Controllable disassembly self-expanding ingestible device

Abstract

The present disclosure relates to an expandable device, in particular a self-expanding device designed for ingestion and deployment in the gastrointestinal tract and configured for controlled disintegration. The device comprises an expandable compartment (102) separated by a sealing region (108), the compartment being designed for controlled disintegration upon exposure to a liquid, allowing controlled disintegration of the device after a predefined time from deployment.

Description

Technical Field

[0001] The present disclosure relates to an inflatable device, particularly a self - inflating device that is designed to be delivered to and deployed in the gastrointestinal tract and is configured for controlled disintegration.

[0002] Background art documents

[0003] References considered relevant to the background of the present disclosure are as follows:

[0004] - PCT Patent Publication WO2016015648

[0005] - PCT Patent Publication WO2008062440

[0006] - PCT Patent Publication WO2009125432

[0007] - PCT Patent Publication WO2013188819

[0008] - PCT Patent Publication WO2015026552

[0009] - PCT Patent Publication WO2015120471

[0010] The acknowledgement of the above - mentioned references herein should not be construed as meaning that these references are in any way relevant to the patentability of the present disclosure. Background Art

[0011] Effectively and targetedly delivering various compounds and active agents to or across specific tissues (such as the intestinal wall) has proven to be a challenge over the years. Due to the mucus secretions that form in various tissues to provide a hydrated environment and lubrication of biological surfaces, targeted delivery of active agents typically requires the use of a mucoadhesive component or other tissue - attachment device that can adhere to the tissue for a predefined period of time, thereby providing a longer contact time between the tissue and the active agent to allow for a longer time for the active agent to be absorbed through and / or into the tissue.

[0012] In some methods, deployable devices are used, where the device is delivered to the vicinity of the target site in a non - deployed form and the device is deployed to deliver a mucoadhesive - based composition to the tissue during such deployment. In the case of delivery to the gastrointestinal tract, careful consideration is required to control the deployment at the appropriate target site and the withdrawal of the device after deployment to avoid obstruction of the gastrointestinal tract. Summary of the Invention

[0013] The present disclosure provides a self-expanding device that can be applied to a subject and deployed in a controlled manner in the gastrointestinal tract. The device can be configured to deliver one or more active agents or one or more tissue-adherable layers (or patches), such as mucoadhesive materials, to tissue at a target site. The devices of the present disclosure are designed to allow controlled disintegration of the device or portions thereof, such that after the device is deployed, for example, after the tissue-adherable layer is delivered and coated onto the tissue at the target site, the device can be appropriately and controllably withdrawn from the target site.

[0014] The devices of the present disclosure are based on the realization that the elaborate construction of the device allows for controlled absorption of liquid (such as water) during and after device deployment, which can be used to control the disintegration location and rate of at least a portion of the device to allow it to break into pieces that are easier to withdraw from the target site.

[0015] Thus, in one of its aspects, the present disclosure provides an ingestible self-expanding device having a contracted state and an expanded state. The device includes two or more self-expanding compartments interconnected by a connecting region. Each compartment is composed of two substantially water-insoluble, deformable film portions that are adhered to each other at the peripheral portion of the compartment by at least one water-decomposable sealing composition to define a sealed region. Each sealed region is a layered structure composed of water-insoluble deformable films with at least one water-decomposable sealing composition layer sandwiched therebetween, and at least one water-decomposable sealing composition layer adhesively bonds the water-insoluble deformable films to each other at the peripheral portion. The two film portions define a closed space of the compartment therebetween within the region enclosed by the peripheral portion. Each compartment has one or more liquid-permeable portions and a gel-forming material within the closed space, and the gel-forming material is configured to expand upon contact with liquid, thereby expanding the compartment and irreversibly switching the device from the contracted state to the expanded state. In the devices of the present disclosure, the water-decomposable sealing composition provides mechanical stability to the sealed region during the transition of the device from the contracted state to the expanded state and is water-soluble and configured to provide controlled disintegration of the sealed region after the device expands to the expanded state, resulting in the loss of integrity (breaking apart and / or disintegrating) of the compartment and / or the device after its deployment.

[0016] In other words, in the device of the present disclosure, the sealing region has several functions. First, the sealing region forms the perimeter of the compartment, as the water-insoluble deformable film portions are attached to each other at the peripheral portion of the compartment by the water-decomposable sealing composition. In addition, during the deployment of the device from the contracted state to the expanded state, the sealing region provides mechanical stability and reinforcement to the compartment, enabling the integrity of the compartment to be maintained during deployment. However, after deployment, the water-decomposable sealing composition in the sealing region serves as a weaker structural region, allowing for the controlled disintegration of the device after its expansion to achieve the splitting of the device into smaller fragments, which can be more easily evacuated from the target site.

[0017] The device of the present disclosure is designed to controllably increase in volume, for example to drive an attachable tissue layer or patch, such as a mucosal adhesive material layer, towards tissue and temporarily apply a force to the tissue in order to attach or adhere the layer or patch to the tissue at the desired location. Thus, once the device is administered, exposure to appropriate deployment conditions will cause the device to expand and deliver the attachable tissue layer to the tissue. After delivering the attachable tissue layer to the target site, it is generally necessary to evacuate the device; since the device is large in volume, evacuation is facilitated by disintegration.

[0018] As previously described, the compartments are interconnected by connection regions. The connection regions are components of the device that are typically integrated with the compartments and form a physical connection between adjacent compartments to obtain the overall shape of the device. According to some embodiments, the connection region includes the sealing region (i.e., the sealing region is part of the connection region).

[0019] According to other embodiments, the compartments are connected to each other by the water-decomposable sealing composition bonding one or more of their respective sealing regions. Since the water-decomposable sealing composition is typically present in the sealing region and the connection region, a controllable splitting of the device and the compartments can be achieved.

[0020] According to some embodiments, the compartments are interconnected by stacking the sealing regions of adjacent compartments such that the connection region consists of the stacked sealing regions to form a layered structure of alternating layers of the water-insoluble deformable film and the water-decomposable sealing composition.

