WO2024038123A1

WO2024038123A1 - Ingestible device with rotational drive mechanism

Info

Publication number: WO2024038123A1
Application number: PCT/EP2023/072632
Authority: WO
Inventors: Nökkvi Steinn SIGURDARSON; Jesper Peter Windum; Anders Hammelev MARSTRAND
Original assignee: Novo Nordisk A/S
Priority date: 2022-08-17
Filing date: 2023-08-16
Publication date: 2024-02-22

Abstract

A capsule device (100.1) suitable for ingestion, comprising: a) a capsule housing (110, 120), b) a tissue penetrating member (130) arranged for advancement along an axis in a distal direction, c) a drive member (160) for advancing the tissue penetrating member (130) into a lumen wall at a target location, the drive member (160) forming an axially elongated element having a first threaded surface (161) and a guide track (166) disposed axially along the drive member, d) a guide member (145) configured for rotation about the axis, e) a drive spring (140) being strained to exert torsional load on the guide member (145), and f) a trigger arrangement (195) configured for releasably retaining the guide member (145) in a non-rotational state against the torsional load and configured for release upon a predetermined condition to allow the guide member (145) to rotate, wherein the capsule housing (110, 120) forms a thread component (111) in threaded engagement with the first threaded surface (161) and wherein the guide member (160) forms a track follower (146) that engages the guide track (166) of the drive member (160).

Description

INGESTIBLE DEVICE WITH ROTATIONAL DRIVE MECHANISM

The present invention relates to ingestible devices adapted for being swallowed into a lumen of a patient and having a tissue penetrating member being shaped to penetrate tissue of a lumen wall.

BACKGROUND OF THE INVENTION

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

May people suffer from diseases, such as diabetes, which requires them to receive injections of drugs on a regular and often daily basis. To treat their disease these people are required to perform different tasks which may be considered complicated and may be experienced as uncomfortable. Furthermore, it requires them to bring injection devices, needles and drugs with them when they leave home. It would therefore be considered a significant improvement of the treatment of such diseases if treatment could be based on oral intake of tablets or capsules.

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

To provide a working solution for delivering insulin into the bloodstream through oral intake, the drug has to be delivered firstly into a lumen of the gastrointestinal tract and further into the wall of the gastrointestinal tract (lumen wall). This presents several challenges among which are: (1) The drug has to be protected from degradation or digestion by the acid in the stomach. (2) The drug has to be released while being in the stomach, or in the lower gastrointestinal tract, i.e. after the stomach, which limits the window of opportunity for drug release. (3) The drug has to be delivered at the lumen wall to limit the time exposed to the degrading environment of the fluids in the stomach and in the lower gastrointestinal tract. If not released at the wall, the drug may be degraded during its travel from point of release to the wall or may pass through the lower gastrointestinal tract without being absorbed, unless being protected against the decomposing fluids.

Prior art references relating to oral dosing of active agents and addressing one or more of the above challenges include WO 2018/213600 A1 , WO 2020/160399 A1 and US 2020/0129441 A1 . For medical capsules, such as the ones disclosed in the said references, the internal configuration design offers several design challenge trade-offs. For an oral device to be viable, e.g. for delivery of an API in form of a solid needle-shaped API, it needs to deliver an amount of API sufficient for the intended therapy. At the same time, for solid needle-shaped API tablets, the API tablet needs to be delivered reliably into a tissue layer in a depth sufficient to enable systemic uptake. Typically, a large injection force is required to deliver the API tablet at the right depth. Hence, the challenge is to design a device that is small enough to be swallowable, while reliably self-righting and injecting a sufficient amount of API deep enough. Furthermore, low cost and robust performance is essential.

In WO 2020/157324 A1 a capsule device is disclosed having an actuation mechanism with a laterally movable latch element which includes a blocking portion that cooperates with a retainer portion in latching engagement. Prior to actuation the latch element is supported by a dissolvable retaining member, which upon dissolution ceases to support the latch element thereby enabling lateral movement or the latch element to release the latching engagement.

For this kind of actuation mechanism, typical constraints and requirements for obtaining a wellperforming mechanism include the following: the ability to maintain an actuation member against the load of a drive spring for a prolonged time, even for a drive spring exerting a load of large magnitude. the actuation member shall be kept in place during dissolving of the dissolvable retaining member in order to maintain the desired acceleration when actuated, and the dissolvable retaining member preferably needs to be totally dissolved to avoid undissolved pieces that could block the actuation mechanism.

WO 2022/162102 A1 provides solutions which to a high degree meet these requirements. However, there is still a need for improved trigger solutions.

Having regard to the above, it is an object of the present invention to provide a ingestible capsule device which is improved with respect to generating a forceful actuation force and obtaining a high impact velocity allowing for different types of tissue penetrating members to be inserted in an optimal way into tissue of a lumen wall of a subject.

It is furthermore an object of the present invention to provide a capsule design which is optimized for providing a forceful actuation force while the outer dimensions of the capsule are kept small. DISCLOSURE OF THE INVENTION

In the disclosure of the present invention, embodiments and aspects will be described which will address one or more of the above objects or which will address objects apparent from the below disclosure as well as from the description of exemplary embodiments.

Thus, in a first aspect, a capsule device is provided which is suitable for ingestion for travelling into a lumen of the gastrointestinal tract of a patient, the lumen having a lumen wall. The capsule device comprises: a capsule housing comprising a compartment and an exterior tissue engaging surface defining an exit opening leading from the compartment to the capsule exterior, a tissue penetrating member arranged for advancement along an axis in a distal direction, a drive member for advancing the tissue penetrating member distally from a first position in the compartment through the exit opening and into the lumen wall at a target location, the drive member forming an axially elongated element having a first threaded surface and a guide track disposed along the drive member, a guide member configured for rotation about the axis, a drive spring being strained to exert torsional load on the guide member for powering advancement of the tissue penetrating member by rotation of the guide member, and a trigger arrangement configured for releasably retaining the guide member in a nonrelational state against the torsional load and configured for release upon a predetermined condition to allow the guide member to rotate, wherein one of the capsule housing and the guide member forms a thread component in threaded engagement with the first threaded surface of the drive member and wherein the other of the capsule housing and the guide member forms a track follower that engages the guide track of the drive member.

In accordance herewith, by introducing a rotating actuator, there is potential to drastically increase the energy density of the device, and allow deposition of the tissue penetrating member through a screw-motion, which opens up entirely new modes of deposition, which are not possible in a purely linear movement

In some embodiments the capsule housing forms the thread component in threaded engagement with the first threaded surface of the drive member and wherein the guide member forms the track follower that engages the guide track of the drive member. In some such embodiments, the thread component of the capsule housing may be configured so as to form a radially inwards facing thread that engages a radially outwards facing thread of the drive member.

In other embodiments the said thread component and the first threaded surface defines a first threaded engagement of first lead, wherein the guide track follower and the guide track engage each other by means of a second threaded engagement of second lead, and wherein the second lead is different from the first lead. In such system, a gearing is provided between the rotational velocity of the drive member as compared with the rotational velocity of the guide member, e.g. either faster or slower.

In another class of embodiments, the guide track follower and the guide track engage each other to form keyed engagement forming an axial guide for preventing rotation of the drive member as the drive member moves axially.

The drive spring typically forms a spiral spring comprising a plurality of windings being coiled around the axis.

In some forms the drive spring is provided as a clock spring. Such spring may be formed to exhibit a low height in the axial direction and thus be arranged far distally in the capsule housing. This may facilitate obtaining a capsule device having a centre of mass being close to the distal end of the device.

In other embodiments, the drive spring is provided as a helical torque spring, such as a conical torsion spring.

In further exemplary embodiments, the capsule exterior defines a distal end portion arranged at the exit opening and a proximal end portion opposite the distal end portion, and wherein the drive spring has a centre of mass disposed closer to the distal end portion than to the proximal end portion. When the capsule device is configured as a self-orienting capsule such mass distribution will generally aid the ability of the capsule device to quickly self-orient, and maintain this orientation in a stable manner.

In further embodiments the trigger arrangement comprises an environmentally sensitive trigger. In some forms the trigger arrangement, such as the environmentally sensitive trigger, comprises a degradable trigger element which degrades, such as by dissolution, upon being exposed to gastric fluid.

In some embodiments, when the capsule device assumes a first configuration, the degradable trigger element rotationally blocks movement of the guide member and, in a second configuration wherein the degradable trigger element is at least partially degraded, the degradable trigger member ceases to rotationally block the guide member allowing the torsional load of the drive spring to power rotation of the guide member thereby axially advancing the tissue penetrating member.

In further embodiments, when the capsule device assumes a first configuration, the degradable trigger element engages the capsule housing and engages at least one of the drive member and the guide member to thereby prevent the guide member from rotating.

Also, in certain embodiments, the trigger arrangement may be arranged to define a trigger element pocket having the degradable trigger element accommodated therein, wherein a first pocket portion of the trigger element pocket is defined by a cavity portion of the capsule housing and a second pocket portion of the trigger element pocket is defined by a cavity portion of the drive member, and wherein, in the state wherein the trigger arrangement releasably retains the guide member in a non-rotational state, the first pocket portion and the second pocket portion rotationally and axially aligns relative to each other to form a contiguous trigger element pocket.

