Patent Application
20240307670
The present invention relates to medical devices, including systems for drug delivery, adapted for being inserted into a lumen of a patient and capable of being activated by means of a fluid, such as a biological fluid.
In the disclosure of the present invention reference is mostly made to the treatment of a disease or other condition by delivery of a therapeutic agent, however, this is only an exemplary use of the present invention.
May people suffer from diseases, which requires them to receive injections of drugs on a regular and often daily basis. To treat their disease these people are required to perform different tasks which may be considered complicated and may be experienced as uncomfortable. Furthermore, it requires them to bring injection devices, needles and drugs with them when they leave home. It would therefore be considered a significant improvement of the treatment of such diseases if treatment could be based on oral intake of tablets or capsules.
However, such solutions are very difficult to realise, since protein-based drugs will be degraded and digested rather than absorbed when ingested.
To provide a working solution for delivering a therapeutic substance into the bloodstream through oral intake, the drug has to be delivered firstly into a lumen of the gastrointestinal tract and further into the wall of the gastrointestinal tract (lumen wall). This presents several challenges among which are: (1) The drug has to be protected from degradation or digestion by the acid in the stomach. (2) The drug has to be released while being in the stomach, or in the lower gastrointestinal tract, i.e. after the stomach, which limits the window of opportunity for drug release. (3) The drug has to be delivered at the lumen wall to limit the time exposed to the degrading environment of the fluids in the stomach and in the lower gastrointestinal tract.
If not released at the wall, the drug may be degraded during its travel from point of release to the wall or may pass through the lower gastrointestinal tract without being absorbed, unless being protected against the decomposing fluids.
Prior art references relating to oral dosing of active agents and addressing one or more of the above challenges include WO 2018/213600 A1, WO 2020/160399 A1 and US 2020/0129441 A1.
For medical capsules, such as the ones disclosed in the said references, the internal configuration design offers several design challenge trade-offs. For an oral device to be viable, e.g. for delivery of an API in form of a solid needle-shaped API, it needs to deliver an amount of API sufficient for the intended therapy. At the same time, for solid needle-shaped API tablets, the API tablet needs to be delivered reliably into a tissue layer in a depth sufficient to enable systemic uptake. Typically, a large injection force is required to deliver the API tablet at the right depth. Hence, the challenge is to design a device that is small enough to be swallowable, while reliably self-righting and injecting a sufficient amount of API deep enough. Furthermore, low cost and robust performance is essential.
In WO 2020/157324 A1 a capsule device is disclosed having an actuation mechanism with a laterally movable latch element which includes a blocking portion that cooperates with a retainer portion in latching engagement. Prior to actuation the latch element is supported by a dissolvable retaining member, which upon dissolution ceases to support the latch element thereby enabling lateral movement or the latch element to release the latching engagement.
For this kind of actuation mechanism, typical constraints and requirements for obtaining a wellfunctioning mechanism include the following:
Having regard to the above, it is an object of the present invention to provide a medical device for insertion into a lumen of a patient, and which to a high degree effectively and reliably allows firing of an actuation mechanism in a controlled and predictable manner by influence of a biological fluid.
It is furthermore an object of the present invention to provide a capsule design which is optimized for providing a forceful actuation force, and wherein the outer dimensions of the capsule are minimized.
In the disclosure of the present invention, embodiments and aspects will be described which will address one or more of the above objects or which will address objects apparent from the below disclosure as well as from the description of exemplary embodiments.
Thus, in a first aspect, a capsule device is provided, comprising:
By configuring the latch mechanism with latch arms that extend proximally and radially outwards from the base portion so that the radially inwards facing latch surface of each latch arm is inclined relative to the axis this enables, in the actuating configuration, the latch arms to collapse radially toward each other in a manner where the latch arms only take up little space in the radial direction. This enables the retainer portions associated with the capsule housing to be formed with a radially minor dimension. This in turn enables use of a more powerful drive spring for obtaining a large actuation force without compromising the overall outer dimensions of the capsule device.
Compared to latch mechanisms of the prior art, the proposed latch mechanism offers improvements to the load bearing surfaces, and the risk of creep in the latch mechanism components is reduced.
