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WO2024184282A1 - Capsule pouvant être insérée dans une lumière - Google Patents

Capsule pouvant être insérée dans une lumière Download PDF

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Publication number
WO2024184282A1
WO2024184282A1 PCT/EP2024/055515 EP2024055515W WO2024184282A1 WO 2024184282 A1 WO2024184282 A1 WO 2024184282A1 EP 2024055515 W EP2024055515 W EP 2024055515W WO 2024184282 A1 WO2024184282 A1 WO 2024184282A1
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WO
WIPO (PCT)
Prior art keywords
trigger
trigger member
drug
pressure position
lumen
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
PCT/EP2024/055515
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English (en)
Inventor
Todd Andrew DUNCOMBE
Brian Mouridsen
Jacob Pyung Hwa JEPSEN
Ava LAROCCA
Anders Hammelev MARSTRAND
Enrique Medina De ALBA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novo Nordisk AS
Original Assignee
Novo Nordisk AS
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 AS filed Critical Novo Nordisk AS
Publication of WO2024184282A1 publication Critical patent/WO2024184282A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

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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

Definitions

  • the present invention relates to drug delivery devices, such as ingestible capsules, for delivery of a drug substance to a subject user.
  • 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).
  • Capsule devices have been proposed for delivery of a drug substance into a lumen or lumen wall. After insertion of the capsule device, such as by swallowing the capsule device into the Gl system of the subject, drug delivery may be performed using am actuator comprising a gas generator which forces the drug substance through an outlet. For certain types of drug delivery rapid delivery is believed to be beneficial but gas generation may not offer sufficient drive pressure in a timely manner.
  • WO 2018/049,133 A1 discloses various ingestible devices wherein some of these include a jet delivery mechanism for delivery through an outlet provided as a jet nozzle, and wherein a gas generating cell propels a piston to move towards the nozzle such that a dispensable substance can be pushed under gas pressure to break a burst disk arranged upstream from the jet nozzle. Further related disclosure of ingestible devices is provided in WO 2020/106,750 A1 and WO 2018/213,600 A1 , WO 2022/074252 A1 , US 2009/043278 A1 , WO 2022/090551 A1 and W02022/069604 A1 .
  • a drug delivery device such as a capsule device suitable for insertion into a lumen of a human or animal subject.
  • the drug delivery device comprises: a housing, a drug chamber (B) configured to accommodate a drug substance, the drug chamber (B) leading to a drug delivery opening, an actuation chamber (A), a gas generator configured for being actuated to generate pressurized gas in the actuation chamber (A) for exerting mechanical load on the drug substance in the drug chamber (B) to thereby cause delivery of the drug substance through the drug delivery opening, and a trigger arrangement initially preventing the pressurized gas from said delivery but allowing said delivery upon gas pressure in the actuation chamber (A) reaching a threshold gas pressure level, wherein the trigger arrangement comprises: a trigger member arranged for displacement from a low-pressure position to a high- pressure position, and a compliant device providing a gradually increasing counter force on the trigger member as the trigger member moves from the low-pressure position to the high-pressure position, wherein the trigger member is
  • an alternative to a traditional burst-disk-like mechanical feature offers the same basic function as a traditional burst-disk, but utilizes a load-compliant device, such as a polymer or foam, and being designed as a mechanical trigger arrangement that is initiated at a particular compression distance, i.e. the distance that the trigger member moves from the low-pressure position to the high-pressure position.
  • This burst-concept according to the first aspect does not produce any hazardous shards after bursting and is potentially compatible with various types of compliant devices, such as components/devices made from a polymer, that can be mass produced at a medical grade.
  • the drug substance is selected as one or more drug substances provided in the form of one or more of the list comprising a liquid, a solid dose, a powder, and a gel.
  • the trigger arrangement defines a trigger lumen having trigger lumen wall surfaces configured for cooperating with the trigger member, wherein the trigger member is arranged within the trigger lumen and wherein either the drug substance or the pressurized gas forms a flowable medium within the trigger lumen, wherein, when the trigger member assumes the low-pressure position, pressure of the flowable medium is allowed to accumulate upstream of the trigger member, and wherein, when the trigger member assumes the high- pressure position, pressure is released by the trigger member thereby allowing the flowable medium to flow within the trigger lumen past the trigger member and/or downstream of the trigger member.
  • the drug delivery device defines a fluid pressure pathway which during generation of pressurized gas allows mechanical load to propagate from the actuation chamber (A) to the trigger arrangement, wherein the trigger arrangement defines a trigger lumen in fluid communication with the fluid pressure pathway, the trigger lumen having trigger lumen wall surfaces for cooperating with the trigger member, and wherein the trigger member performs as a fluid-tight gate disposed within the trigger lumen, the trigger member having a central portion and a peripheral portion, wherein a circumferential seal interconnects the peripheral portion relative to the trigger lumen wall surfaces thereby providing a sealed engagement, such as a slidable sealed engagement, between the trigger member and the trigger lumen wall surfaces.
  • the trigger lumen is arranged either in-line with the fluid pressure pathway or as an appendix relative to the fluid pressure pathway.
  • the trigger member and trigger lumen wall surfaces are configured in a form providing a piston and cylinder configuration.
  • the trigger lumen and the trigger member are disposed between the actuation chamber (A) and the drug chamber (B).
  • the trigger lumen and the trigger member are disposed between the drug chamber (B) and the delivery opening.
  • the central portion of the trigger member remains form-stable or substantially form-stable as the trigger member moves from the low-pressure position to the high- pressure position.
  • the trigger member is configured so that the trigger member moves from the low-pressure position to the high-pressure position with no breaking or mechanical fracturing of the trigger member.
  • a portion of the trigger member, and optionally the entire trigger member is configured for displacement from the low-pressure position through an intermediate-pressure position and further to the high-pressure position, wherein in the intermediate-pressure position the trigger member prevents mechanical load of the pressurized gas to deliver the drug substance through the drug delivery opening.
  • a portion of the trigger member, and optionally the entire trigger member may be configured to move relative to the trigger lumen from the low-pressure position to the intermediate-pressure position by displacement in the range from 0.1 mm to 6.0 mm, such as within 0.3 to 5 mm, and such as within 0.5 mm to 3.0 mm.
  • the trigger arrangement is configured so that a portion of the trigger member, and optionally the entire trigger member, is configured to move relative to the trigger lumen from the low-pressure position to the high-pressure position by a trigger displacement selected within the range from 0.1 mm to 7.0 mm, such as within 0.5 mm to 3.5 mm.
  • an obstruction feature is arranged fixedly relative to the trigger lumen wall surfaces, the obstruction feature being arranged radially offset from the central portion so as to induce a tilting motion of the trigger member as the trigger member moves from the low- pressure position to the high-pressure position and further causing the trigger member to partly or fully disengage the trigger lumen wall surfaces as the trigger member moves into the high- pressure position thereby enabling propagation of mechanical load through the trigger lumen.
  • the trigger member comprises a penetrable film portion, wherein a penetration member is arranged fixedly relative to the fluid pressure pathway, and wherein the penetration member penetrates the penetrable film portion as the trigger member moves towards the high-pressure position thereby enabling propagation of mechanical load through the trigger lumen.
  • a flow passage opening is associated with the trigger arrangement, wherein when the trigger member assumes the low-pressure position, the trigger member occludes the flow passage opening, and wherein when trigger member assumes the high-pressure position, the trigger member permits flow through the flow passage opening thereby enabling propagation of mechanical load through the trigger lumen. Propagation of mechanical load through the trigger lumen may take place by propagation of a pressure wave through the flowable medium (drug substance or pressurized gas) that flows through the trigger lumen.