In a second aspect of the invention the capsule device, in any of the embodiments disclosed above in accordance with the first aspect, may further be provided to defines: a housing lock geometry associated with or formed by the capsule housing, a hub comprising the drive member, the hub being movable distally from a non-de- ployed position to a deployed position, the hub comprising a hub lock geometry, wherein a releasable locking engagement between the hub and the capsule housing maintains the hub in the non-deployed position against the torsional load of the spring, wherein the locking engagement is configured as a rotational lock wherein relative rotational unlocking movement around the axis between the hub lock geometry and the housing lock geometry releases the locking engagement and allows the strained spring to advance the hub from the non-de- ployed position to the deployed position, and wherein a trigger arrangement is arranged between the hub and the capsule housing, wherein the trigger arrangement includes a trigger element configured for changing shape from a first shape to a second shape in response to subjection to gastric fluid to cause the relative rotational unlocking movement, wherein in the first shape, the trigger element cooperates with the hub and the capsule housing to restrict the relative rotational unlocking movement and, in the second shape, enables the relative rotational unlocking movement.

Additional benefits of the invention according to the second aspect relate to improvement with regard to ensuring effective interaction between trigger element and gastric fluid that surrounds the capsule device subsequent to swallowing. The relative rotational unlocking movement enables the trigger element to reside very close to the outer profile of the capsule device, enabling increased access to the gastric fluid for interacting with the trigger element. By placing the trigger element on or at the outmost surface portions of the device, good wettability and liquid access is ensured, expectedly enabling a consistent and reliable activation time. In accordance herewith, the activation time will be more predictable. Further beneficial features and embodiments will be highlighted below.

According to the second aspect, the capsule device assumes a non-deployed, also referred to as a pre-triggered configuration, when the trigger element assumes its first shape and the hub assumes its non-deployed position. After triggering, and the hub has moved to its deployed position, the capsule device assumes a deployed configuration. As a consequence of triggering, the capsule device will become operated to assume a triggered configuration. When referring to the triggered configuration, this refers to the configuration the capsule device assumes when assuming the deployed configuration.

It is to be noted that, in accordance with the second aspect, the trigger element may in different embodiments be configured so that the trigger element changes shape from the first shape to the second shape by broadly referring to a shape transition occurring by a change in the total volume of the trigger element, i.e., either by reduction or expansion, or simply changing the trigger element geometry along multiple orientations simultaneously, such as a shape transition occurring without an associated change in the total volume of the trigger element.

In some embodiments, the trigger element is configured for changing shape from a first shape to a second shape in response to subjection to gastric fluid, e.g. from the initial first shape and by partially or fully dissolving or degrading until the trigger element assumes the second shape, the “second shape” generally referring to a reduced shape, such as having reduced dimension, or a fully dissolved state, the latter “second shape” condition, although termed in an artificial and not strictly correct manner, referring to the state of the trigger element wherein it is fully dissolved or displaced away from engagement with the hub/capsule housing.

In other embodiments, the trigger element may include a material having a shape memory effect which is utilized when the trigger element changes shape from the first shape to the second shape. For example, the trigger element may be configured to include a shape memory alloy and the trigger arrangement may be configured to cause the shape memory alloy to shift geometry in in response to one or more predetermined conditions. In some embodiments, the one or more predetermined conditions includes the condition of sensing that the capsule device is subjected to gastric fluid. In other embodiments, the one or more predetermined conditions includes one or more of a predetermined time after ingestion of the capsule device, a predetermined location in the Gl tract, physical contact with the Gl tract, physical manipulation in the Gl tract (e.g., compression via peristalsis), one or more characteristics of the Gl tract (e.g., pH, pressure, acidity, temperature, etc.), or combinations thereof.

For some variants of the capsule device, the hub is configured to rotate relative to the capsule housing during the rotational unlocking movement. In other variants, an intermediate component associated with the capsule housing, and being rotationally movable but axially fixed relative to the remaining part of the capsule housing, couples between the hub and said remaining part of the capsule housing. In such system, the intermediate component will rotate relative to both the remaining part of the capsule housing and relative to the hub during the rotational unlocking movement. In some such embodiments, the hub will remain rotationally locked relative to the remaining part of the capsule housing, whereas in other embodiments, the hub will also rotate relative to the remaining part of the capsule housing.

In particular embodiments the thread engagement comprises a hub retaining surface oriented with a surface normal component pointing distally and a housing retaining surface oriented with a surface normal component pointing proximally, wherein, in the non-deployed position, the hub retaining surface engages the housing retaining surface to prevent the hub from moving distally.

In various variants the hub retaining surface slides relative to the housing retaining surface during the relative rotational unlocking movement, such as during the entire relative rotational unlocking movement needed from disengaging the hub lock geometry relative to the housing lock geometry. In some variants the hub retaining surface slides relative to the housing retaining surface as the hub moves from the non-deployed position to the deployed position. Typically, for such design, the hub comprises an axially extending thread that is in threaded engagement with another part of the capsule device, and wherein a rotatable guide member serves to drive the hub axially from the non-deployed position to the deployed position by means of the threaded engagement.

In some embodiments, the hub forms an axial elongated object, wherein a continuous thread or a series of thread segments are formed along a major extension of the elongated object.

In some variants the trigger element is made from or includes a portion of one of a degradable material and a dissolvable material, wherein the trigger element at least partially degrades and/or dissolves when subjected to gastric fluid thereby changing from the first shape to the second shape.

In some embodiments, the capsule device is so configured that upon swallowing and the trigger element becoming exerted to gastric fluid, the rotational unlocking movement is configured to finalize less than 10 minutes from swallowing, such as between 1 minute and 10 minutes from swallowing.

The capsule housing may for example be formed so that the pocket defines an open cavity, i.e. with an opening leading to the exterior of the capsule housing. The pocket may for example define a partly open compartment with a cavity opening oriented proximally and radially outwards.

The pocket will in some embodiments be arranged at a perimeter portion of the proximal end of the capsule housing. This allows effective wetting of the trigger element and reduces the risk that air bubbles adhering to the pocket will remain adhered for a prolonged time after swallowing.

In some embodiments the trigger element, when assuming the first shape, is arranged in the open cavity so that a radially outwards facing surface portion of the trigger element is substantially flush with neighbouring radially outwards facing surface portions of the capsule housing, such as radially within 1.0 mm therefrom. In some configurations, the trigger element, when assuming the first shape, is arranged in the open cavity while being exerted to gastric fluid at exterior surface portions forming at least 40% of the total exterior surface area of the trigger element.

In other configurations, the pocket and the trigger element are shaped and configured such that, when the trigger element assumes the first shape while the capsule device is submerged in gastric fluid, at least 40 % of the total exterior surface of the trigger element is exposed to gastric fluid.

In some capsule embodiments, the pocket is formed so that the trigger element, when assuming the first shape and being received by the pocket, is arranged radially offset from the axis.

In some further capsule embodiments, the trigger element, when assuming the first shape, is formed having first and second opposing faces and an interconnecting surface that interconnects the first and the second opposing faces, wherein with the capsule device being submerged in gastric fluid, one of the first and second opposing faces and at least a portion of the interconnecting surface are exposed to gastric fluid. In some forms, when assuming the first shape, the trigger element defines a generally cylindrical shaped element.

In still further capsule embodiments, the hub, the drive spring, the trigger element and the pocket are so configured that, in the pre-triggering configuration, the hub is biased by the drive spring towards rotation, and so that the trigger element restricts the relative rotational unlocking movement while the trigger element is mainly being exerted to compression forces.

In exemplary embodiments, the capsule device is configured for swallowing by a patient and travelling into a lumen of a gastrointestinal tract of a patient for subsequent deployment, such as deployment when located in the stomach, in the small intestines or in the large intestines. The capsule device may be shaped and sized to allow it to be swallowed by a subject, such as a human.

In some embodiments the capsule device has an average density greater than 1 g/cm3. Hence, subsequent to the capsule device has been swallowed by the subject and enters the stomach lumen, the capsule device will quickly submerge and become supported by the stomach wall. In some embodiments, the tissue penetrating member defines a tissue interfacing component that either alone, or in combination with a component that moves together with the tissue interfacing component, is/are configured to penetrate tissue as the hub is deployed distally. For example, the component that moves together with the tissue interfacing component may be provided as a component of the hub, or a component being slaved for distal movement with the hub.

In some embodiments, the tissue penetrating member couples to the hub, such as by being retained by the hub, either by being held or gripped by the hub, or via an intermediate component. In some forms, the tissue penetrating member comprises a therapeutic payload.

In some further forms the tissue penetrating member is provided as a solid delivery member formed partly or entirely from a preparation comprising a therapeutic payload, and wherein the preparation is made from a dissolvable material that dissolves when inserted into tissue of the lumen wall to at least partly release the therapeutic payload into the blood stream.

The therapeutic payload may in other embodiments be in the form of an encapsulated solid, a liquid, a gel or a powder, or any combination thereof and configured for delivery through a delivery member.

In some embodiments, the capsule device comprises a delivery member being associated with the therapeutic payload, the delivery member being configured for insertion into the lumen wall to deliver at least a portion of the therapeutic payload. The delivery member may have an outer shape as a needle. However, in alternative embodiments, different shapes for the delivery member may be provided.

