Controllably disintegrating self-expanding ingestible devices

Abstract

The present disclosure relates to expandable devices, particularly self-deploying devices designed to be delivered to and deployed within the gastrointestinal tract and configured for controlled collapse, the devices including expandable compartments separated by seal zones designed for controlled collapse upon exposure to liquid, thereby enabling controlled collapse of the device after a predefined time from deployment.

Description

[Technical Field]

[0001] The present disclosure relates to expandable devices, particularly self-expanding devices designed to be delivered to and deployed within the gastrointestinal tract and configured for controlled collapse. [Background technology]

[0002] The following references are considered to be relevant as background to the presently disclosed subject matter. -International Publication No. 2016 / 015648 -International Publication No. 2008 / 062440 -International Publication No. 2009 / 125432 -International Publication No. 2013 / 188819 -International Publication No. 2015 / 026552 -International Publication No. 2015 / 120471

[0003] Acknowledgment of the above references herein should not be inferred as meaning that they are in any way relevant to the patentability of the subject matter of the present disclosure.

[0004] Effective and targeted delivery of various compounds and active agents to or across tissues, such as the intestinal lining, has proven to be a long-standing challenge.Due to the mucus secretions that cover various tissues to provide a hydrated environment and lubricate biological surfaces, the targeted delivery of active agents often requires the use of mucoadhesive components or other tissue-adhesive arrangements, which can adhere to tissues for a predefined period of time, thereby increasing the contact time between tissues and active agents, and allowing the active agents to be absorbed through and / or into tissues.

[0005] Some approaches involve the use of deployable devices, where the device is delivered in an undeployed form to the vicinity of the target site and deployed to deliver the mucoadhesive-based component to the tissue during such deployment. For delivery to the gastrointestinal tract, careful consideration is required in controlling both deployment to the appropriate target site and expulsion of the device after deployment to avoid obstruction of the gastrointestinal tract. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2016 / 015648 [Patent Document 2] International Publication No. 2008 / 062440 [Patent Document 3] International Publication No. 2009 / 125432 [Patent Document 4] International Publication No. 2013 / 188819 [Patent Document 5] International Publication No. 2015 / 026552 [Patent Document 6] International Publication No. 2015 / 120471 Summary of the Invention

[0007] The present disclosure provides a self-expanding device that can be administered to a subject and undergo controlled deployment in the gastrointestinal tract. The device can be configured to deliver one or more active agents or one or more tissue adhesive layers (or patches), such as mucoadhesive materials, to the tissue at the target site. The device of the present disclosure is designed to allow controlled collapse of the device or a portion thereof once the device is deployed, for example, once the tissue adhesive layer is delivered and applied to the tissue at the target site, to allow proper and controlled discharge of the device from the target site.

[0008] The devices of the present disclosure are based on the recognition that careful construction of the device, which allows for controlled absorption of fluid (e.g., water) during and after deployment of the device, can be utilized to control the location and rate of disintegration of at least a portion of the device, allowing the device to break down into fragments that are more easily expelled from the target site.

[0009] Thus, in one aspect, the present disclosure provides an ingestible self-expanding device having a collapsed state and an expanded state. The device includes two or more self-expandable compartments connected to each other by a connection zone. Each compartment is formed from two substantially water-insoluble deformable film sections joined to each other at a peripheral segment of the compartment by at least one water-collapsible sealing composition to define a sealing zone. Each sealing zone is a layered structure of water-insoluble deformable film sandwiched between them by at least one water-collapsible sealing composition layer that joins the water-insoluble deformable film to each other at the peripheral segment. The two film sections define an enclosed compartment space between them in an area surrounded by the peripheral segment. Each compartment has one or more liquid-permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to swell upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from the collapsed state to the expanded state. In the devices of the present disclosure, the water-disintegrable sealing composition has water solubility configured to provide mechanical stability to the sealing zone during the transition of the device from the collapsed state to the expanded state and to provide controlled disintegration of the sealing zone after the device is expanded to the expanded state, thereby causing loss of integrity (degradation and / or collapse) of the compartments and / or device after deployment.

[0010] In other words, in the devices of the present disclosure, the sealing zone has several functions. First, the sealing zone forms the periphery of the compartment because the water-insoluble deformable film portions are adhered to each other at the peripheral segments of the compartment by the water-collapsible sealing composition. Furthermore, the sealing zone provides mechanical stability and reinforcement to the compartment during deployment of the device from a collapsed state to an expanded state, thereby allowing the compartment to maintain its integrity during deployment. However, once deployed, the water-collapsible sealing composition in the sealing zone serves as a weak structural area that allows for controlled collapse of the device after expansion, allowing the device to break down into smaller pieces for easier expulsion from the target site.

[0011] The devices of the present disclosure are designed to controllably increase in volume, for example, to drive a tissue adhesive layer or patch, such as a layer of mucoadhesive material, toward tissue and temporarily apply a force thereon to adhere or attach the layer or patch to the tissue at a desired location. Thus, once the device is administered, exposure to conditions appropriate for expansion causes the device to expand and deliver the tissue adhesive layer to the tissue. After the tissue adhesive layer is delivered to the target site, expulsion of the device is typically required, and the large volume of the device facilitates expulsion by collapse.

[0012] As mentioned above, the compartments are connected to each other by a connection zone, which is an element of the device that is usually integrated with the compartments and forms a physical link between adjacent compartments, resulting in the overall shape of the device. According to some embodiments, the connection zone comprises the sealing zone (i.e., the sealing zone is part of the connection zone).

[0013] According to other embodiments, the compartments are connected to one another by joining one or more of their respective sealing zones with a water-disintegrating sealing composition, which is typically present in the sealing zones and the connecting zones, thereby allowing for controlled degradation of both the device and the compartments.

[0014] According to some embodiments, the compartments are connected to one another by overlapping the seal zones of adjacent compartments one on top of the other, the connection zones consisting of stacked seal zones forming a layered structure of alternating layers of water-insoluble deformable film and water-disintegrable sealing composition.

[0015] In some embodiments, the seal zones are comprised of a first water-collapsible seal composition, and adjacent compartments are connected to one another by joining one or more of the respective seal zones with a second water-collapsible seal composition, and the first water-collapsible seal composition and the second water-collapsible seal composition are different from one another or the same.

[0016] By controlling various parameters of the water-collapsible sealing composition, a balance can be achieved between the stability of the water-collapsible sealing composition during device deployment and the collapse of the seal zone after device deployment in order to maintain the mechanical integrity of the device during this transition.

[0017] The term seal zone is intended to describe a circumferential contour along which peripheral segments of water-insoluble deformable film portions are adhered to one another by a water-disintegrable sealing composition. Such adhesion results in the formation of a compartment in which the segments of water-insoluble deformable film portions sealed by the circumferential contour define a sealed space therebetween.

[0018] As described above, the seal zone has a layered structure, with a water-insoluble deformable film defining the two outer layers of the seal zone and a layer of water-disintegrable sealing composition sandwiched between the films at the peripheral segments of the compartment. Because the outer layers of the seal zone are substantially water-insoluble, water penetration into the seal zone is permitted only through a small surface perpendicular to the plane of the seal zone layer where the water-disintegrable sealing composition is exposed to the liquid. Therefore, control of the exposure of the water-disintegrable sealing composition to water, and thus the rate of disintegration (and / or the onset of disintegration) of the seal zone, can be achieved, particularly by controlling the surface area of ​​the water-disintegrable sealing composition exposed to water. Further control of the seal zone's disintegration can be achieved, for example, by controlling the disintegration rate of the water-disintegrable sealing composition, for example, by controlling its composition.

[0019] In some embodiments, the onset of collapse of the seal zone occurs at least about 5 minutes after complete deployment of the device to the expanded state. In other embodiments, the onset of collapse of the seal zone occurs at least about 10 minutes after complete deployment of the device to the expanded state.

[0020] According to some embodiments, multiple seal zones comprise a water-disintegrable sealing composition, in which case the seal zones can all comprise the same water-disintegrable sealing composition, or the seal zones can comprise different water-disintegrable sealing compositions, thereby allowing the device to disintegrate gradually.

[0021] According to some other embodiments, regions are defined in the seal zone that contain the water-disintegrable sealing composition, and each seal zone can include one or more such regions, each of which can contain the same or a different water-disintegrable sealing composition.

[0022] According to some embodiments, the water-collapsible seal composition connecting the seal zones to one another at the connection zone may be the same as the water-collapsible seal composition within the seal zone. According to other embodiments, the water-collapsible seal composition connecting the seal zones to one another at the connection zone is different from the water-collapsible seal composition within the seal zone.

[0023] According to some embodiments, the water-disintegrable sealing composition comprises at least one first hydrophilic material and at least one second hydrophilic material having different hydrophilicity and water solubility, wherein the first hydrophilic material is less hydrophilic than the second hydrophilic material, and the first hydrophilic material is also less water soluble than the second hydrophilic material.

[0024] The difference in hydrophilicity and solubility can be used to control the timing and rate of disintegration of the water-disintegrable sealing composition.

[0025] The term hydrophilic material refers to a compound or composition that has a high affinity for water. In a water-disintegrable sealing composition, the difference in hydrophilicity allows the water-disintegrable sealing composition to function as an adhesive composition between two layers of water-insoluble deformable film in the seal zone while simultaneously providing controlled disintegration of the seal zone.

[0026] The first hydrophilic material is less hydrophilic and less soluble than the second hydrophilic material. The first hydrophilic material is selected to be chemically and / or thermodynamically compatible with the water-insoluble deformable film due to its low hydrophilicity. Such compatibility allows peripheral segments of the water-insoluble deformable film to be joined together with a water-collapsible sealing composition. The first hydrophilic material is selected to allow at least partial dissolution or physical integration into the water-insoluble deformable film portion during formation of the seal zone (e.g., by heat welding, ultrasonic welding, solvent bonding, etc.), thereby achieving a continuous interface between the water-insoluble deformable film portion and the water-collapsible sealing composition. This compatibility therefore allows for the formation of a sealed compartment having a seal zone that maintains mechanical integrity despite changes in the compartment's volume as it transitions between a collapsed state and an expanded state.

[0027] The first hydrophilic substance typically undergoes chemical or physical disintegration when exposed to the appropriate pH conditions in the intestine, typically a pH of about 6 to 7. Because the first hydrophilic material is selected to react when exposed to defined conditions in the intestine, such selection can further control the disintegration of the device after ingestion, preventing undesired disintegration as the device passes through the stomach, but allowing disintegration under the pH conditions of the intestine.

[0028] However, due to its low solubility and limited exposure to water due to the structure of the seal zone (i.e., the limited surface area of ​​the water-disintegrable seal composition layer exposed to water), a suitable environment is required for disintegration.

[0029] To achieve this favorable disintegration environment, the water-disintegrating sealing composition includes a second hydrophilic material having a higher hydrophilicity. The second hydrophilic material quickly absorbs and captures water that diffuses into the seal zone, thereby creating an environment that supports the solubilization of the first hydrophilic material, allowing the seal zone to disintegrate and the device to lose integrity (i.e., disintegrate or collapse). Because the second hydrophilic material is more hydrophilic, it can control the delivery of water to the seal zone after device deployment, thereby controlling the exposure of the first hydrophilic material to water and the initiation of its disintegration.

