latch arm 353, is resiliently movable in a radially inward direction by rotational movement relative to the upper retaining portion of hub 350. Latch arms 353 each define a radially outwardly facing latching surface configured to engage in latching engagement with a corresponding portion of conical retaining surface portion 313. Each latch arm 353 further includes a radially inwardly facing latching surface configured to cooperate with a centrally disposed conical dissolvable latch support 395.

For the second embodiment capsule device 300, the capsule also includes a pair of sealing elements 380, 390 for maintaining the payload portion 330 in fluid isolation from the environment outside the capsule device 300 prior to actuation. In the illustrated embodiment, the upper sealing element 390 formed as a ring of a soft, pliable material such as an elastomeric material is inserted between the lowermost annular surface of the structure 313 and the proximally facing annular flange surface of the hub 350.

In this embodiment, the hub stop surface 328 of the lower capsule portion 320 is formed with an inclined surface that acts as a release surface of the hub 350, resulting in the release of the payload portion 330 from the hub 350 when the hub 350 cooperates with the hub stop surface 328, i.e., at a position slightly earlier than the end-of-stroke position. The sealing element 380 also includes an inclined surface similar to the hub stop surface 328.

FIG3b schematically shows the capsule device 300 in the actuated configuration, wherein the hub 350 has been completely forced distally against the hub stop surface 238. However, it should be noted that in FIG3b, the cooperating inclined surface 380a of the hub sealing element 380 and the inclined surface 355a of the hub 350 are incorrectly shown as intervening elements, which does not accurately reflect the true situation of the impacted element. The following figure is used to more correctly describe the system before the end of the stroke impact between the hub 350 and the hub stop surface 328.

Fig. 3c shows the capsule device 300 in the state before the actuation state immediately before Fig. 3b. In this illustration of Fig. 3c, it can be seen how the inclined surface 328a/380a with the surface normal pointing to the proximal side and radially outward is configured to cooperate with the inclined surface 355a (of the hub 350) with the surface normal pointing to the distal side and radially inward. The pair of cooperative surfaces are provided as multiple pairs of cooperative surfaces distributed around the firing axis, i.e., symmetrically arranged relative to the firing axis. When the paired cooperative surfaces are engaged, i.e., near the stroke end position of the hub 350 inside the capsule 300, the inclined surface 380a induces a radially outwardly directed force (shown with arrows) on the lower interface part 355, causing these parts of the lower interface part 355 to deform radially outward. This in turn causes the material portion at the interface surface 356a to move radially outward, thereby causing the hole 356 to widen radially, and in this way releases the clamping of the payload part 330.

In the illustrated embodiment, the capsule can be designed so that when the clamp on the payload portion 330 is released, i.e., shortly before the hub 350 is stopped relative to the hub stop surface 328, the inertia of the payload portion 330 will cause the payload to be ejected a little further relative to the release position represented by the post-actuation configuration, and the payload portion will be inserted into the tissue of the lumen wall at the desired insertion depth. However, such a "throwing" effect is merely optional and can be omitted if desired.

4a to 4d , a drug delivery device 400 according to a third embodiment of the present invention is shown and will be described below.

In terms of the principle of self-righting capability and the deployment of the payload into the tissue, the third embodiment capsule device 400 generally corresponds to the overall design of the first example capsule device 200, but the actuator principle and the way the hub is released from the capsule shell are different. In the illustrated embodiment, the assembly consisting of the hub lower portion 460, the retainer sleeve 470 and the payload portion 430 generally corresponds to the design shown in FIG. 2c.

Fig. 4a and Fig. 4b are respectively the side views of the third embodiment capsule device 400 in the configuration before actuation and the configuration after actuation. The drive spring 440 in this design is provided with a tension spring, and its main part extending axially has a constant outer diameter. The winding with increased diameter at the far end of the drive spring 440 helps to install the far end of the drive spring relative to the capsule housing. The spacing element 486 is inserted into the cylindrical hole of the upper capsule part 410. The winding and the spacing element 486 with increased diameter of the spring 440 are axially clamped between the distally facing surface of the upper capsule part 410 and the proximally facing surface of the lower capsule part 420. By introducing a tension spring, the spring interface towards the hub can be placed away from the bottom of the device, thereby maximizing the spring force and the total stroke.