[0021] According to some embodiments, the sealing region includes a first water-decomposable sealing composition, and adjacent compartments are interconnected by bonding one or more of their respective sealing regions with a second water-decomposable sealing composition, and the first water-decomposable sealing composition and the second water-decomposable sealing composition are different from or the same as each other.

[0022] By controlling various parameters of the water-decomposable sealing composition, a balance can be achieved between the stability of the water-decomposable sealing composition (maintaining the mechanical integrity of the device during this transition period) and the disintegration of the sealed area after device deployment.

[0023] The term sealed area is intended to denote a circumferential profile where the peripheral portions of the water-insoluble deformable film portions are interconnected by the water-decomposable sealing composition. As a result of such attachment, a compartment is formed where portions of the water-insoluble deformable film portions surrounded by the circumferential profile define an enclosed space between them.

[0024] As previously described, the sealed area has a layered structure where the water-insoluble deformable film defines the two outer layers of the sealed area, and a layer of the water-decomposable sealing composition is sandwiched between the films at the peripheral portion of the compartment. Since the outer layers of the sealed area are substantially water-insoluble, only water is allowed to penetrate into the sealed area through small surfaces perpendicular to the plane of the layers in the sealed area, where the water-decomposable sealing composition is exposed to the liquid. Thus, the exposure of the water-decomposable sealing composition to water can be controlled, especially by controlling the surface area of the water-decomposable sealing composition exposed to water, thereby controlling the disintegration rate (and / or the onset of disintegration) of the sealed area. Further control of the disintegration of the sealed area can be obtained by controlling the decomposition rate of the water-decomposable sealing composition (e.g., by controlling its composition) to control the disintegration of the sealed area.

[0025] In some embodiments, the disintegration of the sealed area begins at least about 5 minutes after the completion of the deployment when the device enters its expanded state. In other embodiments, the disintegration of the sealed area begins at least about 10 minutes after the completion of the deployment when the device enters its expanded state.

[0026] According to some embodiments, a plurality of sealed areas include the water-decomposable sealing composition. In such cases, the sealed areas can all contain the same water-decomposable sealing composition, or the sealed areas can contain different water-decomposable sealing compositions, thereby causing the gradual disintegration of the device.

[0027] According to some other embodiments, areas are defined in the sealed areas containing the water-decomposable sealing composition, and each sealed area can include one or more such areas. The areas can include the same or different water-decomposable sealing compositions.

[0028] In some embodiments, the water-decomposable sealing composition connecting the sealed areas to each other within the connection area can be the same as the water-decomposable sealing composition within the sealed areas. In other embodiments, the water-decomposable sealing composition connecting the sealed areas to each other within the connection area is different from the water-decomposable sealing composition within the sealed areas.

[0029] According to some embodiments, a water-decomposable sealant composition includes at least one first hydrophilic material and at least one second hydrophilic material having different hydrophilicities and water solubilities. According to some embodiments, the first hydrophilic material has a lower hydrophilicity than the second hydrophilic material, and the first hydrophilic material also has a lower water solubility than the second hydrophilic material.

[0030] The differences in hydrophilicity and solubility can be used to control the decomposition time and rate of the water-decomposable sealant composition.

[0031] The term hydrophilic material refers to a compound or composition having a high affinity for water. In the water-decomposable sealant composition, the difference in hydrophilicity enables the water-decomposable sealant composition to be used both as an adhesive composition between two water-insoluble deformable films in a sealed area and to provide a controlled disintegration of the sealed area.

[0032] Both the hydrophilicity and solubility of the first hydrophilic material are lower than those of the second hydrophilic material. The first hydrophilic material is selected such that, due to its lower hydrophilicity, it is chemically and / or thermodynamically compatible with the water-insoluble deformable film. This compatibility allows the peripheral portions of the water-insoluble deformable films to be adhered to each other by the water-decomposable sealant composition. The first hydrophilic material is selected to allow at least partial dissolution or physical incorporation into the water-insoluble deformable film portion during the formation of the sealed area (e.g., by heat welding, ultrasonic welding, solvent bonding, etc.), thereby allowing a continuous contact surface to exist between the water-insoluble deformable film portion and the water-decomposable sealant composition. Thus, this compatibility enables the formation of a closed compartment having a sealed area that maintains its mechanical integrity during volume changes of the compartment when the compartment is transitioning between a contracted state and an expanded state.

[0033] When exposed to appropriate pH conditions in the intestine, typically at a pH of about 6 - 7, the first hydrophilic material generally undergoes chemical or physical decomposition. When the first hydrophilic material is selected to react under defined conditions in the intestine, this selection provides further control over the disintegration of the device after ingestion, thereby preventing undesired disintegration when the device passes through the stomach but allowing disintegration under the pH conditions in the intestine.

[0034] However, due to its lower solubility and the limited exposure to water due to the structure of the sealed area (i.e., the limited surface area of the water-decomposable sealant composition layer exposed to water), a suitable decomposition environment is required.

[0035] To obtain such a suitable decomposition environment, the water-decomposable seal composition includes a second hydrophilic material having a relatively high hydrophilicity. The second hydrophilic material is used to rapidly absorb and trap water diffusing into the sealed area, thereby forming an environment that supports the solubilization of the first hydrophilic material to allow for the disintegration of the sealed area and the loss of integrity of the device (i.e., disassembly or disintegration). Due to its relatively high hydrophilicity, the second hydrophilic material also allows for the controlled delivery of water to the sealed area after device deployment, thereby controlling the exposure of the first hydrophilic material to water and further controlling the onset of its decomposition.

[0036] The combination of the first hydrophilic material and the second hydrophilic material allows for a high degree of controllability of the disintegration rate of the sealed area: Since the water-decomposable seal composition is sandwiched between water-insoluble films, and since the diffusibility of water through the film is limited, a relatively small amount of water can penetrate into the sealed area. The second hydrophilic material allows for the rapid absorption and trapping of water diffusing into the sealed area, thereby enabling the control of the exposure of the first hydrophilic material to water for its solubilization. Since the first hydrophilic material is used to form an adhesion between two water-insoluble films, the increased absorption of water by the second hydrophilic material provides appropriate conditions for the solubilization of the first hydrophilic material, thereby causing the disintegration of the sealed area and the loss of integrity of the compartment and / or device. By balancing and selecting the first hydrophilic material and the second hydrophilic material, different onset times and disintegration rates can be obtained.