Furthermore, the solution enables more effective wetting of the dissolvable latch support resulting in improved precision for timely releasing of the latching engagement.
In some embodiments, when in the pre-actuation configuration, the dissolvable latch support is primarily acted upon by compression forces exerted onto the dissolvable latch support by the latch arms being urged radially towards the dissolvable latch support.
In some embodiments, in the pre-actuation configuration, at least one pair of a latch arm and a retainer portion is structured to maintain, i.e., releasably retain, the actuation member.
In some forms of the capsule device, when assuming the pre-actuation configuration, the spring exerts a load on the actuation member, and the at least one pair of a latch arm and a retainer portion retains the actuation member relative to the base member against the load exerted by the spring.
In other forms, when the capsule device is taken into use, the spring will not initially exert a load on the actuation member, but may be operated, such as by a user-initiated step, to provide said load.
In some embodiments the plurality of latch arms are provided as two radially opposed latch arms arranged in a V-shaped configuration, and wherein the dissolvable latch support is generally wedge shaped or shaped as a cone. In other embodiments, the number of latch arms may be three, four, five or more, wherein the latch arms are distributed around the axis.
The capsule device may be formed so that a fluid ingress opening is provided in the capsule housing proximal end, wherein the dissolvable latch support is disposed in the fluid ingress opening to enable wetting of the dissolvable latch support.
In some embodiments, the plurality of retainer portions each comprise an inclined surface with a surface normal pointing proximally and radially inwards, and wherein the radially outwards facing latch surface of each latch arm comprises a correspondingly inclined surface.
The capsule housing defines an exterior surface. The inclined surfaces of the retainer portions may be formed to intersect with the capsule housing exterior surface.
The engagement interfaces between the radially outwards facing latch surfaces and the respective retainer portions may in certain embodiments be provided either as planar interfaces or single curvature interfaces, such as conically shaped interfaces.
In further embodiments, the engagement interfaces between the radially inwards facing latch surfaces and the respective radially outwards facing surfaces of the dissolvable latch support may be provided as planar interfaces or single curvature interfaces, such as conically shaped interfaces.
The exterior of the capsule housing defines a housing extreme proximal end surface. In some embodiments, the dissolvable latch support defines a dissolvable latch support proximal end surface, and wherein, in the pre-actuation configuration, the dissolvable latch support proximal end surface is located proximally relative to the housing exterior extreme proximal end. In alternative embodiments the dissolvable latch support proximal end surface is located distally within 2 mm, such as within 1.5 mm such as within 1.0 mm, such as within 0.5 mm from the housing exterior extreme proximal end.
In some forms, the drive spring is provided as a coiled tapered spring, the drive spring having a wide first end coupled to the capsule housing and a narrow second end coupled to actuation member.
The drive spring may in some forms be provided as a compression spring. In other forms the drive spring is provided is provided as a tension spring.
In the pre-actuation configuration, the total axial length of the drive spring defines a pre-actuation length. In some embodiments the dissolvable latch support is disposed proximally relative to the drive spring either with no axial overlap or with an axial overlap corresponding to less than half of said pre-actuation length.
In exemplary embodiments, the capsule device is configured for ingestion and for travelling into a lumen of a patient, the lumen having a lumen wall.
In such embodiments, the capsule device may be 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 self-orients relative to gravity with the axis arranged vertically and the distal end pointing downwards.
In other forms, the capsule device orients relative to the lumen wall by other means, such as by being squeezed by opposing tissue wall sections.
In some forms the capsule device comprises a tissue interfacing component, wherein the tissue interfacing component is disposed within the capsule housing when the actuation member assumes the first position and wherein the tissue interfacing component is advanced from the capsule housing and into engagement with tissue as the actuation member moves from the first position to the second position.
In some forms the tissue interfacing component couples to the actuation member. In some forms, the tissue interfacing component comprises a therapeutic payload.
In some forms the tissue interfacing component defines a tissue penetrating member.
In some forms the capsule device comprises a tissue penetrating member coupled to the actuation member, wherein the tissue penetrating member is disposed within the capsule housing when the actuation member assumes the first position and wherein the tissue penetrating member is advanced from the capsule housing and into the wall of the lumen as the actuation member moves from the first position to the second position.