[0030] The combination of the first and second hydrophilic materials allows for a high degree of control over the rate of disintegration of the seal zone. The water-insoluble films sandwich the water-disintegrating seal composition, limiting water diffusion through the films and allowing relatively small amounts of water to penetrate the seal zone. The second hydrophilic material can quickly absorb and capture water that diffuses into the seal zone, thereby controlling the exposure of the first hydrophilic material to water and solubilizing it. Because the first hydrophilic material functions to form bonds between the two water-insoluble films, increased water absorption by the second hydrophilic material provides the appropriate conditions for the first hydrophilic material to solubilize, resulting in the disintegration of the seal zone and loss of the integrity of the compartment and / or device. Different disintegration onsets and disintegration rates can be achieved by balancing the selection of the first and second hydrophilic materials.

[0031] According to some embodiments, the first hydrophilic material may be selected from hypromellose phthalate, hypromellose acetate succinate, methyl methacrylate methacrylate copolymers (e.g., Eudragit L, Eudragit S), ethyl methacrylate acrylate copolymers (e.g., Kollicoat MAE), cellulose acetate phthalate, and others, and combinations thereof.

[0032] According to some embodiments, the second hydrophilic material may be selected from hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (Klucel), cellulose ethers (e.g., Metolose), polyvinylpyrrolidone and its derivatives (e.g., Povidone, Kollidon, Plasdone), polyvinyl alcohol, and others, and combinations thereof.

[0033] According to some embodiments, the second hydrophilic material is a superhydrophilic material.

[0034] According to some embodiments, the amount of the first hydrophilic material in the water-disintegratable sealing composition is greater than the amount of the second hydrophilic material. According to other embodiments, the weight ratio of the first hydrophilic material to the second hydrophilic material is about 4:1 to about 3:2.

[0035] The device of the present disclosure comprises a sealed compartment formed from a water-insoluble film, with a sealing zone defining the boundary of the compartment. According to some embodiments, the compartment is formed by two sheets of substantially continuous deformable film attached to each other to form the compartment, and the compartments are connected to each other by a connecting zone. In other words, in such embodiments, the device is formed from two continuous films, separated by a sealing zone to form two or more compartments, with adjacent compartments spaced apart by a connecting zone.

[0036] According to some embodiments, the connection zone comprises a seal zone, i.e., the seal zone forms an integral part of the connection zone. According to other embodiments, the connection zone is comprised of two or more seal zones joined together by a water-disintegrable sealing composition.

[0037] According to other embodiments, each compartment is formed from two separate deformable film portions, and the connection zone is constituted by two or more sealing zones of adjacent compartments attached to one another, i.e., in such embodiments, the connection zone is comprised of stacked connection zones, forming a layered structure of alternating layers of water-insoluble deformable film and layers of water-disintegrable sealing composition.

[0038] The compartments are formed of a water-insoluble deformable film, as described above, and define spaces therein for holding one or more gel-forming materials. The term continuously deformable film is intended to refer to a monolithic film, i.e., a film constructed as a single seamless unit. The term deformable film portions is intended to refer to film segments that, once attached to one another, form the continuous structure of the device.

[0039] The film is typically made of one or more substantially water-insoluble polymeric materials.

[0040] The compartment has one or more liquid-permeable sections to allow water to enter the compartment and activate the gel-forming material, inducing expansion and thus deployment of the device. In some embodiments, the one or more sections are of liquid-permeable material, and the deformable film is made of an impermeable material. In other words, the deformable film can be made of two or more different materials integrally formed with one another, one material being liquid-permeable and the other material being liquid-impermeable.

[0041] According to some embodiments, the one or more sections of the deformable film differ from one another in their liquid permeability, for example, the sections may differ in their composition, porosity, thickness, size, density of perforations, etc.

[0042] The liquid-permeable section is made of a liquid-permeable material. Within the context of the present disclosure, the term liquid-permeable material is intended to refer to a material (compound or composition of matter) that allows the diffusion or passage of liquid therethrough. For example, the liquid-permeable material may be perforated or porous. According to some embodiments, the liquid-permeable material may comprise one or more compounds selected from hypromellose phthalate, cellulose acetate phthalate, hypromellose acetate succinate, cellulose acetate, cellulose acetate butyrate, ethyl cellulose, polymethyl methacrylate, polyethyl acrylate, polyvinyl acrylate phthalate, polyvinyl acetate, shellac, carboxymethylethyl cellulose (CMEC), and any combination thereof.

[0043] The liquid permeable material, according to some embodiments, may further comprise at least one binder, plasticizer, pore former, emulsifier, film former, and any combination thereof.

[0044] For administration, the device is in a collapsed state, i.e., a compact configuration with a given initial volume. Once administered and exposed to appropriate conditions, as further described below, permeation of liquid through the liquid-permeable sections of the film causes the gel-forming material to swell, thereby increasing in volume and irreversibly unfolding the device to an expanded state.

[0045] According to some embodiments, the device is designed to deliver one or more active agents to a target site in the intestine by directly contacting the active agent or a composition comprising the active agent with intestinal tissue. To this end, according to some embodiments, the device can include at least one active agent-carrying element attached to at least a portion of the outer surface of at least one of the compartments, such that expansion of the device from a collapsed state to an expanded state causes expansion of the compartment, driving the active agent-carrying element toward the tissue and holding the active agent-carrying element against the tissue for a predetermined period of time, allowing delivery of the active agent to the tissue.

[0046] The term "active agent-carrying element" is intended to refer to a structure or composition capable of containing an active agent and enabling release of the active agent upon contact with intestinal tissue. The active agent-carrying element can be, for example, a layer covering at least a portion of the exterior surface of the compartment and comprising an active agent or a carrier matrix in which the active agent is dispersed or embedded. In another example, the active agent-carrying element can be a solid composition, such as a tablet or pill made of (or containing) the active agent. In other examples, the active agent-carrying element can be in the form of a gel or gel-forming matrix containing the active agent. In a further example, the active agent-carrying element can be in the form of a pressure-sensitive element designed to rupture once pressure is applied after the compartment expands while the reservoir is held against the tissue (e.g., the reservoir can be in the form of a casing / envelope that holds the active agent or a composition thereof, the casing / envelope having at least one wall configured to rupture under a predefined applied pressure).

[0047] According to some embodiments, the device is designed to deliver at least one tissue adhesive element to a target site in the intestine. Thus, according to some embodiments, the device comprises at least one tissue adhesive element attached to at least a portion of an outer surface of at least one compartment, such that expansion of the device from a collapsed state to an expanded state causes expansion of the compartment to drive the tissue adhesive element toward the tissue of the gastrointestinal tract so as to adhere at least a portion of the tissue adhesive element to the tissue.

[0048] The tissue adhesive element is intended to refer to a layer that can self-adhere to tissue, typically mucosal epithelial tissue. The adhesion of the tissue adhesive element to the tissue can be achieved by mechanical means, such as microneedles or microhooks, which can be temporarily fixed in the tissue upon application of pressure by the self-expandable core. Alternatively, the tissue adhesive element can be made of or consist of a mucoadhesive material.

[0049] In the context of this disclosure, the term tissue refers to any organ surface or biological membrane that may be typically covered by mucus or mucosa (eg, mucosal epithelial tissue).

[0050] According to some embodiments, the compartments may be identical to one another or may differ from one another (e.g., in any one of size, shape, active agent, type, size or shape of active agent carrying element and / or tissue adhesive element, rate of disintegration, etc.). According to some embodiments, the device may include one or more compartments that carry active agent carrying elements or tissue adhesive elements, while other compartments of the device may not.

[0051] By varying the size, shape, number, etc. of the compartments and the type of gel-forming material and / or tissue-adhesive element, different expansion rates, expansion shapes, and / or targeted delivery can be achieved. Varying the size, number, geometric shape, etc. of the compartments can also be used to achieve symmetrical or asymmetrical expanded shapes of the device. Varying the properties of the gel-forming material and / or deformable film can also make it possible to control the force applied by the device to tissue in its expanded state to contact the active agent-carrying element or the tissue-adhesive layer therewith. Furthermore, by folding the device to achieve a folded state and / or controlling the number and / or position of the liquid-permeable sections of the deformable film, the exposure of the gel-forming material to liquid can be controlled, and therefore the overall expansion rate of the device can be controlled.

[0052] According to some embodiments, the tissue adhesive element is a tissue adhesive layer. In some embodiments, the tissue adhesive layer is a mucoadhesive layer consisting of at least one mucoadhesive material.

[0053] The term mucoadhesive (or any linguistic variant thereof) is intended to refer to a compound or composition of matter that is capable of adhering to tissue, typically via mucus or mucosa. Mucoadhesive materials typically interact with mucus present on or secreted by tissue, e.g., by one or more interactions, such as electrostatic interactions, physical entanglement or interpenetration, diffusion, adsorption, mechanical interlocking, etc.

[0054] Mucoadhesive materials are typically polymers that can be natural, semi-synthetic, or synthetic. Non-limiting examples of mucoadhesives include tragacanth, sodium alginate, guar gum, xanthan gum, karaya gum, gellan gum, carrageenan, soluble starch, gelatin, chitosan, cellulose derivatives (methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose (NaCMC)), polyacrylic acid (PAA) polymers (carbomer, polycarbophil, etc.), polyhydroxyethylmethylacrylate, polyethylene oxide ( These include PEO (typically high molecular weight PEO), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), lectin, pectin, thiolated polymers (e.g., chitosan-iminothiolane), poly(acrylic acid)-cysteine, poly(acrylic acid) homocysteine, polyethylene glycol, chitosan-tricoglycolic acid, chitosan-thioethylamidine, alginate-cysteine, poly(methacrylic acid)-cysteine, sodium carboxymethylcellulose cysteine, and others.

[0055] In some additional embodiments, the device may include two or more types of tissue adhesive layers. Different areas of the exterior surfaces of the compartments and / or different compartments may be covered with different types of tissue adhesive layers. These different types of tissue adhesive layers may include different types of active agents.

[0056] In some additional embodiments, the tissue-facing surface of the tissue adhesive layer (or portion thereof) may be covered by a non-mucoadhesive material (layer) that may be configured to collapse to allow exposure of the mucoadhesive layer during or after expansion of the device.

[0057] The device can function to deliver at least one active agent to a target site through and / or across tissue. Thus, according to some embodiments, the tissue-adhesive element contains or carries one or more active agents. Depending on the type of active agent to be delivered (e.g., polarity, hydrophobicity / hydrophilicity, size, etc.), the active agent can be contained within or on the surface of the tissue-adhesive layer (the outer surface facing the tissue and / or the inner surface facing the gel-forming material).

[0058] In some embodiments, when the tissue adhesive layer is a mucoadhesive layer, the active agent is embedded within the mucoadhesive material, for example, the active agent can be dispersed or dissolved in the mucoadhesive material.