In still other embodiments the delivery member is an injection needle having a longitudinal lumen extending within the injection needle, wherein the therapeutic payload is provided as a liquid, gel or powder being expellable through the injection needle from a reservoir accommodated within the capsule device.

In some embodiments, the capsule device is configured as a self-orienting capsule device wherein, when the self-orienting capsule device is at least partially supported by the tissue of the lumen wall, the self-orienting capsule device orients in a direction to allow the tissue penetrating member to be inserted into the lumen wall In further embodiments the capsule device is configured as a monostatic body due to at least one of a center of mass of the capsule device and the shape of the capsule device, such that the capsule device has a single stable resting position.

In some embodiments the capsule device is configured as a monostatic body such that when the capsule device is at least partially supported by a horizontally arranged tissue surface of the lumen wall, the capsule device orients in a direction wherein the axis is oriented vertically or at least generally vertical with the axis oriented less than 20 degrees from vertical, such as less than 15 degrees from vertical.

In still further exemplary embodiments, the capsule device is configured as a self-righting capsule, wherein when the capsule device is at least partially supported by the tissue of the lumen wall, the capsule device orients autonomously in a direction to allow a delivery member to be inserted into the lumen wall to deliver at least a portion of a therapeutic payload into the tissue. The capsule device may in certain embodiments be configured as a self-righting capsule device having a geometric center and a center of mass offset from the geometric center along the axis, wherein when the capsule device is supported by the tissue of the lumen wall while being oriented so that the centre of mass is offset laterally from the geometric center the capsule device experiences an externally applied torque due to gravity acting to orient the capsule device with the axis oriented along the direction of gravity to enable 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 a Gdmbdc or Gdmbdc-type shape that, when placed on a surface in any orientation other than a single stable orientation of the body, the body will tend to reorient to its single stable orientation. In typical embodiments, the single stable orientation of the body aligns the tissue penetrating member such that the tissue penetrating member is arranged vertically with the tissue penetrating end pointed vertically downwards. Typically, the body defines an exit hole at a tissue interfacing surface of the body. With the self-righting capsule assuming its single stable orientation the exit hole faces vertically downward towards supporting tissue at a target location so that the exit hole will allow the tissue penetrating member to extend vertically downwards through the exit hole for cooperation with the tissue at the target location.

By the above arrangements an orally administered drug substance forming or forming part of the therapeutic payload can be delivered safely and reliably into the stomach wall or intestinal wall of a living mammal subject. The drug substance may e.g. be in the form of a solid, an encapsulated solid, a liquid, a gel or a powder, or any combination thereof.

As used herein, the terms "drug", “drug substance” or “payload” is meant to encompass any drug formulation capable of being delivered into or onto the specified target site. The drug may be a single drug compound or a premixed or co-formulated multiple drug compound. Representative drugs include pharmaceuticals such as peptides (e.g. insulins, insulin containing drugs, GLP-1 containing drugs as well as derivatives thereof), proteins, and hormones, biologically derived or active agents, hormonal and gene-based agents, nutritional formulas and other substances in both solid, powder or liquid form. Specifically, the drug may be an insulin or a GLP-1 containing drug, this including analogues thereof as well as combinations with one or more other drugs.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following embodiments of the invention will be described with reference to the drawings, wherein fig. 1a shows a perspective view of a first embodiment capsule device 100.1 in accordance with the invention, the device assuming a pre-triggering configuration, fig. 1b shows a top view of the first embodiment capsule device 100.1 , figs. 1c and 1d are cross-sectional side views of the capsule device 100.1 in the pre-triggering configuration, rotated relative to each other by 90°, figs. 1e-1g are cross-sectional perspective views of capsule device 100.1 in the pre-triggering configuration in different cut levels, fig. 1 h is a detailed perspective cross sectional side view of a lower sub assembly of hub 150 of the first embodiment capsule device 100.1 including hub lower part 162, holder sleeve 170 and payload portion 130, figs. 2a and 2b are side views of a second embodiment capsule device 100.2 in a pre-triggering configuration and a deployed configuration, respectively, figs. 2c and 2d are cross-sectional side views of capsule device 100.2 corresponding to figs. 2a and 2b, respectively, fig. 2e is a cross-sectional side view of capsule device 100.2 rotated by 90° relative to the view of fig. 2d, fig. 2f shows a top view of upper capsule part 110 of the second embodiment capsule device 100.2 in the pre-triggering configuration, fig. 2g shows a top view of the second embodiment capsule device 100.2, figs. 2h and 2i are detailed perspective views of upper capsule part 110 of the second embodiment capsule device 100.2, fig. 2j is a perspective view of hub upper part 160 according to the second embodiment, figs. 2k and 2I are detailed perspective views of select internal components of second embodiment capsule device 100.2, fig. 3a shows a top view of a third embodiment capsule device 100.3 in the pre-triggering configuration, fig. 3b is a view corresponding to fig. 3a but showing upper capsule part 110 only, figs. 3c and 3d are perspective views of upper components of capsule device 100.3 corresponding to figs. 3a and 3b, respectively, figs. 3e and 3f are perspective views of hub upper part 160 according to the third embodiment, fig. 2i is a perspective view of a part of push member 160, figs. 4a and 4b are side views of a fourth embodiment capsule device 100.4 in the pre-triggering configuration and deployed configuration, shown in views rotated relative to each other by 90°, figs. 4c and 4d are cross-sectional side views of capsule device 100.4 in the pre-triggering configuration and deployed configuration, fig. 5a is a cross-sectional side view of a fifth embodiment capsule device 100.5 in the pretriggering configuration, fig. 5b is a side view of the fifth embodiment capsule device 100.5 in the pre-triggering configuration, fig. 5c-5e are different views of select components of the fifth embodiment capsule device 100.5, and figs. 5f and 5g are perspective views of the fifth embodiment capsule device 100.5 in the pretriggering configuration and in a configuration shortly after triggering.

In the figures like structures are mainly identified by like reference numerals.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

When in the following terms such as “upper” and “lower”, “right” and “left”, “horizontal” and “vertical” or similar relative expressions are used, these only refer to the appended figures and not necessarily to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only. When the term member or element is used for a given component it generally indicates that in the described embodiment the component is a unitary component, however, the same member or element may alternatively comprise a number of sub-components just as two or more of the described components could be provided as unitary components, e.g. manufactured as a single injection moulded part. The terms “assembly” and “subassembly” do not imply that the described components necessarily can be assembled to provide a unitary or functional assembly or subassembly during a given assembly procedure but is merely used to describe components grouped together as being functionally more closely related.

With reference to figures, first through fifth embodiments of a drug delivery device in accordance with different aspects of the invention will be described, the embodiments being designed to provide a capsule device having a desired triggering and deployment arrangement for deployment of a solid dosage form from an ingestible self-righting capsule device. The disclosed embodiments provide capsule devices 100.1 , 100.2, 100.3, 100.4 and 100.5 each enabling ingestion by a patient to allow the capsule device to enter the stomach lumen, subsequently to orient relative to the stomach wall, and finally to trigger an actuation mechanism to deploy a solid dose payload for insertion pf the payload at a target location in tissue of the stomach wall. Generally, at least a portion of the solid dose payload inserts, such as penetrates, into tissue of the subject and at least a portion of a therapeutic agent within the payload dissolves into the tissue for uptake in the blood stream of the subject. For the capsule devices 100.1 , 100.2, 100.3, 100.4 and 100.5 the general principle for orienting the capsule relative to the stomach wall may utilize any of the principles disclosed in WO 2018/213600 A1. However, other principles for orienting the capsule may be utilized in alternative embodiments. In addition, the trigger release principles and the drive principles in accordance with the different aspects of the present invention can be utilized for ingestible devices per se, such as ingestible capsule devices not associated with the ability of self-righting, e.g. including ingestible capsule devices for payload delivery in the Gl tract or walls of the Gl tract, including the stomach, small intestine and large intestine.

The various embodiments shown in the figures define capsule devices wherein a payload defining a solid dosage form accommodated within the device is shaped as a generally cylindrical shaped dosage form. The dosage form is only exemplary and differently shaped dosage forms may be used instead. In the embodiments shown herein, the dosage form may be formed partly or entirely from a preparation comprising a therapeutic payload. In other embodiments, in accordance with the invention, the payload delivered by means of the capsule device may comprise kinds of payloads which are not solid, such as one or more powdered drugs, one or more liquid drugs or one or more drugs formed as a gel, or any combination thereof. For different forms of payloads to be delivered by the capsule device, a tissue penetrating member, such as an injection needle, may be incorporated and actuated for being inserted into tissue so as to enable delivery of the payload for uptake in the bloodstream.

The capsule device may be brought from a pre-deployment configuration wherein the payload portion is accommodated at least partly within a housing of the capsule device, and into a deployed configuration wherein the payload portion has been deployed external to the capsule device and into tissue. In the non-deployed configuration, the capsule device assumes a pretriggering configuration. As a consequence of triggering, the capsule device will become operated to assume a triggered configuration. When referring to the triggered configuration, in some embodiments, this refers to an intermediate state prior to the deployed configuration. In other embodiments, when referring to the triggered configuration, this refers to the configuration the capsule device assumes when assuming the deployed configuration.