[0037] According to some embodiments, the first hydrophilic material can be selected from hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, methacrylic acid-methyl methacrylate copolymer (e.g., acrylic resin L, acrylic resin S), methacrylic acid-ethyl acrylate copolymer (e.g., Kollicoat MAE), cellulose acetate phthalate, etc., and combinations thereof.

[0038] According to some embodiments, the second hydrophilic material can be selected from hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (Klucel), cellulose ethers (e.g., Metolose), polyvinylpyrrolidone and its derivatives (e.g., povidone, kollidone, plasdone), polyvinyl alcohol, etc., and combinations thereof.

[0039] According to some embodiments, the second hydrophilic material is a super hydrophilic material.

[0040] In some embodiments, the amount of the first hydrophilic material in the water-decomposable seal composition is greater than the amount of the second hydrophilic material. According to other embodiments, the weight ratio between the first hydrophilic material and the second hydrophilic material is between about 4:1 and about 3:2.

[0041] The device of the present disclosure includes a closed compartment formed by a water-insoluble film, and a sealing area defines the peripheral boundary of the compartment. According to some embodiments, the compartment is formed by two substantially continuous deformable films, which are connected to each other to form the compartment, and the compartments are connected to each other through a connecting area. In other words, through such embodiments, the device is formed by two continuous films, and the two continuous films are separated by a sealing area to form two or more compartments, such that adjacent compartments are separated by a connecting area.

[0042] In some embodiments, the connecting area includes a sealing area, that is, the sealing area forms an integral part of the connecting area. In other embodiments, the connecting area is composed of two or more sealing areas, and these sealing areas are adhesively bonded to each other through a water-decomposable sealing composition.

[0043] According to other embodiments, in which each compartment is formed by two different deformable film portions, the connecting area is composed of two or more sealing areas of adjacent compartments that are adhesively bonded to each other; that is, in such embodiments, the connecting area is composed of stacked connecting areas, thereby forming a layered structure of alternating layers of a water-insoluble deformable film layer and a water-decomposable sealing composition layer.

[0044] As described above, the compartment is formed by a water-insoluble deformable film and defines a space for accommodating one or more gel-forming materials therein. The term continuous deformable film refers to a single-piece film, that is, a film composed of a seamless unit. The term deformable film portion refers to a film portion that represents a continuous structure of the device after being connected to each other.

[0045] The film is generally made of one or more substantially water-insoluble polymer materials.

[0046] To allow water to enter the compartment and activate the gel-forming material to cause its swelling, and thus cause the deployment of the device, the compartment has one or more liquid-permeable portions. In some embodiments, in addition to one or more portions of the liquid-permeable material, the deformable film is made of an impermeable material. In other words, the deformable film can be made of two or more different materials, one of which is integrally formed with the other, one material is liquid-permeable, and the other material is liquid-impermeable.

[0047] In some embodiments, the portions of the deformable film are different from each other in terms of their liquid permeability. For example, the portions can differ in terms of their composition, porosity, thickness, size, and perforation density, etc.

[0048] The liquid-permeable portion is made of a liquid-permeable material. In the context of the present disclosure, the term liquid-permeable material refers to a material (a composition of compounds or substances) that permits the diffusion or passage of liquids therethrough. For example, the liquid-permeable material can be perforated or porous. According to some embodiments, the liquid-permeable material can comprise one or more compounds selected from hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate, cellulose acetate butyrate, ethylcellulose, polymethyl methacrylate, polyethyl acrylate, polyvinyl phthalate acrylate, polyvinyl acetate, shellac, carboxymethyl ethylcellulose (CMEC), and any combination thereof.

[0049] According to some embodiments, the liquid-permeable material can further include at least one binder, plasticizer, pore former, emulsifier, film former, and any combination thereof.

[0050] For administration, the device is in a contracted state, i.e., a compact configuration having a given initial volume. After administration and exposure to appropriate conditions, as will be further discussed below, the penetration of liquid through the permeable portion of the film causes the gel-forming material to expand, thereby increasing in volume and irreversibly deploying the device to an expanded state.

[0051] According to some embodiments, the device is designed to deliver one or more active agents to a target site in the intestine by direct contact of the active agent or a composition containing the same with intestinal tissue. For this purpose, in some embodiments, the device can include at least one active-agent-carrying member that is attached to at least a portion of the outer surface of at least one compartment such that the expansion of the device from the contracted state to the expanded state causes the compartment to expand to drive the active-agent-carrying member toward the tissue and to hold the active-agent-carrying member against the tissue for a predetermined period of time to allow delivery of the active agent to the tissue.

[0052] An active agent carrying component refers to any structure or composition that can contain an active agent and permit its release upon contact with intestinal tissue. The active agent carrying component can be, for example, a layer covering at least a portion of the outer surface of a compartment and consisting of the active agent, or include a carrier matrix in which the active agent is dispersed or embedded. By another example, the active agent carrying component can be a solid composition, such as a tablet or pill made of (or containing) the active agent. By some other examples, the active agent carrying component can be in the form of a gel or a gel-forming matrix containing the active agent. By a further example, the active agent carrying component can be in the form of a pressure-sensitive component that is designed to rupture upon application of pressure once the reservoir is held against the tissue after the compartment expands (e.g., the reservoir can be in the form of a shell / envelope that houses the active agent or its composition and has at least one wall portion configured to rupture under a predefined applied pressure).

[0053] According to some embodiments, the device is designed to deliver at least one tissue attachable component to a target site in the intestine. Thus, by some embodiments, the device includes at least one tissue attachable component attached to at least a portion of the outer surface of at least one compartment such that expansion of the device from a contracted state to an expanded state causes expansion of the compartment to drive the tissue attachable component toward the gastrointestinal tissue, thereby attaching at least a portion of the tissue attachable component to the tissue.

[0054] A tissue attachable component refers to a component that can self-attach to tissue (typically mucosal epithelial tissue). Attachment of the tissue attachable component to the tissue can be by mechanical means, such as microneedles or microhooks, which can be temporarily anchored in the tissue when pressure is applied by a self-expanding core. Alternatively, the tissue attachable component can comprise or be made of a mucoadhesive material.