  • the delivery device defines a bypass feature which is occluded by the trigger member when the trigger member assumes the low-pressure position, and wherein fluid communication through the trigger lumen and/or bypass feature is blocked by the trigger member until the trigger member is moved into the high-pressure position wherein the bypass feature is opened for allowing fluid communication through the trigger lumen and/or bypass feature.
  • a snap feature arranged fixedly relative to the trigger lumen wall surfaces cooperates with a snap counter feature defined by the trigger member, wherein the snap feature and/or the snap counter feature comprise a flexible compliant structure providing a snap movement for the trigger member as the trigger member is displaced from the low-pressure position to the high-pressure position.
  • the snap feature may be formed to maintain a bypass channel closed until the occurrence of the trigger member entering into the high-pressure position.
  • the trigger arrangement comprises a retaining mechanism arranged between the trigger member and the trigger lumen wall surfaces, the retaining mechanism configured for retaining the trigger member in the high-pressure position subsequent to the trigger member having moved from the low-pressure position to the high-pressure position.
  • the trigger arrangement comprises a coupling mechanism arranged between the trigger member and the trigger lumen wall surfaces, the coupling mechanism providing for unidirectional movement of the trigger member only. Hence, movement from the low-pressure position to the high-pressure position is permitted but the coupling mechanism prevents or inhibits the trigger member from returning to the low-pressure position.
  • the trigger member and the compliant device are formed as separate members which optionally may be fixedly attached relative to each other.
  • the two members are arranged in a non-detached manner and wherein the two members engage or move relative to each other as the trigger member moves gradually towards the high-pressure position.
  • the trigger member and the compliant device are formed in one piece, i.e. provided as a unitary component.
  • the drug delivery opening defines a drug outlet, wherein the drug substance comprises is a liquid component, and wherein the drug substance is configured for being expelled through the drug outlet.
  • the drug chamber (B) may at least partially be formed as a capillary tubing which accommodates the drug substance, wherein the drug substance in the capillary tubing is acted on by mechanical load of the pressurized gas by means of a liquid/gas interface in the capillary tubing.
  • the pressurized gas interfaces directly with the drug substance at the liquid/gas interface.
  • the pressurized gas interfaces through a portion of a fluid medium arranged between the pressurized gas and the drug substance, wherein said portion of a fluid medium may contain a gas and/or liquid differing from the pressurized gas and drug substance.
  • the drug delivery device is configured as an ingestible capsule suitable for swallowing into a Gl lumen of a gastrointestinal tract of a subject user, the Gl lumen having a lumen wall, and wherein the ingestible capsule is configured for delivery of the drug substance within a Gl lumen of the subject user, or into the lumen wall of a Gl lumen of subject user.
  • the drug delivery device comprises an environmentally sensitive mechanism configured for initializing actuation of the gas generator upon the sensing of at least one predetermined condition in the gastrointestinal tract.
  • the environmentally-sensitive mechanism may in certain embodiments be a Gl tract environ- mentally-sensitive mechanism.
  • the Gl tract environmentally-sensitive mechanism may comprise a gas actuating arrangement, wherein the gas actuating arrangement is characterised by at least one of the group comprising: a) the gas actuating arrangement comprises a material that degrades, erodes and/or dissolves due to a change in pH in the Gl tract; b) the gas actuating arrangement comprises a material that degrades, erodes and/or dissolves due to a pH in the Gl tract; c) the gas actuating arrangement comprises a material that degrades, erodes and/or dissolves due to a presence of an enzyme in the Gl tract; and d) the actuating arrangement comprises a material that degrades, erodes and/or dissolves due to a change in concentration of an enzyme in the Gl tract.
  • the gas generator associated with the actuation chamber comprises effervescent material and wherein the capsule housing comprises a fluid inlet portion leading to the effervescent material.
  • the fluid inlet portion initially comprises an enteric coating adapted to dissolve when subjected to a biological fluid within the lumen, wherein biological fluid within the lumen is allowed to flow through the fluid inlet portion upon dissolving of the enteric coating to cause contact between the biological fluid and the effervescent material.
  • the fluid inlet portion comprises a semi-permeable membrane allowing biological fluid within the lumen to migrate through the semi-permeable membrane and enter into contact with the effervescent material.
  • the capsule device comprises a liquid compartment filled with a liquid
  • the gas generator comprises an effervescent material configured to generate gas when subjected to contact with liquid from the liquid compartment, and wherein operation of the trigger arrangement enables contact between the effervescent material and the liquid.
  • the gas generator comprises at least a first reactant and a second reactant configured to generate gas upon contact between the first reactant and the second reactant.
  • the drug delivery device is configured as a an ingestible capsule suitable for swallowing into a Gl lumen of a gastrointestinal tract of a subject user, the Gl lumen having a lumen wall, wherein the drug outlet comprises a jet nozzle arrangement configured for needleless jet delivery, and wherein the capsule is configured to expel the drug substance through the jet nozzle arrangement with a penetration velocity allowing the drug substance to penetrate tissue of the lumen wall.
  • the drug delivery device is configured as an autoinjector, e.g. a syringe or cartridge based autoinjector, configured for administration of the drug substance dermally into a subject user, such as by injection through a needle canula, or by needleless jet injection.
  • the device comprises a driver, such as a movable wall or movable separator, arranged between the actuation chamber (A) and the drug chamber (B), wherein the driver is configured for being driven by said mechanical load from a first position to a second position to act on the drug substance in drug chamber (B) so that the drug substance is delivered through the drug delivery opening.
  • the driver forms or comprises at least one piston configured for slidable movement within the drug chamber (B).
  • the driver forms a piston configured for slidable movement within the drug chamber (B), wherein the trigger member cooperates with the piston in a mechanical latch configuration so that, in the low-pressure position, the trigger member latches the piston in a mechanically locked position in the drug chamber (B), and so that, in the high-pressure position, the trigger member unlatches the piston from the locked position allowing the piston to be driven to the second position.
  • the trigger member sealingly engages the trigger lumen wall surfaces by means of frictional sliding engagement.
  • a flexible foil annular section may be arranged to permanently interconnect the trigger member relative to the trigger lumen wall surfaces at a fixed location thereof, such as by means of a flexible foil section, e.g., a bellows configuration.
  • the flexible foil section performs as a seal preventing gas leakage across the trigger member but allows limited displacement of the trigger member relative to the trigger lumen wall surfaces.
  • the trigger member such as a disk-shaped occlusion member, rests against a mouth portion of a conduit that leads away from the actuation chamber (A) towards the drug delivery opening.
  • the compliant device may be ring-shaped and disposed between the trigger member and the mouth portion of the conduit so that upon increasing gas pressure in the actuation chamber (A) the compliant device becomes increasingly compressed as the trigger member moves from the low-pressure position towards the high-pressure position.
  • the compliant device comprises at least one compliant component selected from the group consisting of a compressible foam, a strainable spring, a gas spring, a structural or deflection compliant member and a compressible polymer made from a material comprising at least one of a silicone material, polyisopropene, PTFE, and soft-polyurethane.
  • the capsule 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 intestine or the large intestine, respectively.
  • the capsule device may be shaped and sized to allow it to be swallowed by a subject, such as a human.
  • the gas generator comprises one or more of: a gas generating cell, such as a hydrogen generating cell, a gas generator comprising at least a first reactant and a second reactant configured to generate gas upon contact between the at least first reactant and the second reactants, and a pyrotechnic charge gas generator configured to generate gas upon detonation of a pyrotechnic charge.