The first embodiment capsule device 100.1 is configured as an ingestible self-righting capsule device comprising a first upper portion having a first density, a second lower portion having a second density different from the first density of the upper portion. The capsule device 100.1 accommodates a payload portion 130, forming a tissue penetrating member, for carrying an agent for release internally of a subject user that ingests the article. In the shown device, the density of the capsule device, at least in the state prior to deployment, is greater than that of gastrointestinal fluid, enabling the capsule device to sink to the bottom of the stomach lumen. In the shown embodiment, the capsule device defines a monostatic body. The outer shape of the self-righting article is a Gdmbdc shape, i.e. a Gdmbdc-type shape that, when placed on a surface in any orientation other than a single stable orientation of the shape, will tend to reorient to its single stable orientation. The density distribution of the first upper portion and the second lower portion is provided so that the capsule device 100.1 quickly seeks towards entering a stable orientation wherein a central longitudinal axis of the capsule body is oriented vertically or generally vertical so that the tissue penetrating member 130 aligned with a trigger axis (coaxial with the longitudinal axis) assumes an orientation generally perpendicular to the portion of the tissue wall that supports the lower portion of the capsule.

In accordance herewith, the capsule device 100.1 includes an upper (proximal) capsule part 110 which mates and attaches to a lower (distal) capsule part 120. The two parts 110 and 120 are interconnected by means of a snap fit connection 118. In other embodiments, the two parts 110 and 120 are joined by other mounting methods such as by means of a threaded connection or a bayonet connection. The upper capsule part 110 and the lower capsule part 120 together forms the capsule of the device, i.e. the exterior of the capsule housing. The capsule defines an interior hollow which accommodates the payload portion 130, an assembly of components which in combination form a push member or hub 150 which holds and drives forward the payload portion 130, and a trigger and propulsion mechanism including an actuator configured to actuate and drive forward the push member/hub 150 carrying with it the payload portion 130 for drug delivery. The payload portion 130 is initially arranged within a sealed payload chamber and oriented along said trigger axis. The payload portion 130 is configured, upon triggering of the capsule device, for movement along the trigger axis. In the shown device, the exterior portions of upper and lower capsule parts 110, 120 form generally rotation symmetric parts which are symmetric around the trigger axis. In the drawings, the device is oriented with the trigger axis pointing vertically, and with the payload portion 130 pointing vertically downwards towards an exit hole 124 arranged centrally in the lower capsule part 120, the exit hole allowing the payload portion 130 to be transported through exit hole and moved outside the capsule device 100.1. As shown in fig. 1c, the lower part 120 includes a tissue engaging surface 123 which is formed as a substantially flat lower outer surface surrounding the exit hole 124.

With the capsule device 100.1 in the pre-triggering configuration, the payload portion 130 assumes the shown position within the sealed payload chamber so that the distal end surface of the payload portion is axially separated, i.e. by a separating distance, from the distal surface encircling the exit opening thereby enabling the payload portion to be accelerated towards the exit opening and further to the surface of the tissue by an acceleration stroke corresponding to the separating distance. In this embodiment the separating distance is selected in the order of 2-3 mm.

Regarding exemplary materials for the capsule parts for the capsule device 100.1 , the upper part 110 may suitably be made from a low-density material, such as polycaprolactone (PCL) or Polyether ether ketone (PEEK), whereas the lower part 120 may be suitably made from a high-density material, such as 316L stainless steel.

In the embodiment shown in figs. 1a-1 h the push member/hub 150 is formed by an assembly of components, i.e. a hub upper part 160, a hub lower part 162 and a holder sleeve 170. The hub upper part 160 serves the purpose of coupling to the actuator for transferring the force exerted by the actuator as well as forming part of a trigger mechanism that prior to triggering retains the hub 150 relative to the capsule housing 110/120 against the force exerted by the actuator. In the embodiment shown, the hub upper part 160 additionally serves to aid in the advancement of the hub subsequent to triggering of the trigger mechanism. In the pre-triggering configuration, a hub lock geometry and a housing lock geometry engage each other so as to maintain the hub 150 positioned in an initial first position against the axial load exerted by the actuator The hub lock geometry defines a hub retaining surface whereas the housing lock geometry defines a housing retaining surface. In this embodiment the hub retaining surface and the housing retaining surface are provided as thread geometries 161 and 111 which will be described further below.

In the embodiments of capsule devices disclosed herein, payload portion 130 defines a solid delivery member formed entirely or partly from a preparation comprising the therapeutic payload and with an outer shape forming a short cylinder with truncated 90 degrees ends. In other embodiments, the solid delivery member may be formed as a thin cylindrical rod shaped to penetrate tissue of the lumen wall, the cylindrical rod having a tissue penetrating end and trailing end opposite the tissue penetrating end. The tissue penetrating end of the rod may be pointed to facilitate easy insertion into tissue of the lumen wall whereas the trailing end may define a truncated cylinder cut off by a 90-degree cut. These shapes of payload portions are only exemplary and other shapes of payloads may be used in accordance with the present invention. A non-limiting example of a drug suitable for delivery by the capsule devices is dried compressed API such as insulin.

In the shown device, due to the density distribution of the entire capsule device 100.1 , and due to the outside shape of the device, no matter which orientation the device assumes immediately after passing into the stomach, the capsule device 100.1 will tend to orient itself with the trigger axis substantially of a tissue such as the wall of the gastrointestinal tract). Hence, the capsule device tends to orient relative to the direction of gravity so that the tissue engaging surface 123 faces vertically downward.

The interior of the upper capsule part 110 includes a sleeve shaped structure 115 which extends concentrically with the trigger axis from the upper part of the upper capsule part 110 in the distal direction towards lower capsule part 120. The sleeve shaped structure 115 is formed with a number of thread sections 111 protruding radially inwards from the surface of sleeve 115. The sleeve shaped structure 115 serves as a retainer structure for retaining the hub 150 against the drive force emanating from a strained drive spring 140 arranged within the capsule, i.e. the drive spring serving as an actuator for driving forward the hub from the first position to a second position. The lower capsule part 120, at its proximal end and coaxially with the trigger axis, includes a large first cylindrical cut-out leading distally towards a small second cylindrical cut-out which forms part of the payload chamber that accommodates the payload portion 130. The second cylindrical cut-out extends distally towards a proximally facing bottom surface, this will later be referred to as “hub stop surface” 128. The exit hole 124 is arranged centrally on-axis in the proximally facing bottom surface and emerges on the tissue engaging surface 123. A cylindrical tubular member 191 (see fig. 1f) is arranged at the proximal end of the second cylindrical cut-out as an extension of the wall surrounding the second cut-out.

As mentioned above, to protect the payload portion from being degraded prematurely, the payload chamber is sealed. A lower sealing element 180 formed as a circular membrane is arranged within the exit hole 124. An upper sealing element 190, also formed as a circular membrane, is closing off the payload chamber at the proximal end. In the embodiment shown, the upper sealing element 190 is fastened within a proximal portion of cylindrical tubular member 191 , and in a way wherein at least a portion of the hub 150 that holds the payload portion 130 extends, in a sealed manner, through the upper sealing element 190. Hence, the payload portion 130 is maintained fluidically isolated from the environment external to capsule device 100.1 prior to triggering.

The drive spring 140 is in the first embodiment provided in the form of a torque spring, more specifically in the shape of a spiral spring arranged with a multitude of windings. In other embodiments the torque spring may be shaped differently, such as in the form of a helical torque spring. The drive spring 140 is accommodated within a space partly defined by the first large cylindrical cut-out of the lower capsule part 120 and partly defined by a hollow distal section of the upper capsule part 110.

The drive spring 140 is configured to be strained torsionally, typically during the assembly steps of mounting of the spring within the capsule housing portions 110/120. A radially outer first end of drive spring 140 forms an anchoring section 141 that mounts relative to a first spring mount portion 121 (see fig. 1e). Referring mainly to figs. 1c and fig. 1f the drive spring 140 encircles a hub guide member 145 which is mounted rotatably inside the capsule housing 110/120 at a fixed axial location, in this embodiment at an axial position somewhat distally from the volumetric centre of capsule housing 110/120. A radially inner second end of drive spring forms an anchoring section (not visible on drawings) that mounts relative to a second spring mount portion 147 formed by hub guide member 145. As the spring is strained torsionally the drive spring 140 exerts a rotational driving force on a hub guide member 145 serving to rotate the hub guide member upon release of accumulated energy from the strained spring. With the capsule device 100.1 in its assembled state, the hub guide member 145 is axially clamped between the sleeve shaped structure 115 of upper capsule part 110 and the cylindrical tubular member 191 . The interface portions between these components form bearing surfaces serving to offer easy rotation of hub guide member 145 relative to the capsule housing.

The hub guide member 145 defines an axially extending central opening which a hub upper part 160, i.e. an upper part of hub 150, is adapted to move through. In the shown embodiment the opening is provided with a cross-sectional opening formed as a racetrack, i.e. such that the opening forms an axial passage of generally cylindrical shape but provided with flattened parallel surfaces 146 opposing each other. The racetrack formed opening provides a keyed engagement interface relative to hub upper part 160 to allow relative axial movement but prevent relative rotational movement between the hub guide member 145 and hub upper part 160.

Referring mainly to fig. 1h this figure shows a perspective cross sectional side view of a lower portion of push member/hub 150 of the first embodiment capsule device 100.1 including hub lower part 162, holder sleeve 170 and payload portion 130.

