WO2024115766A1 - Dispositif ingestible avec agencement protecteur - Google Patents

Dispositif ingestible avec agencement protecteur Download PDF

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Publication number
WO2024115766A1
WO2024115766A1 PCT/EP2023/083991 EP2023083991W WO2024115766A1 WO 2024115766 A1 WO2024115766 A1 WO 2024115766A1 EP 2023083991 W EP2023083991 W EP 2023083991W WO 2024115766 A1 WO2024115766 A1 WO 2024115766A1
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WO
WIPO (PCT)
Prior art keywords
shielding
capsule
configuration
tissue
arrangement
Prior art date
Application number
PCT/EP2023/083991
Other languages
English (en)
Inventor
Anders Hammelev MARSTRAND
Jesper Peter Windum
Original Assignee
Novo Nordisk A/S
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Novo Nordisk A/S filed Critical Novo Nordisk A/S
Publication of WO2024115766A1 publication Critical patent/WO2024115766A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2210/00—Anatomical parts of the body
    • A61M2210/10—Trunk
    • A61M2210/1042—Alimentary tract

Definitions

  • the present invention relates to ingestible devices adapted for being swallowed into a lumen of a patient and having a tissue interfacing component being shaped to penetrate or otherwise insert into tissue of a lumen wall.
  • 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).
  • Ingestible capsules comprising a delivery member formed as a solid formed from a preparation comprising a therapeutic payload, wherein the delivery member is forced from the capsule and into tissue of the lumen wall for delivering the payload.
  • the payload is inserted into tissue and will over time dissolve and be absorbed into the body of the patient. Even though the capsule may be able to properly orient relative to a target site it can still move to another location after deployment of the payload. This introduces the risk that the payload will be partly or fully removed from the target site due to movement of the capsule.
  • an ingestible device suitable for swallowing into a lumen of a gastrointestinal tract of a patient comprising: a housing defining a compartment and an exterior tissue engaging surface defining an exit opening leading from the compartment to the capsule exterior, a tissue interfacing component arranged in the compartment along an axis and having a distal first end and an opposite proximal second end, the tissue interfacing component configured for being advanced axially from a first position wherein the first end does not protrude from the exit opening and into a second position wherein the first end protrudes from the exit opening for insertion in the lumen wall at a target location, an actuator arrangement coupled to the tissue interfacing component and having a first configuration and a second configuration, wherein the actuator arrangement is configured so that, upon actuation, the actuator arrangement moves from the first configuration to the second configuration thereby advancing the tissue interfacing component from the first position to the second position, and a shielding arrangement
  • a distal direction is defined as the direction the tissue interfacing component is moved axially from said first position to said second position.
  • the distal end of the ingestible device refers to the end that comprises the exit opening, and the proximal end refers to the end opposite to the distal end.
  • the device in the following referenced “the device” or “the capsule device”, when referring to the “non-shielding configuration” and the “shielding configuration”, these two states refer only to states the device assumes after the tissue interfacing component has been advanced axially away from the first position so that the first end protrudes from the exit opening. Hence, prior to the tissue interfacing component moves distally, e.g.
  • the tissue interfacing component when the tissue interfacing component assumes the first position, the tissue interfacing component will typically be surrounded by one or more of the components of the device, such as a housing component that forms a shell-part of the housing and/or the shielding arrangement, so as to envelope the tissue interfacing component and prevent it from interfacing with tissue or other entities exterior to the device.
  • a housing component that forms a shell-part of the housing and/or the shielding arrangement
  • the ingestible device includes a shielding arrangement configured for entering into a shielding configuration, after actuation of the actuator arrangement, the shield member effectively shields the patient from unintended tissue interaction with potentially sharp or pointed component features or other geometries that may pose a risk when travelling through the remainder of the Gl tract.
  • the shielding arrangement may be configured to actively force the first end (distal end portion) of the tissue interfacing component away from the lumen wall as the shielding arrangement shifts from the non-shielding configuration to the shielding configuration.
  • the shielding arrangement of the device may be configured so that the housing of the device will be actively separated from tissue interaction when the shield enters into the shielding configuration.
  • the shielding arrangement comprises a shield member formed to at least partially, and optionally fully, encircle or envelope the tissue interfacing component, wherein the shield member is axially movable from a first retracted position into an axially extended position to shift the shielding arrangement from the non-shielding configuration to the shielding configuration.
  • the shield member moves axially relative to a housing portion of the housing when being shifted from the non-shielding configuration to the shielding configuration.
  • the shield member is configured for axial sliding movement, such as a purely axial telescoping movement.
  • the shield member may be configured for axial and rotational movement, such as by a rotationally guided movement, e.g. movement in accordance with a track and follower coupling or a threaded engagement.
  • the shielding arrangement may comprise one or more shield members configured to unfold as the shielding arrangement shifts from the non-shielding configuration to the shielding configuration, so that at least a portion of the one or more shield members move towards an axial distal position to assume an extended position relative to the tissue interfacing component thereby rendering the first end of the tissue interfacing component protected by the shielding arrangement.
  • the shield member or shield members is/are arranged with distal facing shield surface portions arranged in a circle, wherein the distal facing shield surface portions in combination extend circumferentially by a combined annular extension of at least 90 degrees, such as at least 180 degrees, such as at least 270 degrees, such as at least 315 degrees, and such as 360 degrees around the axis.
  • the shielding arrangement comprises a shield activation mechanism being activatable to move the shielding arrangement into the shielding configuration.
  • the shielding arrangement may further comprise shield driving means configured for providing a biasing force on the shielding arrangement for driving the shielding arrangement towards the shielding configuration.
  • the shield driving means may in some configurations bias the shielding arrangement towards the shielding configuration.
  • the shielding arrangement may further be configured to comprise a shield release mechanism that releasably maintains the shielding arrangement in the nonshielding configuration against the biasing force of the shield driving means.
  • the shielding arrangement comprises a swellable component initially being held in a compact state to provide the non-shielding configuration, and wherein the swellable component, subject to being exposed to a fluid, such as gastrointestinal fluid, is configured to swell to transform into a shape that shields the tissue interfacing component to thereby provide a shield that assumes the shielding configuration.
  • a fluid such as gastrointestinal fluid
  • the swellable component may be accommodated within an enclosure arranged adjacent the exit opening, such as encircling the exit opening.
  • the swellable component When exposed to a fluid, the swellable component expands axially to partly or fully envelope the exposed part of the tissue interfacing component to thereby render the tissue interfacing component covered and thereby non-ac- cessible, or only to a minor extent accessible, by portions of the Gl tract.
  • the ingestible device is configured for swallowing by a patient and travelling into a lumen of a Gl tract of a patient, such as the small intestine or the large intestine, respectively. In other embodiments, the ingestible device is configured for swallowing by the patient for deployment in the stomach.
  • the shield activation mechanism operably couples with the actuator arrangement such that, when the actuator arrangement moves into the second configuration, the actuator arrangement activates the shield activation mechanism thereby moving the shielding arrangement into the shielding configuration.
  • the shield activation mechanism is controlled by a first gastrointestinal tract environmentally-sensitive mechanism.
  • the Gl tract environmentally-sensitive mechanism may comprise a trigger member, wherein the trigger member is characterised by at least one of the group comprising: a) the trigger member comprises a material that degrades, erodes and/or dissolves due to a change in pH in the Gl tract; b) the trigger member comprises a material that degrades, erodes and/or dissolves due to a pH in the Gl tract; c) the trigger member comprises a material that degrades, erodes and/or dissolves due to a presence of an enzyme in the Gl tract; and d) the trigger member comprises a material that degrades, erodes and/or dissolves due to a change in concentration of an enzyme in the Gl tract.
  • the trigger arrangement may also be or include an electronic trigger.
  • the actuation of the actuator arrangement is controlled by a second gastrointestinal tract environmentally-sensitive mechanism.
  • the second gastrointestinal tract environmentally-sensitive mechanism may comprise a trigger member or trigger arrangement comprising at least one of the triggers mentioned in connection with the first gastrointestinal tract environmentally-sensitive mechanism.
  • the ingestible device is configured for delivery of a therapeutic payload from the compartment and into the lumen wall and where the tissue interfacing component comprises a delivery member configured for delivery of a payload portion comprising the therapeutic payload.