  • a gas generating cell such as a hydrogen generating cell
  • a gas generator comprising at least a first reactant and a second reactant configured to generate gas upon contact between the at least first reactant and the second reactants
  • a pyrotechnic charge gas generator configured to generate gas upon detonation of a pyrotechnic charge.
  • the gas generator may be configured so that, when actuated, the gas generator forms gas within the housing i.e. the gas is being produced with the device in situ and, hence, subsequent to swallowing.
  • drug drug, drug substance”, “drug product” 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, a premixed or co-formulated multiple drug compound, or even a drug product being mixed by two or more separate drug constituents wherein the mixing is performed either before or during expelling.
  • 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. 1a-1c are cross-sectional side views of an ingestible capsule device 100 according to a first embodiment of the invention, the device 100 being shown in three consecutive states
  • figs. 2a-2c are cross-sectional side views of an ingestible capsule device 200 according to a second embodiment of the invention, the device 200 being shown in three consecutive states
  • figs. 3a-3c are cross-sectional side views of an ingestible capsule device 300 according to a third embodiment of the invention, the device 300 being shown in three consecutive states, figs.
  • FIGS. 4a and 4b show side cross-sectional views of an ingestible capsule device 400 according to a fourth embodiment of the invention, the device assuming a first state prior to triggering and with the views rotated relative to each other by 90°
  • figs. 4c and 4d show side cross-sectional views of ingestible capsule device 400 in a second state subsequent to triggering, the views rotated relative to each other by 90°
  • fig. 4e shows a perspective view of ingestible capsule device 400
  • figs. 5a-5c are cross-sectional side views of an ingestible capsule device 500 according to a fifth embodiment of the invention, the device 500 being shown in three consecutive states, figs.
  • FIGS. 6a-6c are cross-sectional side views of an ingestible capsule device 600 according to a sixth embodiment of the invention, the device 600 being shown in four consecutive states
  • figs. 7a-7c are cross-sectional side views of an ingestible capsule device 700 according to a seventh embodiment of the invention, the device 700 being shown in three consecutive states
  • figs. 8a and 8c are cross-sectional side views of an ingestible capsule device 800 according to an eighth embodiment of the invention, the device 800 being shown in two consecutive states
  • fig. 8b is a perspective view of a component 120 of device 800 of figs. 8a and 8c, figs.
  • FIGS. 9a and 9b are cross-sectional views of a trigger arrangement of a ninth embodiment ingestible capsule device 900 according to the invention, he device 900 being shown in two consecutive states
  • figs. 10a and 10b are cross-sectional views of a trigger arrangement of a tenth embodiment ingestible capsule device 1000 according to the invention, he device 1000 being shown in two consecutive states
  • figs. 11a and 11b a trigger arrangement of an eleventh embodiment ingestible capsule device 1100 according to an eleventh embodiment of the invention, the device assuming a first state prior to triggering and with the views rotated relative to each other by 90°
  • figs. 11c and 11d are views of device 1100 in a second state subsequent to triggering, the views corresponding to figs.
  • figs. 12a-12b are cross-sectional side views of an ingestible capsule device 1200 according to a twelfth embodiment of the invention, the device 1200 being shown in two consecutive states
  • figs. 13a-13b are cross-sectional side views of an ingestible capsule device 1300 according to a thirteenth embodiment of the invention, the device 1300 being shown in two consecutive states
  • figs. 14a-14d provide example diagrams illustrating aspects of drug delivery and drug substance outlet configurations for use in combination with the present invention.
  • 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.
  • a first embodiment of a drug delivery device in accordance with the invention will be described, the embodiment being designed to provide an ingestible capsule device 100 sized and shaped to be ingested by a patient.
  • the device is configured for subsequently being deployed when in a target lumen of the patient so as to cause a dose of a liquid drug to be expelled through a drug outlet provided at an external portion of the capsule device 100.
  • the disclosed ingestible capsule device 100 in the following referred to simply as “capsule”, is only exemplary and, in accordance with the invention, may be provided in other forms having different capsule outer shapes.
  • the shown outlet provides an outlet nozzle opening for expelling a substance directly through the outlet
  • the outlet may be provided in alternative forms, such as having a drug outlet opening associated with an injection needle or a solid dose API portion intended for drug delivery in a lumen of a Gl tract or for insertion into mucosal tissue of a wall of a Gl tract lumen.
  • the disclosed embodiment relates to a capsule 100 suitable for being ingested by a patient to allow the capsule to enter a lumen of the Gastro-Intestinal tract, more specifically the small intestine, and subsequently to eject a liquid dose of a payload, such as a drug substance at a target location.
  • the capsule may be configured for expelling a substance in other locations of the Gastro-Intestinal system, such as the stomach, the large intestine or even in other lumen parts of a subject.
  • the drug substance is intended to be prepared from or provided as a single drug product.
  • the substance may be prepared from at least two drug products.
  • a first product may be stored within a first reservoir whereas a second product may be stored in a second reservoir and mixed prior to expelling or even mixed during expelling through the outlet.
  • the first drug component is provided initially as a lyophilized drug substance, such as a powder
  • the second drug component is a reconstitution liquid, such as a diluent.
  • the two or more drug products are initially provided as two liquid portions which are mixed with each other prior to or during drug expelling.
  • the capsule 100 includes a multi-part housing having an elongated shape extending along an axis, which is also referred to in the following as “the longitudinal axis”.
  • the shown elongated housing includes a cylindrical section and further include a rounded proximal end portion.
  • An opposite distal second end is shown truncated but may be formed differently.
  • each opening forming a drug outlet 195 positioned laterally to the longitudinal axis, e.g. at a sidewall portion of the cylindrical section, such as the distal end of the capsule 100.
  • Each drug outlet 195 may be an aperture to permit jet injection to occur. The outlet thus points radially outwards from a surface arranged to be adjacent the tissue of the lumen wall.
  • the capsule is formed in shape and size to roughly correspond to a 00 elongated capsule. However, in alternative embodiments, other capsule sizes and capsule shapes may be used.
  • the number of outlet openings may be provided as a single or a multitude of drug outlets. In case of multiple outlets, these may for example be arranged opposed to each other, or distributed evenly around the longitudinal axis, e.g., so as to eliminate any potential recoil effects during rapid expelling of drug substance through the outlets.
  • the jet stream created by the jet injector interfaces the lumen of the Gl tract and the surface of the Gl tract facing the lumen.
  • the drug substance is deposited into the submucosal and/or the mucosal tissue by the substance impacting the mucosal layer of the Gl tract (e.g. the epithelial layer and any mucus that may be present on the epithelial layer) as a stable jet stream of fluid with minimal breakup into a spray.
  • the volume of fluid of the drug substance experiences a peak fluid pressure that generates the jet stream that exits the jet injector with a peak jet velocity.
  • the jet stream impacts the interface of the lumen of the Gl tract and the surface of the Gl tract facing the lumen with a peak jet power, peak jet pressure and peak jet force.
  • one way to assess the jet power is to release the jets onto force sensors which measure the force the jet. Based on the force reading, and knowing the area of the nozzle and density of the jetted liquid, the jet velocity can be determined using equation 1 . Based on the calculated velocity, the power (in Watts) can be calculated using equation 2. To evaluate the jet pressure (i.e. the pressure at which the jet stream is expelled), equation 3 can be used.
  • V Velocity (m/s)
  • the shown multi-part housing includes a first housing portion, i.e. a proximal housing portion 110, arranged at the proximal end, a generally cylindrical sleeve shaped distal housing portion 120 with an end wall arranged at the distal end. A central opening 123 is formed in the distal end wall.