[0055] In the context of the present disclosure, the term tissue refers to any organ surface or biofilm that is typically covered by mucus or mucosa (such as mucosal epithelial tissue), and typically the tissue is gastric tissue or intestinal tissue.

[0056] According to some embodiments, the compartments can be identical to or different from each other (e.g., in any one of size, shape, active agent, type, size or shape of the active agent carrying component and / or the tissue attachable component, disintegration rate, etc.). According to some embodiments, the device can include one or more compartments having an active agent carrying component or a tissue attachable component, while other compartments of the device can not have such components.

[0057] By varying the size, geometry, number, etc. of the compartments, as well as the type of the gel-forming material and / or the active agent-carrying component and / or the tissue-attachable component, different swelling rates, swelling shapes, and / or targeted delivery can be obtained. It is also possible to utilize the variation of the size, number, geometry, etc. of the compartments to obtain symmetric or asymmetric swelling shapes of the device. Changing the properties of the gel-forming material and / or the deformable film can also allow control of the force exerted by the device on the tissue in its swollen state for contact with the active agent-carrying component or with the tissue-attachable component. Additionally, by folding the device to obtain a contracted state and / or controlling the number and / or position of the liquid-permeable portions of the deformable film, control over the exposure of the gel-forming material to the liquid can be obtained, thereby controlling the overall swelling rate of the device.

[0058] According to some embodiments, the tissue-attachable component is a tissue-attachable layer. In some embodiments, the tissue-attachable layer is a mucoadhesive layer that comprises at least one mucoadhesive material.

[0059] The term mucoadhesive (or any linguistic variant thereof) refers to a compound or composition of substances that are capable of adhering to tissue, typically through mucus or mucosa. Mucoadhesive materials typically interact with the mucus present on or secreted by the tissue, such as one or more of electrostatic interactions, physical entanglement or interpenetration, diffusion, adsorption, mechanical interlocking, etc.

[0060] Mucoadhesive materials are typically polymers, and the polymers can be natural, semi-synthetic, or synthetic. Non-limiting examples of mucoadhesives are: gum tragacanth, sodium alginate, guar gum, xanthan gum, karaya gum, gellan gum, carrageenan, soluble starch, gelatin, chitosan, cellulose derivatives (such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose (NaCMC)), polyacrylic acid (PAA) polymers (such as carbomer gum, polycarbophil), poly(2-hydroxyethyl methacrylate), poly(ethylene oxide) (PEO, typically high molecular weight PEO), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), lectin, pectin, thiolated polymers (such as chitosan-iminothiolane), polyacrylic acid-cysteine, polyacrylic acid-homocysteine, polyethylene glycol, chitosan-mercaptoacetic acid, chitosan-thioethylamine, alginic acid-cysteine, poly(methacrylic acid)-cysteine, sodium carboxymethylcellulose-cysteine, etc.

[0061] In some additional embodiments, the device can include more than one type of tissue-attachable layer. Different regions of the outer surface of the compartment and / or different compartments can be covered with different types of tissue-attachable layers. These different types of tissue-attachable layers can include different types of active agents.

[0062] In some additional embodiments, the tissue-facing surface of the tissue-adherable layer (or a portion thereof) may be covered by a non-mucoadhesive material (layer) that may be configured to degrade to allow exposure of the mucoadhesive layer during or after device expansion.

[0063] The device may be used to deliver at least one active agent to a target site through and / or across tissue. Thus, according to some embodiments, the tissue-adherable component includes 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 may be incorporated within or on the surface of the tissue-adherable layer (the tissue-facing outer surface and / or the inward-facing surface toward the gel-forming material).

[0064] In some embodiments, when the tissue-adherable component is a mucoadhesive layer, the active agent is embedded within the mucoadhesive material. For example, the active agent may be dispersed or dissolved within the mucoadhesive material.

[0065] In other embodiments, the active agent may be encapsulated within various microparticle or nanoparticle structures, such as liposomes, microparticles, microcapsules, nanospheres, or nanocapsules, distributed within the mucoadhesive material.

[0066] By another embodiment, the active material coats at least a surface portion of the tissue-adherable component; for example, the active material may coat at least a portion of one or both of the tissue-facing surface and the surface facing the deformable film of the tissue-adherable component.

[0067] According to further embodiments, the active agent may be linked to the mucoadhesive material by one or more linking groups susceptible to defined biological conditions so as to allow release of the active agent therefrom upon exposure to these conditions.

[0068] In some embodiments, when the tissue-adherable component (e.g., the tissue-adherable layer) includes microneedles, the active agent may be embedded within the microneedles, such as within the polymer used to form the microneedles.

[0069] The active agent is generally a pharmaceutically active agent. The term pharmaceutically active agent refers to a molecule, compound, or composition that is safe and effective for pharmaceutical use in a subject (typically a mammal) and has the desired biological activity. The active agent may be selected, for example, from antibiotics, proteins, peptides, polypeptides, lipids, nucleic acids, hormones, steroids, antibodies, vitamins, anti-inflammatory drugs, antihistamines, antiemetics, analgesics, chemotherapeutic drugs, prophylactic drugs, blood clotting factors, radiopharmaceuticals, contrast agents, electrolytes, nutraceuticals, small molecules (molecular weight less than about 1000 Da or less than about 500 Da), etc.

[0070] In other embodiments, the active agent can be one or more microorganisms (e.g., gut-friendly bacteria) and / or viruses.

[0071] In other embodiments, the active agent can be a functional nutritional compound.

[0072] The active agent can be in the form of a salt, acid addition salt, free base, hydrate, solvate, or prodrug.

[0073] The active agent can be suitable for administration to humans. In other embodiments, the active agent can be a veterinary active agent.

[0074] When the active agent is present in the tissue-attachable component or when the active agent-carrying component is present in the device, the active agent is typically a therapeutically effective amount. The effective amount for the purposes herein can be determined by considerations known in the art. The dosage must be effective to achieve the desired therapeutic effect, especially depending on the type and severity of the disease to be treated and the treatment regimen. The effective amount is typically determined in appropriately designed clinical trials (dose range studies), and a person skilled in the art will know how to conduct such trials correctly to determine the effective amount. It is well known that the effective amount depends on various factors, including the affinity of the ligand for the receptor, its distribution profile in the body, various pharmacological parameters (such as in vivo half-life), adverse side effects (if any), factors such as age and gender.