In some further forms the tissue penetrating member is provided as a solid delivery member formed partly or entirely from a preparation comprising a therapeutic payload, and wherein the preparation is made from a dissolvable material that dissolves when inserted into tissue of the lumen wall to at least partly release the therapeutic payload into the blood stream.
The therapeutic payload may in other embodiments be in the form of an encapsulated solid, a liquid, a gel or a powder, or any combination thereof and configured for delivery through a delivery member.
In some embodiments, the capsule device comprises a delivery member being associated with the therapeutic payload, the delivery member being configured for insertion into the lumen wall to deliver at least a portion of the therapeutic payload. The delivery member may have an outer shape as a needle. However, in alternative embodiments, different shapes for the delivery member may be provided.
In still other embodiments the delivery member is an injection needle having a longitudinal lumen extending within the injection needle, wherein the therapeutic payload is provided as a liquid, gel or powder being expellable through the injection needle from a reservoir accommodated within the capsule device.
When the therapeutic payload is in a flowable form, such as a liquid or powder, the drug may be expelled from the capsule through an outlet by means of jet action, i.e. expelling the drug at a penetration velocity allowing the drug substance to penetrate the lumen wall, such as the mucosal lining of the intestines or the stomach. By jet action, no delivery member is needed for penetrating the tissue. In such case, in some embodiments, the drug delivery device does not comprise any delivery member.
In some forms the capsule device defines an ingestible device suitable for swallowing by a patient and travelling into a lumen of a gastrointestinal tract of a patient, such as the stomach or the small intestines. The capsule hosing of the device may be shaped and sized to allow it to be swallowed by a subject, such as a human.
By the above arrangements an orally administered drug can be delivered safely and reliably into the stomach or intestinal wall of a living mammal subject, such as a human.
In some embodiments, the actuation member may define a hub configured for moving the tissue interfacing component from a first position stored within the capsule housing to a second position different than the first position so that, in the second position, at least a part of the tissue interfacing component is brought into direct engagement with tissue exterior to the capsule housing. In some embodiments, the tissue interfacing component forms a tissue penetrating member configured for penetrating tissue and wherein the tissue penetrating member is inserted into tissue in the second position.
In some embodiments, the actuation mechanism is operable from a pre-actuation configuration, through an actuating configuration and end in an actuated configuration. The actuating configuration may be referred to as an intermediary configuration wherein the actuation mechanism releases the actuation member for movement towards the actuated configuration.
In some embodiments, in the pre-actuation configuration, the tissue interfacing component is attached to the hub.
In other embodiments, in the pre-actuation configuration, the tissue interfacing component is not engaged by the hub, but wherein during the hub moving from the first position to the second position, the hub initially engages the tissue interfacing component, and subsequently moves the tissue interfacing component so that at least a part of the tissue interfacing component is brought into direct engagement with tissue exterior to the capsule housing.
The hub may be configured to carry or push one or more of a therapeutic payload, a delivery member, and a sensor from a first position relative to the capsule housing to a second position relative to the capsule housing.
In particular forms the hub itself forms one or more of a therapeutic payload, a delivery member, and a sensor that moves from a first position relative to the capsule housing to a second position relative to the capsule housing.
In some forms the hub comprises an interface portion, wherein the tissue interfacing component attaches relative to the interface portion of the hub.
In such embodiments the hub may be actuated to move the hub from a first position to a second position, and wherein the tissue interfacing component is configured for detachment relative to the interface portion of the hub when the hub assumes the second position.
In further exemplary embodiments the capsule device defines a capsule device comprising a capsule housing having an outside shape formed as a rounded object and defining an exterior surface. The capsule device further comprises a solid delivery member having a needle or dart-shaped form and being formed partly or entirely from a preparation comprising a therapeutic payload, wherein the preparation is made from a dissolvable material that dissolves when inserted into tissue of the lumen wall. The actuation member is formed as a hub that comprises an interface portion, wherein the solid delivery member is held or attached relative to the interface portion of the hub. The capsule device is configured as a self-righting capsule having a geometric center and a center of mass offset from the geometric center along the axis, wherein when the capsule device is supported by the tissue of the lumen wall while being oriented so that the centre of mass is offset laterally from the geometric center the capsule device experiences an externally applied torque due to gravity acting to orient the capsule device with the axis oriented along the direction of gravity to enable the solid delivery member to interact with the lumen wall at the target location. Upon entering into the actuating configuration, the hub moves along the axis thereby inserting the solid delivery member into tissue. Subsequent to insertion, the solid delivery member may at least partially dissolve and release one or more therapeutic agent(s) into the tissue.