[0059] In other embodiments, the active agent may be encapsulated within various microparticulate or nanoparticulate structures, such as liposomes, microparticles, microcapsules, nanoparticles, or nanocapsules, which structures are distributed within the mucoadhesive material.

[0060] According to another embodiment, the active material coats at least a surface portion of the tissue adhesive layer, for example, the active material can coat at least a portion of one or both of the tissue-facing surface and the deformable film-facing surface of the tissue adhesive layer.

[0061] According to further embodiments, the active agent may be linked to the mucoadhesive material by one or more linker moieties that are susceptible to defined biological conditions, so as to allow release of the active agent therefrom once exposed to such conditions.

[0062] In some embodiments, when the tissue adhesive element (eg, tissue adhesive layer) comprises microneedles, the active agent can be embedded within the microneedles, for example, within the polymer from which the microneedles are formed.

[0063] The active agent is typically a pharmaceutically active agent. The term pharmaceutically active agent is intended to refer to a molecule, compound or composition that is safe and effective for pharmaceutical use in a subject, typically a mammal, and has a desired biological activity. The active agent can be selected from, for example, antibiotics, proteins, peptides, polypeptides, lipids, nucleic acids, hormones, steroids, antibodies, vitamins, anti-inflammatory drugs, antihistamines, antiemetics, analgesics, chemotherapeutic agents, prophylactic agents, clotting factors, radiopharmaceuticals, contrast agents, electrolytes, nutritional supplements, small molecules (with a molecular weight of less than about 1,000 Da or less than about 500 Da), etc.

[0064] In other embodiments, the active agent may be one or more microorganisms (eg, gut-friendly bacteria) and / or viruses.

[0065] In other embodiments, the active agent may be a nutraceutical compound.

[0066] The active agent can be in the form of a salt, acid addition salt, free base, hydrate, solvate, or prodrug.

[0067] The active agent may be suitable for administration to humans. In other embodiments, the active agent may be a veterinary active agent.

[0068] When the active agent is present in the tissue adhesive element or when the active agent-carrying element is present in the device, it is typically in a therapeutically effective amount. For purposes herein, the effective amount can be determined by considerations known in the art. This amount must be effective to achieve the desired therapeutic effect, depending, inter alia, on the type and severity of the disease being treated and the treatment regime. The effective amount is typically determined in a well-designed clinical trial (dose-ranging study), and those skilled in the art will know how to properly conduct such a study to determine the effective amount. As is generally known, the effective amount depends on various factors, such as the affinity of the ligand to the receptor, its distribution profile in the body, various pharmacological parameters such as half-life in the body, unwanted side effects, if any, and factors such as age and gender.

[0069] The pharmaceutically active agent may be selected to induce at least one effect, e.g., a therapeutic effect that can induce, enhance, stop, or reduce at least one effect, by treating or preventing an undesirable condition or disease in a subject. The at least one agent (substance, molecule, element, compound, entity, or combination thereof) may be selected from among therapeutic agents, i.e., agents that can induce or modulate a therapeutic effect when administered in a therapeutically effective amount.

[0070] In other embodiments, the active agent may be a diagnostic agent, i.e., an agent that allows for the diagnosis of one or more conditions or disorders. A diagnostically effective amount refers to an amount of active diagnostic agent that allows for efficient molecular imaging, depending on the type of imaging technique (e.g., PET, SPECT, etc.) used, the acquisition parameters of the particular imaging technique used, the area of ​​the body scanned, the physical condition of the subject, the purpose of the test, or any other factors apparent to one of skill in the art.

[0071] In some embodiments, the device may include at least one additional active agent that is different from the at least one active agent. The additional active agent may have a pharmaceutical activity similar to that of the active agent or a pharmaceutical activity that is different from that of the active agent.

[0072] According to some embodiments, the active agent-carrying element or tissue-adhesive element includes an additional active substance. In such embodiments, the active agent and the additional active substance can have a co-therapeutic effect, i.e., an additive or synergistic effect. For example, the additional active substance can function to increase the permeability or bioavailability of the active agent, or can increase or enhance the therapeutic effect or biological activity of the active agent.

[0073] According to other embodiments, an additional active agent may be included within the compartment, e.g., associated with the deformable film, associated with the gel-forming material, or mixed (or dispersed) in the gel-forming material. In such cases, the additional active agent may be selected to have an immediate or short-term therapeutic effect, while the active agent may be selected to have a long-term or sustained therapeutic effect.

[0074] In other embodiments, the active agent and additional active substance may be selected from agents having similar or identical therapeutic effects, for example, the active agent and additional active substance may be the same, but one contained within the active agent carrying element or tissue-adhesive layer and the other contained within a compartment, respectively.

[0075] According to other embodiments, the device comprises both an active agent-carrying element and a tissue-adhesive element containing the same or different active agents. Such an arrangement can be utilized to divide the required dose of agent so that a portion of the agent is released immediately upon expansion of the active agent-carrying element and / or adhesion to the tissue, and the remainder is slowly absorbed from the tissue-adhesive layer once adhered to the tissue. In another example, the active agent and the additional active substance can have similar effects, with the additional active substance having an immediate effect and the active agent having a long-term or sustained effect.

[0076] In other words, the device can be used to simultaneously administer two or more pharmaceutically active agents, i.e., can be administered one after the other simultaneously.Simultaneous administration allows one agent in the combination to be administered within a certain period (for example, 5 minutes, 10 minutes, or even several hours) after the other agent, provided that the circulating half-life concentration of the first administered agent in the combination is present in a therapeutically effective amount at the same time as the other agent that is subsequently administered.The time delay between the administration of agents can vary depending on the exact nature of the agents, the interaction between the individual agents, their respective half-lives, and other factors that can be easily recognized by skilled technicians.

[0077] In further embodiments, the active agent and the additional substance can have different effects, and the device is designed for sequential administration, meaning that there is a time lag between when one agent is administered and when the other agent is administered. Such a time lag may be short or may be significant. That is, the first administered agent may no longer be present in the bloodstream in therapeutically effective amounts (or may only be present in subclinical amounts) by the time the second (or subsequent) agent is administered.

[0078] In some embodiments, the tissue-adhesive element may further comprise one or more additional components, such as emulsifiers (surfactants) such as poloxamer or carbomer, stabilizers such as carboxymethylcellulose, suspending agents such as cellulose or talc, acidifying agents such as citric acid or ascorbic acid, viscosity-increasing agents such as carbopol or polyethylene oxide, effervescent agents such as sodium bicarbonate or ammonium carbonate, solubilizing agents such as lecithin, antimicrobial preservatives such as sorbic acid or potassium sorbate, antioxidants such as alpha tocopherol or butylhydroxyanisole, release modifiers such as Tween 80 or sodium lauryl sulfate, coating agents such as ethyl cellulose or cellulose acetate, binders such as hydroxypropyl cellulose or polyvinylpyrrolidone, stiffening agents such as stearic acid or wax, plastic agents such as diethyl phthalate or triethyl citrate, and others.

[0079] As previously mentioned, the device changes from the collapsed state to the expanded state as a result of the expansion of the gel-forming material contained within the compartment.

[0080] The term gel-forming material is intended to refer to a compound or composition that can absorb a liquid(s) and thereby form a three-dimensional volumetric network of molecules. Gel-forming materials can form physical gels (i.e., gels in which the molecules are held within the network by physical forces) or chemical gels (i.e., gels in which the molecules are chemically bonded to each other to form a network structure). In some embodiments, the gel-forming material comprises one or more gel-forming compounds. In other embodiments, the gel-forming material comprises one or more additives.

[0081] According to some embodiments, the gel-forming material comprises one or more polymers. According to other embodiments, the gel-forming material may be charged or neutral.

[0082] According to some other embodiments, the gel-forming material is crosslinked or crosslinkable. Without wishing to be bound by theory, the molecular weight and degree of crosslinking of the gel-forming material significantly affect the consistency (e.g., hardness or rigidity) of the gel, as well as its rheological properties (e.g., viscosity). Thus, varying molecular weights and degrees of crosslinking are some of the parameters that can be used to control the behavior of the zones, and thereby the deployment rate and / or expansion size of the device.

[0083] In some embodiments, the gel-forming material may be selected from gelatin, alginate, chitosan, dextran, collagen, hyaluronic acid, polyglutamic acid, elastin, calcium polycarbophil, acrylamide, styrene maleic anhydride, polyethylene oxide, polyacrylic acid, polyethylene glycol, carboxymethylcellulose, polyvinylpyrrolidone, sodium polyacrylate, hydroxypropyl methylcellulose, or any combination or composition thereof.

[0084] In some embodiments, the gel-forming material is a composition comprising at least one charged gel-forming compound and at least one compound having an opposite charge, which form a PEC (polyelectrolyte complex) upon liquid adsorption. In some embodiments, the at least one charged gel-forming compound is selected from polyvinyl acetate diethylaminoacetate (AEA), polylysine, chitosan, polymethacrylate (Eudragit E), and polyarginine. In other embodiments, the oppositely charged compound is selected from gelatin, hyaluronic acid, sodium polyacrylate, heparin, polyacrylic acid (carbomer), alginate, pectin, and carboxymethylcellulose.

[0085] In some other embodiments, the gel-forming material is at least one superabsorbent polymer (SAP). The term superabsorbent polymer refers to a polymer (typically crosslinked) or polymer composition that can absorb and retain large amounts of liquid, such as water (or liquids containing water), relative to the dry mass of the polymer. Non-limiting examples of SAPs are polyethylene glycol (PEG), polyglutamic acid (PGA), polyacrylamide, alginate, dextran, polyacrylic acid, carboxymethylcellulose (CMC), pullulan, starch, and any combination thereof.

[0086] In some other embodiments, the gel-forming material has a swelling ratio (under conditions of gastrointestinal pH at 37° C. for 1 hour) of about 10-100 times (w / w).

[0087] The term swelling ratio refers to the degree of expansion of a gel-forming material between its state before absorbing liquid (i.e., in dry or semi-dry form) and its state after absorbing the maximum possible amount of liquid. The swelling ratio is determined on a weight basis and calculated according to the following equation: [(wet weight) - (dry weight)] / [(dry weight)].

[0088] The gel-forming material may be in the form of a gel film (i.e., a substantially continuous layer of gel). According to some embodiments, the gel-forming material is in the form of gel particles. According to other embodiments, the gel-forming particles are in the form of a gel film, with the gel particles embedded within a matrix to form the film. In some embodiments, the gel-forming particles within the gel film are arranged in substantially a monolayer of gel particles.

[0089] According to yet other embodiments, the gel-forming material may be in the form of a powder. In some embodiments, when the gel-forming material is in the form of gel particles, the average diameter of the particles of the gel-forming material may range from about 100 μm to about 300 μm.

[0090] According to some embodiments, each of the compartments may contain a different gel-forming material, while in some other embodiments, all of the compartments may contain the same gel-forming material.

[0091] Because the compartments are made of deformable film segments or continuous deformable film, the device can be folded in various ways to reduce its size and achieve a collapsed state. Thus, the device can be easily administered to a patient in need thereof into a target organ or organ cavity. In some embodiments, the device is enclosed in its collapsed state in a self-administerable capsule and swallowed by the patient.