  • the delivery member may be provided in an elongated form and comprising a longitudinally extending lumen and wherein the ingestible capsule is configured for delivery of a therapeutic payload portion from a reservoir through the lumen of the delivery member and into the lumen wall.
  • the lumen of the delivery member stores the therapeutic payload portion for delivery from the lumen and into the lumen wall.
  • the therapeutic payload is provided as one or more selected from the group consisting of: a liquid, gel or powder being expellable through the lumen of the delivery member.
  • a first end of the tissue interfacing component carries a solid payload portion formed partly or entirely from a preparation comprising a therapeutic payload, wherein the payload portion is made from a dissolvable material that dissolves when inserted in a lodged position in tissue of the lumen wall.
  • the solid payload portion may be configured for subsequent release of at least a portion of the therapeutic payload into the blood stream.
  • the ingestible device is configured so that:
  • the housing comprises a stop geometry
  • the first end of the tissue interfacing component defines a pushing portion configured for pushing the solid payload portion from an initial position within the housing to a lodged position into tissue, wherein a holder portion is initially coupled to the tissue interfacing component so as to perform slaved movement with the tissue interfacing component, the holder portion releasably holding the payload portion by gripping action, such as by frictional engagement, relative to the tissue interfacing component, and wherein, as the tissue interfacing component moves towards the second position, the holder portion enters directly or indirectly into engagement with the stop geometry of the housing to thereby uncouple relative to the tissue interfacing component and initiate release of the gripping action, whereafter the pushing portion moves further towards the second position until the solid payload portion assumes its lodged position in tissue.
  • the first end of the tissue interfacing component, in the second position may be configured to protrude a predefined distance from the exterior tissue engaging surface, said pre-defined distance selected between 1 and 5 mm, such as between 2 and 4.5 mm and such as between 2.5 and 4 mm. Other ranges are also possible.
  • the ingestible device is configured as a monostatic body at least due to one of the shape and the mass distribution of the ingestible device and wherein the axis of the ingestible device is disposed to self-right into vertical.
  • an ingestible device is provided that is suitable for swallowing into a lumen of a gastrointestinal tract of a patient, in particular into a lumen having a lumen wall.
  • the ingestible device comprises: a housing defining an internal hollow and comprising a stop geometry arranged within the internal hollow, a tissue penetrating member disposable in the housing, the tissue penetrating member having a tissue penetrating first end, a second end opposite the first end and a radially outwards facing surface between the first end and the second end, and an actuator arrangement comprising: a) a pushing portion configured for movement from a first position and into a second position, the pushing portion being configured for providing a force onto the tissue penetrating member to move the tissue penetrating member from an initial position within the housing to a lodged position where at least a portion of the tissue penetration member is external to the housing and at least partially lodged in tissue of the lumen wall, and b) a holder portion which, when the
  • the tissue penetrating member is effectively detached from the pushing portion at the point in time relative the moving of tissue penetrating member from the initial position within the housing to the lodged position.
  • the tissue penetrating member forms part of, or comprises, a therapeutic payload
  • the solution according to the second aspect enables a larger percentage of the therapeutic payload to be available for being lodged in tissue and for subsequent release into the blood stream.
  • the holder portion when the tissue penetrating member assumes the initial position, the holder portion assumes a start position, and wherein the holder portion is moved from the start position towards the stop geometry by being displaced by slaved movement relative to the pushing portion.
  • the holder portion when assuming the start position, is in friction engagement with the pushing portion, and wherein pushing portion overcomes the friction engagement when the holder portion enters into engagement with the stop geometry.
  • the holder portion is formed as a sleeve that, when the holder portion is slaved relative to the pushing portion, interconnects the pushing portion with the tissue penetrating member.
  • the holder portion may in some embodiments comprise at least one radially resilient gripping member providing a radially inwards directed force onto the tissue penetrating member, wherein the radially resilient gripping member cooperates with the stop geometry of the housing to release the radially inwards directed force upon the holder portion engaging the stop geometry.
  • the housing may be so configured that is comprises an exit hole and an exterior surface portion surrounding the exit hole, the exit hole permitting the tissue penetrating member, and optionally an end portion of the pushing portion, to protrude through the exit hole, and wherein the pushing portion in its second position pushes the second end of tissue penetrating member a predefined distance from the exterior surface portion, said pre-defined distance selected between 1 and 5 mm, such as between 2 and 4.5 mm and such as between 2.5 and 4 mm.
  • the tissue penetrating member is a solid formed partly or entirely from a preparation comprising a therapeutic payload, wherein the tissue penetrating member is made from a dissolvable material that dissolves when inserted into tissue of the lumen wall to deliver at least a portion of the therapeutic payload into tissue.
  • an exterior portion of the tissue penetrating member defines an enclosure, and wherein a preparation comprising a therapeutic active substance forms a liquid, gel or powder accommodated within the enclosure.
  • the actuator arrangement comprises an energy source configured for powering the tissue penetrating member for being advanced from the housing and into the lumen wall by operation of the actuator arrangement from the first configuration to the second configuration.
  • the actuator arrangement comprises a drive spring, such as a compression spring or a tension spring, the spring being strained or configured for being strained for powering the pushing portion for movement from the first position to the second position.
  • a drive spring such as a compression spring or a tension spring
  • the ingestible 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.
  • the housing comprises an exit hole and wherein, when the tissue penetrating member assumes the initial position, the tissue penetrating first end is axially separated from the exit hole by a separating distance, thereby enabling the tissue penetrating member to be advanced towards the exit hole by an acceleration stroke corresponding to the separating distance.
  • separating distances may be provided as larger than 0.5mmm, such as larger than 1 mm, such as larger than 1.5 mm, such as larger than 2 mm, such as larger that 3 mm.
  • the pushing portion and/or the tissue penetrating member is configured for movement along an axis.
  • the actuator arrangement comprises a hub that comprises at least one pair of a latch and a retainer portion structured to maintain the hub in a pre-actuation configuration.
  • the ingestible device defines a dissolvable firing member, the dissolvable firing member being at least partially dissolved in a fluid, such as a biological fluid, a retainer portion comprised by one of the housing and the hub, and a deflectable latch comprised by the other of the housing and the hub.
  • the deflectable latch may be configured for lateral movement relative to the axis, and the deflectable latch defines a first surface with a blocking portion, and a support surface disposed oppositely to the first surface and configured for interacting with the dissolvable firing member.
  • the blocking portion of the deflectable latch engages the retainer portion in a latching engagement, and the support surface of the deflectable latch interacts with the dissolvable firing member to restrict movement of the deflectable latch thereby preventing release of the latching engagement.
  • the deflectable latch is allowed to move thereby releasing the latching engagement between the blocking portion of the deflectable latch and the retainer portion to allow the energy source to actuate/fire the hub.
  • the dissolvable part is designed to simply block a mechanical activation system.
  • the mechanical activation system may be designed to rely on parts made from a suitable high-strength material, such as plastic, and do not leave any undissolved pieces that potentially could jam the mechanical activation system.
  • the deflectable latch is configured for radial movement relative to the axis.
  • the trigger axis and the hub movement is linear.
  • the trigger axis may be not linear, e.g. the firing trajectory of the hub may be arcuate or curved, or may include arcuate or curved trajectories.
  • the latch may be configured for lateral movement relative to the trajectory of the hub to release the hub.
  • a plurality of pairs of latch and retainer portions such as two, three, four, five or more pairs of latch and retainer portions are provided, the pairs of latch and retainer portions being disposed equally around the axis.
  • said dissolvable firing member is common to all pairs of latch and retainer portions.
  • the dissolvable firing member is arranged along the axis, wherein the at least one pair of latch and retainer portion is disposed radially outside of the dissolvable firing member.
  • one or more dissolvable firing members is/are disposed, such as in a ringshaped configuration around the axis, wherein the one or more dissolvable firing members encircle the at least one pair of latch and retainer portion.
  • the capsule may comprise one or more openings to allow a biologic fluid, such as gastric fluid, to enter the capsule for dissolving the dissolvable firing member(s).
  • a biologic fluid such as gastric fluid
  • the ingestible device is configured for swallowing by a patient and travelling into a lumen of a gastrointestinal tract of a patient, such as the stomach, the small intestines or the large intestines.
  • the capsule of the device may be shaped and sized to allow it to be swallowed by a subject, such as a human.