In still further embodiments, the capsule device may be configured with capsule housing shaped differently, such as having a capsule housing with an elongated cylindrical middle portion with a rounded end portion at each end of the cylindrical middle portion. Also, an oval shaped capsule housing may be used for alternative embodiments.
Non-limiting examples of a self-righting capsule device may include devices configured for actuation when the device is located in the stomach lumen of a patient. Other non-limiting examples may include devices configured for actuation when the device is located in the small intestines or the large intestines.
In a second aspect, a capsule device is provided, comprising:
In further embodiments, the capsule device according to the second aspect may be configured with any combination of features disclosed in relation to the capsule device embodiments according to the first aspect.
Whereas this disclosure mainly refers to drug delivery from a capsule device to a lumen or lumen wall, the invention in its broadest aspect is not limited to drug or substance delivery, but rather concerns a particular actuation assembly. The capsule device comprising the actuation mechanism according to the present invention may be configured for other uses. Non-limiting uses include obtaining one or more samples from a body lumen, e.g. by including a sample taking device for introducing a sample from a body lumen or lumen wall into the capsule device, and delivering a monitoring or analysis device, e.g. by disposing or positioning a sensor device from the capsule device into the lumen or lumen wall.
As used herein, the terms “drug” “therapeutic agent”, “payload” or “therapeutic 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 non-limiting drugs include pharmaceuticals such as peptides (e.g. insulins, insulin containing drugs, GLP-1 containing drugs as well as derivatives thereof), proteins, and hormones, biologically derived or active agents, hormonal and gene-based agents, nutritional formulas and other substances in both solid, powder or liquid form. Specifically, the drug may be an insulin or a GLP-1 containing drug, this including analogues thereof as well as combinations with one or more other drugs.
In the following embodiments of the invention will be described with reference to the drawings, wherein:
In the figures representing views of the different embodiments like structures are mainly identified by like reference numerals.
When in the following terms such as “upper” and “lower”, “right” and “left”, “horizontal” and “vertical” or similar relative expressions are used, these only refer to the appended figures and not necessarily to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only. When the term member or element is used for a given component it generally indicates that in the described embodiment the component is a unitary component, however, the same member or element may alternatively comprise a number of sub-components just as two or more of the described components could be provided as unitary components, e.g. manufactured as a single injection moulded part. The terms “assembly” and “subassembly” do not imply that the described components necessarily can be assembled to provide a unitary or functional assembly or subassembly during a given assembly procedure but is merely used to describe components grouped together as being functionally more closely related.
With reference to
The ingestible self-righting capsule device 100 comprises a first portion 100A having an average density, a second portion 100B having an average density different from the average density of the first portion 100A. The capsule device 100 accommodates a tissue penetrating member forming a payload portion 130 for carrying an agent for release internally of a subject user that ingests the article. In the shown embodiment, the average density of capsule device prior to deployment is larger than that of gastrointestinal fluid, enabling the capsule device to sink to the bottom of the stomach lumen. The outer shape of the self-righting article is a gomboc shape, i.e. a gomboc-type shape that, when placed on a surface in any orientation other than a single stable orientation of the shape, then the shape will tend to reorient to its single stable orientation.
The capsule device shown includes an upper (proximal) capsule housing 110 which mates and attaches to a lower (distal) capsule housing 120. The upper capsule housing 110 and the lower capsule housing 120 together forms the capsule housing of the device. In the shown embodiment upper capsule housing 110 and lower capsule housing 120 are mounted relative to each other by way of a snap engagement. The capsule housing parts 110/120 define a shell having an interior hollow which accommodates the payload portion 130 and an actuation and propulsion mechanism. The latter comprises an energy source in the form of a pre-strained drive spring 140, and an actuation member in the form of hub 150 which holds and drives forward the payload portion 130 for payload delivery upon release of energy from the drive spring 140.