[0075] The pharmaceutical active agent can be selected to elicit at least one effect, such as a therapeutic effect, which can cause, enhance, inhibit, or attenuate at least one effect by treating or preventing an unwanted condition or disease in a subject. At least one formulation (substance, molecule, element, compound, entity, or combination thereof) can be selected in the therapeutic agent, i.e., a formulation that can cause or modulate a therapeutic effect when administered in a therapeutically effective amount.

[0076] In other embodiments, the active agent can be a diagnostic agent, i.e., a formulation that allows the diagnosis of one or more conditions or diseases. The diagnostic effective amount refers to the dosage of the diagnostic agent that allows efficient molecular imaging to be achieved depending on the type of imaging technique used (such as PET, SPECT, etc.), the acquisition parameters of the specific imaging technique used, the body region being scanned, the physical condition of the subject, the purpose of the detection, and other relevant factors that are obvious to those skilled in the art.

[0077] In some embodiments, the device can comprise at least one additional active substance different from the at least one active agent. The additional active substance can have a drug activity similar to that of the active agent or a drug activity different from that of the active agent.

[0078] In some embodiments, the active agent carrying component or the tissue attachable component includes additional active substances. In these embodiments, the active agent and the additional active substances may have co-therapeutic effects, i.e., additional or synergistic effects. For example, the additional active substances may be used to increase the permeability or bioavailability of the active agent, or may increase or enhance the therapeutic effect or bioactivity of the active agent.

[0079] In other embodiments, the additional active substances may be contained in compartments, such as associated with a deformable film, associated with a gel-forming material, or mixed (or dispersed) into a gel-forming material. In such cases, the additional active substances may be selected to have immediate or short-term therapeutic effects, while the active agent may be selected to have extended or sustained therapeutic effects.

[0080] In other embodiments, the active agent and the additional active substances may be selected from formulations having similar or identical therapeutic effects. For example, the active agent and the additional active substances may be the same, but one is contained in the active agent carrying component or the tissue attachable component, while the other is contained in a compartment.

[0081] According to other embodiments, the device includes an active agent carrying component and a tissue attachable component that contain the same active agent or different active agents. Such an arrangement can be utilized to divide the desired dose of the formulation such that a portion of the formulation is released immediately when the component carrying the active agent expands and contacts the tissue, while the remainder is slowly absorbed from the tissue attachable component after attachment to the tissue. By another example, the active agent and the additional active substances may have similar effects, where the additional active substances have an immediate effect, while the active agent has an extended or sustained effect.

[0082] In other words, the device can be used to administer two or more pharmaceutical active agents simultaneously, i.e., sequentially simultaneously. Simultaneous administration can allow one formulation in the combination to be administered within a certain time period (e.g., 5 minutes, 10 minutes, or even several hours) after another, provided that the circulating half-life concentration of the first administered formulation in the combination is present simultaneously with the other formulation administered thereafter in a therapeutically effective amount. The time delay between the administrations of the formulations may depend on the exact nature of the formulations, the interactions between the individual formulations, their respective half-lives, and other factors readily recognizable by one skilled in the art.

[0083] In another example, the active agent and the additional substances may have different effects, and the device is designed for sequential administration; this means that there is a time difference between the administration of one formulation and another. This time difference can be very short or very long, i.e., when the second (or subsequent) formulation is administered, the first administered formulation may no longer be present in the bloodstream in a therapeutically effective amount (or be present in a subclinical amount).

[0084] In some embodiments, the tissue attachable component may further include one or more additional components. These additional components may be, for example: emulsifiers (surfactants) such as poloxamer or carbomer; stabilizers such as carboxymethyl cellulose; suspending agents such as cellulose, talc; acidifying agents such as citric acid or ascorbic acid; thickening agents such as carbomer, polyethylene oxide; effervescent agents such as sodium bicarbonate, ammonium carbonate; solubilizers such as lecithin; antimicrobial preservatives such as sorbic acid, potassium sorbate; antioxidants such as α-tocopherol, butylated hydroxyanisole; release modifiers such as Tween 80, sodium dodecyl sulfate; coating agents such as ethyl cellulose, cellulose acetate; binders such as hydroxypropyl cellulose, polyvinylpyrrolidone; hardening agents such as stearic acid, wax; plasticizers such as diethyl phthalate, triethyl citrate; and so on.

[0085] As previously described, due to the swelling of the gel-forming material contained within the compartment, the device undergoes a transition from a contracted state to an expanded state.

[0086] The term gel-forming material refers to a compound or composition capable of absorbing liquid to form a three-dimensional volume network of molecules. The gel-forming material may form a physical gel (i.e., a gel in which molecules are held in the network by physical forces) or a chemical gel (i.e., a gel in which molecules are chemically bonded to each other to form a network structure). In some embodiments, the gel-forming material includes one or more gel-forming compounds. In other embodiments, the gel-forming material contains one or more additives.

[0087] According to some embodiments, the gel-forming material includes one or more polymers. According to other embodiments, the gel-forming material may be charged or neutral.

[0088] 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 have a significant impact on the consistency (e.g., hardness or rigidity) of the gel and its rheological properties (e.g., viscosity). Thus, various molecular weights and degrees of crosslinking are some of the parameters that can be used to control the regional behavior and thereby control the deployment rate and / or the expanded size of the device.

[0089] In some embodiments, the gel-forming material may be selected from gelatin, alginate, chitosan, dextran, collagen, hyaluronic acid, polyglutamic acid, elastin, polycarbophil calcium, acrylamide, styrene maleic anhydride, polyethylene oxide, polyacrylic acid, polyethylene glycol, carboxymethyl cellulose, polyvinylpyrrolidone, sodium polyacrylate, hydroxypropyl methylcellulose, or any combination or composition thereof.