  • the proximal housing portion 110 includes a portion comprising one or more openings 115, schematically illustrated as a single cylindrical band (see ref. 140), which serve as a fluid inlet arrangement allowing ingress of gastrointestinal fluid present in the Gl tract towards the interior of the capsule 100.
  • Fig. 1a shows a cross sectional view of the capsule 100 in an initial state wherein the capsule is ready to be ingested by a patient.
  • a hollow first cylindrical section 124 is arranged extending along the longitudinal axis, this section having a radially inwards facing surface having a first diameter.
  • the first cylindrical section 124 is terminated at the distal end by distally arranged end face.
  • the first cylindrical section 124 extends proximally towards a hollow second cylindrical section 118, coaxially arranged with the first cylindrical section 124 and having a radially inwards facing surface with a smaller diameter than the diameter of the first cylindrical section 124.
  • the second cylindrical section 118 is terminated by proximal end wall.
  • proximal end wall 119 has a shape similar to a half-dome.
  • a first piston 150 forms a drive piston arranged for distally directed axial slidable movement inside the hollow space formed by the first cylindrical section 124, the drive piston 150 having a circumferential sealing portion (non-referenced) that seals against the radially inwards surface of the first cylindrical section 124.
  • the drive piston 150 is disposed in a start position remote from the distal end wall. In this initial state, the circular distal end face of the drive piston 150, the radially inwards surface of the first cylindrical section 124 and the distal end wall in combination defines a drug chamber B.
  • a second piston 160 which may be formed similar to drive piston 150, is arranged in the distal end of the drug chamber B, initially disposed with a minor spacing from the distal end wall. In this initial position, the second piston 160 axially overlaps the drug outlets 195 so as to prevent fluid communication between the chamber B and the drug outlets 195.
  • the second piston 160 is configured for being displaced distally towards the distal end wall thereby establishing fluid communication between the drug chamber B towards the drug outlets 195.
  • the second piston 160 hence acts as an outlet control piston.
  • a liquid drug substance is accommodated in the drug chamber B, i.e., axially in between the drive piston 150 and the outlet control piston 160.
  • the drug outlets 195 arranged at the distal end of drug chamber B define fluid outlet passages from the drug chamber B to the exterior of the capsule 100.
  • the outlets 195 include jet nozzles dimensioned and shaped to create a liquid jet stream of drug when the drug is forced through the outlet.
  • other means for sealing or blocking the outlets prior to administration may be utilized, such having the drug chamber sealed at the outlet with a foil seal (not shown) overlapping the drug outlets 195, e.g., designed to break when the fluid pressure of the liquid drug in chamber B is sufficiently elevated.
  • a drive system is arranged configured for forcing the drive piston 150 towards the drug outlets 195 upon activation of the drive system, i.e. upon triggering by a predefined condition in the Gl tract.
  • the drive system comprises a gas generator arranged in an actuation chamber, the gas generator being capable of producing pressurized gas upon actuation.
  • the drive system generates a drive force for urging forward the pistons 150 and 160 when elevated gas pressure from the gas generator in the actuation chamber A exceeds a predefined threshold.
  • the gas generator is arranged inside hollow second cylindrical section 118 which forms part of the actuation chamber A.
  • a fluid pressure pathway is defined which caused by release of accumulated gas at high pressure allows mechanical load of the pressurized gas to propagate from the actuation chamber (A) to the trigger arrangement, and further on to the drug outlets 195.
  • Gas may be generated by chemical reaction so that, once the gas generator is actuated, gas is produced to form pressurized gas in the actuation chamber A inside capsule 100.
  • a gas producing cell such as a hydrogen cell, an airbag inflator, a gas generator utilizing phase change, or a generator which incorporates mixing of reactants to chemically react to form a gas, such as by mixing sodium bicarbonate and acid.
  • mixing of reactants either all reactants may be stored on board the capsule prior to actuation, or at least one reactant may be introduced into the capsule for mixing with a reactant stored on board the capsule.
  • Example 1 (calcium carbonate with hydrochloric acid): CaCo3 + 2HCI CaCI2 + H2O + CO2
  • Example 3 (tartaric acid with sodium bicarbonate): H2C4H4O6 + 2NaHCO3 - Na2C4H4O6 + 2H2O + 2CO2
  • the effervescent reaction may occur by one or more solid state components being wetted (e.g. exposed to intestinal fluid or other fluid stored in capsule 100) which causes the effervescent reaction.
  • gas is generated in the actuation chamber A by means of an internally arranged effervescent material, schematically illustrated by reference 142, arranged in the actuation chamber, and by means of a semipermeable membrane arranged at 140 arranged to overlap openings 115, said membrane 140 serving to introduce gastrointestinal fluid into the actuation chamber A to react with the effervescent material portion 142.
  • Effervescent material portion 142 which may be formed from powder components that are subsequently compressed into block-shape, includes an effervescent couple comprised of at least one acidic material and one basic material, such as sodium bicarbonate and citric acid.
  • the block of effervescent material 142 may be fixed to semipermeable membrane 140 to ensure close proximity with the membrane while leaving a volume of actuation chamber A available for gas generation.
  • the proximal housing portion 110 includes a multitude of openings or channels 115 which allows ingress of gastrointestinal fluid into the actuation chamber A.
  • the semi-per- meable membrane 140 is arranged with its proximally facing surface in intimate contact with the before mentioned single cylindrical band. Hence, gastrointestinal fluid that enters the capsule 100 needs to pass through the openings 115 and the semi-permeable membrane 140.
  • the proximal housing portion 110 provides sufficient rigidity to serve as a backing or support for the semi-permeable membrane 140 when pressure builds up in the actuation chamber A.
  • capsule 100 example materials for the semipermeable membrane 140 may be made from Standard Grade Regenerated Cellulose (RC).
  • the material for the semipermeable membrane 140 may be selected so that it is biodegradable when subjected to biological fluid.
  • the openings 115 are prior to administration covered by a pH-sensitive enteric coating 105 which initially blocks fluid ingress through the openings 115.
  • the enteric coating may be configured to utilize the marked shift in pH-level that the capsule 100 experiences when travelling from the stomach to the small intestine. After being exposed to gastrointestinal fluid for a specified duration the enteric coating will be degraded to a degree which allows the gastrointestinal fluid to contact the semipermeable membrane 140 and start migration of fluid through the membrane towards the effervescent material portion 142.
  • the enteric coating forms part of a gas initiation arrangement for actuating the gas generator formed by the semi-permeable membrane 140 and the effervescent material portion 150.
  • an autonomously triggered system which in accordance with the present invention includes a burst-like trigger mechanism.
  • This mechanism is of particular importance when pressure is accumulated in the device, such as by an effervescence reaction over time.
  • the pressurized chamber bursts into an adjacent chamber initiating drug delivery at a reproducible pressure I energy level.
  • a trigger arrangement is incorporated between the actuation chamber A and the drive piston 150.
  • the trigger arrangement of capsule 100 includes a trigger member which is displaced by means of a mechanical load generated by gas pressure against a counter-load provided by a compliant device, wherein upon a pressure-specified compliance distance of the trigger member, the trigger arrangement initiates the drive system for drug delivery.
  • the trigger arrangement primarily comprises a displaceable trigger member 170 which is moved towards a partition wall 129 being fixedly arranged in the hollow first cylindrical section 124, i.e., inside the large diameter section of capsule 100.
  • Partition wall 129 forms a support structure which is perforated to permit gas generated within the actuation chamber A to flow unhindered through the partition wall 129 towards the first piston 150.