The payload portion 130 is oriented along an actuation axis and configured for movement along the actuation axis. In the shown embodiment, the upper and lower capsule housing parts 110, 120 form generally rotation symmetric parts with the axis of symmetry arranged along the actuation axis. In the drawings, the device is oriented with the actuation axis pointing vertically, and with the payload portion 130 pointing vertically downwards towards an exit hole 124 arranged centrally in the lower capsule housing 120, the exit hole allowing the payload portion 130 to be transported through exit hole and moved outside the capsule device 100. The lower capsule housing part 120 includes a tissue engaging surface 123 which is formed as a substantially flat lower outer surface surrounding the exit hole 124.
In the shown embodiment in
Regarding suitable materials for the capsule housing for the embodiment shown in
In the shown embodiment, due to the density distribution of the entire capsule device 100, and due to the outside shape of the device, when the capsule device is supported on a wall such as a tissue wall, and being subjected to gravitational forces, the capsule device 100 will tend to orient itself with the actuation axis substantially perpendicular to the surface (e.g., a surface substantially orthogonal to the force of gravity, a surface of a tissue such as the wall of the gastrointestinal tract). Hence, the capsule device seeks to orient relative to the direction of gravity so that the tissue engaging surface 123 faces vertically downward.
The interior of the upper capsule housing 110 includes a mounting structure provided as an inner sleeve 115 which extends concentrically with the actuation axis from the upper part of the upper capsule housing 110 towards a proximally facing bottom surface formed in the lower capsule housing 120.
Further, in the shown embodiment, a hub retainer structure 113 is provided as an inwardly extending round-going flange that is arranged concentrically with the actuation axis and which extends radially inwards relative to the inner sleeve 115 from the upper capsule housing 110 and downwards along the actuation axis. The hub retainer structure 113 serves as a retaining geometry for releasably retaining the hub 150 against the drive force emanating from a strained drive spring 140 arranged within the capsule. Referring mainly to
At the distal most portion of the conical retainer surface 113a, a central opening is formed at the centre thereof. The central opening is dimensioned so that the hub 150 is movable axially through the central opening when the hub assumes a released state but wherein the hub 150 cannot move axially through the central opening when the hub 150 assumes a state corresponding to the actuation configuration. The conical retainer surface 113, at the locations where upper edges of the conical retainer surface 113 intersect with the exterior surface of the capsule housing 110, the structure defines a fluid ingress opening allowing gastric fluid to enter into contact with a fluid operated actuation mechanism.
In the first embodiment shown in
Referring mainly to
The upper retaining part 151 of the hub 150 forms a base portion which at a proximal end connects with two latches provided in the form of two independently deflectable latch arms 153. In the state shown in
The two latch arms are thus configured in a v-shaped configuration. Each latch arm 153 is resiliently movable in the radial inwards direction by a swivelling movement relative to the upper retaining part 151. The latch arms 153 each defines a radially outwards facing latch surface 153a configured to engage with respective portions of the conical retainer surface 113a in a latching engagement. Each of the latch arms 153 further includes a radially inwards facing latch surface 153b configured for cooperating with a centrally disposed dissolvable latch support 160, see
In the shown first embodiment, in the pre-actuation configuration shown in
In the shown embodiment of hub 150, the latch arms 153 connect to the base portion of upper retaining part 151 by means of a hinge section allowing the two latch arms, relative to the positions they assume in
It is to be noted that
This enables easy assembling of the capsule device, by allowing the hub 150 to be inserted in the proximal direction through the central opening formed in the conical retainer surface 113a without requiring a separate step of moving the latch arms towards the collapsed state.
b show two perspective views of the dissolvable latch support 160. In the shown embodiment, the dissolvable latch support 160 is formed as a generally cone-shaped member sized to be inserted between the two latch arms 153 in a wedging manner forcing the latch arms 153 in intimate contact with the conical retainer surface 113a of the hub retainer structure 113. In the shown embodiment, the conical surface 163b matches the surface 153b of the latch arms with an angle of inclination of 22 degrees relative to the central axis of the cone.