[0090] 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 constructs PEC (polyelectrolyte complex) formation upon liquid adsorption. In some embodiments, the at least one charged gel-forming compound is selected from polyvinyl acetate diethylaminoacetate (AEA), polylysine, chitosan, polymethacrylate (acrylic resin E), polyarginine. In other embodiments, the compound having an opposite charge is selected from gelatin, hyaluronic acid, sodium polyacrylate, heparin, polyacrylic acid (carbomer), alginate, pectin, carboxymethyl cellulose.

[0091] In some other embodiments, the gel-forming material is at least one superabsorbent polymer (SAP). The term superabsorbent polymer refers to a polymer (usually cross-linked) or polymer composition that can absorb and retain a large amount of liquid, such as water (or aqueous liquid) relative to the dry mass of the polymer. Non-limiting examples of SAPs are polyethylene glycol (PEG), polyglutamic acid (PGA), polyacrylamide, alginic acid, dextran, polyacrylic acid, carboxymethyl cellulose (CMC), pullulan, starch, and any combination thereof.

[0092] In some other embodiments, the gel-forming material has a swelling ratio (w / w) of about 10 to 100 times (under the condition that the gastrointestinal pH is maintained at 37 °C for 1 hour).

[0093] The term swelling ratio represents the degree of swelling between the state of the gel-forming material before liquid adsorption (i.e., dry or semi-dry form) and the state after adsorbing the maximum possible amount of liquid. The swelling ratio is determined based on weight and calculated according to the following formula:

[0094] [(wet weight) - (dry weight)] / [(dry weight)].

[0095] The gel-forming material can be in the form of a gel film (i.e., a substantially continuous gel layer). According to some embodiments, the gel-forming material exists in the form of gel particles. By other embodiments, the gel-forming particles exist in the form of a gel film, and the gel particles are embedded in a matrix forming the film. In some embodiments, the gel-forming particles in the gel film are substantially arranged as a single layer of gel particles.

[0096] According to other embodiments, the gel-forming material can 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 can be between about 100 μm and about 300 μm.

[0097] According to some embodiments, each compartment can include a different gel-forming material. In some other embodiments, all compartments can contain the same gel-forming material.

[0098] Since the compartment is made of a deformable membrane portion or a continuous deformable membrane, it can be folded in various ways to reduce the size of the device and obtain a contracted state. Thus, the device can be easily applied to a patient in need thereof and enter a target organ or body cavity. In some embodiments, the device is encapsulated in a self-administerable capsule in its contracted state for the patient to swallow.

[0099] In some embodiments, when in the contracted state, the device is folded into a primary folding structure and is configured to deploy during the transition from the contracted state to the expanded state. In other words, the device can be folded to present its contracted state with an overall reduced size or overall reduced volume. After liquid penetrates through the liquid-permeable portion of the membrane, the gel-forming material begins to expand and increase in volume. This in turn applies a force to the deformable membrane, and due to its flexibility and / or deformability, the membrane unfolds and expands simultaneously to present the expanded state of the device.

[0100] According to some embodiments, to further assist in deployment, the device includes at least one deployment unit that is located between the folded portions of the device when in the primary folding structure. The deployment unit is configured to expand upon contact with liquid to assist in the deployment of the device.

[0101] According to some embodiments, the deployment unit includes a liquid-permeable outer shell and at least one gas-forming material contained therein. The liquid-permeable outer shell of the deployment unit allows liquid to penetrate therein, thereby reacting with the gas-forming material to obtain a rapid formation of gas species. The liquid-permeable outer shell is generally formed as a closed structure, and when the gas rapidly expands the outer shell, a "balloon" filled with gas is obtained, which pushes the folds of the device. Together with the expanding gel-forming material, the expansion of the deployment unit helps to deploy the device into its unfolded configuration.

[0102] The gas-forming material is a compound or composition that undergoes a chemical reaction in the presence of water (a reaction of the compound with water, or a reaction promoted between the components of the composition by exposure to water), where at least some of the reaction products are in gaseous form. 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 can dissolve and react with each other after exposure to water to produce carbon dioxide as one of the reaction products.

[0103] In some embodiments, when the device is in its primary folded configuration, the device is encapsulated by an intestinal envelope. The intestinal envelope is configured to hold the device in its primary folded configuration, for example, by causing the intestinal envelope to form dimensions similar to those of the device when in its primary folded configuration. In some embodiments, the intestinal envelope conforms tightly to the device in its primary folded configuration, with substantially no space formed between the intestinal envelope and the device.

[0104] The term enteric material refers to a compound or composition that is configured to be decomposed or dissolved by a liquid only within a specified pH range. For example, preferably, the enteric material is stable (i.e., maintains its physical and chemical structure) when exposed to an acidic environment (such as in the stomach) and is dissolved by a more alkaline liquid (such as those in the intestine).

[0105] The intestinal envelope is used to maintain the device in its folded configuration after ingestion until appropriate conditions (e.g., appropriate pH) are reached within the gastrointestinal tract, at which point the appropriate conditions degrade the intestinal envelope to allow the device to be exposed and to unfold and expand.

[0106] To achieve further compacting in the contracted state, in some embodiments, the device has a secondary rolled-up structure, whereby the device folded into its primary folded configuration is further rolled up around its axis and is configured to unroll and unfold simultaneously during the transition from the contracted state to the expanded state.

[0107] According to some embodiments, when in its secondary folded configuration, the device can be encapsulated in an intestinal envelope. Alternatively, the device can be encapsulated by a first intestinal envelope when in its primary folded configuration and by a second intestinal envelope when in its secondary folded configuration. In other words, the device can be encapsulated by a first intestinal envelope after being folded into its primary folded configuration and then folded or rolled up into its secondary folded configuration and encapsulated by a second intestinal envelope to hold the device in its secondary folded configuration.

[0108] According to other embodiments, the device can first be rolled up and then folded to present its contracted state.

[0109] To prevent undesired or premature deployment of the device, and / or to allow delivery of the device to an appropriate target site, the device can include a biodegradable housing that encapsulates the device in its contracted state. Accordingly, the biodegradable housing is selected to degrade when exposed to appropriate biological conditions (such as pH, presence of certain compounds, etc.).

[0110] Since the device is typically for oral administration and is designed to deploy in the intestine, the biodegradable housing can be made of or coated with an enteric coating.