  • the ingestible device is configured as a self-righting capsule, wherein when the self-righting capsule is at least partially supported by the tissue of the lumen wall, the self-righting capsule orients in a direction to allow the delivery member to be inserted into the lumen wall to deliver at least a portion of the therapeutic payload into the tissue.
  • the ingestible device may in certain embodiments be configured as a self-righting capsule device having a geometric centre and a centre of mass offset from the geometric cen- trealong 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 centte 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.
  • 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.
  • 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.
  • 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.
  • drug drug substance
  • 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.
  • 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.
  • figs. 1 a and 1 b are cross-sectional front views of a first example capsule device 200 in accordance with an auxiliary aspect of the invention, the device assuming a pre-actuation configuration and an actuated configuration, respectively
  • fig. 1 c shows a detailed perspective cross sectional view of a subassembly of the first example capsule device 200 providing a push rod 260, a holder sleeve 270 and a payload portion 230, figs.
  • FIGS. 2a and 2b are cross-sectional front views of a second example capsule device 300 in accordance with the auxiliary aspect of the invention, the device assuming a pre-actuation configuration and an actuated configuration, respectively
  • fig. 2c is a perspective view of an upper capsule part 310 of the capsule device 300 of figs. 2a and 2b
  • fig. 2d is a perspective view of an actuator hub upper part 351 of the capsule device 300 of figs. 2a and 2b
  • figs. 3a and 3b show cross-sectional schematic front and side views of a first embodiment capsule device 100.1 in accordance with the invention, the device assuming a pre-actuation configuration
  • fig. 3c is a bottom planar external view of the capsule device 100.1 shown in fig.
  • fig. 3d is a perspective side view of a shield member 131 of capsule device 100.1
  • figs. 3e and 3f are cross-sectional schematic front views of a first embodiment capsule device 100.1 , the device assuming an intermediate configuration and an shielding configuration, respectively
  • figs. 4a and 4b show cross-sectional schematic front views of a second embodiment capsule device 100.2 in accordance with the invention, the device assuming a pre-actuation configuration and an shielding configuration, respectively
  • figs. 4c and 4d are bottom planar external views of the capsule device 100.2 in the states shown in fig. 4a and 4b, figs.
  • FIG. 5a and 5b show cross-sectional schematic front views of a third embodiment capsule device 100.3 in accordance with the invention, the device assuming a pre-actuation configuration and a shielding configuration, respectively
  • figs. 6a, 6b, and 6c are cross-sectional schematic front views of a fourth embodiment capsule device 100.4, the device assuming a pre-actuation configuration, an intermediate configuration and a shielding configuration, respectively
  • figs. 6d and 6e are perspective views of a drive member 145 of the capsule device 100.5 of figs. 6a-6c, figs.
  • FIGS. 7a, 7b, and 7c are cross-sectional schematic front views of a fifth embodiment capsule device 100.5, the device assuming a pre-actuation configuration, an intermediate configuration and a shielding configuration, respectively
  • fig. 7d is a detailed view of upper capsule part 110
  • fig. 7e is a sequence of views of fifth embodiment capsule device 100.5 during shielding
  • figs. 7f, 7g, and 7h are detailed views of push rod 160 and holder sleeve 170 for the states shown in figs. 7a, 7b, and 7c, respectively
  • figs. 8a, 8b, and 8c are cross-sectional schematic front views of a sixth embodiment capsule device 100.6, the device assuming a pre-actuation configuration, an intermediate configuration and a shielding configuration, respectively.
  • 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.
  • the first and second example capsule devices shown in figs. 1a through 2d and, in accordance with different aspects of the invention, the first through sixth embodiments of capsule devices 100.1 , 100.2, 100.3, 100.4 100.5 and 100.6, will be described.
  • the different variants are designed to provide a capsule device having a desired actuator arrangement for deployment of a solid dosage form from an ingestible self-righting capsule device and wherein the capsule device is configured for travelling through the alimentary canal for excretion subsequent to deployment.
  • the disclosed capsule devices each enables 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 actuator arrangement to deploy a solid dose payload for insertion of the payload at a target location in tissue of the stomach wall.
  • a 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.
  • 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.
  • payload deposition principles and shielding arrangement 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.
  • the dosage form may be formed partly or entirely from a preparation comprising a therapeutic payload.
  • 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.
  • the capsule device may be brought from a first configuration wherein the payload portion is accommodated at least partly within a housing of the capsule device, and into a second deployed configuration wherein the payload portion has been deployed external to the capsule device and into tissue.
  • the capsule device assumes a pre-actuation configuration.
  • the capsule device will become operated to assume an actuated configuration wherein the tissue interfacing component protrudes a distance from an exit opening of the capsule device.
  • the capsule device when the capsule device has been brought into the actuated configuration, the capsule device assumes a non-shielding configuration.
  • this when referring to the actuated configuration, in some embodiments, this refers to an intermediate state prior to a final shielding configuration.
  • the first example capsule device 200 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 200 accommodates a payload portion 230, forming part of a tissue penetrating member, for carrying an agent for release internally of a subject user that ingests the article.
  • the tissue penetration member further comprises a push rod 260 and a holder sleeve 270.
  • the density of the capsule device is greater than that of gastrointestinal fluid, enabling the capsule device to sink to the bottom of the stomach lumen.
  • 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 200 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 230 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.
  • the capsule device 200 includes an upper (proximal) capsule part 210 which mates and attaches to a lower (distal) capsule part 220.
  • the two parts 210 and 220 are interconnected by means of a snap fit connection. In other embodiments, the two parts 210 and 220 are joined by other mounting methods such as by means of a threaded connection or a bayonet connection.
  • the upper capsule part 210 and the lower capsule part 220 together forms a shell part of the capsule device 200, i.e. the exterior of the capsule housing.
  • the capsule defines an interior hollow which accommodates the payload portion 230, an assembly of components which in combination form a push member/hub 250 which holds and drives forward the payload portion 230, and an actuator arrangement configured to actuate and drive forward the push member/hub 250 carrying with it the payload portion 230 for drug delivery.
  • the payload portion 230 is initially arranged within a sealed payload chamber and oriented along said trigger axis.
  • the payload portion 230 is configured, upon triggering of the capsule device, for movement along the trigger axis.
  • the exterior portions of upper and lower capsule parts 210, 220 form generally rotation symmetric parts arranged with their axis of symmetry coaxially with the trigger axis.
  • the device is oriented with the trigger axis pointing vertically, and with the payload portion 230 pointing vertically downwards towards an exit hole 224 arranged centrally in the lower capsule part 220, the exit hole allowing the payload portion 230 to be transported through exit hole and moved outside the capsule device 200.
  • the lower part 220 includes a tissue engaging surface 223 which is formed as a substantially flat lower outer surface surrounding the exit hole 224.
  • the payload portion 230 assumes the position shown in fig. 1a 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.
  • the separating distance is selected in the order of 2-3 mm.
  • the upper part 210 may suitably be made from a low-density material, such as polycaprolactone (PCL) or Polyether ether ketone (PEEK), whereas the lower part 220 may be suitably made from a high- density material, such as 316L stainless steel.
  • PCL polycaprolactone
  • PEEK Polyether ether ketone
  • the interior of the upper capsule part 210 includes a first sleeve shaped structure 215 extending concentrically with the trigger axis and providing a radially inwards facing cylindrical hub guiding structure which extends concentrically with the trigger axis from the upper part of the upper capsule part 210 towards the lower capsule part 220. Further, in the first example, a second sleeve shaped structure 214 extends concentrically with the trigger axis and radially inside the hub guiding structure from the upper capsule part 210 and downwards along the trigger axis.
  • the second sleeve shaped structure serves as a retainer structure and includes retainer portions 213 for retaining the hub 250 against the drive force emanating from strained compression drive spring 240 arranged within the capsule, i.e. the drive spring serves as an energy source for driving forward the hub from a first position to a second position.
  • the upper retaining part 251 of the hub 250 includes deflectable latches provided in the form of two deflectable arms 252 which extend in distal direction from the upper end of the hub, each arm being resiliently deflectable in the radial inwards direction.
  • the end of each deflectable arm 252 includes a blocking portion 253 protruding radially outwards from the resilient arm. In the pre-actuation configuration shown in fig. 1a, a distal facing surface of each of the blocking portions 253 engage a proximal facing surface of a corresponding one the retainer portions 213.