For the dissolvable latch support 160, different forms and compositions may be used. Nonlimiting examples include pellets made from Sorbitol or Microcrystalline cellulose (MCC). Other non-limiting examples include injection moulded Isomalt pellets, compressed granulate Isomalt pellets, compressed pellets made from a granulate composition of Citrate/NaHCO3, or compressed pellets made from a granulate composition of Isomalt/Citrate/NaHCO3.
Such dissolvable latch support will become disintegrated when subjected to a liquid such as gastric juice of the GI-tract. By carefully selecting the composition, the geometry of the dissolvable latch support and optionally exposure channels to ensure wetting of the dissolvable latch support, the release time can be controlled to occur within a chosen time delay after swallowing of the capsule device 100.
The first embodiment capsule device 100 additionally comprises a pair of sealing elements 170, 180 for maintaining the tissue interfacing component, i.e. the payload portion 130, fluidically isolated from the environment external to capsule device 100 prior to actuation. In the shown embodiment, an upper sealing element 170 formed as a ring of soft pliable material, such an elastomeric material, is inserted between the lowermost annular surface of the conical retainer surface 113a and an annular proximal facing flange surface 158 of the hub 150.
The further sealing element, i.e. the lower sealing element 180, forms a fluidic gate configured to maintain the exit hole 124 fluidically blocked prior to actuation. In the shown embodiment, the sealing element 180 comprises an elastomeric seal member having a generally disc shaped form. An outer periphery of the sealing element 180 is mounted below the lowermost winding of the drive spring 140 and clamped above an annular proximally facing surface of lower capsule housing 120. As disclosed in US 2020/0129441 A1 the central area of the sealing element 180 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 170 and 180 thus cooperate to form a compartment internally in capsule device 100 that serves, prior to actuation, to maintain the payload portion 130 fluidically isolated from biological fluid externally to capsule device 100 but allows the payload portion to penetrate easily through sealing element 180 at the time of actuation for payload delivery into tissue.
During assembly, after the latch arms of the hub 150 has been inserted fully proximally through the central opening formed in the conical retainer surface 113a and with the sealing element 170 clamped between the hub 150 and the upper capsule housing 110, the latch support 160 is forced axially in the distal direction in between the latch arms 153. Due to the conical interface between the dissolvable latch support 160 and the latch arms 153, the dissolvable latch support 160 is allowed to be moved distally in a wedging action while the latch arms 153 become spread radially outwards into engagement with the conical retainer surface 113a. At the end of this assembly step, the wedging action provides stiction between the dissolvable latch support 160 and the latch arms 153 resulting in mounting engagement where the dissolvable latch support 160 remains fixedly attached to the latch arms 153. This enables safe storage and handling without the risk of dissolvable latch support 160 becoming accidentally dismounted from the latch arms 153. As seen in
With regard to the above-mentioned drive spring 140, in capsule device 100, the drive spring is provided in the form of a pre-strained helical tension spring arranged coaxially with the actuation axis inside the capsule housing. The drive spring, in the pre-actuation configuration shown in
The first end 147 of drive spring 140 is seated against a first spring seat arranged in the distal end portion of the capsule device 100. In the shown embodiment, the first spring seat is formed by a distal end face of inner sleeve 115. The distal end face of inner sleeve 115 is arranged with a slight axial spacing relative to a proximally facing surface of the lower capsule housing 120. A substantial portion of the lower-most winding of the drive spring 140 defines a diameter comparable with the diameter of inner sleeve 115. Inner sleeve 115 is formed with a distal end face disposed with some distance relative to a proximal facing end surface of lower capsule housing 120 allowing said portion of the lower-most winding of the drive spring 140 to radially overlap with the inner sleeve 115 and in this way become clamped in a circumferential slot between inner sleeve 115 and lower capsule housing 120.
The second end 146 of drive spring 140 is seated against a second spring seat 156 formed by the lower interface part 155 of the hub 150. As part of assembling the capsule device 100 the drive spring 140 has been energized by axially tensioning the drive spring 140 between the two spring seats. Hence, the hub 150 is initially under tension load from drive spring.