In the assembled state of the capsule device 100.1 the hub lower part 162 is mounted firmly to hub upper part 160, such as by being in threaded engagement, in press fit engagement, or engaged by any other means for retaining the two components, at least in the axial dimension. In alternative embodiments the hub lower part 162 and the hub upper part 160 are formed unitarily. Hub lower part 162 forms a push rod 163 which extends axially in the distal direction towards the payload portion 130. The payload portion is in this embodiment not not directly attached to the push rod 163 but will either maintain in abutment or engage push rod 163 during a part of the displacement hub lower part 162 experiences during triggering. Instead, a holder portion provided as a holder sleeve 170 encircles both the push rod 163 and a proximal portion of the payload portion 130 to retain the payload portion relative to the holder sleeve.

In the pre-triggering configuration the holder sleeve 170 attaches both to push rod 163 and to payload portion 130. The holder sleeve 170 is formed with a distal portion 171 formed as a generally cylindrical sleeve with an inner diameter generally corresponding to an outer diameter of a distal portion of push rod 163. The inner diameter of the cylindrical sleeve also generally corresponds to the outer diameter of the payload portion 130. The holder sleeve 170 is further formed so that, at the proximal end of the cylindrical sleeve, a circular flange 177 extends radially outwards from an outer wall of the cylindrical sleeve. The circular flange 177 defines a distally facing stop surface 178 configured for cooperation with the hub stop surface 128 via upper sealing element 190 and lower sealing element 180 and a proximal facing surface 179 configured for cooperation with the distal end surface 168 of the hub upper part 160.

In the embodiment shown, the dimensions of the inner surface of the cylindrical sleeve of holder sleeve 170 is chosen so that a retaining grip engagement, such as a frictional fit, between a distal end 172 of the holder sleeve 170 and the payload portion 130 is provided. Also, in the shown embodiment, cooperating releasable snap geometries are formed between the push rod 163 and the holder sleeve 170. In fig. 1 h, the snap geometries can be seen as an inner snap geometry 174 formed to protrude radially inwards from distal portion 171 of holder sleeve 170 and an outer snap geometry 164 formed as a radially inwards recess on push rod 163. In the shown embodiment, the holder sleeve 170 is so dimensioned that the holder sleeve distal portion 172 overlaps axially with the payload portion 130 in a way so that approximately half of the axial height of the payload portion is gripped by holder sleeve distal portion 172, i.e. the distance denoted “d” in fig. 1 h.

Non-limiting exemplary materials for the holder sleeve 170 and the hub lower part 162 may be selected as a relatively resilient polymeric material such as a material formed from PEEK. Alternative materials for holder sleeve 170 may be formed by an elastomeric material, such as silicone rubber.

As shown in figs. 1c and 1g, the hub upper part 160 is formed as a generally cylindrical object arranged with its central longitudinal axis coaxial with the trigger axis. The cylindrical outer surface of hub upper part 160 comprises a number of thread segments 161 which engages the thread segments 111 of sleeve shaped structure 115. The segments 111 and 161 are so formed that the hub upper part 160 is in continuous threaded engagement with the sleeve shaped structure 115. Also, the radial dimension of the thread segments 161 is sufficiently small so that the upper part 160 is slidable within the racetrack opening of the hub guide member 145. In addition, the hub upper part 160 comprises, along two opposing surfaces, a pair of planar surfaces 166. As shown in fig. 1d and 1g, the planar surfaces 166 are so dimensioned that the planar surfaces of the hub upper part 160 are matingly received radially inside the flattened parallel surfaces 146 of hub guide member 145, i.e., so that the upper hub part 160 slides easily axially within the hub guide member 145 and so that relative rotational movement therebetween is substantially prevented. Due to the threaded engagement 111/161 , once allowed due to the triggering of the device, the hub upper part 160 and thus the entire assembly forming the hub 150 and payload portion 130 are guided for helical movement relative to the capsule housing 110/120 along the trigger axis as driven by the drive spring 140.

As indicated in fig 1d and 1e, i.e., in the pre-triggering configuration, a cut out of a radial section of hub upper part 160 and a cut out of a radial section of sleeve shaped structure 115/upper capsule part 110 in combination forms a contiguous pellet receiving space (non-referenced). For the specific shown orientation of the hub upper part 160 relative to the upper capsule part 110 the said two cut outs form a generally cylindrical shaped space which is configured for matingly receiving trigger element provided as a cylindrical dissolvable pellet 195 which, when present in the pellet receiving space, serves to block relative movement between the hub upper part 160 and the capsule housing 110/120.

In the shown embodiment, the dissolvable pellet 195 is arranged in a compartment forming a pocket and having an opening within the perimeter of the top of upper capsule part 110, i.e., in a manner wherein the pocket retains the pellet in the pocket while exposing a substantive portion of the pellet to the capsule exterior. As shown in fig. 1a, the first embodiment capsule device 100.1 utilizes a pellet shape being generally cylindrical but with a portion being chamfered to form a smooth transition relative to neighbouring exterior surfaces of the capsule part 110. As the exposed surface of the dissolvable pellet is substantially flush with the exterior surfaces of the capsule part 110 the presence of the pocket and the pellet will not, or only to a minor degree, interfere with the self-righting ability. Other embodiments may use other shapes of dissolvable pellets in accordance with the location of the pellet receiving space and the design of the drive and trigger arrangement.

The trigger element or pellet 195 is configured for changing shape from a first shape to a second shape in response to subjection to gastric fluid, e.g. from the initial first shape and by partially or fully dissolving until the pellet assumes the second shape, the “second shape” generally referring to either a reduced shape, such as having reduced dimension, or a fully dissolved state, the latter “second shape” condition, although phrased in amanner that is not strictly correct, referring to the state of the trigger element wherein it is fully dissolved or displaced away from the pocket.

For the dissolvable trigger element discussed, i.e. the dissolvable pellet 195, different forms and compositions may be used. Non-limiting examples include injection moulded Isomalt pellets, compressed granulate Isomalt pellets, compressed pellets made from a granulate composition of Citrate/ NaHCO3, or compressed pellets made from a granulate composition of lsomalt/Citrate/NaHCO3. A non-limiting exemplary size of a dissolvable pellet is a pellet which at the time of manufacturing measures approximately 03 mm x 1 .5 mm.

The design of the pellet receiving space and the dissolvable pellet 195 facilitates fluid exposure to the dissolvable pellet when the capsule device is being submerged in a fluid. In the pretriggering configuration shown in fig. 1a, as the dissolvable pellet 195 assumes a non-com- pressible state, the pellet prevents the hub upper part 160 from sliding movement in accordance with the threaded engagement 111/161 and the entire hub 150 is prevented from moving rotationally and axially relative to the capsule housing even though being biased towards rotation by the torsional load provided by drive spring 140 via hub guide member 145.

However, upon exposure to a fluid, such as gastric fluid present in the stomach of a patient, the dissolvable pellet 195 starts to dissolve. The pellet 195 is designed to become gradually dissolved so that after a predefined activation time, the pellet will be forced away from pellet receiving space, or dissolved completely, to enable the drive spring 140 to rotate the hub upper part 160. Hence, the entire hub 150 will become released from the capsule housing. This state corresponds to the triggered configuration (not shown). Due to the threaded engagement 111/161 the hub 150 will be forced distally and drives the payload portion 130 distally with the payload distal portion initially protruding from the tissue engaging surface 123 of the capsule, and gradually pressing out the remaining payload portion 130.

As drive spring 140 exerts torsional load onto hub 150, the push rod 163, the holder sleeve 170 and the payload portion 130 are caused to travel unhindered towards the exit hole 124 as slaved with the movement of hub upper part 160, with the payload portion penetrating through the lower sealing element 180 and advancing further into mucosal tissue at the target location. During the distal movement of the said components, the distally facing stop surface 178 of holder sleeve 170 will enter into engaging abutment with the upper sealing element 190 which will cause to separate upper sealing element from the cylindrical tubular member 191 and become carried further distally with holder sleeve. Next, the distally facing stop surface 178 will engage the lower sealing element 180 (via upper sealing element 190) and will be prevented from moving further distally. However, in this state, the remaining load of drive spring 140 will still urge to advance push rod 163 further distally. As the snap engagement 164/174 defines a relatively weak force transmission, the snap engagement will release causing the push rod 163 to be moved further distally carrying with it the payload portion 130 for distal sliding movement relative to the holder sleeve 170. Soon after, the payload portion will be pushed by the push rod 163 to the target depth in tissue which occurs when hub upper part 160/hub lower part 162 bottoms out relative to the lower capsule part 120, i.e., by distal end surface 168 of hub upper part 160 cooperating with hub stop surface 128 through compressing circular flange 177, upper sealing element 190 and lower sealing element 180, these latter components at this stage assuming a sandwich or stacked configuration. This prevents components 160/162 from moving further distally.

It is to be noted that for the embodiment shown, due to the circular flange 177 being flattened at two opposed sides 176 and thus slidingly fitting flattened parallel surfaces 146 of hub guide member 145, the racetrack formed opening provides a keyed engagement interface relative to holder sleeve 170 to allow relative axial movement but prevent relative rotational movement between the hub guide member 145 and holder sleeve 170. Hence the holder sleeve 170 and payload portion 130 are caused to turn with hub upper part 160 and will make a helical movement during advancement of the payload portion 130. Without wishing to be bound by theory, it is considered that insertion of the payload portion into tissue by a helical movement, at least for some payload designs, will enable improvements with regard to tissue penetration.