  • the trigger member 170 is formed as a rigid circular disk and includes a circumferential seal 178.
  • the trigger member 170 in the non-triggered state of the device shown in fig. 1a, is positioned in a passage of the second cylindrical section 118, i.e., in the small-diameter section of capsule 100 and more specifically positioned within a designated area which will be referred to as a “trigger lumen”, i.e., a portion of a gas pressure pathway having lumen walls adapted for engaging cooperation with the trigger member 170.
  • the trigger member 170 In this initial state, shown in fig. 1a, the trigger member 170 is disposed at the most distal portion of the trigger lumen defined by second cylindrical section 118. In this position, the trigger assumes a position which later will be referenced “the low-pressure position”.
  • the trigger member As the trigger member is arranged for axial sliding movement the trigger member forms a trigger piston arranged for slidable movement inside the trigger lumen.
  • the trigger member 170 is primarily retained axially inside the trigger lumen of section 118 by frictional engagement, i.e. , by means of the circumferential seal 178 pressing outwardly onto the radially inwards facing surface of second cylindrical section 118.
  • the trigger member 170 is furthermore supported on its distal facing side by means of a load- compliant polymer or foam 180 arranged between the partition wall 129 and the distal facing surface of the trigger member 170.
  • capsule 100 Next the operation of capsule 100 will be described. Subsequent to a patient or user swallows capsule 100, upon entering the small intestine, the enteric coating 142 of the capsule 100 will begin dissolving and gastric fluid will soon after be available through openings 115 enabling fluid transport across the semi-permeable membrane 140.
  • the view shown depicts the situation during pressure build-up in actuation chamber A wherein pressurized gas has forced the trigger member 170 into a position where the trigger member has been moved slightly distally but is still engaging the small diameter opening of the trigger lumen. In this position, the trigger member 170 still prevents mechanical load of the pressurized gas to move the drive piston 150. This position of the trigger member 170 may be termed “the intermediate-pressure position”. The compliant portion 180 is heavily compressed.
  • the gas pressure inside actuation chamber A has reached the threshold gas pressure level and the trigger member 170 has moved distally to a “high-pressure position” in which the trigger member has detached from the small diameter opening of the trigger lumen and thus moved into the large diameter opening wherein generated gas flow bypasses the trigger member 170.
  • the trigger member may be arranged to fully detach from the transition area of the trigger lumen between sections 118 and 124, such as by tilting or tumbling to a position not coaxially aligned with the longitudinal axis. Such state for the trigger member may still be referred to as the “high-pressure position”.
  • the full mechanical load of the pressurized gas acts on the drive piston 150.
  • the mechanical load is further transferred onto the drug substance in drug chamber B and further on to the second piston 160, i.e. the outlet control piston, which is being forced distally towards the distal end wall of the capsule housing thereby exposing the drug outlets 195. Any air initially present distant to second piston 160 will be allowed to escape through opening 123.
  • the accumulated gas acts to expel the drug substance of the drug chamber B through the jet nozzles at each drug outlet 195, i.e. by means of separate jet streams of liquid impinging on target tissue portions of the delivery site causing penetration into the mucosal lining for drug depositing.
  • the drive piston 150 will bottom out relative to the outlet control piston 160 and the jet stream of drug substance through the drug outlets 195 will end.
  • the capsule 100 is allowed to pass the alimentary canal and be subsequently excreted.
  • the capsule may be designed so that pressure accumulates in the actuation chamber A (e.g., cylinder with 5 mm diam, 5 mm height) building to a burst pressure in the range of 1 to 3 MPa.
  • the compliant portion 180 there are a number of mass-produced soft polymers, often produced for o-rings and gaskets, that have the requisite compressible-mechanical properties to be used for such application.
  • Potential material options include silicones, polyisopropene, PTFE, soft-polyurethanes, and more.
  • the trigger member may be configured for displacement from the low-pressure position through an intermediate-pressure position and further to the high-pressure position.
  • the trigger member may for example be configured to move relative to the trigger lumen from the low-pressure position to the intermediate-pressure position by displacement in the range from 0.1 mm to 6.0 mm, such as within 0.3 to 5 mm, or such as within 0.5 mm to 3.0 mm. Other ranges are also possible.
  • the capsule 200 corresponds in most aspects to the capsule 100 but the trigger arrangement has been modified.
  • the partition wall 129 of capsule 100 has been replaced by a support structure which forms a radially inwards protruding flange 129 arranged axially in between the trigger 170 and the drive piston 150.
  • a central aperture or axial passage is formed in flange 129.
  • a first obstruction geometry 129a and a second geometry 129b Arranged radially offset from the longitudinal axis and protruding axially in the proximal direction from the inner flange are two geometries, i.e., a first obstruction geometry 129a and a second geometry 129b.
  • the obstruction geometry 129a extends further proximally than the geometry 129b.
  • a compliant ring 180 in the drawing shown as a ring shaped polymeric compressible member having an oval shaped cross-section, is arranged to be clamped axially in between the trigger member 170 and the flange 129 so that the compliant ring lies against radially outwards portions of the disk-shaped trigger member 170.
  • the trigger member 170 assumes the low-pressure position wherein the compliant ring 180 is compressible axially. In this state, generated gas is not allowed to pass the trigger arrangement either due to the seal 178, alternatively due to both the seal 178 and the compliant ring 180 or, still alternatively, in embodiments where seal 178 is omitted, by compliant ring 180 only.
  • the trigger member 170 has now been provided as a rigid peripheral section and a thin puncturable membrane 170c formed from a polymer material arranged in the centre of trigger member 170.
  • the trigger member still performs as an occluding element within the trigger lumen.
  • the first obstruction geometry 129a of the second embodiment has in the third embodiment been modified into a penetrating member 129c having a pointed proximal end configured for penetrating the penetrable film 170c of the trigger member 170.
  • the sequence of trigger movement is schematically shown, i.e. from the low-pressure position (fig. 3a) through the intermediate-pressure position (fig. 3b) to the high-pressure position (fig. 3c).
  • the membrane 170c In the low-pressure position and the intermediate-pressure position the membrane 170c is still intact and prevents gas to flow through the trigger lumen.
  • the membrane 170c In the high-pressure position, the membrane 170c has been penetrated by the penetrating member 129c and the full mechanical load of the pressurized gas acts on the drive piston 150 for causing the expelling procedure to be carried out.
  • a fourth embodiment capsule 400 is schematically shown.
  • the capsule 400 corresponds in most aspects to the capsule 100 but the trigger arrangement has been modified so as to include a snap engagement between the capsule housing 120 and the trigger member 170.
  • the internal diameter openings of the distal and proximal housing sections are equal in size.
  • two bypass sections (bypass channels) 128 have been formed in the interior wall sections in the region between the proximal and distal sections of capsule device 400 (refer to fig. 4b and 4e), i.e. downstream from the trigger lumen.
  • FIG. 4a and 4b these views show the device 400 in the initial state prior to actuation of the gas generator with the trigger member 170 assuming the low-pressure position and the enteric coating 105 intact.
  • a pair of radially inwards protruding snap geometries 129 are configured to engage respective snap geometries of the trigger member 170 thereby serving to releasably maintaining the trigger member 170 in the low-pressure position.
  • the bypass sections 128 are positioned downstream from the trigger member 170 assuming its intermediate-pressure position.
  • Either the snap geometries 129, the trigger member 170, or both, may include compliant material sections to enable the snap interaction geometries to initiate release of the snap retainment upon increasing gas pressure in the actuation chamber A. At a certain gas pressure level, i.e. the threshold gas pressure level, the snap geometries have released the trigger member 170. Release is designed to occur abruptly and right after the intermediate-pressure position.