In the embodiment shown, prior to final assembly and with the drive spring 140 arranged along the actuation axis but with the drive spring assuming a non-energized state, the second narrow end 146 of the spring would be positioned distally to the first wide end 147 of the spring. However, during assembly wherein the drive spring 140 is increasingly strained, the second narrow end 146 will be moved proximally relative to the first wide end 147 to enter into the pre-actuation state shown in
Turning now to the operation of the capsule device 100, reference is initially made to
The upper sealing element 170 engages the flange 158 as well as the lower surface of hub retainer structure 113 to keep this interface fluid tight. Also, the lower sealing element 180 keeps the exit hole 124 fluid tight.
After ingestion of capsule device 100, 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 123 engaging the tissue stomach wall with the firing axis of the capsule device oriented virtually vertical, i.e. with the payload portion 130 pointing downwards. Dissolvement of dissolvable latch support 160 has begun due to exposure to gastric fluid. This is represented in
In situation of intended use, the payload portion 130 is inserted into tissue of the lumen wall where it will anchor generally in a direction along the actuation axis. As discussed above, depending on the specific design of the capsule device, the payload portion 130 may be released actively from the remaining parts of the capsule at the end of the insertion stroke. When the capsule device 100 has delivered the intended dose the capsule will release relative to the deposited payload portion 130 which remains inside the tissue wall for release of therapeutic agent into the blood stream of the subject.
Although not shown in the embodiments disclosed herein, any of the embodiments may be modified to include a mechanism for separating the payload portion 130 from the hub 150 upon the assembly of the payload portion 130 and the hub 150 arriving at the most distal position in the capsule housing. Suitable non-limited principles may include the principles disclosed in WO 2020/157324 A1 wherein a ram (similar to a hub) becomes tilted at the end of the insertion stroke for detaching the tissue inserted portion of the delivery member from the ram.
Alternatively, the capsule may be held stationary for a prolonged time allowing the payload portion 130 to release a therapeutic agent into the blood stream of the subject as the capsule is held stationary relative to the tissue. In any of these cases, subsequently to drug delivery, the remaining parts of the capsule device will travel out through the digestive system of the user and be disposed of.
Switching now to a second embodiment of a capsule device 100′ in accordance with the invention, reference is made to
Comparing
In the second embodiment capsule device 100′, a lower sealing element 180 has been clamped between the upper capsule housing 110 and the lower capsule housing 120. In accordance herewith, the peripheral portion 181 of lower sealing element 180 is arranged slightly below a point axially midways between distal and proximal end portions of the capsule housing 110/120. In the shown embodiment, the first end 147 of the drive spring is mounted proximally to the lower sealing element 180 where it is clamped between spring seat portions arranged at the interface between the upper capsule housing 110 and the lower capsule housing 120.
In the shown embodiment, the upper capsule housing 110 includes at its most distal portion an annular flange with a distally facing surface adapted to provide a seat for the first end of the drive spring 140.
The lower sealing element 180 additionally performs the function of guiding the payload portion 130, and more specifically guiding the tip portion of payload portion 130, as it travels during the delivery stroke, i.e. internally in the compartment of capsule device 100′ towards the exit hole 124. The seal element 180 again comprises a generally disc shaped structure and may be made of an elastic rubber-like material, such as silicone rubber. In the shown embodiment, in the pre-actuation configuration, a central portion 182 of sealing element 180 defines a conical portion sized and shaped to fit with the distal shape of payload portion 130 so as to provide a self-centring guide portion for the pointed tip of payload portion 130. As the sealing element 180 is made of elastic material, the material portions connecting the peripheral portion 181 with the central portion 182 forms a flexible connector 183 and allows the central portion 182 to be moved axially distally relative to the peripheral portion 181.
Initially, in the pre-actuation configuration, the sealing element 180 may provide a seal tight barrier preventing fluid externally to the compartment from entering into the compartment, thus protecting payload portion 130 from degradation. Resembling the first embodiment, the central portion 182 of the lower sealing element 180 may include one or more thin cuts, scores or similar weakened portions allowing the tip of payload portion 130 to force its way through the lower sealing element during the delivery stroke.