  • a dissolvable pellet serves as a dissolvable latch support 295 being arranged between the two deflectable arms 252 so that radial opposing surfaces of the dissolvable latch support 295 engage a radially inwards facing support surface of the two deflectable arms 252.
  • the dissolvable latch support 295 is arranged in a compartment inside the upper capsule part 210, and a proximally arranged upper opening in upper capsule part 210 facilitates fluid exposure to the dissolvable latch support when the capsule device is submerged in a fluid.
  • the dissolvable latch support 295 assumes a non-compressible state the pellet prevents the two deflectable arms from bending inwards.
  • a fluid such as gastric fluid present in the stomach of a patient, the dissolvable latch support starts to dissolve.
  • the dissolvable latch support 295 is designed to become gradually dissolved so that after a predefined activation time, the pellet has been dissolved to a degree allowing the two deflectable arms 252 to become sufficiently deflected inwards enabling the blocking portions 253 of hub 250 to be moved distally past the retainer portions 213.
  • the hub 250 has been actuated with the load of the drive spring 240 forcing the hub 250 distally towards the exit hole 224.
  • the hub 250 drives the payload portion 230 distally with the payload protruding initially from the capsule, and gradually pressing the payload portion 230 deeper into the supporting tissue.
  • the forward movement of the payload portion 230 is halted when hub 250 bottoms out relative to the lower capsule part 220. This condition is depicted in fig. 1 b.
  • the interface between the retainer portions 213 and the blocking portions 253 is sloped by approximately 30° so that the deflectable arms will slide inwards when the dissolvable pellet is dissolved.
  • the angle determines the shear forces on the pellet and to which degree the deflectable arms will tend to slide inwards when subjected to the load force.
  • the optimal angle is 0°, but it requires a much higher spring force to activate such configuration.
  • angles other than 30° may be used.
  • the first example capsule device 200 additionally comprises a pair of sealing elements 280, 290 for maintaining the payload portion 230 fluidically isolated from the environment external to capsule device 200 prior to actuation.
  • an upper sealing element 290 formed as a ring of soft pliable material, such an elastomeric material, is inserted between the lowermost annular surface second sleeve shaped structure 214 and an annular proximal facing flange surface of the hub 250.
  • the further sealing element i.e. the lower sealing element 280, forms a fluidic gate configured to maintain the exit hole 224 fluidically blocked prior to actuation.
  • the sealing element 280 comprises an elastomeric seal member having a generally disc shaped form.
  • An outer periphery of the sealing element 280 is mounted below the lowermost annular surface of hub guiding structure 215 and clamped above an annular proximally facing surface of lower capsule part 220.
  • the central area of the sealing element 280 may comprise a fluidic gate formed to provide a self-sealing valve, such as formed by one or more thin cuts (e.g., one or more thin slits) that extend partially or completely through a thickness of the fluidic gate.
  • the sealing elements 280 and 290 thus cooperate to form a compartment internally in capsule device 200 that serves, prior to actuation, to maintain the payload portion 230 fluidically isolated from biological fluid externally to capsule device 200 but allows the payload portion to penetrate easily through sealing element 280 at the time of actuation for payload delivery into tissue.
  • the hub 250 comprises an upper retaining part 251 and a lower interface part 255.
  • the lower interface part 255 defines an annular outer flange having a diameter slightly smaller than the diameter of the hub guiding structure 215.
  • the distal facing end surface of lower interface part 255 includes a bore that extends proximally at the centre of lower interface part 255.
  • a proximally facing bore 256 is formed in distal facing surface of lower interface part 255. This bore 256 is configured to fixedly receive the most proximal portion of a push rod 260 which serves to transmit distal forces from hub 250 to a payload portion 230.
  • the payload portion 230 is formed as a small cylindrical tablet with outer dimensions of approximately 00,8 x 0,82 mm height. Other dimensions and different shapes of the payload portions may be used in alternative embodiments.
  • the shown distal facing surface of payload portion 230 may be formed differently, such as being provided with a pointed distal spike portion pointing towards the centre of exit hole 224.
  • the payload portion 230 is not attached to the push rod 260 but will either abut from the outset or will engage push rod 260 during a part of the displacement push rod 260 experiences during actuation.
  • a holder portion provided as a holder sleeve 270 encircles both the push rod 260 and a proximal portion of the payload and which in the pre-actuation configuration attaches both to push rod 260 and to payload portion 230.
  • the holder sleeve 270 is formed with a distal portion 271 formed as a generally cylindrical sleeve with an inner diameter generally corresponding to an outer diameter of a distal portion of push rod 260.
  • the inner diameter of the cylindrical sleeve also generally corresponds to the outer diameter of the payload portion 230.
  • the holder sleeve 270 is further formed so that, at the proximal end of the cylindrical sleeve, a circular flange 277 extends radially outwards from an outer wall of the cylindrical sleeve.
  • the circular flange 277 of the holder sleeve 270 defines a distally facing stop surface 278 configured for cooperation with the hub stop surface 228 via sealing element 280 and a proximal facing surface 279 configured for cooperation with the lower interface part 255 of hub 250.
  • the dimensions of the inner surface of the cylindrical sleeve of holder sleeve 270 is chosen so that a frictional fit between a distal end 272 of the holder sleeve 270 and the payload portion 230 is provided.
  • cooperating releasable snap geometries are formed between the push rod 260 and the holder sleeve 270.
  • the snap geometries can be seen as an inner snap geometry 274 formed on holder sleeve 270 and an outer snap geometry 264 formed on push rod 260.
  • the holder sleeve 270 is so dimensioned that the holder sleeve distal portion 272 overlaps axially with the payload portion 230 in a way so that approximately half of the axial height of the payload portion is gripped by holder sleeve distal portion 272, i.e. the distance denoted “d” in fig. 1c.
  • Non-limiting exemplary materials for the holder sleeve 270 and the push rod 260 may be selected as a relatively resilient polymeric material such as a material formed from PEEK.
  • Alternative materials for holder sleeve 270 may be formed by an elastomeric material, such as silicone rubber.
  • the push rod 260 is seen suspended from lower part interface 255 of hub 250.
  • these two components in the shown embodiment are formed as two independent parts that are joined during assembly, alternative embodiments may provide corresponding features by means of a unitary component.
  • the system is in this embodiment designed so that, in the pre-actuation configuration, the distal face of payload portion 230 is disposed approximately 2 mm from the tissue engaging surface 223, meaning that the assembly formed by the hub 250, the push rod 260, the holder sleeve 270 and the payload portion 230, is moved together by an acceleration stroke of approximately 2mm before the payload portion engages adjacent tissue situated below exit hole 224.
  • the push rod 260 is further dimensioned to provide an insertion depth of the distal portion of payload portion 230 in the order of approximately 4 mm relative to the tissue engaging surface 223.
  • the lower interface part 255 of hub 250 forms a distal facing blocking surface which is configured for abutting contact with proximal facing surface 279 of holder sleeve 270.
  • the distal facing surface 278 of holder sleeve 270 is configured for abutting contact with a proximal facing surface of sealing element 280.
  • fig. 2a shows the capsule in an initial state representing the state the capsule device assumes during storage or just after ingestion.
  • the hub 250 assumes the preactuation configuration where the two deflectable arms 252 are maintained in the shown position by engagement with the radially outwards facing surface of the dissolvable latch support 295 engaging the radially inwards facing surface 252a of the deflectable arms 252.
  • the blocking portions 253 engage a proximal surface of a respective one the retainer portions 213 preventing the deflectable arms from sliding relative to the retainer portions.
  • the hub 250 cannot be moved distally even though the drive spring 240 exerts its full compressive load onto the hub 250.
  • the upper sealing element 290 engages the lowermost annular surface of second sleeve shaped structure 214 as well as the annular proximal facing flange surface of the hub 250 to keep this interface fluid tight. Also, the lower sealing element 280 keeps the exit hole 224 fluid tight.
  • the capsule device After ingestion of capsule device 200, the capsule device quickly sinks to the bottom of the stomach. Upon being supported by the stomach wall, due to the self-righting ability of the capsule device, the capsule device will quickly reorient to have its tissue interfacing surface 223 engaging the tissue stomach wall with the trigger axis of the capsule device oriented virtually vertical, i.e. with the payload portion 230 and the push rod 260 pointing downwards. Dissolve- ment of dissolvable latch support 295 has begun due to exposure to gastric fluid. This is represented in fig. 1 b in connection with reference 295. The support from dissolvable latch support 295 against the deflectable arms 252 will cease at a specific time after swallowing.