  • FIGS. 4c and 4d represent the state wherein the trigger member has been moved rapidly into the high-pressure position.
  • the trigger member 170 is positioned midways axially relative to the bypass sections 128 and the full mechanical load of the pressurized gas acts on the drive piston 150 for causing the expelling procedure to be carried out.
  • a blocking member 126 arranged fixedly relative to the housing 110,120 serves to stop the trigger member in the high-pressure position and prevent it from moving further distally.
  • the blocking member 126 is formed to allow gas to flow uninterrupted axially past the blocking member.
  • the trigger member When the trigger member is position in the high- pressure position it is prevented from returning towards the intermediate-pressure position due to the snap geometries and the trigger arrangement cannot be returned towards the state where the trigger member blocks against gas flow through the trigger lumen.
  • the potential risk that the trigger member 170 may oscillate back and forth between open and closed states during gas pressure equalization is thereby prevented.
  • a fifth embodiment capsule 500 is schematically shown.
  • This capsule device corresponds in most aspects to the capsule 400 but the snap design of the trigger arrangement has been modified.
  • a pair of radially inwards protruding support structures 129 are in this fifth embodiment located axially between sections 118 and 124. These support structures 129 are formed so as to leave a central opening therebetween, i.e. with opposed radially inward facing edges 129d formed as arc shaped segments. Gas flow is freely permitted at side portions of the support structures 129 towards the drive piston 150.
  • a generally cylindrical control rod 170 is provided so that its axis is arranged coaxially with the longitudinal axis.
  • a distal end of control rod 170 is attached to the drive piston 150.
  • a proximal end of control rod 170 is formed with an enlarged head 180, resembling a sphere, the enlarged head being formed from a compliant polymer, i.e. being able to be squeezed to assume a radially narrow and axially elongated shape.
  • the trigger member and compliant device are provided by a combination of elements, i.e. the drive piston 150, the control rod 170 and the enlarged head 180.
  • a narrow portion of the control rod extends form-fittingly between the support structures 129 so that the enlarged head 180 is situated proximally to the support structures so that the control rod is clamped radially between the support structures.
  • the assembly formed by the enlarged head 180, the remaining part of the control rod 170 and the drive piston 150 is retained by means of the support structures 129.
  • the drive piston assumes a low-pressure position.
  • Fig. 5b shows the drive piston 150 in an intermediate-pressure position.
  • the enlarged head 180 upon further gas generation in actuation chamber A, due to increased tension in the control rod 170, the enlarged head 180 has reached a state wherein its shape allows to be moved distally through the opening between the support structures 129. This releases the enlarged head 180 and causes it to be driven freely distally by the gas pressure in the actuator chamber A. At the time of release the drive piston 150 assumes a high-pressure position. Consequently, the full mechanical load of the pressurized gas acts on the drive piston 150 for causing the expelling procedure to be carried out.
  • a sixth embodiment capsule 600 is schematically shown.
  • the capsule 400 corresponds in working principle mainly to the fourth embodiment capsule 400 but the trigger arrangement has been modified. For simplicity, only the proximal section of the capsule 600 including the trigger arrangement is visible whereas the distal part of the capsule device has been omitted from view.
  • this view shows the device 600 in the initial state prior to actuation of the gas generator with the trigger member 170 assuming the low-pressure position and the enteric coating 105 intact.
  • the trigger member 170 is shaped as a planar circular disk being made from a compliant material so that it is able to change shape into a cup-shape.
  • a support structure 129 protrudes radially inwards into the trigger lumen so that the support structure forms a round going flange with a reduced diameter opening smaller than the exterior diameter of the disk-shaped trigger member 170.
  • the trigger member 170 includes on its distal facing surface a peripheral section which in the state shown in fig.
  • the trigger member 170 may be adhered to the flange to keep the components releasably adhered to each other.
  • Figures 6b-6d show the device 600 after initiation of gas generation with gradually increasing gas pressure level inside actuation chamber A.
  • the trigger member 170 gradually turns concave with the central portion gradually protruding through the reduced diameter opening of the support structure 129.
  • the trigger member assumes the intermediary-pressure position and assumes a cup-shaped form wherein the edges of the trigger member engage inner edges 129d of the support structure 129.
  • the trigger member upon further gas generation in actuation chamber A, releases from the support structure 129 and moves into the high-pressure position. In this position air flow through the trigger lumen is enabled as the trigger member no longer occludes the reduced diameter opening of the support structure 129. Consequently, the full mechanical load of the pressurized gas acts on the drive piston for causing the expelling procedure to be carried out.
  • a seventh embodiments capsule is depicted. Whereas this embodiment still utilizes a compliant trigger arrangement the functional principle has been modified in the trigger arrangement is utilized for releasably maintaining an actuator component of the drive system mechanically latched in a starting position and only releasing the latched actuator component upon the gas pressure level in the actuation chamber A reaching a threshold gas pressure level resulting in the elevated gas pressure to drive the actuator from the starting position to an end position for drug delivery to be carried out.
  • the actuator component is provided as a modified drive piston 150.
  • the actuator component may be configured as members other than a drive piston, such as an outlet control piston or other component of a drive system.
  • the drive piston 150 in this example includes a proximal extension having a latch geometry for latching the drive piston in a starting position relative to the housing of the capsule device. As gas pressure builds up in the actuation chamber, the drive piston will be exerted to mechanical load but the drive piston will be prevented from moving until the target gas pressure threshold has been reached.
  • the fluid pressure pathway in this embodiment includes an appendix 129e which thus is not in-line with the remaining fluid pressure pathway.
  • the trigger member 170 in this embodiment is arranged within the appendix 129e with the proximal end exposed to gas pressure of the actuation chamber A and with the distal end facing oppositely, which in this example is a blind end of the appendix.
  • a circumferential seal 178 is arranged on the trigger member 170 which thus is configured as a trigger piston for limited displacement along a trigger axis within the lumen of the appendix 129e.
  • the trigger axis is arranged in parallel with the longitudinal axis.
  • this is a non-limiting example as other embodiments are configured with a trigger axis angled relative to the longitudinal axis along which the drive piston moves.
  • a compliant device 180 is arranged in the blind end of the appendix 129e such that compliant device is trapped between a distal facing surface of the trigger member 170 and the blind end of the appendix. Upon increasing gas pressure the trigger member is configured to move from a low-pressure position, via an intermediary-pressure position and into a high-pressure position during which the compliant device 180 will be increasingly compressed.
  • the compliant device in the embodiment shown may be formed as a load-compliant polymer or foam. However, in other embodiments alternative load compliant materials or structures may be used, such as by means of a compression spring, a gas spring, a permanently deformable material or similar load-compliant arrangement.
  • the proximal extension of the drive piston 150 includes a notch 155 arranged transversally to the longitudinal axis and which is configured for receiving only a portion of a retention pin 145.
  • the retention pin 145 is arranged with its longitudinal axis to extend along the notch 155, i.e. in the transversal direction. In the latched state, a little less than half of the retention pin is received in the notch, with the remaining part of the retention pin extending above the notch and being held in abutment with a proximally facing retention surface of the support structure 129 arranged fixedly with the housing of the capsule. Diametrically opposite to the notch portion of the drive piston 150 the retention pin 145 is supported by the trigger member which assumes the low-pressure position.
  • Figs. 7b and 7c show the device 700 after initiation of gas generation with gradually increasing gas pressure level inside actuation chamber A.
  • the trigger member 170 gradually moves from the low-pressure position wherein the trigger member 170 safely retains the retention pin in place in the notch 155 and against the support structure.