In
With the capsule device 100′ assuming the actuated configuration, refer to
Turning next to the third embodiment of a capsule 100″ reference will be made to
Comparing
As shown in
The drive spring 140 is provided as a helically coiled conical compression spring arranged within the inner sleeve 115. The drive spring forms a wide first end 147 arranged to be seated against an upper spring seat formed in the most proximal portion of upper capsule housing 110. This upper spring seat is formed radially between the inner sleeve and the hub retainer structure 113, i.e. at a radially outwards facing part of the structure defining the hub retainer structure 113. A second narrow end 146 of spring 140 is seated in the second spring seat 156 formed by the lower interface part 155 of the hub 150.
Due to the design of the actuation mechanism including a conically shaped dissolvable latch support and the v-shaped configuration of the latch arms in combination with the shape of the drive spring which includes a tapering outside diameter with a large diameter first end 147, the actuation mechanism and the drive spring has been designed to axially overlap each other.
The said combination of features allows the load bearing surfaces of the actuator mechanism to be optimized, i.e. the interfaces between the hub retainer structure 113 and the latch arms 153 and the interfaces between the latch arms 153 and the dissolvable latch support 163b.
Compared to previously suggested designs disclosed in the art, the spring force of the drive spring has been increased without compromising the load bearing surfaces, and at the same time reducing the risk of creep in the parts forming the actuator mechanism. Hitherto, corresponding benefits were only available by compromises being made in the exterior size of the capsule.
It is to be noted that further not shown embodiments in accordance with the invention may include actuator mechanisms having actuator interfaces formed differently than the conical shaped interface surfaces shown in connection with the first, second and third embodiments.
For example, the actuator interfaces may be formed with planar surfaces instead of conical surfaces, either at the interface between the hub retainer structure 113 and the latch arm 153 and/or between the latch arm 153 and the dissolvable latch support 160. For such embodiment having two radially opposed latch arms, the dissolvable latch support 160 may be formed as a wedge having two planar surfaces intersecting each other at the sharp edge of the wedge.
Furthermore, the number of latch arms may be different than two, such as three, four or even more individual latch arms. In certain embodiments, the plurality of latch arms may be disposed equally around the actuation axis, although this may not be strictly necessary for any embodiment in accordance with the principles of the present invention.
The above-described variants of interfaces between the payload portion 130 and the hub 150 are only exemplary and other configurations may be used instead. The detachable attachment between the payload portion and the hub may be obtained by using a friction or press fit.
Alternatively, an adhesive may be used at the interface, such as sucrose. Still alternatively, the attachment may be obtained by initially wetting the payload portion and utilizing inherent stiction between the hub and the payload portion. In situation of use, upon the hub reaching its final destination, detachment may occur at the interface between the payload portion and the hub. In other embodiments, a desired detachment may be obtained by detaching a major portion of the payload portion from the remaining payload portion being still adhered or fastened to the hub. In some embodiments, the payload portion includes a weakened point which determines the point of separation. In still further embodiments, the hub and the payload portion may be formed as a unitary component all made of a composition containing API, and wherein the intended payload portion to be pushed out from capsule device is separated from the hub portion. Also, in alternative embodiments, the payload may act as a hub by itself to be fully transported away from the capsule device.
Although the above description of exemplary embodiments mainly concern ingestible capsules for delivery in the stomach, the present actuation principle generally finds utility in capsule devices for lumen insertion in general, wherein a capsule device is positioned into a body lumen, and wherein a fluid activates an actuation mechanism by dissolving a dissolvable latch support for bringing a component from a first configuration into a second configuration, such as from a first position into a second position. Non-limiting examples of capsule devices may include capsule devices for intestinal delivery of a payload or drug either by delivery into the intestinal lumen or into the tissue wall of an intestinal lumen. Drug delivery may be performed using a delivery member, such as a needle for injection of a liquid drug or powder, or via microneedles which is inserted into the tissue wall of a lumen, or which actuates directly into the lumen. Alternatively, drug delivery may be performed through one or more exit openings of the capsule device without the use of a delivery member, such as by jet injection of either a liquid drug or a particle stream into a mucosal lining of a lumen wall.
In the above description of exemplary embodiments, the different structures and means providing the described functionality for the different components have been described to a degree to which the concept of the present invention will be apparent to the skilled reader. The detailed construction and specification for the different components are considered the object of a normal design procedure performed by the skilled person along the lines set out in the present specification.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/051968 | 1/27/2022 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63142737 | Jan 2021 | US |