[0092] In some embodiments, when in the collapsed state, the device is configured to fold in a primary collapsed configuration and undergo unfolding during transition from the collapsed state to the expanded state. In other words, the device may be collapsed to assume a collapsed state having an overall reduced size or overall reduced volume. When liquid penetrates the liquid-permeable section of the film, the gel-forming material begins to swell and increase in volume. This, in turn, applies a force to the deformable film, and due to its flexibility and / or deformability, the film simultaneously unfolds and expands to assume the expanded state of the device.

[0093] According to some embodiments, to further assist in unfolding, the device comprises at least one unfolding unit disposed between the folded sections of the device when in the primary folded configuration, the unfolding unit configured to expand upon contact with liquid to assist in unfolding the device.

[0094] According to some embodiments, the deployment unit includes a liquid-permeable casing and at least one gas-forming material contained therein. The liquid-permeable casing of the deployment unit allows liquid to penetrate therein, thereby reacting with the gas-forming material and rapidly forming gas species. The liquid-permeable casing is typically formed as a closed structure. Thus, when gas rapidly expands the casing, a gas-filled "balloon" is obtained, which pushes open the pleats of the device. The expansion of the deployment unit, along with the expanding gel-forming material, assists in unfolding the device into the unfolded configuration.

[0095] A gas-forming material is a compound or composition that undergoes a chemical reaction in the presence of water (either a reaction of a compound with water or a reaction between components of the composition that is facilitated by exposure to water), where at least some of the reaction products are gaseous. An example of such a material can be a solid composition of an acid and a base (e.g., a composition containing citric acid and a metal bicarbonate), which, once exposed to water, can dissolve and react with each other to produce CO2 as one of the reaction products.

[0096] In some embodiments, the device is enclosed by an enteric envelope when the device is in the primary folded configuration. According to some embodiments, the enteric envelope is configured to hold the device in its primary folded configuration, for example, by forming the enteric envelope to have dimensions similar to those of the device when in its primary folded configuration. According to some embodiments, the enteric envelope is securely attached over the device in its primary folded configuration, with substantially no space between the enteric envelope and the device.

[0097] The term enteric material is intended to refer to a compound or composition that is configured to be disintegrated or solubilized by liquids only in a defined pH range. For example, and preferably, an enteric material is stable (i.e., maintains its physical and chemical structure) when exposed to an acidic environment (e.g., in the stomach) and is solubilized by more alkaline liquids (such as those in the intestines).

[0098] The enteric envelope functions to maintain the device in its folded configuration after ingestion until appropriate conditions are reached in the gastrointestinal tract (e.g., appropriate pH) that will allow the enteric envelope to degrade, exposing and allowing the device to unfold and expand.

[0099] To achieve further compactness in the collapsed state, the device, in some embodiments, has a secondary rolled configuration whereby the device, folded into its primary folded configuration, is further rolled about its axis and is configured to undergo simultaneous unrolling and unfolding during transition from the collapsed state to the expanded state.

[0100] According to some embodiments, the device may be wrapped in an enteric envelope when in its secondary folded configuration. Alternatively, the device may be wrapped by a first enteric envelope when in its primary folded configuration and by a second enteric envelope when in its secondary folded configuration. In other words, the device may be wrapped by a first enteric envelope after folding it into its primary folded configuration, and then folded or rolled into its secondary folded configuration and wrapped by a second enteric envelope to maintain the device in its secondary folded configuration.

[0101] According to other embodiments, the device may first be rolled and then folded to assume the folded state.

[0102] To prevent undesired or premature deployment of the device and / or to enable delivery of the device to the appropriate target site, the device may comprise a biodegradable shell that encapsulates the device in its folded state. Thus, the biodegradable shell is selected to degrade upon exposure to appropriate biological conditions (e.g., pH, the presence of certain chemical compounds, etc.).

[0103] If the device is typically intended for oral administration and is designed to be deployed in the intestine, the biodegradable shell may be made from or coated with an enteric coating.

[0104] In some embodiments, the device is an ingestible device, intended for deployment in, for example, the stomach or intestine. Therefore, such devices are typically enclosed within a degradable shell within the gastrointestinal track, enclosing the device in its folded state. For deployment within the intestine, the shell may be designed or selected to provide a safe first passage through the stomach and biodegrade only upon exposure to defined conditions within the intestine. In some embodiments, the gastrointestinal track degradable shell is designed to disintegrate as a function of the pH of the environment, thereby enabling deployment in the desired portion of the intestine. For example, different portions of the gastrointestinal tract are known to have different pH values. While the stomach typically has a pH of 1.5 to 3.5, the pH of the duodenum is typically 6 and gradually increases to approximately 7.4 in the small intestine (until the terminal ileum is reached). The pH drops to 5.7 in the cecum, but gradually increases again, reaching pH 6.7 in the rectum. Therefore, by utilizing a gastrointestinal track degradable shell that degrades at a predetermined pH value (or range of values), deployment of the device in the desired portion of the gastrointestinal track can be achieved.

[0105] The biodegradable shell can be, for example, a capsule.

[0106] In some embodiments, the device has two shells, one encasing the other. The outer shell, which is in the form of a capsule to facilitate swallowing of the device, is designed to be degradable in the stomach environment. The second, inner shell can be a coating or encapsulation layer that coats / encapsulates the device and is configured to maintain the device in its folded state for a predetermined period before unfolding. For example, the inner shell can be made of an enteric material, thus preventing the device from unfolding in the stomach and allowing it to unfold only upon entry into the intestine.

[0107] The device can be used to deliver at least one active agent to a target site, but can also lack an active agent or contain only the active agent in a compartment. For example, the device can be utilized to deliver a patch to a tissue wall, e.g., to temporarily block substances passing through mucosal / epithelial tissue (both to and / or from the lumen), or to cover a perforation or ulcer in the tissue.

[0108] As noted above, in some embodiments, the tissue-adhesive element may not contain an active agent, but the compartments and / or gel-forming material may contain an active substance / drug, such as an analgesic or anti-inflammatory agent, which can be released during the breakdown of the gel-forming material to provide a desired local effect relatively quickly after administration.

[0109] In the expanded state, the device may have a circular, polygonal, or irregular shape. The device may be designed to assume a three-dimensional (3D) shape in its expanded state that generally conforms to the shape of at least a section of the lumen or cavity into which it expands (or deploys).

[0110] In other embodiments, in the expanded state, the device may have an annular or ring-like shape.

[0111] In some other embodiments, the device can be configured to assume a substantially cylindrical shape when in the expanded state to define a hollow lumen. Such a hollow cylindrical shape prevents the formation of an obstruction in a hollow organ or organ cavity when the device is in its expanded state and allows liquids or solids to pass through the organ while the device is deployed therein.

[0112] According to some embodiments, the device is in the form of a sleeve, the sleeve walls being comprised of a deformable film, the compartments being defined along the circumference of the sleeve, and the tissue-adhesive layer coating at least a portion of the outer surface of the compartments and facing outward from the surface of the sleeve. Typically, the compartments are elongated along the longitudinal axis of the sleeve and are disposed parallel to one another along the circumference of the sleeve.

[0113] According to some embodiments, one or more separation layers are disposed between one or more of the folds of the device to prevent the outer layer of the device from adhering to itself when the device is in its primary and / or secondary folded configuration. These one or more separation layers may be adhered to the device at one or more adhesive locations to maintain their position and function when the device is folded into its primary and / or secondary folded configuration. Alternatively, the separation layer(s) can be located between the folds without being secured to the device (e.g., by placing such a layer on the device prior to folding and then folding the device together with the separation layer(s) to form the primary and / or secondary folded configuration).

[0114] Various components of the device, such as the liquid-permeable section, gel-forming material, etc., can be biodegradable. The term biodegradable is intended to refer to any type of disintegration of the device caused by exposure to suitable biological conditions after administration and expansion. This term encompasses mechanical failure, chemical or physical degradation, or any other type of disruption of the integrity of the device that occurs as it passes through the digestive tract to exit the body.

[0115] In another aspect, the present disclosure provides an ingestible self-expanding device configured to deliver at least one active agent to tissue, the device having a collapsed state and an expanded state; and two or more self-expandable compartments connected to one another by connection zones, each compartment formed from two substantially water-insoluble deformable film sections joined to one another at a peripheral segment of the compartment by at least one water-disintegrable sealing composition to define a seal zone, each seal zone being a layered structure of the water-insoluble deformable film with at least one water-disintegrable sealing composition layer sandwiched therebetween that joins the water-insoluble deformable film sections to one another at a peripheral segment; the two film portions defining an enclosed space of compartments therebetween in the area sealed by the peripheral segment, each compartment having one or more liquid permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to swell upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state; a compartment, wherein the water-disintegrable sealing composition has water solubility configured to provide mechanical stability to the seal zone during transition of the device from a collapsed state to an expanded state and to provide controlled collapse of the seal zone after the device is expanded to the expanded state, thereby causing loss of integrity of the compartment and / or device after deployment; at least one active agent carrying element adhered to at least a portion of an exterior surface of at least one of the compartments; Expansion of the device from the collapsed state to the expanded state causes the compartments to expand, driving the active agent carrying element toward the tissue and holding the active agent carrying element against the tissue for a predetermined period of time, allowing delivery of the active agent from the active agent carrying element to the tissue.

[0116] According to another aspect, the present disclosure provides an ingestible self-expanding device configured to adhere a tissue adhesive layer to tissue, the device having a collapsed state and an expanded state; two or more self-expandable compartments connected to one another by connection zones, each compartment formed from two substantially water-insoluble deformable film sections joined to one another at a peripheral segment of the compartment by at least one water-disintegrable sealing composition to define a seal zone, each seal zone being a layered structure of the water-insoluble deformable film with at least one water-disintegrable sealing composition layer sandwiched therebetween that joins the water-insoluble deformable film sections to one another at a peripheral segment; the two film portions defining an enclosed space of compartments therebetween in the area sealed by the peripheral segment, each compartment having one or more liquid permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to swell upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state; a compartment, wherein the water-disintegrable sealing composition has water solubility configured to provide mechanical stability to the seal zone during transition of the device from a collapsed state to an expanded state and to provide controlled collapse of the seal zone after the device is expanded to the expanded state, thereby causing loss of integrity of the compartment and / or device after deployment; at least one tissue-adherent layer coating at least a portion of an exterior surface of at least one of the compartments; Expansion of the device from the collapsed state to the expanded state causes expansion of the compartments, driving the tissue adhesive layer towards the tissue to adhere at least a portion of the tissue adhesive layer to the tissue.