  • the trigger member 170 assumes the intermediary-pressure position wherein the release pin is about to be pushed out of the notch, due to mechanical load of the generated gas exerting mechanical load on the drive piston 150 urging the drive piston distally.
  • the gas pressure inside actuation chamber A has reached the threshold gas pressure level and the trigger member 170 has moved distally to a “high-pressure position” wherein the compliant device has been maximally compressed.
  • the trigger member 170 no longer support the retention pin 145 within the notch, and since the major part of the release pin 145 extends above the notch 155 a force component of the mechanical load attempting to move the drive piston distally is transformed into a force acting to push the retention pin 145 out of notch 155.
  • This causes to discontinue the mechanical coupling between the drive piston 150 and the support structure 129 allowing the mechanical load of the pressurized gas to push the drive piston in the distal direction, thereby causing the drug delivery to be carried out.
  • latch mechanism between the drive piston and the housing is only exemplary and that other mechanisms according to the invention may utilized other latch configurations, such as a direct engagement between the trigger member and the drive piston to releasably maintain the drive piston latched until the trigger member moves out of engagement with the drive piston.
  • Figs. 8a through 8c provides still another embodiment of the invention, i.e. an eighth embodiment device 800.
  • the device 800 corresponds in many aspects to the prior art device shown in WO patent application no. WO 2022/074252 A1 , more specifically the fig. 4 embodiment disclosed therein.
  • the present eighth embodiment capsule 800 includes a trigger arrangement 170/180/129 similar to the trigger arrangement of the capsule device 100 of fig. 1 of the present disclosure and this time arranged at the end of the axially extending channel indicated as forming the actuator chamber A, i.e. with the trigger member initially positioned with a trigger lumen.
  • the burst disc 280 of the prior art has been omitted.
  • fig. 8c shows the device with the trigger member 170 assuming the high-pressure position wherein the trigger member 170 has detached from the trigger lumen.
  • a fluid pressure pathway is established from the actuator chamber A via channel segments 125A, 125B, 125C, 125D, 125E and 125F to the jet nozzle arranged at the drug outlet 195.
  • the gas pressure of the generated gas acts directly on the gas-liquid interface, i.e. without the requirement of having a drive piston arranged between the pressurized gas and the drug substance.
  • a ninth embodiment capsule 900 will be briefly described.
  • the overall design corresponds to the first embodiment 100 described above but includes additionally a retaining mechanism arranged and coupled between the trigger member and the trigger lumen wall surfaces, the retaining mechanism being configured for retaining the trigger member 170 in the high-pressure position subsequent to the trigger member having moved from the low-pressure position to the high-pressure position.
  • the purpose of this is to mitigate the potential risk that a slightly leaking system may tend to return the trigger member towards the intermediary-pressure position causing an oscillating movement which potentially may reduce the intended effect of having a burst-like pressure release.
  • the trigger member will be arrested in the high-pressure position.
  • a penetrating member 177 penetrates gradually into the compliant portion 180 and in this way creates a retention force causing the trigger member 170 to be retained in the high-pressure position after initial burst release.
  • Figs. 11a-11 d show a further alternative in an eleventh embodiment 1100.
  • This embodiment utilizes a threaded engagement 175/185 between the trigger member 170 and the compliant device 180.
  • the threaded engagement 175/185 is configured to require an increasing force for inducing relative rotation until the trigger member reaches the intermediary-pressure position.
  • the threaded engagement 175/185 requires a marked drop in the required force for inducing relative rotation acting to aid the trigger member towards the high-pressure position.
  • Different designs of the threaded engagement may be utilized such as a varying the threadangle, e.g. the thread pitch, along the threaded portions, or such as increasing and decreasing the amount of thread segments that are engaging each other during the course of gradually establishing the threaded engagement.
  • the above-described trigger arrangement may be disposed at different locations inside different embodiments of a capsule device, such as at the input side of a drive system, e.g. between an actuator chamber and a drive piston, adjacent a drug delivery outlet, or in connection with a piston of a drive system, such as wherein the function of a trigger member is provided by a drive piston and/or an outlet control piston.
  • the outlet control piston 160 includes a snap engagement between a distally arranged snap geometry 167 formed in the piston 160 and a corresponding snap geometry 127 formed in the distal end wall of the capsule housing 120.
  • a pair of radially inwards movable snap arms 127 engages a corresponding pair of snap geometries 167 formed integrally with the piston 160.
  • the piston 160 and/or the end wall of the housing 120 thus comprises compliant sections 180 which exhibits the desired compliance to gradually accept the mechanical load exerted in the distal direction on piston 160, i.e.
  • an outlet control piston 160 includes geometries on its radially outwards facing surface that are cooperating with notch features formed within a radially inwards facing surface of section 124 of the capsule housing at the distal end thereof.
  • the notch configurations provide compliance by structural resistance where the piston 160 passes through an annular snap-like feature only once a certain pressure is exerted on the piston 160.
  • a dedicated separate compliance device may be provided as an alternative, or in addition to the shown snap and notch couplings, such as a compliant polymer portion or foam arranged between the distal facing end surface of the piston 160 and the end wall of the housing 120.
  • the said structural resistance features may be utilized in association with the outlet control piston 160, or alternatively in association drive piston 150, in both cases offering the possibility of forming the piston in question with the function of a trigger member 170.
  • the structural resistance feature described above may serve the function of retaining the piston in the high-pressure position so as to prevent the piston from returning, i.e. similar as in the ninth through eleventh embodiments.
  • figs. 14a-14d provide non-limiting example diagrams illustrating aspects of drug delivery and drug substance outlet configurations for use in combination with the present invention.
  • Fig. 14a for example show how a needle assisted drug delivery device may be provided, i.e. by having an injection needle 196 connected to an outlet control piston 160 and optionally with a burst membrane 161 initially blocking the needle lumen.
  • a trigger arrangement in accordance with any of the principles discussed herein may be incorporated in the drug delivery device to control the point in time wherein sufficient pressure has been generated by the gas generator for initializing movement of the needle and/or for initializing delivery of the drug substance through the needle.
  • Fig. 14b left-hand drawing, shows an embodiment utilizing a needle which is pre-strained towards a curved configuration, but held initially in a straight configuration when accommodated within the capsule housing.
  • the needle becomes extended axially from the housing during the initial stage of deployment the needle adopts its relaxed curved configuration which aids the tissue proximity for proper needle insertion into tissue.
  • Fig. 14 c shows the proximal part of an embodiment wherein a solid needle-shaped solid dose tablet 196 comprising an API is configured to be held within a sealed drug compartment prior to deployment.
  • a solid needle-shaped solid dose tablet 196 comprising an API is configured to be held within a sealed drug compartment prior to deployment.
  • the solid dose tablet comprising an API may be configured for being dissolved or eroded when the solid dose tablet is lodged within a tissue wall of the Gl tract so as to release at least a portion of the API into the blood stream of the subject that swallows the drug delivery device.
  • a multitude of needle-shaped API tablets may be arranged on opposed platforms 150 which by release of pressurized gas of a drive system in accordance with the invention, are moved radially outwards, causing the multiple API tablets to be forced through respective seals 162 covering each drug outlet opening 195 for insertion of the API tablets radially outwards from the device and into mucosal tissue.
  • a trigger arrangement in accordance with any of the principles discussed in this disclosure may be incorporated in the drug delivery device to control the point in time wherein sufficient pressure has been generated by the gas generator for initializing movement of the one or more API tablets.