The proximal end of the drive spring 440 includes a reduced diameter winding that facilitates coupling with the hub 450. In the illustrated design, the reduced diameter winding is axially clamped between the proximal flange 456 and the distal flange 459. The distal flange 59 acts as a washer and is rotatably mounted relative to the hub upper portion 451 and the hub lower portion 462 so that torsional forces caused by rotational movement of the hub upper portion 451 and the hub lower portion 462 are not transmitted to the drive spring 440.

In the pre-actuation configuration, the hub lock geometry and the housing lock geometry engage one another to hold the hub 450 in the initial first position against the axial tension load applied by the drive spring 440. The hub lock geometry defines a hub retention surface, while the housing lock geometry defines a housing retention surface. In this embodiment, the hub retention surface and the housing retention surface are provided as inclined geometries 453.1 and 413.1, which will be further described below.

The third embodiment again includes a lower sealing element 480 and an upper sealing element 490 for closing the outlet opening 424, the upper sealing element 490 being arranged between the flange 460 on the hub upper portion 451 and the distally facing rim surface formed in the upper capsule portion 410 for sealing the payload chamber at the interface. In addition, an intermediate seal 485 is also arranged at the interface between the upper capsule portion 410 and the lower capsule portion 420.

The upper capsule portion 410 of the capsule device 400 is depicted in FIG. 4c. The upper capsule portion 410 at this time includes two pellet receiving bags 419 arranged symmetrically about an axis. Only one of the pellet receiving bags 419 is specified for use during assembly, but the symmetry enables the components to be installed in either orientation. Surrounding the central axial channel formed in the upper capsule portion 410, two ramp-shaped geometries 413.1 are formed on the respective shell lock geometries 413, each ramp forming a spirally curved arc surface spanning an angle of approximately 80 degrees and oriented so that the curved surface extends in a distal clockwise direction (from above, see top views 2f and 2g). Each curved surface 413.1 is specified for use with a corresponding curved surface 453.1 of the hub lock geometry formed as a wing-shaped portion 453 by the upper portion 451 of the hub.

As shown in Fig. 4d, the hub upper portion 451 includes a flange 456 and a cylindrical top extending from the flange 456 in the proximal direction. The wing-shaped portion 453 is arranged on the cylindrical top so that the wing-shaped portion protrudes radially outward in a radially opposite manner. Each wing-shaped portion defines a 60-degree wide arc in the rotation direction around the axis. The central axial channel formed by the upper capsule part 410 allows the wing-shaped portion 453 of the hub upper portion 451 to pass through, but only when the hub upper portion 451 is oriented to allow the wing-shaped portion 453 to pass through the spiral curved arc surface 413.1. When the capsule device 400 adopts the pre-trigger configuration, the curved surface 453.1 of the wing-shaped portion 453 is closely engaged with the ramp-shaped geometry 413.1 of the upper capsule part 410, so that the hub upper portion 451 rests on these inclined surfaces, and the tension of the tensioned drive spring 440 pushes the hub upper portion 451 in the distal direction.

Due to the inclined surfaces 413.1 and 453.1, the tension from the drive spring 440 induces a torsional force in a clockwise direction (as viewed from above) on the hub upper portion 451. However, as shown in FIG. 4a, the dissolvable pellet 495 is disposed in one of the pellet receiving pockets 419, and the radially extending surface 453.2 of one of the wings 453 engages with the side surface of the dissolvable pellet 495, thereby preventing the hub upper portion 451 from sliding distally on the inclined surface 413.1.

Turning now to the operation of the third embodiment, after ingestion of the capsule device 400, the capsule device rapidly sinks to the bottom of the stomach. When supported by the stomach wall, and due to the self-righting ability of the capsule device, the capsule device will quickly reorient so that its tissue engaging surface 423 engages the tissue of the stomach wall, wherein the trigger axis of the capsule device is oriented almost vertically, i.e., the payload portion 430 and the push rod 460 are pointing downward. Due to exposure to gastric fluid, the dissolvable pellet 495 has begun to dissolve. This is schematically represented in FIG. 4 b in relation to the reference 495. The support of the dissolvable pellet 495 on the radially extending surface 453.2 will cease at some point, allowing the wing-shaped portion 453 of the upper portion of the hub to slide distally along the curved arc surface 413.1. After the pellet 495 is completely dissolved, or after the pellet 495 is dissolved to a certain extent that the pellet 495 is pushed away from its blocking position in the bag 419, and after the hub upper portion 451 is rotated about 60 degrees, the inclined surface 453.1 of the wing 453 can slide out of the curved arc surface 413.1 and move freely further distally in the capsule device through the central axial passage. As shown in Figure 4b, the distal movement of the hub 450 stops when the hub lower portion 462, more specifically the distal surface 468, bottoms out inside the capsule. In this position, the drive spring 440 has pulled the hub 450 to an axial position in which the flange 477 of the retainer sleeve 470 is clamped between the distal surface 468 and the hub stop surface 428. In this state, the capsule device 400 adopts its deployed configuration.