In other embodiments, relative rotation between the hub upper part 160 and the hub lower part 162 and/ holder sleeve 170 is enabled and in such systems the payload portion may be configured for axial only movement with no induced rotation of the payload portion as it is advanced when the hub moves from the first position to the second position.

In situation of intended use, the payload portion 130 is rapidly inserted into tissue of the lumen wall where it will anchor generally in a direction along the trigger axis. At this point the capsule device 100.1 has delivered the intended dose and will release relative to the deposited payload portion 130 which rests inside the tissue wall. Subsequently, the remaining parts of the capsule device will travel out through the digestive system of the user and be disposed of.

It is noted that for the first embodiment the hub 150 performs as a drive member having a first threaded surface 161 for cooperating with thread 111 of the capsule housing and planar surfaces 146 of hub guide member 145 serving as guide tracks for cooperating with planar surfaces 166 that serve as track followers in engagement with the guide track. In other not shown exemplary designs according to the invention the thread configurations and the guide track and track followers may be configured differently. Example designs include embodiments wherein the guide tracks/guide followers are shaped differently and may in some embodiments be formed to allow rotation between the hub 150 and the hub guide member 145 as the hub moves relative to the hub guide member.

For example, in a first group of embodiments, the hub and hub guide member are configured with a threaded engagement between the two whereas the hub is coupled with the capsule housing by means of an engagement formed as an axial guide.

In a second group of embodiments, the hub and hub guide member are configured by means of a first threaded engagement between the two wherein the first threaded engagement is of a first lead. The engagement between the hub and the capsule housing is provided as a track and track follower engagement wherein this engagement defines a second threaded engagement of second lead different to the first lead. In such system, the drive member, i.e. , the hub, performs a relative rotational movement both to the capsule housing as well as to the hub guide member.

The threaded engagement and the track and track follower engagement may in some examples be arranged in axially spaced relationship so as to be disposed along separate axial paths, i.e., not axially overlapping whereas in other examples the two pairs of engagements are arranged along the same axial path, i.e., in axially overlapping relationship. For example, the radially inner and radially outer surfaces of the hub may be utilized serving to couple with the hub guide member and the capsule housing, respectively. In addition, the engagements providing as threaded engagement and a track and track follower engagement may define helically guided interfaces wherein the lead of the helical guided engagement are varying along the axial extension, e.g. so as to obtain a desired course of velocity vs. distance travelled during the advancement of the payload portion.

Turning now to figs. 2a-2l, a second embodiment of a drug delivery capsule device 100.2 is shown and will be described. With regard to the self-righting ability and the principle for deployment of the payload into tissue, the second embodiment capsule device 100.2 generally corresponds to the overall design of the first embodiment capsule device 100.1 , but the actuator principle and the way the hub is released from the capsule housing is different. In the shown embodiment, the assembly made up of hub lower part 162, holder sleeve 170 and payload portion 130 generally correspond to the design shown in fig. 1h.

Figs. 2a and 2b are side views of the second embodiment capsule device 100.2 in the pretriggering configuration and the deployed configuration, respectively. Referring to figs. 2c and 2d which show corresponding cross-sectional side views in the pre-triggering configuration and the deployed configuration, the drive spring 140 in this design is provided as a tension spring having a constant outer diameter along a major part of its axial extension. An enlarged diameter winding at the distal end of drive spring 140 aids in mounting the distal end of the drive spring relative to the capsule housing. A spacer element 186 is inserted into a cylindrical bore of the upper capsule part 110. The enlarged diameter winding of spring 140 and the spacer element 186 are clamped axially between a distally facing surface of upper capsule part 110 and a proximally facing surface of the lower capsule part 120. By incorporating a tension spring, the spring interface towards the hub can be placed far away from the bottom of the device, maximizing both spring force and total stroke.

The proximal end of drive spring 140 includes a reduced diameter winding which aids in coupling to the hub 150. In the shown design the reduced diameter winding is clamped axially between a proximal flange 166 and a distal flange 167. The distal flange 167 performs as a washer and is mounted rotatably relative to hub upper part 160 and hub lower part 162 so that torsional forces incurred by rotational movement of hub upper part 160 and hub lower part 162 are not transferred to the drive spring 140.

In the pre-triggering configuration, a hub lock geometry and a housing lock geometry engage each other so as to maintain the hub 150 positioned in an initial first position against the axial tension load exerted by drive spring 140. The hub lock geometry defines a hub retaining surface whereas the housing lock geometry defines a housing retaining surface. In this embodiment the hub retaining surface and the housing retaining surface are provided as ramped geometries 164.1 and 114.1 , these to be described further below.

The second embodiment again comprises a lower sealing element 180 to seal off the exit opening 124 and an upper sealing element 190, arranged between a flange 160 on the hub upper part 160 and a distal facing rim surface formed in upper capsule part 110, to seal the payload chamber at this interface. In addition an intermediate seal 185 is arranged at the interface between the upper capsule part 110 and the lower capsule part 120.

The upper capsule part 110 of capsule device 100.2 is depicted in figs. 2f through 2i. Referring to fig. 2f, upper capsule part 110 this time includes two pellet receiving pockets 119 which are symmetrically disposed around the axis. Only one of the pellet receiving pockets 119 is designated for being used during assembly but the symmetry enables the mounting of components in either of two orientations. Encircling a central axial passage formed within upper capsule part 110 are two ramp shaped geometries 114.1 formed on respective housing lock geometries 114, each ramp forming a helically curved arc surface spanning an angle of approximately 80 degrees and oriented so that the curved surface extends in a distal-clockwise direction (as viewed from above, see top views 2f and 2g). Each of the curved surfaces 114.1 are designated for use with correspondingly curved surfaces 164.1 of hub lock geometries formed as wings 164 by hub upper part 160 (see also figs. 2g and 2j).

As shown in fig. 2j the hub upper part 160 comprises the flange 166 and a cylindrical top part extending in the proximal direction from flange 166. The wings 164 are disposed on the cylindrical top part so that the wings protrude radially outwards in a radially opposed manner. Each wing defines an arc which is 60 degrees wide in the rotational direction around the axis. The central axial passage formed by upper capsule part 110 allows passage of the wings 164 of hub upper part 160 but only when the hub upper part 160 is oriented so that the wings 164 clear the helically curved arc surfaces 114.1. With the capsule device 100.2 assuming the pretriggering configuration, the curved surfaces 164.1 of wings 164 intimately engages the ramp shaped geometries 114.1 of upper capsule part 110 so that the hub upper part 160 rests on these inclined surfaces while the tension force of the strained drive spring 140 urges the hub upper part 160 in the distal direction.

The tension force from drive spring 140 induces a torsional force on the hub upper part 160 in clockwise direction (seen from above) due to the inclined surfaces 114.1 and 164.1. However, as shown in fig. 2g, a dissolvable pellet 195 is arranged in one of the pellet receiving pockets 119 and a radial extending surface 164.2 of one of the wings 164 engages a side surface of the dissolvable pellet 195 thereby preventing the hub upper part 160 from sliding distally on the inclined surfaces 114.1. This state is also depicted in the cross-sectional side view provided in fig. 2c. Further detailed views of the assembly of internal components hub upper part 160, drive spring 140, spacer element 186, holder sleeve 130 are visible in figs. 2k and 2I in views omitting the upper and lower capsule parts 110/120.

Turning now to the operation of the second embodiment, after ingestion of capsule device 100.2, the capsule device quickly sinks to the bottom of the stomach. Upon being supported by the stomach wall, and due to the self-righting ability of the capsule device, the capsule device will quickly reorient to have its tissue interfacing surface 123 engaging tissue of the stomach wall with the trigger axis of the capsule device oriented virtually vertical, i.e. with the payload portion 130 and the push rod 163 pointing downwards. Dissolution of dissolvable pellet 195 has begun due to exposure to gastric fluid. This is schematically represented in fig. 2d in connection with reference 195. The support from dissolvable pellet 195 on the radial extending surface 164.2 will at some point cease allowing the wings 164 of hub upper part to slide distally along the curved arc surfaces 114.1. Subsequent to full dissolution of pellet 195, or subsequent to the pellet 195 becoming dissolved to a degree so that the pellet 195 will be pushed away from its blocking position within pocket 119, and after approximately 60 degrees of turning movement of the hub upper part 160, the inclined surfaces 164.1 of wings 164 will slide off the curved arc surfaces 114.1 and be free to move further distally within the capsule device through the central axial passage. As shown in fig. 2d and 2e, the distal movement of the hub 150 is halted when the hub lower part 162, and more specifically the distal end surface 168 bottoms out in the capsule interior. In this position the drive spring 140 has pulled the hub 150 into an axial position wherein the flange 177 of holder sleeve 170 is clamped between distal end surface 168 and hub stop surface 128. In this state the capsule device 100.2 assumes its deployed configuration.