  • the capsule device subsequent to a subject user swallowing the device, the capsule device first moves through the stomach and subsequently enters the small intestine. Due to the enteric coating becomes dissolved when entering a lumen of the small intestine the fluid ingress into capsules 100 and 200 will only be initiated upon the enteric coating becoming sufficiently dissolved for fluid ingress through the fluid inlet/semi-permeable membrane is enabled.
  • An enteric coating may be any suitable coating that allows the coated object to be activated for release in the intestine.
  • an enteric coating may dissolve preferentially in the small intestine as compared to the stomach.
  • the enteric coating may hydrolyse preferentially in the small intestine as compared to the stomach.
  • materials used as enteric coatings include methyl acrylate-methacrylic acid copolymers, cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate, hydroxy propyl methyl cellulose acetate succinate (i.e.
  • a given object here: capsule
  • a fluid inlet only may be coated with an enteric coating.
  • the enteric coating may be composed to be soluble at a given pH or within a given pH range, e.g. at a pH greater than 5.5, at a pH greater than 6.5, within a range of about 5.6 to 6 or within a range of about 5.6 to 6.5 or 7.
  • the dissolution time at an intestinal pH may be controlled or adjusted by the composition of the enteric coating.
  • the dissolution time at an intestinal pH may be controlled or adjusted by the thickness of the enteric coating.
  • the condition for controlling when triggering is to occur may be provided by means of other principles.
  • a dissolvable layer may be disposed initially blocking the fluid inlet of the capsule, with dissolution of the dissolvable layer being initiated at first exposure to gastric fluid, and with the timing of the dissolvable layer being decisive for the location at which the capsule deploys.
  • no coating may be present, so that the triggering of the gas generator occurs as soon as sufficient liquid has been transferred through the semi-permeable membrane.
  • Still other triggering principles may rely on temperature change induced passage of gastric fluid though the fluid inlet and into the capsule gas generator.
  • exemplary embodiments mainly concerns ingestible capsules for delivery in the small intestine
  • the present invention generally finds utility in drug delivery devices, such as gas-driven external autoinjectors and miniature capsule devices for lumen insertion in general, wherein a capsule device is positionable into a body lumen for delivery of a drug product.
  • Non-limiting examples of capsule devices include capsule devices for delivery in the stomach or delivery into the tissue of the stomach wall.
  • various self-righting or self-orienting structures and/or methods described in WO 2018/213,600 A1 can be employed by the capsule device in accordance with the present disclosure.
  • WO 2018/213,600 A1 is incorporated herein by reference in its entirety.
  • drug delivery may be performed using a delivery member, such as a needle, via a jet stream of liquid to provide needle-free liquid jet penetration into the mucosal lining or via spraying inside the lumen.
  • a delivery member such as a needle
  • inventive gas generation release arrangement set forth in this disclosure may be used to trigger delivery of a solid drug pellet which is to be inserted into a lumen wall.

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Abstract

1. L'invention concerne un dispositif d'administration de médicament (100) comprenant : a) une chambre de médicament (B) configurée pour recevoir une substance médicamenteuse, la chambre de médicament (B) conduisant à une ouverture d'administration de médicament (195), b) une chambre d'actionnement (A), c) un générateur de gaz (140, 142) configuré pour être actionné pour générer un gaz sous pression dans la chambre d'actionnement (A) pour exercer une charge mécanique sur la substance médicamenteuse dans la chambre de médicament (B) pour ainsi provoquer l'administration de la substance médicamenteuse à travers l'ouverture d'administration de médicament (195), et d) un agencement de déclenchement (170, 180, 129) empêchant initialement le gaz sous pression d'être administré mais permettant ladite administration lorsque la pression de gaz dans la chambre d'actionnement (A) atteint un niveau de pression de gaz seuil, l'agencement de déclenchement comprenant : d1) un élément déclencheur (170) conçu pour se déplacer d'une position basse pression à une position haute pression, et d2) un dispositif souple (180) fournissant une contre-force augmentant progressivement sur l'élément déclencheur (170) lorsque l'élément déclencheur se déplace de la position basse pression à la position haute pression, l'élément déclencheur (170) étant conçu pour se déplacer, en raison du gaz généré, de la position basse pression dans laquelle aucune charge mécanique n'est exercée par le gaz sous pression pour provoquer l'administration de la substance médicamenteuse à la position haute pression dans laquelle ladite charge mécanique est autorisée à provoquer l'administration de la substance médicamenteuse à travers l'ouverture d'administration de médicament (195).
PCT/EP2024/055515 2023-03-03 2024-03-02 Capsule pouvant être insérée dans une lumière Pending WO2024184282A1 (fr)

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Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992021307A1 (fr) * 1991-05-30 1992-12-10 Schentag Jerome J Procede et capsule de telemesure
CN1730118A (zh) * 2005-08-19 2006-02-08 华南理工大学 化学反应气压式微胶囊药物释放方法及其装置
US20090043278A1 (en) 2005-05-27 2009-02-12 Shinsuke Tanaka Body-insertable apparatus
WO2018049133A1 (fr) 2016-09-09 2018-03-15 Mitchell Lawrence Jones Dispositif ingérable électromécanique pour l'administration d'une substance distribuable
US20180193621A1 (en) 2015-06-30 2018-07-12 Entrega Inc. Device for oral delivery of active agents
WO2018213600A1 (fr) 2017-05-17 2018-11-22 Massachusetts Institute Of Technology Systèmes à redressement automatique, et composants et procédés associés
WO2020106750A1 (fr) 2018-11-19 2020-05-28 Progenity, Inc. Méthodes et dispositifs pour traiter une maladie au moyen d'une biothérapie
US20210161805A1 (en) * 2013-09-26 2021-06-03 Progenity, Inc. Delivery Capsule with Threshold Release
WO2022069604A1 (fr) 2020-09-30 2022-04-07 Novo Nordisk A/S Capsule pouvant être insérée dans une lumière
WO2022074252A1 (fr) 2020-10-09 2022-04-14 Novo Nordisk A/S Dispositif de capsule
WO2022090551A1 (fr) 2020-11-02 2022-05-05 Novo Nordisk A/S Capsule d'administration de substance

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992021307A1 (fr) * 1991-05-30 1992-12-10 Schentag Jerome J Procede et capsule de telemesure
US20090043278A1 (en) 2005-05-27 2009-02-12 Shinsuke Tanaka Body-insertable apparatus
CN1730118A (zh) * 2005-08-19 2006-02-08 华南理工大学 化学反应气压式微胶囊药物释放方法及其装置
US20210161805A1 (en) * 2013-09-26 2021-06-03 Progenity, Inc. Delivery Capsule with Threshold Release
US20180193621A1 (en) 2015-06-30 2018-07-12 Entrega Inc. Device for oral delivery of active agents
WO2018049133A1 (fr) 2016-09-09 2018-03-15 Mitchell Lawrence Jones Dispositif ingérable électromécanique pour l'administration d'une substance distribuable
WO2018213600A1 (fr) 2017-05-17 2018-11-22 Massachusetts Institute Of Technology Systèmes à redressement automatique, et composants et procédés associés
WO2020106750A1 (fr) 2018-11-19 2020-05-28 Progenity, Inc. Méthodes et dispositifs pour traiter une maladie au moyen d'une biothérapie
WO2022069604A1 (fr) 2020-09-30 2022-04-07 Novo Nordisk A/S Capsule pouvant être insérée dans une lumière
WO2022074252A1 (fr) 2020-10-09 2022-04-14 Novo Nordisk A/S Dispositif de capsule
WO2022090551A1 (fr) 2020-11-02 2022-05-05 Novo Nordisk A/S Capsule d'administration de substance

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