The subassembly of push rod 460, retainer sleeve 470 and payload part 430 is substantially similar to the corresponding elements of the first embodiment shown in Fig. 2c. However, for the first embodiment, the circular flange 277 of retainer sleeve 270 defines a stop surface 278 facing the distal side, and the stop surface 278 is configured to cooperate with the hub stop surface 228 indirectly through the sealing element 280 to define the stroke end position of push rod 260. In such an embodiment, the housing stop geometry is provided by the surface facing the proximal side of the sealing element 280, and the element is fixedly associated with the capsule housing. In contrast, in the third embodiment capsule device 400, the distal surface 468 of the hub lower part 462 directly engages with the hub stop surface 428, which defines a housing stop geometry that axially prevents the retainer part 460 from moving further.

Turn now to Fig. 5a to Fig. 5d, these figures are different representations of the subassembly of the fourth embodiment capsule device, and this subassembly is made up of push rod 560, retainer sleeve 570 and effective load part 570, and these parts roughly correspond to push rod 260, retainer sleeve 270 and effective load part 230 of the first embodiment.In the fourth embodiment, retainer part 570 is provided as a roughly sleeve-shaped element again.This sleeve is formed with distal part 571, and this distal part 571 is formed as a roughly cylindrical sleeve, and its internal diameter roughly corresponds to the outer diameter of the distal part 563 of the push part (push rod 560).In the embodiment shown, the distal part 571 of retainer sleeve is slightly conical, thereby gradually tapers to a smaller diameter towards its distal end face.This can be conducive to easily inserting retainer sleeve 570 into/cutting into the tissue at the target position of the inner cavity wall.

Since the axially extending slots extend proximally from the most distal part of the retainer sleeve 570 for a short distance, the distal portion 571 forms a number of partially cylindrical shells 572, which are formed as two half shells in the illustrated embodiment. Due to the presence of the slots, the half shells 572 have a certain elasticity in the radial direction and are configured to bend slightly radially outward. The diameter of the payload portion 530 is slightly larger than the inner diameter of the half shells 572, that is, when they take an unbiased state. Therefore, when the payload portion 530 is coaxially radially positioned between the half shells 572, the half shells bend radially outward and are provided with frictional engagement clamping by the retainer sleeve 570, thereby facilitating the releasable axial retention engagement of the payload portion 530 relative to the retainer sleeve 570. It should be noted that other means of providing radial elasticity of the distal portion 571 can be provided in other designs, such as providing a different number of slots and a different geometric shape of the shell or similar element, such as an axially extending arm or a circumferentially extending arm. Such arms are typically defined by a slot separating the arm from the rest of the retainer portion, for example formed by a slot extending in a non-axial direction, such as transverse to the axis and/or having a helical shape.

In yet other embodiments, the retainer portion may not be sleeve-shaped, but may be formed in other ways, such as as a plurality of axially extending arms that are configured to provide radially resilient clamping, such as similar to tweezers, which releasably retains the payload portion on a radially outward surface and/or a distally facing surface.

In the fourth embodiment, at the proximal end of the retainer sleeve 570, a radially outwardly extending flange 577 is provided. The proximal portion of the sleeve also includes two axially extending through slots 573, which are cut axially through the flange 577 and distally into the retainer sleeve. This makes it possible to define two proximal part cylindrical shells, both of which provide a certain elasticity against radial outward movement.

The push rod 560 includes a circular flange 555 at its proximal portion which provides a distally facing stop surface 568 for abutting engagement with a proximally facing surface of a flange 577 of a retainer sleeve 570. Along opposite side portions of the push rod 560, a pair of diametrically opposed snap projections 564 extend radially outward. Each snap projection 564 is configured to be received in a corresponding one of the slots 573 of the retainer sleeve. Each snap projection is formed as an elongated axially extending ridge having a variable width profile in the tangential direction, with a relatively wide first distal projection 564.1, a relatively wide second proximal projection 564.2, and a narrow bridge portion 564.3 connecting the distal projection 564.1 and the proximal projection 564.2.