With reference to figs. 3a-3f, a third embodiment of a drug delivery capsule device 100.3 in accordance with the invention is shown and will be described. With regard to the self-righting ability and the principle for deployment of the payload into tissue, the third embodiment capsule device 100.3 generally corresponds to the overall design of the second embodiment capsule device 100.2. Also, the overall actuator principle is similar but the way the hub is released from the capsule housing is slightly different and the trigger principle differs. In the shown embodiment, the assembly made up of hub lower part 162, holder sleeve 170 and payload portion 130 generally correspond to the design shown in fig. 1h and described in connection with the first embodiment. The housing part 110 mainly corresponds to the corresponding part of the second embodiment, except for the geometries forming the hub locking geometry 114. The lower capsule part 120, the seals 180, 185 and 190, the drive spring 140and the spacer element 186 fully corresponds to the second embodiment.

The upper capsule part 110 of capsule device 100.3 is depicted in the different views shown in figs. 3a through 3d. Referring to fig. 3a, upper capsule part 110 again includes two pellet receiving pockets 119 which are symmetrically disposed around the axis. Only one of the pellet receiving pockets 119 are being designated for use during assembly but the symmetry enables the mounting of components in either of two orientations. Encircling a central axial passage formed within upper capsule part 110 are two proximally oriented housing retaining surfaces 114.1 forming axial planar lands and serving as retaining surfaces for the housing lock geometries. The axial lands are oppositely disposed, i.e.,180 degrees apart around the axis. Each axial land spans an angle of approximately 90 degrees. The axial planar lands are designated for engaging respective planar lands 164.1 formed as distal facing surfaces of hub lock geometries formed as wings 164 by hub upper part 160 (see also figs. 3e and 3f).

As shown in fig. 3f the hub upper part 160 comprises the flange 166 and a cylindrical top part extending in the proximal direction from flange 166. The wings 164 are disposed on the cylindrical top part so that the wings protrude radially outwards in a radially opposed manner. Each wing defines an arc which is 53 degrees wide in the rotational direction around the axis. The central axial passage formed by upper capsule part 110 allows passage of the wings 164 of hub upper part 160 but only when the hub upper part 160 is oriented so that the wings 164 clear the planar axial lands 114.1 . With the capsule device 100.3 assuming the pre-triggering configuration, the retaining surfaces 164.1 of wings 164 intimately engages the planar axial lands 114.1 of upper capsule part 110 so that the hub upper part 160 rests and retains the hub 250 against the tension force of the strained drive spring 140. The friction provided between components 110 and 160 prevents the hub upper part 160 from rotating counter-clockwise direction.

As shown in fig. 3a, an expandable pellet 195 is arranged in one of the pellet receiving pockets 119 and a radial extending surface 164.2 of one of the wings 164 engages a side surface of the expandable pellet 195 thereby preventing the hub upper part 160 from rotating in the clockwise direction. The physical appearance of expandable pellet 195 according to the third embodiment resembles the appearance of dissolvable pellet 195 according to the second embodiment. However, instead of reducing its volume when exposed to gastric fluid and thus change shape from the first to the second shape, the expandable pellet 195 of the third embodiment changes its shape from a first shape to a second shape by volume expansion upon being exposed to gastric fluid. Hence, the expandable pellet 195 swells by absorbing gastric fluid and, due to being confined by the pocket surfaces, will tend to expand in a direction directed generally towards the neighbouring wing 164 and will thus exert a driving force that urges the hub upper part 160 in the counter-clockwise direction. For materials for inclusion in the fabrication of the expandable pellet 195 a list of suitable non-limiting examples of materials include single or combinations of materials such as a hydroscopic sponge material, a cellulose based sponge material, a superabsorbent polymer, a semipermeable membrane container comprising a salt, or configurations of a combination of materials.

Upon exposure to gastric fluid for a time interval longer than a predefined time the expandable pellet 195 will be sufficiently expanded in the rotational direction so that wings 164 have turned about 53 degrees of counter-clockwise movement of the hub upper part 160 so that the planar surfaces 164.1 of wings 164 will slide off the axial planar lands 114.1 and be free to move distally within the capsule device through the central axial passage. Similar to the second embodiment, as shown in fig. 2d and 2e, the distal movement of the hub 150 is halted when the hub lower part 162, and more specifically the distal end surface 168 bottoms out in the capsule interior. In this position the drive spring 140 has pulled the hub 150 into an axial position wherein the flange 177 of holder sleeve 170 is clamped between distal end surface 168 and hub stop surface 128. In this state the capsule device 100.3 assumes its deployed configuration.

For alternative embodiments, depending on the amount of force needed for the rotational unlocking movement, and based on specific requirements for ensuring that the hub will not release unintended, the interface surfaces 114.1/164.1 may be formed with some inclination in the rotational direction, i.e. forming an “uphill slope” or a “downhill slope”, or a sequence thereof, for obtaining a desired release function for the hub 150. Also, in other embodiments, the expanding pellet configuration may include two or more pellets disposed around the axis, all pellets being arranged to provide a torsional force in the same rotational direction onto the upper hub part 160 for actuating the rotatable unlocking movement of the hub.

Referring next to figs. 4a-4d, a fourth embodiment capsule device 100.4 is shown. The fourth embodiment resembles the design of the second embodiment capsule 100.2 but utilizes a conical helical tension spring which enables a redesign of the capsule interior. Figs. 4a and 4b are side views of the second embodiment capsule device 100.2 in the pre-triggering configuration and the deployed configuration, respectively, shown in views rotated relative to each other by 90°.

Referring to figs. 4c and 4d which show cross-sectional side views corresponding to view 4b in the pre-triggering configuration and the deployed configuration, respectively. As shown in figs. 4c, the drive spring 140 includes a wide diameter distal first end and a narrow diameter proximal second end, the latter being mounted onto the hub 150 by being arranged in a spring seat proximal to flange 168.

In capsule device 100.4, the trigger arrangement between upper capsule part 110 and hub 150 is left almost unaltered relative to the second embodiment capsule device 100.2. However, in the fourth embodiment, the flange 166 does not as such perform as a washer being rotatable relative to the remaining parts of hub 150 as the flange 166 is made integral with lower hub lower part 162. Instead, in the pre-triggering configuration, the drive spring 140, in addition to the tension strain accumulated in the spring, is kept with a torsional load acting towards rotating the hub in the rotational direction for the rotational unlocking movement. Hence, the rotational movement of hub during unlocking will not be restrained or dampened by drive spring 140, which would otherwise occur by torsional load in drive spring 140 being accumulated if the drive spring had no compensational torsional load in the pre-triggering configuration.

In the fourth embodiment capsule device 100.4, the lower sealing element 180 is shaped to provide a cup-shaped element with an upwards open cavity facing the hub. The lower sealing element 180 is clamped at its radially outside peripheral portion between the upper capsule part 110 and the lower capsule part 120 to act as a seal at the interface between the upper and lower capsule parts. In accordance herewith, the peripheral portion of lower sealing element 180 is arranged slightly below a point axially midways between distal and proximal end portions of the capsule parts 110/120. In the shown embodiment, the first distal end of the drive spring 140 is mounted slightly proximally to the interface line between the capsule parts 110 ad 120 where it rests against a distally facing rim portion of upper capsule part 110. Additionally, lower sealing element 180 still seals the exit opening 124. An upper sealing element 190, arranged between a flange 160 on the hub upper part 160 and a distal facing rim surface formed in upper capsule part 110, to seal the payload chamber at this interface.

With the capsule device 100.4 assuming the deployed configuration, refer to fig. 4d, the hub 150 has moved all the way distally and halted by cooperation with proximally facing hub stop surface 128 arranged at the bottom part of capsule housing 120, and the payload portion has been moved into a position where the payload portion has penetrated and been inserted into tissue. The drive spring 140 assumes a configuration almost inverted relative to the initial pretriggering configuration so that the narrow second end of drive spring 140 is positioned distally to the wide first end of the drive spring and in near proximity to the exit hole 124.

Turning lastly to the fifth embodiment capsule device 100.5 reference is made to figs. 5a-5g. Fig. 5a shows a cross-sectional side view of capsule device 100.5 in the pre-triggering configuration. Fig. 5b shows a corresponding side exterior view. Compared to the second embodiment capsule device 100.2, the design of the fifth embodiment capsule device 100.5 is based upon a drive spring provided as a compression spring 140, wherein compressional load stored by the spring in the pre-triggering configuration is sufficient for driving the hub distally for payload deposition. In the pre-triggering configuration, a hub lock geometry and a housing lock geometry engage each other so as to maintain the hub 150 positioned in an initial first position against the axial compression load exerted by drive spring 140. The hub lock geometry defines a hub retaining surface whereas the housing lock geometry defines a housing retaining surface.

While omitting the remaining components of the device 100.5, figs. 5c-5d show an assembly of the drive spring 140, a pellet 195, an upper sealing element 190 a hub upper part 160, a hub lower part 162, a holder sleeve 170 and a payload portion 130. The hub lower part 162, the holder sleeve 170 and the payload portion 130 correspond largely to the assembly shown in fig. 1h. Apparent from these views it is observed that the hub upper part 160 is provided as a cup-shaped member with a cylindrical wall section providing a proximally facing cavity. The cavity is structured to accommodate drive spring 140 in the compressed state, i.e. , in the pretriggering configuration wherein the distal end of the spring rests against the bottom of the cavity whereas the proximal end of the spring is seated against an upwards facing cavity formed in the upper capsule part 110. A circular flange 167 is provided on the distal end of the cylindrical wall of the hub upper part 160, the flange 167 providing a sealing surface for the upper seal element 190 in relation to sealing of the payload chamber proximal end.