[0117] Another aspect of the present disclosure provides an ingestible self-expanding arrangement comprising an ingestible self-expanding device having a collapsed state and an expanded state, and at least one deployment unit having an unexpanded state and an expanded state. The ingestible self-expanding device comprises two or more self-expandable compartments connected to each other by a connection zone, each compartment formed from two substantially water-insoluble deformable film portions joined to each other at peripheral segments of the compartment by at least one water-collapsible sealing composition to define a sealing zone, each sealing zone being a layered structure formed by water-insoluble deformable film sandwiching between them at least one layer of water-collapsible sealing composition that joins the water-insoluble deformable film to each other at the peripheral segments, the two film portions defining a sealed space between them in the area sealed by the peripheral segments, each compartment having one or more liquid-permeable sections and a gel-forming material within the sealed space, the gel-forming material configured to swell upon contact with liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state. When in the collapsed state, the device is folded in a primary folded configuration, and at least one deployment unit is disposed between the folds of the device when in the primary folded configuration and is configured to switch from a non-inflated state to an inflated state upon contact with a liquid, allowing the device to unfold.

[0118] According to another aspect, the present disclosure provides an ingestible arrangement for delivering at least one active agent to a tissue, the arrangement comprising: an ingestible self-expanding device having a collapsed state and an expanded state, and at least one deployment unit having a non-expanded state and an expanded state; This ingestible, self-expanding device two or more self-expandable compartments connected to one another by connection zones, each compartment formed from two substantially water-insoluble deformable film sections joined to one another at a peripheral segment of the compartment by at least one water-disintegrable sealing composition to define a seal zone, each seal zone being a layered structure of the water-insoluble deformable film sandwiched therebetween with at least one layer of water-disintegrable sealing composition joining the water-insoluble deformable film sections to one another at the peripheral segment; The two film portions define an enclosed space therebetween in the area enclosed by the peripheral segment; compartments, each compartment having one or more liquid-permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to expand upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state; at least one active agent carrying element adhered to at least a portion of an exterior surface of at least one of the compartments, an active agent carrying element, wherein expansion of the device from the collapsed state to the expanded state causes expansion of the compartment, driving the active agent carrying element toward the tissue, holding the active agent carrying element against the tissue for a predefined period of time, and enabling delivery of an active agent from the active agent carrying element to the tissue; In the collapsed state, the device is folded in a primary folded configuration, and at least one deployment unit is disposed between the folded sections of the device when in the primary folded configuration and is configured to switch from a non-expanded state to an expanded state upon contact with a liquid, allowing deployment of the device.

[0119] According to another aspect, the present disclosure provides an ingestible arrangement for adhering a tissue adhesive layer to tissue, the arrangement comprising: an ingestible self-expanding device having a collapsed state and an expanded state, and at least one deployment unit having a non-expanded state and an expanded state; This ingestible, self-expanding device two or more self-expandable compartments connected to one another by connection zones, each compartment formed from two substantially water-insoluble deformable film sections joined to one another at a peripheral segment of the compartment by at least one water-disintegrable sealing composition to define a seal zone, each seal zone being a layered structure of the water-insoluble deformable film sandwiched therebetween with at least one layer of water-disintegrable sealing composition joining the water-insoluble deformable film sections to one another at the peripheral segment; The two film portions define an enclosed space therebetween in the area enclosed by the peripheral segment; compartments, each compartment having one or more liquid-permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to expand upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state; a tissue-adherent layer coating at least a portion of an exterior surface of at least one of the compartments, a tissue adhesive layer, wherein expansion of the device from the collapsed state to the expanded state causes expansion of the compartments and drives the tissue adhesive layer toward the tissue to adhere at least a portion of the tissue adhesive layer to the tissue; In the collapsed state, the device is folded in a primary folded configuration, and at least one deployment unit is disposed between the folded sections of the device when in the primary folded configuration and is configured to switch from a non-expanded state to an expanded state upon contact with a liquid, allowing deployment of the device.

[0120] In other words, an arrangement including a self-deployable device and at least one deployment unit is another aspect of the present disclosure. The combination of the device and deployment unit is referred to herein as an ingestible arrangement.

[0121] According to some embodiments, the deployment unit includes a liquid-permeable casing and at least one gas-forming material contained therein, wherein contact of the gas-forming material with a liquid releases gas for inflating the deployment unit.

[0122] Typically, the activation timing of the gas-forming material is faster than the activation timing of the gel-forming material, so that the deployment unit is first inflated to at least partially unfold the folded device, and then the gel-forming material is inflated to further unfold the device into the unfolded configuration.

[0123] According to some embodiments, the arrangement comprises a single deployment unit.

[0124] According to another embodiment, the arrangement comprises two or more deployment units. The two or more deployment units may be attached to each other or may be separate from each other. The two or more deployment units may be identical to each other or may differ from each other in at least one of the following: liquid permeability of the liquid permeable casing, type of gas-forming material, amount of gas-forming material, size and / or shape.

[0125] In some embodiments, at least one deployment unit is adhered to the self-expanding device, while in other embodiments, at least one deployment unit is not connected to the self-expanding device in the configuration.

[0126] The seal zone has water solubility configured to provide mechanical stability to the seal zone during the transition of the device from the collapsed state to the expanded state and to provide controlled collapse of the seal zone after the device is expanded to the expanded state, thereby causing loss of compartment and / or device integrity after deployment.

[0127] According to another of its aspects, the present disclosure provides a method for delivering at least one active agent to tissue of a subject in need thereof, the method comprising administering to the subject a self-expanding device as disclosed herein encapsulated in a biodegradable shell.

[0128] According to a further aspect, there is provided a method for long-term or sustained delivery of at least one active agent to tissue in a subject in need thereof, the method comprising administering to the subject a self-expanding device as disclosed herein encapsulated in a biodegradable shell, such that the device of the present disclosure forms a reservoir of active agent for long-term delivery to the target site.

[0129] A further aspect provides a method for long-term or sustained delivery of at least one active agent to tissue of a subject in need thereof, the method comprising administering to the subject a self-expanding device as disclosed herein encapsulated in a biodegradable shell.

[0130] According to yet another aspect, there is provided a method of adhering a tissue adhesive layer to tissue of a subject in need thereof via a mucosa, the method comprising administering to the subject a self-expanding device as disclosed herein encapsulated in a biodegradable shell.

[0131] As used herein, the term about is intended to encompass a ±10% deviation from a specifically stated value of a parameter such as concentration, time, etc.

[0132] Whenever a numerical range is given herein, it is intended to include any recited numbers (fractional or integer) within the stated range. The phrases "ranging between" a first and a second stated number and "ranging between" a first stated number and a second stated number are used interchangeably herein and are intended to include the first and second stated numbers and all fractional and integer numbers therebetween.

[0133] Unless the context requires otherwise, the word "comprise", as well as variations such as "comprises" or "comprising", will be understood to imply, for example, the inclusion of a stated integer or step or group of integers or steps, but not the exclusion of any integer or step or group of integers or steps.

[0134] It should be noted that in general, the term "at least one" as applied to any component of a device or arrangement of the present disclosure should be read to encompass one, two, three, four, or more different occurrences of that component in the device or arrangement.

[0135] It should be understood that certain features of the present disclosure, which are for clarity described in the context of separate embodiments, may also be provided in combination in a single embodiment. Rather, for brevity, various features of the invention that are described in the context of a single embodiment may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments should not be considered essential features of those embodiments, unless the embodiment is inoperable without those elements.

[0136] In order to better understand the subject matter disclosed herein and to illustrate how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0137] [Figure 1A] 1 is a schematic diagram of an exemplary device configured as a sleeve, in front perspective view, according to one embodiment of the present disclosure; FIG. [Figure 1B] 1 is a schematic diagram of an exemplary device according to one embodiment of the present disclosure, the device being configured as a sleeve, and a top cross-sectional view taken across line II. FIG. [Figure 1C] FIG. 1 is a schematic diagram of an exemplary device according to one embodiment of the present disclosure, the device being configured as a sleeve and showing the device in an expanded configuration. [Figure 1D] FIG. 1 is a schematic front perspective view of another exemplary device according to an embodiment of the present disclosure, in which an active agent carrying element is utilized in place of a tissue adhesive element. [Figure 1E] FIG. 2 is a schematic diagram of another exemplary device according to an embodiment of the present disclosure, in which an active agent carrying element is utilized in place of a tissue adhesive element, and is a top cross-sectional view taken across line II-II. [Figure 1F] FIG. 10 is a schematic diagram of another exemplary device according to an embodiment of the present disclosure, utilizing an active agent carrying element instead of a tissue adhesive element, showing the device in an expanded configuration. [Figure 2A] A separate, self-expandable compartment is defined between the two seal zones. [Figure 2B] FIG. 10 is a top cross-sectional view of a device according to an embodiment of the present disclosure, showing the seal zone. [Figure 3] FIG. 10 is a schematic top view of a device according to another embodiment of the present disclosure, in which compartments are made from separate pieces of deformable film. [Figure 4A] FIG. 10 is a schematic diagram of a device according to another embodiment of the present disclosure, in which the compartments are made from separate sections of deformable film. [Figure 4B] FIG. 10 is a schematic diagram of a device according to another embodiment of the present disclosure, in which the compartments are made from separate sections of deformable film. [Figure 4C] FIG. 10 is a schematic diagram of a device according to yet another embodiment of the present disclosure, in which the compartments are made from separate sections of deformable film. [Figure 4D] FIG. 10 is a schematic diagram of a device according to yet another embodiment of the present disclosure, in which the compartments are made from separate sections of deformable film. [Figure 5A] 1B illustrates various primary folding configurations of the device of FIG. 1A. [Figure 5B]1B illustrates various primary folding configurations of the device of FIG. 1A. [Figure 5C] 1B illustrates various primary folding configurations of the device of FIG. 1A. [Figure 5D] FIG. 1 is a top view showing a primary folding device wrapped in an enteric envelope. [Figure 5E] FIG. 1 is a side view showing a primary folding device enclosed in an enteric envelope. [Figure 5F] 1 shows a temporary folded device enclosed in an enteric envelope and then enclosed in a degradable shell. [Figure 6A] 1 illustrates an exemplary primary folded configuration of a device including a deployment unit in an uninflated state. [Figure 6B] 1 illustrates an exemplary primary folded configuration of a device including a deployment unit in an expanded state. [Figure 6C] 10 illustrates another exemplary primary folded configuration of a device including a deployment unit in an uninflated state. [Figure 6D] 10 illustrates another exemplary primary folded configuration of a device including a deployment unit in an expanded state. DETAILED DESCRIPTION OF THE INVENTION

[0138] The following describes exemplary devices according to the present disclosure. While certain examples show the devices as being substantially symmetrical, it should be understood that the devices may also be asymmetrical or of any other shape. Furthermore, the elements of the devices are not drawn to scale for ease of illustration. Furthermore, while the exemplary devices are shown having active agent-carrying or tissue-adhesive elements, it should be understood that similar devices that do not include such elements are also included within the scope of the examples.

[0139] 1A illustrates a self-expanding device in a collapsed (unexpanded) state according to an embodiment of the present disclosure. Device 100 of FIGS. 1A-1C has a generally cylindrical, sleeve-like shape and includes a plurality, in this case six, self-expandable compartments, collectively designated 102, formed from a substantially water-insoluble deformable film 104. While six compartments are shown in this example, it should be understood that any number of compartments may be utilized, for example, 2, 3, 4, 5, 6, 7, 8, or even more compartments.