The through slot 573 is provided with a corresponding snap opening 574 at an axial position of the flange 577, each snap opening being configured to cooperate with the profiled ridges of the protrusions 564.1, 564.2, 564.3. In the view shown in FIG. 5 a, the push rod 560 assumes an initial position, corresponding to a pre-actuation configuration, in which the bridge portion 564.3 is received in the snap opening 574 and the two proximal part cylindrical shells are in a relaxed state. Due to the presence of a wide first distal protrusion 564.1 arranged distally of the snap opening 574 and a wide second proximal protrusion 564.2 arranged proximal to the snap opening, the retainer sleeve 570 is prevented from unintentionally moving proximally and distally relative to the push rod 560.

The retainer sleeve 570 defines a distally facing end face. When the retainer portion 570 holds the payload portion 530 in axially retaining engagement, as shown in FIG5 a, the distally facing end face of the retainer sleeve 570 partially surrounds the payload portion 530, and the payload portion extends distally from the distally facing end face of the retainer portion. Therefore, when the push rod 560 begins to advance, the retainer portion and the payload portion are carried along the distal movement, and the payload portion 530 acts as a tissue penetration member, forcing through the tissue during the entire tissue insertion procedure. More details of the assembly in the pre-actuation configuration can be seen in the side view shown in FIG5 c.

Fig. 5b shows the assembly in the actuation post configuration, wherein the force of the energy source of the capsule device has been triggered for release, and the load of the energy source has completely moved the push rod 560 to the housing stopper. Since the flange 577 will be stopped during the actuation procedure, the push rod will apply a continuous force to the connection between the wide second proximal protrusion 564.2 and the snap opening 574, so that the protrusion 564.2 passes through the snap opening, because the two proximal part cylindrical shells of the retainer sleeve are forced to move radially away from each other. This will enable the push rod 560 to be displaced distally relative to the retainer sleeve 570, and will cause the push rod to force the payload part 530 to move distally relative to the retainer sleeve 570, thereby releasing the axial retention engagement between the two. The molded ridges of the protrusions 564.1, 564.2, 564.3 will further enter the slot 573 until the circular flange 555 of the push rod 560 abuts against the flange 577. The payload portion will be arranged at the desired tissue insertion depth at the target location for proper drug deposition. It should be noted that the payload portion 530 has been axially separated by a distance from the distally facing surface of the retainer sleeve 570. More details of the assembly in the post-actuation configuration can be seen in the side view shown in FIG. 5 d.

Turning now to Figures 6a to 6d, which are different representations of a subassembly of the capsule device of the fifth embodiment, the subassembly consisting of a push rod 660, a retainer sleeve 670 and a payload portion 670, which components generally correspond to the push rod 260, retainer sleeve 270 and payload portion 230 of the first embodiment.

The main difference of the fifth embodiment compared to the first embodiment is that the puncture element 675 extends distally relative to the distal portion of the retainer sleeve 670. According to different embodiments, the puncture element 675 can protrude farther distally than the distal end of the payload portion 630, for example, 0.5 mm to 3 mm farther than the payload portion, that is, the assembly takes a pre-actuation configuration.

The puncture element 675 can be provided with one or more sharp edges and/or sharp geometries to facilitate the puncture of the tissue penetration element 675 and further help improve the penetration of the payload portion 630 when the payload portion 630 enters the shallow portion of the mucosa. One or more optimized geometries provide cutting surfaces at its tip to initiate tissue rupture and thus result in a reduced penetration force for inserting the payload portion. Thus, for some embodiments, the puncture element 675 pierces the tissue only during the initial insertion into the tissue, and when the push rod 660 is displaced relative to the retainer sleeve 670, the payload portion penetrates deeper into the mucosa.

In further embodiments, the retainer sleeve can include a plurality of piercing elements extending distally from the payload portion, with the remainder of the distal sleeve surrounding the payload portion, such as approximately in the axial middle of the payload portion.

For certain embodiments, such as according to various embodiments of the present invention, the presence of small, sharp protruding elements in an oral device may potentially pose a risk of lacerations, tears, punctures, etc. of tissue, particularly the intestine, during transit through the gastric system.

Utilizing softening/swellable/degradable materials to fabricate any components that protrude from the device after drug deposition, such as the retainer sleeve and push rod, would eliminate the risk of injury to gastrointestinal tissue due to reduced mechanical integrity of the protruding elements.

These materials come into contact with the biological environment of the gastric system, i.e., blood, gastric contents (gastric juice), mucus in the stomach, intestinal juice, etc. during API insertion, and induce changes in physical properties. Changes in properties may include, but are not limited to: reduction in material strength and stiffness, or complete dissolution of protruding parts. This may be caused by material degradation (reduction in molecular weight), material softening (weakened intermolecular bonds), material swelling/expansion (binding with water), etc.