  • the load of the drive spring 240 will cause the deflectable arms 252 to be gradually deflected radially inwards thereby allowing the arms to slide off from engagement with the retainer portions 113.
  • the deflectable arms 252 will reach their radially collapsed position where after the hub 250 with the payload, the push rod 260, the holder sleeve 270 and the payload portion 230 will become released from the capsule housing. This state corresponds to the actuating configuration (not shown).
  • the push rod 260, the holder sleeve 270 and the payload portion 230 are caused to travel unhindered towards the exit hole 224 as slaved with the hub 250, with the payload portion penetrating the lower sealing element 280 and further into mucosal tissue at the target location.
  • the holder sleeve distally facing stop surface 278 will enter into engaging abutment with the lower sealing element 280 and will be prevented from moving further distally.
  • the remaining load of drive spring 240 will still urge the push rod 260 further distally.
  • the snap engagement 264/274 defines a relatively weak force transmission
  • the snap engagement will release causing the push rod 260 to be moved further distally carrying with it the payload portion 230 for distal sliding movement relative to the holder sleeve 270.
  • the payload portion will be pushed by the push rod 260 to the target depth in tissue which occurs when the distal facing blocking surface of lower interface part 255 of hub 250 engages in abutting contact with proximal facing surface 279 of holder sleeve 270.
  • This state is depicted in fig. 2b, note however that the spring is only schematically shown as deployed. In real-life settings the spring would have expanded between a proximal spring seat and the lower interface portion 255.
  • the target insertion depth of the distal face of the payload portion is designed to be approximately 4 mm into mucosal tissue.
  • further exemplary insertion depths may be selected between 2 to 6 mm, such as between 2.5 mm and 4.5 mm.
  • the payload portion 230 is inserted into tissue of the lumen wall where it will anchor generally in a direction along the actuation axis. As discussed in this disclosure, depending on the specific design of the capsule device, the payload portion 230 will be released actively from the remaining parts of the capsule at the end of the insertion stroke. When the capsule device 200 has delivered the intended dose the capsule will release relative to the deposited payload portion 230 which remains inside the tissue wall for release of therapeutic agent into the blood stream of the subject.
  • a second example drug delivery device 300 in accordance with an auxiliary aspect relating to the invention is shown and will be described in the following.
  • the second example capsule device 300 generally corresponds to the overall design of the first example capsule device 200, but the actuator principle and the way the hub is released from the capsule housing is different.
  • the assembly made up of hub lower part 360, holder sleeve 370 and payload portion 330 generally correspond to the design shown in fig. 1c.
  • Figs. 2a and 2b are side views of the second example capsule device 300 in the pre-actuation configuration and the actuated configuration, respectively.
  • the drive spring 340 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 340 aids in mounting the distal end of the drive spring relative to the capsule housing.
  • a spacer element 386 is inserted into a cylindrical bore of the upper capsule part 310.
  • the enlarged diameter winding of spring 340 and the spacer element 386 are clamped axially between a distally facing surface of upper capsule part 310 and a proximally facing surface of the lower capsule part 320.
  • the proximal end of drive spring 340 includes a reduced diameter winding which aids in coupling to the hub 350.
  • the reduced diameter winding is clamped axially between a proximal flange 356 and a distal flange 359.
  • the distal flange 359 performs as a washer and is mounted rotatably relative to hub upper part 351 and hub lower part 362 so that torsional forces incurred by rotational movement of hub upper part 351 and hub lower part 362 are not transferred to the drive spring 240.
  • a hub lock geometry and a housing lock geometry engage each other so as to maintain the hub 350 positioned in an initial first position against the axial tension load exerted by drive spring 340.
  • the hub lock geometry defines a hub retaining surface whereas the housing lock geometry defines a housing retaining surface.
  • the hub retaining surface and the housing retaining surface are provided as ramped geometries 353.1 and 313.1 , these to be described further below.
  • the second embodiment again comprises a lower sealing element 380 to seal off the exit opening 324 and an upper sealing element 390, arranged between a flange 360 on the hub upper part 351 and a distal facing rim surface formed in upper capsule part 310, to seal the payload chamber at this interface.
  • an intermediate seal 385 is arranged at the interface between the upper capsule part 310 and the lower capsule part 320.
  • the upper capsule part 310 of capsule device 300 is depicted in fig. 2c.
  • Upper capsule part 310 this time includes two pellet receiving pockets 319 which are symmetrically disposed around the axis. Only one of the pellet receiving pockets 319 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 310 are two ramp shaped geometries 313.1 formed on respective housing lock geometries 313, 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 (when viewed from above).
  • Each of the curved surfaces 313.1 are designated for use with correspondingly curved surfaces 353.1 of hub lock geometries formed as wings 353 by hub upper part 351 .
  • the hub upper part 351 comprises the flange 356 and a cylindrical top part extending in the proximal direction from flange 356.
  • the wings 353 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 310 allows passage of the wings 353 of hub upper part 351 but only when the hub upper part 351 is oriented so that the wings 353 clear the helically curved arc surfaces 313.1.
  • the curved surfaces 353.1 of wings 353 intimately engages the ramp shaped geometries 313.1 of upper capsule part 310 so that the hub upper part 351 rests on these inclined surfaces while the tension force of the strained drive spring 340 urges the hub upper part 351 in the distal direction.
  • the tension force from drive spring 340 induces a torsional force on the hub upper part 351 in clockwise direction (seen from above) due to the inclined surfaces 313.1 and 353.1.
  • a dissolvable pellet 395 is arranged in one of the pellet receiving pockets 319 and a radial extending surface 353.2 of one of the wings 353 engages a side surface of the dissolvable pellet 395 thereby preventing the hub upper part 351 from sliding distally on the inclined surfaces 313.1.
  • the capsule device after ingestion of capsule device 300, 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 323 engaging tissue of the stomach wall with the trigger axis of the capsule device oriented virtually vertical, i.e. with the payload portion 330 and the push rod 360 pointing downwards. Dissolution of dissolvable pellet 395 has begun due to exposure to gastric fluid. This is schematically represented in fig. 2b in connection with reference 395.
  • the support from dissolvable pellet 395 on the radial extending surface 353.2 will at some point cease allowing the wings 353 of hub upper part to slide distally along the curved arc surfaces 313.1. Subsequent to full dissolution of pellet 395, or subsequent to the pellet 395 becoming dissolved to a degree so that the pellet 395 will be pushed away from its blocking position within pocket 319, and after approximately 60 degrees of turning movement of the hub upper part 351 , the inclined surfaces 353.1 of wings 353 will slide off the curved arc surfaces 313.1 and be free to move further distally within the capsule device through the central axial passage. As shown in fig.
  • the distal movement of the hub 350 is halted when the hub lower part 362, and more specifically the distal end surface 368 bottoms out in the capsule interior.
  • the drive spring 340 has pulled the hub 350 into an axial position wherein the flange 377 of holder sleeve 370 is clamped between distal end surface 368 and hub stop surface 328.
  • the capsule device 300 assumes its deployed configuration.
  • FIG. 100.1 For a first embodiment of a capsule device 100.1 in accordance with the primary aspect, reference will be made to figures 3a-3f, which all show schematic representations.
  • the capsule device 100.1 shares many constructional features with the corresponding general features of the first and second example capsule devices 200/300 described above, and the general principle of operation is the same.
  • the capsule device 100.1 has been modified to include a shielding arrangement which provides for an opportunity, subsequent to actuation, to increase safety against accidental penetration by the protruding push rod and/or the protruding holder sleeve as the capsule travels through the Gl tract towards secretion.
  • the overall design of the actuation mechanism is somewhat modified for the first embodiment device 100.1 as compared with the second example device 300, i.e. with a trigger release mechanism which relies on a rotational release of hub 150 relative to the retainer structure 113, instead of relying on deflectable arms that deflect to allow axial movement.
  • the capsule device 100.1 comprises an upper capsule part 110 and a lower capsule part 120 which are fixedly attached to each other so as to define exterior shell portions of the capsule device.
  • the hub 150 comprises an upper retaining part configured for releasably retaining the hub 150 by means of blocking portions 153 being axially retained relative to a retainer structure 113 of the capsule housing.
  • Hub 150 further comprises a lower interface part which defines an annular spring seat for the drive spring 140, the drive spring this time being provided as a strained compression spring.