[0140] In this embodiment, the entire sleeve is constructed from two overlapping layers of substantially water-insoluble deformable film, with liquid-permeable sections 106 to allow liquid to enter the compartments. The deformable films are connected to each other by sealing zones 108 along the periphery of the compartments, which in this embodiment also constitute connection zones connecting adjacent compartments 102. However, it should be understood that the sealing zones can also be part of larger connection zones that connect the compartments and space them from each other (not shown).

[0141] Because the films are adhered to each other only at the seal zones (by a water-disintegrating sealing composition, as described below), the compartments define a sealed space surrounding the gel-forming material 110. The gel-forming material 110 is activated when liquid penetrates the compartments 102 through the sections 106, causing the gel-forming material to expand and switch the device from the collapsed state (shown in FIGS. 1A-1B) to the expanded state shown in FIG. 1C. A tissue-adhesive layer 112 is located on the outer surface of each compartment 102 (i.e., the surface of the film 104 facing outward from the compartment). The tissue-adhesive element 112 can be, for example, in the form of a tissue-adhesive layer. As described above, the tissue-adhesive element 112 can include one or more active agents to be delivered to the tissue. Also, as described above, the device can lack the tissue-adhesive element 112, for example, as a device configured to deliver an active agent present on the surface of the compartment or as a device configured to temporarily apply pressure to the tissue (when the device is in the expanded state).

[0142] The tissue adhesive element 112 may be provided as a patch that is applied (e.g., attached) to the film 104 over the compartments 102. For example, if the tissue adhesive element is a mucoadhesive layer, the patch may include the mucoadhesive material layered over a backing layer (not shown) that allows the patch to be attached or adhered onto the exterior surface of the compartment and provides support for the mucoadhesive material. Alternatively, the mucoadhesive material may be first applied to specific locations on the film 104, followed by forming compartments 102 in locations corresponding to the areas of the film that include the mucoadhesive material, thereby forming a multi-layer film structure.

[0143] 1C shows the device in an expanded configuration, i.e., after exposure to a liquid that causes the gel-forming material to expand, thereby expanding the device. The expansion of the device brings the tissue-adhesive elements into proximity with the tissue and is held against the tissue by the increased volume of the compartment, thereby adhering the tissue-adhesive elements to the tissue.

[0144] Another configuration of the device shown in FIGS. 1D-1F is a device 100' similar to the device of FIGS. 1A-1C, but instead of tissue adhesive layer 112, device 100' includes an active agent carrying element 113.

[0145] Visible in Figure 1D is device 100', in which active agent carrying element 113 is adhered to self-expandable compartment 102, which is comprised of a substantially water-insoluble, deformable bilayer film 104. Section 106 is liquid permeable, allowing liquid to enter compartment 102 and react with gel-forming material 110, thereby expanding compartment 102 and transforming the device from a collapsed state (Figure 1E) to an expanded state (Figure 1F). Similar to device 100, in device 100', the deformable films are connected to each other along the periphery of the compartment by seal zone 108.

[0146] 1F, when the device transitions to the expanded state, the expansion of compartment 102 increases its volume, driving active agent carrying element 113 toward the tissue, e.g., the wall of the intestinal tract 113. The change in volume brings active agent carrying element 113 into proximity with tissue 115 until active agent carrying element 113 contacts tissue 115. Due to its volumetric state, active agent carrying element 113 is held against the tissue, allowing delivery of the active agent carried by element 113 to the tissue, so long as device 100 maintains its integrity in the expanded state.

[0147] 2A is an enlarged cross-sectional view of one of the compartments (of devices 100 and 100') showing the structure of the seal zone. Compartment 102 is defined between portions of film 104 that are attached to one another at seal zone 108 along the periphery of the compartment. Seal zone 108 consists of at least one water-disintegrable sealing composition 114 disposed as a layer between peripheral segments of film 104, thereby forming an enclosed space that defines the interior of the compartment and encloses gel-forming material 110.

[0148] The water-disintegrable sealing composition comprises at least one first hydrophilic material and at least one second hydrophilic material that differ in hydrophilicity and water solubility.

[0149] The first hydrophilic material is less hydrophilic and less soluble than the second hydrophilic material. The first hydrophilic material is selected to be chemically and / or thermodynamically compatible with the water-insoluble deformable film due to its low hydrophilicity. Such compatibility allows peripheral segments of the water-insoluble deformable film to be joined together with a water-collapsible seal composition. The first hydrophilic material is selected to allow at least partial dissolution or physical integration into the water-insoluble deformable film portion during formation of the seal zone (e.g., by heat welding, ultrasonic welding, solvent bonding, etc.), thereby allowing a continuous interface between the water-insoluble deformable film portion and the water-collapsible seal composition. This compatibility therefore allows for the formation of a sealed compartment having a seal zone that maintains mechanical integrity despite changes in the compartment's volume as it transitions between a collapsed state and an expanded state.

[0150] The first hydrophilic substance typically undergoes chemical or physical disintegration when exposed to the appropriate pH conditions in the intestine, typically a pH of about 6 to 7. Because the first hydrophilic material is selected to react when exposed to defined conditions in the intestine, such selection can further control the disintegration of the device after ingestion, preventing undesired disintegration as the device passes through the stomach, while still allowing disintegration under the pH conditions of the intestine.

[0151] However, due to its low solubility and limited exposure to water due to the structure of the seal zone (i.e., the limited surface area of ​​the water-disintegrable seal composition layer exposed to water), a suitable environment is required for disintegration.

[0152] To achieve this favorable collapse environment, the water-collapsible sealing composition comprises a second hydrophilic material with a higher hydrophilicity. The second hydrophilic material functions to rapidly absorb and capture water that diffuses into the seal zone, thereby creating an environment that supports the solubilization of the first hydrophilic material, allowing the seal zone to collapse and the loss of device integrity. Due to its higher hydrophilicity, the second hydrophilic material can also control the supply of water to the seal zone after deployment, thereby controlling the exposure of the first hydrophilic material to water and further controlling the initiation of its collapse.

[0153] The combination of the first and second hydrophilic materials allows for greater control over the rate of disintegration of the seal zone. Because the water-insoluble film segments sandwich the water-disintegrating seal composition and limit water diffusion through the film segments, a relatively small amount of water can penetrate the seal zone. The second hydrophilic material can quickly absorb and capture water that diffuses into the seal zone, thereby controlling the exposure of the first hydrophilic material to water and solubilizing it. Because the first hydrophilic material functions to form bonds between the two water-insoluble film segments, increased water absorption by the second hydrophilic material provides the appropriate conditions for the first hydrophilic material to solubilize, thereby causing the seal zone to disintegrate and the compartment and / or device to lose its integrity. By balancing the selection of the first and second hydrophilic materials, different disintegration onsets and disintegration rates can be achieved.

[0154] FIG. 2B is a cross-sectional view of the device of FIGS. 1A-1B, showing the formation of compartments between the seal zones. It should be understood that the same compartment and seal zone structure applies to the device of FIGS. 1D-1E. Because the device has a typical closed configuration, the layer 114 of water-collapsible sealing composition is sandwiched between films 104, significantly limiting the exposure of the water-collapsible sealing composition to liquids. Therefore, the second hydrophilic material, which promotes water absorption into the seal zone, allows increased water absorption into the seal zone, allowing the seal zone to collapse due to dissolution of the first hydrophilic material.

[0155] During operation, after ingestion and exposure to appropriate conditions, the device undergoes a series of changes. Typically, the device is in a folded configuration and is encased in a biodegradable shell, e.g., capsule 118 (illustrated in FIG. 5F). After the device is administered, e.g., orally, biodegradable capsule 118 passes through the stomach and disintegrates upon exposure to suitable conditions in the intestine, thus exposing device 100. As mentioned above, in some configurations, biodegradable capsule 118 disintegrates in the stomach, and the device is encapsulated / coated with an enteric layer 122 (FIGS. 5E-5F) that protects the device as it passes through the stomach and is designed to disintegrate upon exposure to suitable conditions in the intestine. Note, however, that in other configurations, enteric layer 122 may be absent. The enteric layer typically includes or is formed from one or more enteric polymers.

[0156] Upon disruption of the capsule 118 (or enteric layer), intestinal fluid penetrates the liquid-permeable section of the deformable film 104 of the compartment 102, causing the gel-forming material 110 contained therein to expand. The expansion of the gel-forming material causes the compartment to expand and the film to deform, forcing the device to assume its expanded state. In the expanded state, the expansion of the gel-forming material exerts a force on the film 104 against the tissue at the target site, forcing the tissue-adhesive element 112 to contact and adhere to the tissue ( FIG. 1C ) or hold the active agent-carrying element 113 against the tissue 115 as long as the device maintains its integrity in the expanded state ( FIG. 1F ). Thus, the transition of the device from the collapsed state to the expanded state drives the tissue-adhesive element 112 (e.g., the mucoadhesive layer) or active agent-carrying element 113 associated with the compartment toward the tissue and into intimate contact with it under the application of force (applied by the expanded gel-forming material).

[0157] After expansion, the water-disintegrating sealing composition of the sealing zone 108 absorbs water from the environment, causing a controlled collapse of the sealing zone 108, resulting in loss of compartment integrity (i.e., degradation or disintegration) and fragmentation of the device, resulting in expulsion from the target site. Once the compartment loses its integrity, the gel-forming material 110 is expelled from the target site by intestinal peristalsis, while the tissue-adhesive element remains adhered or attached to the tissue. Thus, if the tissue-adhesive element 112 contains an active agent, the active agent contained within the mucoadhesive element is delivered to the tissue during the period that the tissue-adhesive element remains adhered to the tissue.

[0158] As tissue is routinely sloughed off from the intestinal wall every few hours, tissue sloughing also results in the separation and disintegration of the tissue adhesive elements and the expulsion of the tissue adhesive layer from the intestine.

[0159] Alternatively, if the device consists of an active agent carrying element 113, loss of compartment integrity will result in cessation of contact between the active agent carrying element 113 and tissue, followed by expulsion of the device fragments from the target site.

[0160] 3 provides another exemplary structure of a device according to an embodiment of the present disclosure. The device 200 is composed of individual portions 204 of a water-insoluble deformable film, arranged in overlapping pairs to form compartments and attached to one another along their periphery to form a seal zone 208 and a compartment space holding a gel-forming material (not shown). Each film portion 204 includes at least one liquid-permeable portion 206, allowing water to pass into the compartment to activate the gel-forming material at the target site, thereby switching the device from its collapsed state to its expanded state (by expansion of the gel-forming material within the compartment) and allowing adhesion of the tissue-adhesive element 212 to tissue at the target site. In this example, after expansion, the device begins to collapse along the peripheral seal zone 208 when sufficient moisture is absorbed by the second hydrophilic material in the water-disintegrable sealing composition to solubilize the first hydrophilic material.

[0161] Instead of the tissue adhesive element 212, an active agent carrying element can be used (not shown), which is held against the tissue to form contact with the tissue (but without adhering to the tissue), allowing delivery of the active agent to the tissue as long as the device maintains its integrity in the expanded state.