When the capsule device enters a narrower section of the gastrointestinal system (ie, intestine or ileocecal valve) and tissue may tightly surround the capsule device, the protruding member will be weak/soft enough to deflect potential forces between the device and the tissue, thereby avoiding any damage to the tissue.

Possible materials may be provided, but are not limited to PVA, copolymers of PCL/PDS/PLA, rigid hydrogels or any dissolvable material that can be manufactured in solid form (eg compressed powder). In alternative embodiments, algae-based materials may also be used.

In alternative embodiments, the components can be designed differently so that only one of the components, primarily the outermost component, needs to swell, soften, or degrade, which can then protect the remaining, still rigid components. For example, the outermost component can be coated in a hydrogel that swells to several times its original geometry. Alternatively, the outermost component is made only of a material that will swell to several times its original size but will not degrade in a biological environment. The method for providing safe passage of a post-actuation capsule device can be used in conjunction with any of the embodiments described in the present disclosure.

Although the above description of the exemplary embodiments is primarily directed to ingestible capsules for delivery in the stomach, the present deployment principles are generally applicable to capsule devices generally for intraluminal insertion, wherein the capsule device is positioned into a body cavity for deployment of a delivery member or other tissue interface component, such as a sensor configured as a monitoring device. In addition to the gastric administration device discussed above, non-limiting examples of capsule devices according to various aspects of the present invention may also include capsule devices for intestinal delivery of drugs by delivery into the tissue wall of an intestinal cavity, such as a small intestinal cavity or a large intestinal cavity.

In the above description of the exemplary embodiments, different structures and means for providing the described functions for the different components have been described to the extent that the concept of the invention will be readily understood by a skilled reader. The detailed construction and specifications of the different components are considered to be the object of a normal design procedure performed by a skilled person along the lines set forth in this specification.

Claims (15)