  • the rotational release of hub 150 is provided by ensuring that the hub 150 is biased by a torque acting to turn hub 150 into a rotational position where the hub 150 will be able to pass the retaining structure 113. In the shown state this is prevented by dissolvable latch support 195.
  • the torque exerted onto hub will in typical applications be provided by the drive spring 140 either by the drive spring being torsionally strained, or by not shown ramp surfaces between hub and upper capsule part 110 which may transform a distally directed biasing force from drive spring 140 into rotational bias on hub 150.
  • a shielding arrangement is shown in the form of a shield member 131 depicted in a perspective view isolated from the remaining parts of capsule device 100.1.
  • the shield member 131 is formed as a mainly tubular component having a plurality of axially extending slits 136 which extends from the distal end face of the shield member 131 towards the proximal end thereof.
  • the slits 136 corresponds in form and number to radial ribs 126 formed in lower capsule part 120 (see fig. 3c) so that the slitted portion of the shield member 131 is able to protrude distally through the lower capsule part 120.
  • the shield member 131 is formed without any sharp or other potentially harmful geometric features which could otherwise potentially give rise to safety concerns.
  • the shield member 131 may be formed from a relatively soft pliable material which may exhibit beneficial safety characteristics.
  • annular sealing elements 185 which in the shown embodiment are provided as gelatine segments designed to become pushed away by shield member 131 when the latter is allowed to move distally.
  • the shield member may include an annular sealing portion at the distal facing surface.
  • the shield member 131 is positioned in a retracted or essentially non-shielding position within the capsule housing in a manner where it is aligned concentrically with the actuation axis, and thus concentrically with payload portion 130, push rod 160 and holder sleeve 170.
  • a shield spring 141 provided as a strained compression spring, exerts a distally directed biasing force urging the shield member 131 in the distal direction relative to the capsule housing.
  • distal movement of shield member 131 is prevented by one or more releasable lock elements.
  • the releasable lock elements are provided as snap arms 137 (provided in the shown embodiment as three separate elements 137), each protruding elastically radially inwards in an inclined manner relative to the actuation axis. In the shown state where they protrude inwardly the snap arms are supported by a blocking surface in the lower capsule part 120 so that they cannot be pushed outwards by the force of the shield spring 141 alone.
  • Hub 150 includes a plurality of lock release surface portions 157 each designated to release a respective one of the lock elements 137.
  • the lock release surface portions 157 are provided as a circular inclined flange portion, i.e. a conical surface portion.
  • Fig. 3e shows the capsule device 100.1 in an intermediate state, i.e. the actuated configuration, wherein the dissolvable latch support 195 has been dissolved and the hub 150 has rotated into the position where it has been released from retainer portion 113 and the drive spring 140 has forced hub 150 all the way distally into a stop position inside the capsule housing.
  • the push rod 160 and the holder sleeve 170 has been moved by hub 150 until the flange of holder sleeve has been halted by stop surface 128.
  • the hub 150 and push rod 160 has pushed payload portion 130 into the desired target position for release relative to the holder sleeve 170 and intended payload deposition in tissue.
  • the shield member 131 has not yet initiated any significant movement.
  • the lock release surface portions 157 Shortly prior to the hub 150 has become arrested inside the capsule housing the lock release surface portions 157 have pushed lock elements 137 radially outwards so that the shield member 131 becomes released for distal movement relative to the housing.
  • the state is depicted wherein the shield member 131 has been pushed all the way distally by shield spring 141 , i.e. into a position where stop elements 133 engage corresponding stop features inside the capsule housing.
  • the shield member 131 has thus been moved from the non-shielding configuration into a shielding configuration wherein the shield member effectively shields the still protruding push rod 160 and holder sleeve 170 from unintended tissue interaction.
  • the movement of the shield member 131 away from the lower capsule part 120 has pushed the entire capsule device 100.1 away from tissue at the target location leaving the payload portion 130 lodged inside the tissue. Also indicated in fig. 3f, the gelatine segments, initially forming annular sealing elements 185, have been detached from the capsule and will gradually degrade. Hereafter, the “empty” capsule device 100.1 will be transported safely through the alimentary canal for subsequent excretion.
  • FIG. 4a-4d these figures represent schematic drawings of a second embodiment capsule 100.2 according to the invention.
  • the shielding arrangement 131 in capsule device 100.2 is maintained in the non-shielding configuration or position by means of a plurality of dissolvable retainer elements 197 which releasably retains the shield member 131 against the bias provided by shield spring 141.
  • the capsule will self-orient while stomach fluid starts to degrade not only the dissolvable latch support 195 but also the dissolvable retainer elements 197.
  • the shield member 131 includes a number of shield snap elements 138 which provide for non-reversible distal movement of the needle shield 131 relative to the capsule housing. As the snap elements 138 snaps radially into a locking position as soon as the shield member arrives in the shielding configuration the shield member is effectively prevented from being pushed proximally. Hence, the risk of unintended contact between the mucosal tissue and the push rod 160 and holder sleeve 170 is effectively minimized.
  • the shielding arrangement 131 of the third embodiment is formed by a shape changing material that is configured to change shape from a non-shielding configuration and into a shielding configuration. In the shown embodiment, this is accomplished by incorporating an amount of a swellable component or substance, such as a hydrogel, in a pocket formed in connection with the lower sealing element 180.
  • the swellable component or substance is able to expand when contacted by a fluid, such as stomach fluid present in the stomach.
  • the pocket forms a rings shaped configuration for containing the swellable component in a ring-shaped confinement arranged coaxially and encircling the actuation axis.
  • the lower sealing element 180 maintains the swellable component isolated from fluids, such as a fluidic environment external to the capsule device.
  • the activation of the shield transformation is subject to the actuation of the actuation arrangement.
  • the trigger arrangement for the third embodiment is provided as an axial trigger release mechanism which does not rely on rotational release but rather relies on deflectable arms that allows axial only movement of actuator hub 150, i.e. similar to the first example device 200 described above.
  • the sealing element upon the protrusion assembly of the payload portion 130, the holder sleeve 170 and the push rod 160 through the lower sealing element 180, the sealing element allows transport of stomach fluid towards the swellable component which, upon exposure to moisture, makes the swellable component swell drastically.
  • the swellable component As the swellable component has been selected so as to provide or exhibit a firm consistency upon swelling the swellable component will be able to expand in directions away from the ring-shaped confinement and this will cause the swelled hydrogel to assume a shape resembling the shape of a sheath that covers both the protruding push rod 560 and holder sleeve 570. Again, for this embodiment, the risk of unintended contact between the mucosal tissue and the push rod 560 and holder sleeve 570 is effectively minimized.
  • the pocket forming the enclosure for the swellable component may include a barrier layer, such as a semi-permeable membrane, and optionally covered by an enteric coating, which after a predefined time after swallowing of the capsule device will allow stomach fluid to contact the swellable component for subsequent transformation into the shielding configuration.
  • a barrier layer such as a semi-permeable membrane
  • an enteric coating which after a predefined time after swallowing of the capsule device will allow stomach fluid to contact the swellable component for subsequent transformation into the shielding configuration.
  • the activation of the shielding function according to the invention may be provided using other methods, such as methods that are dependent on various alternative environmentally-sensitive mechanisms, such as pH sensitive mechanisms.
  • a fourth embodiment capsule device 100.4 is schematically presented and will next be described.
  • the shielding arrangement of the fourth embodiment is provided by means of a plurality of housing components, wherein the shielding function relies on housing parts that are configured for being axially extendable relative to each other.
  • the capsule device 100.4 comprises an upper capsule part 110 and a lower capsule part 120 which are movably arranged relative to each other. However, prior to actuation, the upper capsule part 110 and the lower capsule part 120 are releasably locked relative to each other so as to define exterior shell portions that mate relative to each other for sealingly accommodating the payload portion 130 within the capsule device. Subsequent to actuation of the actuator arrangement the upper capsule part 110 and the lower capsule part 120 become unlocked allowing the lower capsule part 120 to be moved by a pre-defined distal movement relative to the upper capsule part 110, i.e., in a telescopic expanding manner.
  • the lower capsule part 120 serves as a shielding arrangement that acts to shield the tissue interfacing component 160/170 subsequent to actuation for payload deployment.