[0111] In some embodiments, the device is an ingestible device, intended to be deployed, for example, in the stomach or intestine. Thus, such a device is typically encapsulated within a housing that is degradable in the gastrointestinal tract, encapsulating the device in its contracted state. For deployment in the intestine, the housing can be designed or selected, for example, to provide safe passage through the stomach first and to biodegrade only upon exposure to defined conditions in the intestine. By some embodiments, the gastrointestinal tract degradable housing is designed to decompose according to the pH of the environment, thereby deploying at the desired site in the intestine. For example, it is known that different parts of the gastrointestinal tract have different pH values, with the stomach typically having a pH of 1.5 - 3.5, the pH in the duodenum typically being 6, and increasing gradually in the small intestine to approximately 7.4 (until reaching the terminal ileum). The pH in the cecum drops to 5.7 but then gradually rises, reaching a pH of 6.7 in the rectum. Thus, by utilizing a gastrointestinal tract degradable housing that degrades at a defined pH value (or range of values), the device can be deployed at the desired part of the gastrointestinal tract.

[0112] The biodegradable housing can be, for example, a capsule.

[0113] By some embodiments, the device can have two types of housings, one housing wrapping the other. The outer housing is capsule-shaped for easy swallowing of the device and is designed to be degradable in the gastric environment. The second (inner) housing can be a coating or encapsulation layer that coats / encapsulates the device and is configured to hold the device in its contracted state for a predetermined period of time before deployment. For example, the inner housing can be made of an enteric material to prevent deployment of the device in the stomach and to allow its deployment only upon entering the intestine.

[0114] Although the device can be used to deliver at least one active agent to a target site, the device can also be devoid of an active agent or contain only active substances within a compartment. For example, the device can be used to deliver a patch to the wall of a tissue, for example, to temporarily block the passage of substances through the mucosa / epithelial tissue (from the lumen and / or to the lumen), or to cover a perforation or ulcer in the tissue.

[0115] As described, in some embodiments, although the tissue attachable component can be devoid of an active agent, the compartment and / or the gel-forming material can contain active substances / formulations, such as an analgesic or an anti-inflammatory agent, which can be released during the decomposition of the gel-forming material to provide a locally desired effect relatively quickly after administration.

[0116] In the expanded state, the device can have a circular shape, a polygonal shape, or an irregular shape. In its expanded state, the device can be designed to present a three-dimensional (3D) shape, generally conforming to at least a portion of the shape of the lumen or cavity in which it expands (or deploys).

[0117] In other embodiments, in the expanded state, the device can have an annular or ring-shaped configuration.

[0118] In some other embodiments, the device may be configured to substantially assume a cylindrical shape when in the expanded state to define a hollow lumen. This hollow cylindrical shape prevents the formation of an obstruction of the lumen organ or organ cavity when the device is in its expanded state, thereby allowing liquids or solids to pass through the organ when the device is deployed therein.

[0119] In some embodiments, the device is in the form of a sleeve, the sleeve wall being composed of a deformable film, wherein compartments are defined along the circumference of the sleeve, and an attachable tissue layer covers at least a portion of the outer surface of the compartments and extends outwardly from the sleeve surface. Generally, the compartments are elongated along the longitudinal axis of the sleeve and are arranged parallel to each other along the circumference of the sleeve.

[0120] According to some embodiments, when the device is in its primary and / or secondary folded configurations, one or more separation layers are placed between one or more of the folds of the device to prevent the outer layers of the device from adhering to itself. These one or more separation layers may be attached at one or more attachment positions of the device to maintain their position and function when the device is folded into its primary and / or secondary folded configurations. Alternatively, the separation layers may be located between the folds without anchoring them 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 to form the primary and / or secondary folded configuration).

[0121] Various components of the device, such as the liquid-permeable portion, the gel-forming material, etc., may be biodegradable. The term biodegradable refers to any type of breakdown of the device caused by exposure to appropriate biological conditions after administration and expansion. The term includes mechanical disassembly, chemical or physical degradation, chemical or physical decomposition, or any other type of disruption of the integrity of the device during its passage through the gastrointestinal tract and out of the body.

[0122] 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 contracted state and an expanded state, and comprising:

[0123] Two or more self-expanding compartments interconnected by a connecting region, each compartment being formed by two substantially water-insoluble deformable film portions, the two film portions being adhesively bonded to each other at the peripheral portion of the compartment by at least one water-decomposable sealing composition to define a sealed region, each sealed region being a layered structure composed of the water-insoluble deformable films, and at least one water-decomposable sealing composition layer being sandwiched between the water-insoluble deformable films, the water-decomposable sealing composition layer adhesively bonding the water-insoluble deformable films to each other at the peripheral portion.

[0124] Two film portions define a closed space of a compartment therebetween in a region surrounded by a peripheral portion. Each compartment has one or more liquid-permeable portions and a gel-forming material within the closed space. The gel-forming material is configured to swell upon contact with liquid, thereby causing the compartment to swell to irreversibly switch the device from a contracted state to an expanded state;

[0125] The water-decomposable seal composition provides mechanical stability to the sealed area during the transition of the device from the contracted state to the expanded state and is water-soluble. It is configured to provide controlled disintegration of the sealed area after the device expands to the expanded state, thereby causing loss of integrity of the compartment and / or the device after its deployment, and

[0126] At least one active agent carrier member, attached to at least a portion of the outer surface of at least one of the compartments,

[0127] such that the expansion of the device from the contracted state to the expanded state causes the expansion of the compartment to drive the active agent carrier member towards the tissue and hold the active agent carrier member against the tissue for a predefined period of time to allow delivery of the active agent from the active agent carrier member to the tissue.