[0162] Different configurations of the arrangement of the water-insoluble film portions and the construction of the connection zone to obtain devices as shown in Figures 4A-4B and 4C-4D. In these examples, the connection zone is constituted by the sealing zones of adjacent compartments superimposed on one another.

[0163] 4A-4B, the compartments are attached to one another such that both films of each compartment are attached to the adjacent compartment. For example, compartment 102A is attached to two adjacent compartments 102B and 102C, with compartment 102B being attached via the upper film portion 104t in seal zone 108AB and the other compartment 102C being attached via the lower film portion 104b in seal zone 108AC of compartment 102A.

[0164] 4C-4D, the compartments are attached to one another such that only one of the films in each compartment is attached to the adjacent compartment. For example, compartment 102A' is attached to two adjacent compartments 102B' and 102C', and both compartments 102B' and 102C' are attached via their upper film portion 104t' to the lower film portion 104b' of compartment 102A' in seal zones 108AB' and 108AC', respectively.

[0165] The attachment of one compartment to the other is typically achieved using a water-disintegrating sealing composition.

[0166] 4A-4D, the seal zones of adjacent compartments are overlapped one on top of the other to form a connection zone. The overlapping seal zones result in a connection zone comprising a plurality of alternating layers, namely, layers of peripheral segments of substantially water-insoluble deformable film portions interposed with layers of a water-collapsible sealing composition. This layered arrangement allows the water-collapsible sealing composition to function as a structural component of the device, enabling the compartments to be attached to one another during device manufacture, while also providing mechanical integrity between the folded and unfolded configurations and during the transition of the device from a collapsed state to an expanded state.

[0167] It should be noted that the water-collapsible seal composition connecting the seal zones to one another at the connection zone can be the same as the water-collapsible seal composition within the seal zone, or it can be a different water-collapsible seal composition. Such possible variations in the water-collapsible seal composition can result in different onsets and / or rates of collapse for the connection zone and the seal zone. In other words, by selecting different water-collapsible seal compositions within and between the seal zones, a gradual collapse can be achieved, such as first disintegration of the device into individual compartments, followed by disintegration of the individual compartments themselves.

[0168] Furthermore, to obtain compaction of the device in its collapsed (unexpanded) state, the device may be folded in various folding configurations (i.e., the primary folding configurations seen in FIGS. 5A-5C ) and / or rolled configurations (not shown) to allow its unfolding (and / or unrolling) during the transition from the collapsed state to the expanded state. In other words, the device may be folded to assume a collapsed state having an overall reduced size or overall reduced volume. When liquid penetrates the liquid-permeable section of the deformable film, the gel-forming material begins to expand, increasing in volume. This, in turn, exerts a force on the deformable film, and due to its flexibility and / or deformability, the film unfolds to assume the expanded state of the device.

[0169] 5A-5C illustrate various configurations for folding the device to render it in a more compact form for ingestion. For ease of visualization, only the tissue adhesive element 112 is shown on the film 104. It should be further understood that an active agent carrying element 113 can be used in place of the tissue adhesive element 112 (not shown in FIGS. 5A-5F). When in the folded state, the device can be folded into one of the primary folding configurations shown in FIGS. 5A-5C and housed in a biodegradable capsule (not shown). After ingestion and degradation of the biodegradable capsule, exposure to fluids in the GI tract causes expansion of the gel-forming material within the compartment, thereby expanding the compartment and at least partially accompanying its expansion and unfolding to the expanded state.

[0170] Once folded into the primary folded configuration, the folded device may be surrounded by an enteric envelope 122, as shown in Figures 5D and 5E, which serves to maintain the device in its primary folded configuration until the appropriate conditions for deployment within the digestive tract are reached. The device may further be housed within a biodegradable capsule 118.

[0171] To achieve further compaction in the collapsed state, the device, in some embodiments, has a secondary rolling configuration (not shown) whereby the collapsed device is further rolled about its axis and configured to simultaneously unroll and unfold during transition from the collapsed state to the expanded state. Note that an enteric envelope can encase the device in its secondary folded configuration (not shown) instead of, or in addition to, the enteric envelope 122 that encases the device in its primary folded configuration. If the device includes two enteric envelopes, the first and second envelopes can be configured to have the same or different disintegration / dissolution properties.

[0172] 6A-6B show a device or arrangement according to another embodiment of the present disclosure, which also includes an unfolding unit. For clarity, only a rough outline of the device is shown. The arrangement 300, including the device 100′ in its folded and tucked configuration (similar to the folded device of FIG. 5A), is associated with an unfolding unit 302 (FIG. 6A) positioned between the folds of the device. The unfolding unit 302 includes a liquid-permeable casing 304 and at least one gas-forming material 306 contained therein, such that contact between a liquid and the gas-forming material releases gas 308 to expand the unfolding unit (as illustrated by arrow 310) and assist in switching the device 100′ to the unfolded configuration (as seen in FIG. 6B). Typically, the reaction rate of the gas-forming material contained in the casing 304 is faster than the expansion rate of the gel-forming material within the compartment. In other words, the activation timing of the gas-forming material is faster than the activation timing of the gel-forming material. Initial unfolding of the device is facilitated by expansion of the deployment unit, while further unfolding and expansion from the collapsed state to the expanded state is achieved by expansion of a gel-forming material enclosed in a compartment of the device.

[0173] Seen in Figures 6C-6D is a layout diagram 400 of a device 100'' similar to the folded device of Figure 5B, with similar functional features as in Figures 6A-6B (shifted by 100). The devices of Figures 6A-6B and 6C-6D differ in their primary folding configurations.

[0174] While this example illustrates deployment of the device in the intestine, it should be understood that the device can be administered and deployed in any other suitable body cavity or cavity. For example, the device can be administered to other organs, such as the urinary tract, vagina, rectum, or intranasal cavity. If the target organ or cavity is relatively accessible to the user, the device can be administered by utilizing a specialized applicator (not shown) to insert the device into the organ or cavity. The properties of the water-disintegrating sealing composition are then tailored to the specific conditions of the desired target site.

Claims

1. An ingestible self-expanding device, the device having a collapsed state and an expanded state; a self-expandable container comprising two or more self-expandable compartments connected to one another by a connection zone, each compartment formed from two substantially water-insoluble deformable film sections joined to one another at a peripheral segment of the compartment by at least one water-disintegrable sealing composition to define a sealing zone, each sealing zone being a layered structure of the water-insoluble deformable film sandwiched therebetween with at least one water-disintegrable sealing composition layer joining the water-insoluble deformable film sections to one another at the peripheral segment; the two film portions define an enclosed space of the compartment between them in an area sealed by the peripheral segment; each compartment having one or more liquid-permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to swell upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from the collapsed state to the expanded state; The device, wherein the water-disintegrable sealing composition has water solubility configured to provide mechanical stability to the sealing zone during transition of the device from the collapsed state to the expanded state and to provide controlled collapse of the sealing zone after the device is expanded to the expanded state, thereby causing loss of integrity of the compartment and / or the device after deployment.

2. The device of claim 1 , wherein the connection zone comprises the seal zone.

3. 10. The device of claim 1, wherein adjacent compartments are connected to one another by joining one or more of their respective seal zones with a water-disintegrable sealing composition.

4. 4. The device of claim 3, wherein the compartments are connected to one another by overlapping the sealing zones of adjacent compartments, such that the connection zone consists of the stacked sealing zones, forming a layered structure of alternating layers of the water-insoluble deformable film and the water-disintegrable sealing composition.

5. 4. The device of claim 3, wherein the seal zones comprise a first water-collapsible seal composition, and the adjacent compartments are connected to one another by joining one or more of the respective seal zones with a second water-collapsible seal composition, and the first water-collapsible seal composition and the second water-collapsible seal composition are different from one another or the same.

6. the water-disintegratable sealing composition comprises at least one first hydrophilic material and at least one second hydrophilic material; the first hydrophilic material is less hydrophilic than the second hydrophilic material; The device of claim 1 , wherein the first hydrophilic material is less water-soluble than the second hydrophilic material.

7. 7. The device of claim 6, wherein the first hydrophilic material is chemically and / or thermodynamically compatible with the water-insoluble deformable film to bond the water-insoluble deformable film to each other in the seal zone.

8. 8. The device of claim 6 or 7, wherein the amount of the first hydrophilic material in the water-disintegrable sealing composition is greater than the amount of the second hydrophilic material.

9. 9. The device of claim 6, wherein the weight ratio of the first hydrophilic material to the second hydrophilic material is between about 4:1 and 3:

2.

10. 10. The device of claim 1, wherein the water-disintegrable sealing composition is located in the area of ​​the sealing zone.

11. The device of claim 10 , wherein each seal zone comprises one or more of said regions.

12. 12. The device of claim 1, comprising at least one tissue adhesive element connected to at least a portion of an outer surface of at least one of the compartments, wherein expansion of the device from the collapsed state to the expanded state causes expansion of the compartment to drive the tissue adhesive element toward tissue of the gastrointestinal tract and adhere at least a portion of the tissue adhesive element to the tissue.

13. The device of claim 12 , wherein the tissue adhesive element comprises at least one mucoadhesive material.

14. The device of claim 12 , wherein the tissue adhesive element is a tissue adhesive layer.

15. The device of claim 14 , wherein the tissue adhesive layer is a mucoadhesive layer.

16. The device of claim 15 , wherein the mucoadhesive layer comprises at least one mucoadhesive material.

17. 17. The device of claim 15 or 16, wherein the mucoadhesive layer comprises at least one mucoadhesive material and at least one active agent.

18. 18. The device of claim 17, wherein the active agent is a pharmaceutically active agent.

19. 12. The device of claim 1, further comprising at least one active agent carrying element coupled to at least a portion of an outer surface of at least one of the compartments, wherein expansion of the device from the collapsed state to the expanded state causes expansion of the compartments to drive the active agent carrying element toward tissue of the gastrointestinal tract and maintain the active agent carrying element in contact with the tissue while the device is in the expanded state.

20. 20. The device of claim 19, wherein the active agent-carrying element comprises at least one active agent and is in the form of a layer covering at least a portion of the exterior surface of the compartment.

21. 20. The device of claim 19, wherein the active agent-carrying element is a solid composition comprising at least one active agent.

22. 22. The device of claim 21, wherein the solid composition is in the form of a tablet.

23. 23. The device of any one of claims 17 to 22, wherein the device comprises at least one additional active agent different from the at least one active agent.

24. 24. The device of any one of claims 1 to 23, wherein the portions of the deformable film differ from one another in their liquid permeability.

25. 25. The device of any one of claims 1 to 24, wherein the gel-forming material is disintegrable.

26. 26. The device of claim 1, wherein the device is configured to fold in a primary folded configuration when in the folded state and to undergo unfolding during transition from the folded state to the expanded state.

27. 27. The device of claim 26, comprising at least one deployment unit disposed between folded sections of the device when in the primary folded configuration and configured to expand upon contact with liquid to assist in unfolding the device.