  • the lock comprises a releasable lock arm 117 formed in capsule upper part 110 which releasably is held engaged into a retainer opening 127 formed in lower capsule part 120.
  • the hub 150 comprises an upper retaining part configured for releasably retaining the hub 150 by means of blocking portions 153 being axially retained relative to a retainer structure 113 of the capsule housing.
  • Hub 150 further comprises a lower interface part which defines a circular flange 155 which further connects to push rod 160 at its distal side.
  • the drive spring 140 for this embodiment is provided in the form of compression spring which prior to actuation is held in a loaded state with compressional axial load.
  • the rotational release of hub 150 is provided by ensuring that the hub 150 is biased by a torque acting to turn hub 150 into a rotational position where the hub 150 will be able to pass the retaining structure 113. In the shown state this is prevented by dissolvable latch support 195.
  • the torque exerted onto hub will be provided by the drive spring 140 either by the drive spring being torsionally strained, or by not shown ramp surfaces between hub and upper capsule part 110 which may transform a distally directed biasing force from drive spring 140 into rotational bias on hub 150.
  • the proximal facing surface of the circular flange 155 is configured for receiving a distally directed force acted upon by the axial load of the compressed drive spring.
  • An axially movable drive member 145 is arranged inside capsule device 100.4 coaxially with the actuation axis.
  • the drive member 145 serves initially to transfer axial load from the drive spring 140 towards the actuator/hub 150 for moving the actuator/hub 150 from the proximal position to the distal position, and subsequently to shift axial load from drive spring 140 towards the shielding arrangement to thereby cause the lower capsule part 120 to move axially relative to the upper capsule part 110.
  • the drive member 145 forms a generally tubular sleeveshaped member, i.e. a drive sleeve, having a number of axially extending flexible arms 147 distributed around the circumference of drive member 145.
  • the drive sleeve is formed by moulding having three resiliently flexible arms 147 formed generally within the sleeve, and wherein each arm is defined by axially running slits separating flexible parts of the arms from the remaining part of the drive sleeve.
  • other numbers of flexible arms 147 may be provided, such as one, two, four or even more arms distributed around the circumference of drive member 145.
  • Each flexible arm 147 is made unitarily with the drive member, connects to the remaining part of the sleeve shaped member approximately halfway between the proximal and distal end thereof and extends in the distal direction towards a free end having a distally and inwardly protruding end hook part.
  • the end hook part is provided as a segment arranged approximately at a 90-degree angle relative to the flexible arm.
  • Fig. 6d depicts the drive sleeve 145 in its free relaxed state where the flexible arms 147 assume their relaxed state. In this state the flexible arms extend gradually radially outwards towards their free ends, so that the end hook part points in the distal direction and radially inwards.
  • Fig. 6e shows the drive member 145 with the shape of drive member 145 in the state it assumes when built into the capsule device 100.4 and with the actuator assuming the pre-actu- ation configuration shown in fig. 6a.
  • a radially inwards facing cylindrical surface 115 of the upper capsule part 110 cooperates with the flexible arms 147 by forcing them radially inwards so that they lie generally flush with the sleeve portion of drive member 145 and with the end hooks of arms 147 pointing radially inwards, approximately transverse to the actuating axis.
  • the end hooks of arms 147 defines a proximal facing spring seat for supporting the distal end coil of drive spring 140.
  • a distal facing surface of the end hook of each flexible arm 147 engages a proximal facing surface of the circular flange 155 of hub 150.
  • the releasable lock arm 117 is kept engaged with retainer opening 127 formed in lower capsule part 120 by means of the sleeve shaped portion of drive member 145 which supports the radial inner surface of the lock arm 117 and prevents the lock arm 117 from disengaging the retainer opening 127.
  • Fig. 6b shows the capsule device 100.4 in an intermediate state, i.e. the actuated configuration, wherein the dissolvable latch support 195 has been dissolved and the hub 150 has rotated into the position where it has been released from retainer portion 113 and the drive spring 140 has forced hub 150 all the way distally into a stop position inside the capsule housing.
  • the push rod 160 and the holder sleeve 170 has been moved by hub 150 until the flange of holder sleeve has been halted by stop surface 128.
  • the hub 150 and push rod 160 has pushed payload portion 130 into the desired target position for release relative to the holder sleeve 170 and intended payload deposition in tissue.
  • the shielding arrangement has only just been initiated.
  • the drive member 145 Shortly prior to the hub 150 has become arrested inside the capsule housing the drive member 145 has reached its distal position. In this position, the sleeve shaped portion of drive member 145 axially clears the lock arm 117 thereby enabling the lock arm 117 to disengage the retainer opening 127. Also the end hooks of flexible arms 147 axially clears the radially inwards facing cylindrical surface 115 of upper capsule part 110 thereby enabling the flexible arms 147 to deflect radially outwards.
  • the end hooks of flexible arms 147 disengages the circular flange 155 of hub 150 and further allows the distal portion of drive spring 140 to bypass the end hooks as well as the circular flange 155, thereby allowing the distal portion of drive spring 140 to exert axial distal force onto the lower capsule part 120 (via lower sealing element 180).
  • the hub 150 is in this state arrested axially relative to the upper capsule part 110.
  • this state represents the end state corresponding to the shielding configuration.
  • the drive spring distal portion has bypassed the hub and forced the lower capsule housing 120 axially distally away from the upper capsule housing 110.
  • the remaining force of the drive spring has thus caused the lower capsule housing 120 to extend relative to hub 150, push rod 160 and holder sleeve 170.
  • a not shown stop prevents further relative axial movement between upper capsule part 110 and lower capsule part 120 and has been dimensioned to fully shield the tissue interface component, i.e. parts 150, 160 and 170, upon reaching the stop.
  • the tissue interface component become substantially shielded by lower capsule housing 120 acting as a shield 131 , i.e., so that only a minor portion of tissue interfacing component still extends outside the exit hole, but sufficiently shielded for safe transit of the used capsule device 100.4 in the Gl tract towards excretion.
  • a fifth embodiments capsule device 100.5 is schematically depicted in figs. 7a through 7h. Similarly to the fourth embodiment capsule device 100.4, the fifth embodiment capsule device 100.5 incorporates a shielding arrangement which relies on utilizing a housing portion for shielding the tissue interfacing component subsequent to drug payload deposition.
  • the trigger and actuator arrangement is designed similar to the fourth embodiment, i.e. involving a rotational trigger release utilizing a dissolvable latch support 195 and a drive spring 140 working in compression mode.
  • the capsule device 100.5 comprises an upper capsule part 110 and a lower capsule part 120 which are coupled relative to each other by means of a threaded connection 119/129 (see figs. 7a and 7d).
  • the threaded connection is designed so that a distal force from the drive spring 140 and acting on the lower capsule part 120 for pushing the upper capsule part 110 and lower capsule part 120 apart will be sufficient for causing relative rotation as dictated by the threaded connection 119/129.
  • a threaded connection 119/129 see figs. 7a and 7d.
  • a dissolvable retainer element 197 is disposed against a rotational blocking geometry 119a arranged in association with the threaded connection so that, in the state prior to actuation the dissolvable retainer element 197 blocks rotation of the lower capsule part 120 relative to the upper capsule part 110.
  • a simplified drive member 145 is used, provided as a disc shaped element having a proximal facing surface forming a spring seat for the distal portion of drive spring 140.
  • a central opening is formed in the drive member 145 allowing the push rod 160 to protrude through the central opening.
  • the push rod 160 includes two opposed force transfer arms 157, each arm extending from the push rod at an inclined angle so that it extends radially outwards-proximally towards a free end of the arm.
  • the force transfer arms 157 are formed unitarily with the push rod and provided as flexible arms being deflectable radially inwards. Hence, each arm may be moved from a first radial protruding configuration (see figs. 7a and 7f) into a radial collapsed configuration so as to assume a state where the force transfer arms 157 are near parallel with the actuator axis (see figs. 7c and 7g).
  • a distal facing surface of the drive member 145 surrounding the opening will engage the force transfer arms 157 and transfer the force of the drive spring 140 to the hub 150/push rod 160.
  • the base of the arms 157 are positioned just proximally relative to holder sleeve 170.
  • the drive member 145 is arranged axially movable coaxially with the actuation axis inside capsule device 100.5.