The interface between the hub upper part 160 and the upper capsule part 110 are formed to provide a rotational lock between the two, wherein an initial rotational movement of the hub upper part unlocks the hub for subsequent axial deployment of the hub 150. In the fifth embodiment, this is provided by means of hub lock protrusions 164 that cooperate with radial openings defining guide tracks formed in the upper capsule part 110, wherein each of the guide tracks exhibits an approximated inverted L-shape form, i.e., having a circumferentially extending inclined segment connecting to an axial only extending segment.

Protruding radially outwards from the cylindrical wall section of hub upper part 160 are three hub lock geometries 164 distributed symmetrically around the axis, i.e. 120 degrees apart. In the pre-triggering configuration, the hub lock geometries 164 are disposed to reside in respective portions of the side hole tracks in upper capsule part 110, these portions of the side hole tracks serving as housing retaining surfaces 114.1. The housing retaining surface 114.1 are oriented to provide a normal component pointing in the proximal direction and configured to serve as a support surface against a respective of the hub lock geometries 164. In the shown embodiment, the housing retaining surfaces 114.1 are provided as inclined ramp surfaces being oriented to extend slightly distally in the direction of the rotational unlocking. The inclined ramp surfaces 114.1 end abruptly and connects to axial tracks allowing the hub lock geometries 164 to pass unhindered distally when the hub lock geometries 164 align rotationally with the axial tracks 114.3. In the embodiment shown, the hub lock geometries are formed with mating inclined surfaces 164.1 which generally aligns with the inclined ramp surfaces 114.1.

Adjacent each radial opening, in the rotational unlocking direction, a pellet receiving pocket 119 is formed. Only one of the pellet receiving pockets 119 is designated for being used during assembly but the symmetry enables the mounting of components in either of three different orientations with a dissolvable pellet 195 arranged in one of the receiving pockets 119. By placing the dissolvable pellet on the side of the device, good wettability and liquid access is ensured in case of low liquid volume in the gastric cavity.

In the pre-triggering configuration, the mechanical compression load from drive spring 140 induces a torsional force on the hub upper part 160 in clockwise direction (viewed from above) due to the inclined surfaces 114.1 and 164.1. However, as shown in fig. 5b and 5f, a dissolvable pellet 195 is arranged in one of the pellet receiving pockets 119 and a radial extending surface 164.2 of one of hub lock geometries 164 engages an end surface of the dissolvable pellet 195 thereby preventing the hub upper part 160 from rotating and sliding distally on the inclined ramp surfaces 114.1.

Turning now to the operation of the fifth embodiment, after ingestion of capsule device 100.5, the capsule device quickly sinks to the bottom of the stomach. Upon being supported by the stomach wall, and due to the self-righting ability of the capsule device, the capsule device will quickly reorient to have its tissue interfacing surface 123 engaging tissue of the stomach wall with the trigger axis of the capsule device oriented virtually vertical, i.e. with the payload portion 130 and the push rod 163 pointing downwards, see figs. 5a, 5b and 5f. Dissolution of dissolvable pellet 195 has begun due to exposure to gastric fluid. The support from dissolvable pellet 195 on the radial extending surface 164.2 will at some point cease allowing the hub lock geometries 164 of hub upper part to slide distally along the inclined ramp surfaces 114.1. Subsequent to full dissolution of pellet 195 (indicated in fig. 5g), or subsequent to the pellet 195 becoming dissolved to a degree so that the pellet 195 will be pushed away from its blocking position within pocket 119, and after a minor turning unlocking movement of the hub upper part 160, the inclined surfaces 164.1 of hub lock geometries 164 will slide off the inclined ramp surfaces 114.1 and be free to move further distally within the capsule device via the axial tracks 114.3 of upper capsule part 110. The distal movement of the hub 150 is halted when the hub lower part 162, and more specifically the distal end surface 168 bottoms out in the capsule interior. In this position the drive spring 140 has pushed the hub 150 into an axial position wherein the flange 177 of holder sleeve 170 is clamped between distal end surface 168 and hub stop surface 128. In this state the capsule device 100.5 assumes its deployed configuration.

Although the above description of exemplary embodiments mainly concerns ingestible capsules for delivery in the stomach, the present deployment principle generally finds utility in capsule devices for lumen insertion in general, wherein a capsule device is positioned into a body lumen for deployment of a delivery member, or other types of tissue interfacing components, such as monitoring devices. Non-limiting examples of capsule devices in accordance with aspects of the present invention may, apart from the stomach administered devices discussed above, include capsule devices for intestinal delivery of a drug by delivery into the tissue wall of an intestinal lumen, such as a lumen of the small intestines or a lumen of the large intestines.

In the above description of exemplary embodiments, the different structures and means providing the described functionality for the different components have been described to a degree to which the concept of the present invention will be apparent to the skilled reader. The detailed construction and specification for the different components are considered the object of a normal design procedure performed by the skilled person along the lines set out in the present specification.

*****

Claims

1. A capsule device (100.1) suitable for ingestion for travelling into a lumen of the gastrointestinal tract of a patient, the lumen having a lumen wall, a capsule housing (110, 120) comprising a compartment and an exterior tissue engaging surface (123) defining an exit opening (124) leading from the compartment to the capsule exterior, a tissue penetrating member (130) arranged for advancement along an axis in a distal direction, a drive member (160) for advancing the tissue penetrating member (130) distally from a first position in the compartment through the exit opening (124) and into the lumen wall at a target location, the drive member (160) forming an axially elongated element having a first threaded surface (161) and a guide track (166) disposed axially along the drive member, a guide member (145) configured for rotation about the axis, a drive spring (140) being strained to exert torsional load on the guide member (145) for powering advancement of the tissue penetrating member (130) by rotation of the guide member (145), and a trigger arrangement (195) configured for releasably retaining the guide member (145) in a non-rotational state against the torsional load and configured for release upon a predetermined condition to allow the guide member (145) to rotate, wherein one of the capsule housing (110, 120) and the guide member (145) forms a thread component (111) in threaded engagement with the first threaded surface (161) of the drive member (160) and wherein the other of the capsule housing (110, 120) and the guide member (160) forms a track follower (146) that engages the guide track (166) of the drive member (160).

2. The capsule device as in claim 1 , wherein the capsule housing forms the thread component in threaded engagement with the first threaded surface of the drive member and wherein the guide member forms the track follower that engages the guide track of the drive member.

3. The capsule device as in claim 2, wherein the thread component of the capsule housing forms a radially inwards facing thread configured for engaging a radially outwards facing thread of the drive member.

4. The capsule device as in any of claims 2-3, wherein said thread component and the first threaded surface defines a first threaded engagement of first lead, wherein the guide track follower and the guide track engage each other by means of a second threaded engagement of second lead, and wherein the second lead is different from the first lead.

5. The capsule device as in any of claims 2-4, wherein the tissue penetrating member follows rotation of the drive member as the drive member advances the tissue penetrating member axially.

6. The capsule device as in claim 1 , wherein the guide track follower and the guide track engage each other to form an axial guide for preventing rotation of the drive member as the drive member moves axially.

7. The capsule device as in any of claims 1-6, wherein the drive spring is provided as a clock spring.

8. The capsule device as in any of claims 1-6, wherein the drive spring is provided as a helical torque spring, such as a conical torsion spring.

9. The capsule device as in any of claims 1-8, wherein the capsule exterior defines a distal end portion arranged at the exit opening and a proximal end portion opposite the distal end portion, and wherein the drive spring has a centre of mass disposed closer to the distal end portion than to the proximal end portion.

10. The capsule device as in any of claims 1-9, wherein the trigger arrangement comprises an environmentally sensitive trigger.

11 . The capsule device as in claim 10, wherein the trigger arrangement comprises a degradable trigger element which degrades, such as dissolves, upon being exposed to gastric fluid.

12. The capsule device as in claim 11 , wherein, in a first configuration, the degradable trigger element rotationally blocks movement of the guide member and, in a second configuration wherein the degradable trigger element is at least partially degraded, the degradable trigger member ceases to rotationally block the guide member allowing the torsional load of the drive spring to power rotation of the guide member thereby axially advancing the tissue penetrating member.

13. The capsule device as in any of claims 11-12, wherein, in a first configuration, the degradable trigger element engages the capsule housing and engages at least one of the drive member and the guide member to thereby prevent the guide member from rotating.

14. The capsule device as in any of claims 11-13, wherein the trigger arrangement defines a trigger element pocket having the degradable trigger element accommodated therein, wherein a first pocket portion of the trigger element pocket is defined by a cavity portion of the capsule housing and a second pocket portion of the trigger element pocket is defined by a cavity portion of the drive member, and wherein, in the state wherein the trigger arrangement releasably retains the guide member in a non-rotational state, the first pocket portion and the second pocket portion rotationally and axially aligns relative to each other to form a contiguous trigger element pocket.

15. The capsule device as in any of claims 1-14, wherein the capsule device (100.1) is configured as a self-orienting capsule device, wherein when the self-orienting capsule device is at least partially supported by the tissue of the lumen wall, the self-orienting capsule device orients in a direction to allow the tissue penetrating member (130) to be inserted into the lumen wall.

*****