1. An ingestible device (200, 300, 400) adapted to be swallowed into a lumen of a patient's gastrointestinal tract, the lumen having a lumen wall, the ingestible device comprising: - a housing (210, 220, 310, 320, 410, 420) defining an interior hollow and comprising a stop geometry (228, 328, 428) and an outlet aperture (224, 324, 424) arranged within the interior hollow, a tissue penetrating member (230, 330, 430, 530, 630) disposable in the housing, the tissue penetrating member having a tissue penetrating first end, a second end opposite the first end, and a radially outwardly facing surface between the first and second ends, and - an actuator arrangement comprising: a) a push portion (260, 360, 460, 560, 660) configured to move along an axis from a first position to a second position, the push portion being configured to provide a force on the tissue penetrating member to move the tissue penetrating member from an initial position within the housing to a seated position in which at least a portion of the tissue penetrating member is outside the housing and at least partially seated in tissue of the lumen wall, and b) a retainer portion (270, 370, 470, 570, 670) coupled to the push portion (260, 360, 460, 560, 660) for initial axial movement therewith, wherein the retainer portion releasably retains the tissue penetrating member (230, 330, 430, 530, 630) in axial retaining engagement when the push portion assumes the first position, wherein, as the pushing portion (260, 360, 460, 560, 660) moves toward the second position, the tissue penetrating member (230, 330, 430, 530, 630) is moved into the tissue until the retainer portion (270, 370, 470, 570, 670) engages with the stop geometry (228, 328, 428) of the shell, thereby axially stopping the retainer portion, after which the pushing portion (260, 360, 460, 560, 660) moves further to release the axial retaining engagement and advance the tissue penetrating member (230, 330, 430, 530, 630) to its placement position. 2. An ingestible device according to claim 1, wherein, when the tissue penetrating member (230, 330, 430, 530, 630) assumes an initial position, the retainer portion (270, 370, 470, 570, 670) assumes a starting position, and wherein the retainer portion moves from the starting position toward the stop geometry (228, 328, 428) by a driven motion relative to the pushing portion (260, 360, 460, 560, 660). 3. An ingestible device according to claim 2, wherein, when the retainer portion (270, 370, 470, 570, 670) assumes the starting position, it releasably engages the push portion (260, 360, 460, 560, 660), for example by friction engagement or snap engagement (264, 274, 564, 574, 664, 674), and wherein, when the retainer portion engages with the stop geometry (228, 328, 428), the push portion is released from engagement with the retainer portion. 4. An ingestible device according to any one of claims 2-3, wherein the retainer portion (270, 370, 470, 570, 670) is formed as a sleeve, and when the retainer portion is driven relative to the pushing portion (260, 360, 460, 560, 660), the sleeve connects the pushing portion and the tissue penetrating member (230, 330, 430, 530, 630) to each other. 5. An ingestible device according to any one of claims 1-2, wherein the retainer portion (270, 370, 470, 570, 670) includes at least one radial elastic clamping member, which provides a radially inwardly directed force on the tissue penetrating member (230, 330, 430, 530, 630), wherein the radial elastic clamping member cooperates with the stop geometry (228, 328, 428) of the shell to release the radially inwardly directed force when the retainer portion engages the stop geometry. 6. An ingestible device according to any one of claims 1-5, wherein the retainer portion (270, 370, 470, 570, 670) defines a distally facing end surface, and wherein, when the retainer portion retains the tissue penetrating member (230, 330, 430, 530, 630) in axial retaining engagement, the distally facing end surface at least partially surrounds the tissue penetrating member, and the tissue penetrating member extends distally from the distally facing end surface of the retainer portion. 7. An ingestible device according to any one of claims 1-6, wherein the retainer portion (270, 370, 470, 570, 670) includes at least one piercing portion (675) protruding axially from the distal-facing end surface, and the at least one piercing portion extends axially beyond the first end of the tissue penetrating member (230, 330, 430, 530, 630). 8. An ingestible device according to any one of claims 1-7, wherein the shell includes an outer surface portion (223, 323, 423) surrounding the exit hole (224, 324, 424), wherein the exit hole allows the tissue penetrating member (230, 330, 430, 530, 630), the retainer portion (270, 370, 470, 570, 670) and the pushing portion (260, 360, 460, 560, 660) to protrude through the exit hole, and wherein the pushing portion pushes the first end of the tissue penetrating member a predetermined distance away from the outer surface portion in its second position, the predetermined distance being selected from 3 to 7 mm, such as 4 to 6 mm, and such as 4.5 to 5.5 mm. 9. An ingestible device according to any one of claims 1-8, wherein, when the tissue penetrating member (230, 330, 430, 530, 630) assumes an initial position, the tissue penetrating first end is axially separated by a separation distance relative to an outer surface portion surrounding the exit hole (224, 324, 424), thereby enabling the tissue penetrating member to advance toward the tissue at the target position through an acceleration stroke corresponding to the separation distance. 10. An ingestible device according to any one of claims 1-9, wherein the push portion (260, 360, 460, 560, 660) and the retainer portion (270, 370, 470, 570, 670) include a protruding segment configured to protrude through the outlet hole (224, 324, 424), and wherein at least a portion of the protruding segment is made of a material configured to change shape when exposed to a biological fluid such as gastric fluid, for example by degradation, softening or swelling. 11. An ingestible device according to any one of claims 1-10, wherein the tissue penetrating member (230, 330, 430, 530, 630) is a solid formed partially or completely from a formulation containing a therapeutic payload, wherein the tissue penetrating member is made of a dissolvable material that dissolves when inserted into the tissue of the inner cavity wall to deliver at least a portion of the therapeutic payload into the tissue. 12. An ingestible device according to any one of claims 1-10, wherein an outer portion of the tissue penetrating member (230, 330, 430, 530, 630) defines a housing, and the formulation comprising the therapeutically active substance therein forms a liquid, gel or powder contained within the housing. 13. An ingestible device according to any one of claims 1-12, wherein the actuator arrangement includes an energy source configured to power the tissue penetrating member (230, 330, 430, 530, 630) to propel it from the shell to the seating position in the inner cavity wall, and wherein a trigger arrangement is coupled to the actuator arrangement for initiating the release of energy from the energy source to drive the pushing portion (260, 360, 460, 560, 660) from the first position to the second position. 14. An ingestible device according to any one of claims 13, wherein the energy source includes a drive spring (240, 340, 440), such as a compression spring or a tension spring, which is tensioned or configured to be tensioned so as to provide an axial load on the pushing portion (260, 360, 460, 560, 660) for driving the movement of the pushing portion from the first position to the second position. 15. An ingestible device according to any one of claims 1-14, wherein the ingestible device is configured as a self-orienting capsule device, wherein when the self-orienting capsule device is at least partially supported by tissue of the inner cavity wall, the self-orienting capsule device is oriented in a direction allowing the tissue penetrating member (230, 330, 430, 530, 630) to be inserted into the inner cavity wall.