  • the drive member 145 serves initially to transfer axial load from the drive spring 140 towards the actuator/hub 150 for moving the actuator/hub 150 from the proximal position to the distal position, and subsequently to shift axial load of the drive spring 140 towards the shielding arrangement to thereby urge the lower capsule part 120 for movement axially relative to the upper capsule part 110, however only accomplishing the latter step after a time delay subsequent drug deposition.
  • the capsule will self-orient while stomach fluid starts to degrade not only the dissolvable latch support 195 but also the dissolvable retainer element 197.
  • the actuator will be actuated first for lodging the payload portion 130 at one point in time, and, with a short delay, dissolution of the dissolvable retainer element 197 will enable relative rotation between the lower capsule part 120 and upper capsule part 110.
  • Figs. 7b and 7g show the capsule device 100.5 in an intermediate state, i.e. the actuated configuration, wherein the dissolvable latch support 195 has been dissolved and the hub 150 has rotated into the position where it has been released from retainer portion 113 and the drive spring 140 has forced hub 150 all the way distally into a stop position inside the capsule housing.
  • the push rod 160 and the holder sleeve 170 has been moved by hub 150 until the flange of holder sleeve has been halted by stop surface 128.
  • the hub 150/ push rod 160 have pushed payload portion 130 into the desired target position for release relative to the holder sleeve 170 and intended payload deposition in tissue.
  • the shielding arrangement has not yet been initiated as the retainer element 197 is near intact.
  • the hub 150/ push rod 160 have moved axial distally relative to the holder sleeve 170 the latter encircles the force transfer arms 157 which have been moved to their collapsed configuration.
  • the free ends of transfer arms 157 are able to pass through the central opening of the drive member 145 and are thus uncoupled relative to the drive member 145 allowing the drive member to move unhindered past the force transfer arms towards the stop surface 128 of lower capsule housing 120 thereby abutting the stop via lower sealing element 180.
  • FIG. 8a-8c show a sixth embodiment capsule device 100.6.
  • the shielding arrangement of this embodiment largely corresponds with the shielding arrangement of the fifth embodiment, i.e., having a threaded interface between upper capsule part 110 and lower capsule part 120 and, optionally, having a dissolvable retainer element 197 to prevent premature rotation between the two.
  • the actuator arrangement of capsule device 100.6 largely corresponds to the third embodiment, i.e. with an axial only trigger release of hub 150.
  • the drive spring 140 is arranged as a compression spring which furthermore has been loaded to exert a torsional load on a drive member 145.
  • the drive member 145 is provided generally disc-shaped and with a single radial protrusion 146 at one angular position.
  • the drive member 145 is configured for being moved from a first proximal position to a second distal position.
  • a generally circular central opening in drive member 145 allows the hub 150 to protrude through the central opening.
  • a radial recess 147 extends further radially outwards from the generally circular central opening.
  • the drive spring 140 comprises a first proximal end which is mounted rotationally fixed in the upper capsule part 110 and a second distal end which is mounted rotationally fixed relative to the drive member 145. Hence, due to the torsional load of drive spring 140, the drive member is biased for rotation relative to the upper capsule part 110.
  • the hub 150/push rod 160 has been configured for axial-movement-only from a proximal position to an actuated distal position. Rotational movement of hub 150/push rod 160 is prevented due to a not shown engagement with a rotation preventing guide geometry formed in the upper capsule part 110.
  • the hub 150/push rod 160 includes, approximately midways between a proximal end and a distal end, a radially protruding geometry 157 arranged for passing axially through said radial recess 147 formed in the drive member 145, i.e. only when the radially protruding geometry aligns rotationally with the radial recess 147.
  • the said single radial protrusion 146 extending radially outwards from drive member 145 is configured for being received within an axially running guide track 116 formed in the capsule upper part so that as long as the single radial protrusion 146 is received in guide track 116 the drive member is prevented from rotating.
  • a recess 125 in the lower capsule part 120 is similarly formed to receive the single radial protrusion 146 when the single radial protrusion exits the guide track 116, i.e. when the drive member 145 has been moved fully distally.
  • the capsule will self-orient while stomach fluid starts to degrade not only the dissolvable latch support 195 but also the dissolvable retainer element 197.
  • the actuator will be actuated first for lodging the payload portion 130 at one point in time, and, with a short delay, dissolution of the dissolvable retainer element 197 will enable relative rotation between the lower capsule part 120 and upper capsule part 110.
  • the drive member 145 assumes the proximal position where the drive member transfers the axial load from the drive spring 140 towards the hub 150 due to the drive member engaging the radially protruding geometry 157 of hub 150, noting that in this state the radially protruding geometry 157 is not rotationally aligned with the radial recess 147 formed in the drive member 145.
  • the single radial protrusion 146 extending radially outwards from drive member 145 is received within axially running guide track 116 and therefore the drive member is prevented from rotating relative to the upper capsule part 110. This state corresponds to the state the capsule device 100.6 assumes when a patient swallows the capsule device.
  • Fig. 8b shows the capsule device 100.6 in an intermediate state, i.e. the actuated configuration, wherein the dissolvable latch support 195 has been dissolved and the hub 150 has been released from retainer structure 113 and moved axial distally into the second distal position.
  • the drive spring 140 has forced hub 150 all the way distally into a stop position inside the capsule housing. In this position the push rod 160 and the holder sleeve 170 has been moved by hub 150 until the flange of holder sleeve has been halted by stop surface 128.
  • the hub 150/ push rod 160 have pushed payload portion 130 into the desired target position for release relative to the holder sleeve 170 and intended payload deposition in tissue.
  • the single radial protrusion 146 extending radially outwards from drive member 145 has axially exited the axially running guide track 116 and is now located within the recess 125 in the lower capsule part 120.
  • the shielding arrangement has not yet been initiated as the retainer element 197 is near intact and this still prevents the drive member from rotating as the single radial protrusion 146 extending radially outwards from drive member 145 is located within the recess 125.
  • the radially protruding geometry 157 of hub 150 will pass through the radial recess 147 formed in the drive member 145.
  • the radial recess 147 may be formed as a thread segment having a lead corresponding with the lead of the threaded engagement 119/129. However, other designs are also possible.
  • 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 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.

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Abstract

La présente invention concerne un dispositif ingestible destiné à être avalé dans une lumière d'un tractus digestif et inséré dans une paroi de lumière, le dispositif ingestible (100) comprenant : a) un boîtier (110, 120) comportant une ouverture de sortie (124), b) un composant d'interfaçage tissulaire (160, 170) conçu pour être avancé axialement à partir d'une première position dans laquelle sa première extrémité ne dépasse pas de l'ouverture de sortie (124) et dans une seconde position dans laquelle la première extrémité dépasse de l'ouverture de sortie (124) pour être insérée dans la paroi de lumière à un emplacement cible, c) un agencement d'actionneur (140, 150) pour faire avancer le composant d'interface tissulaire (160, 170) de la première position à la seconde position, et d) un agencement protecteur (131) pour protéger le composant d'interface tissulaire (160, 170) et configuré par passage d'une configuration non protectrice à une configuration protectrice après que le composant d'interface tissulaire (160, 170) est passé dans la seconde position.
PCT/EP2023/083991 2022-12-01 2023-12-01 Dispositif ingestible avec agencement protecteur WO2024115766A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP22210928 2022-12-01
EP22210928.2 2022-12-01
EP22216222.4 2022-12-22
EP22216222 2022-12-22

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017156347A1 (fr) 2016-03-09 2017-09-14 Incube Labs, Llc Procédés et articles d'administration de cellules viables dans un tissu solide
WO2018213600A1 (fr) 2017-05-17 2018-11-22 Massachusetts Institute Of Technology Systèmes à redressement automatique, et composants et procédés associés
WO2021250222A1 (fr) * 2020-06-12 2021-12-16 Novo Nordisk A/S Dispositif ingérable ayant un ensemble pointe

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017156347A1 (fr) 2016-03-09 2017-09-14 Incube Labs, Llc Procédés et articles d'administration de cellules viables dans un tissu solide
WO2018213600A1 (fr) 2017-05-17 2018-11-22 Massachusetts Institute Of Technology Systèmes à redressement automatique, et composants et procédés associés
US20200129441A1 (en) 2017-05-17 2020-04-30 Massachusetts Intitute Of Technology Self-righting systems and related components and methods
WO2021250222A1 (fr) * 2020-06-12 2021-12-16 Novo Nordisk A/S Dispositif ingérable ayant un ensemble pointe

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