28. 28. The device of claim 27, wherein the deployment unit includes a liquid-permeable casing forming a closed structure and at least one gas-forming material contained therein.

29. 29. The device of claim 27 or 28, wherein the device is surrounded by an enteric envelope when in the primary folded configuration.

30. 30. The device of any one of claims 27 to 29, wherein the device has a secondary rolling configuration when in the collapsed state, whereby the folded device is further rolled about its axis and configured to simultaneously unroll and unfold during transition from the collapsed state to the expanded state.

31. 31. The device of claim 30, wherein the device is surrounded by an enteric envelope in the secondary rolled configuration.

32. 32. The device of claim 31, wherein the device is surrounded by a first enteric envelope in the primary folded configuration and the device is surrounded by a second enteric envelope in the secondary rolled configuration.

33. 33. The device of any one of claims 1 to 32, comprising a biodegradable shell encapsulating the device in its folded state.

34. 34. The device of any one of claims 1 to 33, wherein the gel-forming material is in the form of a gel film.

35. 35. The device of any one of claims 1 to 34, wherein the gel-forming material is in the form of gel particles.

36. an ingestible self-expanding device configured to adhere a tissue adhesive element to tissue, the device having a collapsed state and an expanded state; two or more self-expandable compartments connected to one another by connection zones, each compartment formed from two substantially water-insoluble deformable film sections joined to one another at a peripheral segment of the compartment by at least one water-collapsible sealing composition to define a seal zone, each seal zone being a layered structure of the water-insoluble deformable film sandwiched therebetween with at least one layer of water-collapsible sealing composition joining the water-insoluble deformable film sections to one another at the peripheral segment; the two film portions define an enclosed space of the compartment between them in an area sealed by the peripheral segment; each compartment having one or more liquid-permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to swell upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from the collapsed state to the expanded state; a compartment, wherein the water-disintegrable sealing composition has water solubility configured to provide mechanical stability to the seal zone during transition of the device from the collapsed state to the expanded state and to provide controlled collapse of the seal zone after the device is expanded to the expanded state, thereby causing a loss of integrity of the compartment and / or the device after deployment; at least one tissue adhesive element adhered to at least a portion of an outer surface of at least one of the compartments; wherein expansion of the device from the collapsed state to the expanded state causes expansion of the compartments and drives the tissue adhesive elements toward the tissue to adhere at least a portion of the tissue adhesive layer to the tissue.

37. 1. An ingestible, self-expanding device for delivering at least one active agent to tissue, the device having a collapsed state and an expanded state; two or more self-expandable compartments connected to one another by connection zones, each compartment formed from two substantially water-insoluble deformable film sections joined to one another at a peripheral segment of the compartment by at least one water-collapsible sealing composition to define a seal zone, each seal zone being a layered structure of the water-insoluble deformable film sandwiched therebetween with at least one layer of water-collapsible sealing composition joining the water-insoluble deformable film sections to one another at the peripheral segment; the two film portions defining an enclosed space of the compartments therebetween in an area sealed by the peripheral segment, each compartment having one or more liquid permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to swell upon contact with a liquid, thereby expanding the compartments and irreversibly switching the device from the collapsed state to the expanded state; a compartment, wherein the water-disintegrable sealing composition has water solubility configured to provide mechanical stability to the seal zone during transition of the device from the collapsed state to the expanded state and to provide controlled collapse of the seal zone after the device is expanded to the expanded state, thereby causing a loss of integrity of the compartment and / or the device after deployment; at least one active agent carrying element adhered to at least a portion of an exterior surface of at least one of the compartments; A device wherein expansion of the device from the collapsed state to the expanded state causes expansion of the compartment, driving the active agent carrying element toward the tissue, holding the active agent carrying element against the tissue for a predetermined period of time, and enabling delivery of the active agent from the active agent carrying element to the tissue.

38. 1. An ingestible self-expanding arrangement, comprising: an ingestible self-expanding device having a collapsed state and an expanded state, and at least one deployment unit having a non-expanded state and an expanded state; the ingestible self-expanding device comprises: two or more self-expandable compartments connected to one another by connection zones, each compartment formed from two substantially water-insoluble deformable film sections joined to one another at a peripheral segment of the compartment by at least one water-collapsible sealing composition to define a seal zone, each seal zone being a layered structure of the water-insoluble deformable film sandwiched therebetween with at least one layer of water-collapsible sealing composition joining the water-insoluble deformable film sections to one another at the peripheral segment; the two film portions define an enclosed space of the compartment between them in an area sealed by the peripheral segment; each compartment having one or more liquid-permeable sections and enclosing a gel-forming material within the enclosed space, the gel-forming material configured to swell upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from the collapsed state to the expanded state; an arrangement in which the device is folded in a primary folded configuration in the folded state, and the at least one unfolding unit is disposed between folded sections of the device when in the primary folded configuration and is configured to switch from the unexpanded state to the expanded state upon contact with a liquid to assist in unfolding the device.

39. 1. An ingestible arrangement for delivering at least one active agent to a tissue, said arrangement comprising: an ingestible self-expanding device having a collapsed state and an expanded state, and at least one deployment unit having a non-expanded state and an expanded state; the ingestible self-expanding device comprises: two or more self-expandable compartments connected to one another by connection zones, each compartment formed from two substantially water-insoluble deformable film portions joined to one another at a peripheral segment of the compartment by at least one water-disintegrable sealing composition to define a sealing zone, each sealing zone being a layered structure of the water-insoluble deformable film sandwiched therebetween with at least one layer of water-disintegrable sealing composition joining the water-insoluble deformable film portions to one another at the peripheral segment; the two film portions define an enclosed space therebetween in the area enclosed by the peripheral segment; compartments, each compartment having one or more liquid-permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to swell upon contact with liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state; at least one active agent carrying element adhered to at least a portion of an exterior surface of at least one of the compartments; an active agent carrying element, wherein expansion of the device from the collapsed state to the expanded state causes expansion of the compartment, driving the active agent carrying element toward the tissue, holding the active agent carrying element against the tissue for a predefined period of time, and enabling delivery of the active agent from the active agent carrying element to the tissue; In the folded state, the device is folded in a primary folded configuration, and at least one deployment unit is disposed between the folded sections of the device when in the primary folded configuration and configured to switch from a non-expanded state to an expanded state upon contact with a liquid, allowing deployment of the device.

40. 1. An ingestible arrangement for adhering a tissue adhesive element to tissue, comprising: an ingestible self-expanding device having a collapsed state and an expanded state, and at least one deployment unit having a non-expanded state and an expanded state; the ingestible self-expanding device comprises: two or more self-expandable compartments connected to one another by connection zones, each compartment formed from two substantially water-insoluble deformable film portions joined to one another at a peripheral segment of the compartment by at least one water-collapsible sealing composition to define a seal zone, each seal zone being a layered structure of the water-insoluble deformable film sandwiched therebetween with at least one water-collapsible sealing composition layer joining the water-insoluble deformable film portions to one another at the peripheral segment; the two film portions define an enclosed space of the compartment between them in an area d sealed by the peripheral segment; compartments, each compartment having one or more liquid-permeable sections and a gel-forming material within the enclosed space, the gel-forming material configured to swell upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from the collapsed state to the expanded state; a tissue adhesive element adhered to at least a portion of an exterior surface of at least one of the compartments; expansion of the device from the collapsed state to the expanded state causes expansion of the compartments and drives the tissue adhesive layer toward the tissue to adhere at least a portion of the tissue adhesive layer to the tissue; an arrangement in which the device is folded in a primary folded configuration in the folded state, and the at least one unfolding unit is disposed between folded sections of the device when in the primary folded configuration and is configured to switch from the unexpanded state to the expanded state upon contact with a liquid to assist in unfolding the device.

41. 41. The arrangement of any one of claims 38 to 40, wherein the deployment unit includes a liquid-permeable casing and at least one gas-forming material contained therein, wherein contact of the gas-forming material with a liquid releases gas that inflates the deployment unit.

42. 42. An arrangement according to any one of claims 38 to 41, comprising two or more deployment units.

43. 43. The arrangement of claim 42, wherein the two or more arrangement units are attached to one another.

44. 43. The arrangement of claim 42, wherein the two or more deployment units are not attached to one another.

45. 45. The arrangement of claim 43 or 44, wherein the two or more deployment units differ from each other by at least one of the liquid permeability of the liquid permeable casing, the type of gas-forming material, the amount, size and / or shape of the gas-forming material.

46. 45. The arrangement of claim 43 or 44, wherein the two or more developments are identical to one another.

47. 47. The arrangement of any one of claims 38 to 46, wherein the at least one deployment unit is attached to the ingestible self-expanding device.

48. 48. The arrangement of any one of claims 38 to 47, wherein the at least one deployment unit is not attached to the ingestible self-expanding device.

49. 49. The arrangement of any one of claims 38 to 48, wherein the water-disintegrating sealing composition is water soluble and configured to provide mechanical stability to the sealing zone during transition of the device from the collapsed state to the expanded state and to provide controlled collapse of the sealing zone after the device is expanded to the expanded state, thereby causing loss of integrity of the compartment and / or device after deployment.

50. 50. The arrangement of any one of claims 38 to 49, wherein the arrangement is enclosed by an enteric envelope when the device is in the primary folded configuration and the deployment unit is in its unexpanded state.

51. 50. The arrangement of any one of embodiments 38 to 49, wherein when the device is in the folded state and the deployment unit is in its unexpanded state, the arrangement has a secondary rolling configuration, whereby the folded device is further rolled around its axis and is configured to simultaneously unroll and unfold during transition from the folded state to the expanded state.

52. 52. The arrangement of claim 51, wherein the arrangement is surrounded by an enteric envelope when the arrangement is in the secondary rolled configuration.

53. 53. The arrangement of claim 52, wherein when the device is in the primary folded configuration and the deployment unit is in its unexpanded state, the arrangement is enclosed by a first enteric envelope, and when in the secondary rolled configuration, the arrangement is enclosed by a second enteric envelope.

54. 54. The arrangement of any one of claims 38 to 53, comprising a biodegradable shell, encapsulating the arrangement in a primary folded configuration.

55. 55. The arrangement according to any one of claims 40 to 54, wherein the tissue adhesive element is a tissue adhesive layer.

56. 56. The arrangement of claim 55, wherein the tissue adhesive layer is a mucoadhesive layer comprising at least one mucoadhesive material and at least one active agent.

57. 55. An arrangement according to any one of claims 39 and 41 to 54, wherein the active agent carrying element is in the form of a layer comprising at least one active agent and covering at least a portion of the outer surface of the compartment.

58. 58. The device of claim 57, wherein the active agent-carrying element is a solid composition comprising at least one active agent.

59. 59. The device of claim 58, wherein the solid composition is in the form of a tablet.

60. 59. The arrangement of any one of claims 56 to 58, wherein the active agent is a pharmaceutically active agent.

61. 61. The arrangement of any one of claims 38 to 60, wherein the gel-forming material is in the form of a gel film.

62. 61. The arrangement of any one of claims 38 to 60, wherein the gel-forming material is in the form of gel particles.

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