[0128] On the other hand, the present disclosure provides an ingestible self-expanding device configured to attach an attachable tissue layer to tissue. The device has a contracted state and an expanded state and includes:

[0129] Two or more self-expanding compartments interconnected by a connecting region. Each compartment is formed by two substantially water-insoluble deformable film portions. The two film portions are adhesively bonded to each other at the peripheral portion of the compartment by at least one water-decomposable seal composition to define a sealed area. Each sealed area is a layered structure composed of the water-insoluble deformable films, and a layer of at least one water-decomposable seal composition is sandwiched between the water-insoluble deformable films. The layer of water-decomposable seal composition adhesively bonds the water-insoluble deformable films to each other at the peripheral portion,

[0130] Two film portions define a closed space of a compartment therebetween in a region surrounded by a peripheral portion. Each compartment has one or more liquid-permeable portions and a gel-forming material within the closed space. The gel-forming material is configured to swell upon contact with liquid, thereby causing the compartment to swell to irreversibly switch the device from a contracted state to an expanded state;

[0131] The water-decomposable seal composition provides mechanical stability to the sealed area during the transition of the device from the contracted state to the expanded state and is water-soluble. It is configured to provide controlled disintegration of the sealed area after the device expands to the expanded state, thereby causing loss of integrity of the compartment and / or the device after its deployment, and

[0132] At least one attachable tissue layer coats at least a portion of the outer surface of at least one of the compartments,

[0133] such that expansion of the device from a contracted state to an expanded state causes expansion of the compartment to drive the attachable tissue layer towards the tissue for attaching at least a portion of the attachable tissue layer to the tissue.

[0134] Another aspect of the present disclosure provides an ingestible self-expanding arrangement, which includes an ingestible self-expanding device having a contracted state and an expanded state, and at least one deployment unit having a non-inflated state and an inflated state. The ingestible self-expanding device includes two or more self-expanding compartments interconnected by a connecting region; each compartment is formed by two substantially water-insoluble deformable film portions, and the two film portions are adhesively bonded to each other at the peripheral portion of the compartment by at least one water-decomposable sealing composition to define a sealing region. Each sealing region is a layered structure composed of the water-insoluble deformable films, and sandwiched between the water-insoluble deformable films is at least one water-decomposable sealing composition layer, and the water-decomposable sealing composition layer adhesively bonds the water-insoluble deformable films to each other at the peripheral portion; the two film portions define a closed space at the region surrounded by the peripheral portion therebetween; each compartment has one or more liquid-permeable portions and a gel-forming material within the closed space, and the gel-forming material is configured to expand upon contact with liquid, thereby expanding the compartment to irreversibly switch the device from the contracted state to the expanded state. When in the contracted state, the device is folded in a primary folded configuration, and when in the primary folded configuration, at least one deployment unit is positioned between the folded portions of the device and is configured to switch from the non-inflated state to the inflated state upon contact with liquid to assist in the deployment of the device.

[0135] In another aspect, the present disclosure provides an ingestible arrangement for delivering at least one active agent to tissue, the arrangement including:

[0136] an ingestible self-expanding device having a contracted state and an expanded state, and at least one deployment unit having a non-inflated state and an inflated state,

[0137] wherein the ingestible self-expanding device includes:

[0138] Two or more self - expanding compartments, interconnected by a connecting region, each compartment being formed by two substantially water - insoluble deformable film portions, the two film portions being adhesively bonded to each other at the peripheral portion of the compartment by at least one water - decomposable sealing composition to define a sealing region, each sealing region being a laminated structure composed of the water - insoluble deformable films, and there being at least one water - decomposable sealing composition layer sandwiched between the water - insoluble deformable films, the water - decomposable sealing composition layer adhesively bonding the water - insoluble deformable films to each other at the peripheral portion,

[0139] The two film portions define a closed space therebetween in a region surrounded by the peripheral portion,

[0140] Each compartment has one or more liquid - permeable portions and a gel - forming material within the closed space, the gel - forming material being configured to expand upon contact with a liquid, thereby causing the compartment to expand to irreversibly switch the device from a contracted state to an expanded state, and

[0141] At least one active agent - carrying member, attached to at least a portion of the outer surface of at least one of the compartments,

[0142] such that the expansion of the device from the contracted state to the expanded state causes the expansion of the compartment to drive the active agent - carrying member towards the tissue and hold the active agent - carrying member against the tissue for a predefined period of time to allow the delivery of the active agent from the active agent - carrying member to the tissue; and

[0143] When in the contracted state, the device is folded in a primary folded configuration, and when in the primary folded configuration, at least one deployment unit is positioned between the folded portions of the device and is configured to switch from the non - inflated state to the inflated state upon contact with a liquid to assist in the deployment of the device.

[0144] On the other hand, the present disclosure provides an ingestible arrangement for attaching an attachable tissue layer to tissue, the arrangement comprising:

[0145] An ingestible self - expanding device having a contracted state and an expanded state, and at least one deployment unit having a non - inflated state and an inflated state,

[0146] The ingestible self - expanding device comprises:

[0147] Two or more self - expanding compartments interconnected by connecting regions, each compartment being formed by two substantially water - insoluble deformable film portions, the two film portions being adhesively bonded to each other at the peripheral portion of the compartment by at least one water - decomposable sealing composition to define a sealed region, each sealed region being a layered structure composed of the water - insoluble deformable films, and there being at least one water - decomposable sealing composition layer sandwiched between the water - insoluble deformable films, the water - decomposable sealing composition layer adhesively bonding the water - insoluble deformable films to each other at the peripheral portion,

[0148] The two film portions define a closed space therebetween in a region surrounded by the peripheral portion,

[0149] Each compartment has one or more liquid - permeable portions and a gel - forming material within the closed space, the gel - forming material being configured to expand upon contact with a liquid, thereby causing the compartment to expand to irreversibly switch the device from a contracted state to an expanded state, and

[0150] An attachable tissue layer coating at least a portion of the outer surface of at least one of the compartments;

[0151] Such that the expansion of the device from the contracted state to the expanded state causes the expansion of the compartment to drive the attachable tissue layer towards the tissue for attaching at least a portion of the attachable tissue layer to the tissue; and

[0152] When in the contracted state, the device is folded in a primary folded configuration, and when in the primary folded configuration, at least one deployment unit is positioned between the folded portions of the device and is configured to switch from the non - inflated state to the inflated state upon contact with a liquid to assist in the deployment of the device.

[0153] In other words, an arrangement including a self - deploying device and at least one deployment unit is another aspect of the present disclosure. The combination of the device and the deployment unit is referred to herein as an ingestible arrangement.

[0154] According to some embodiments, the deployment unit includes a liquid - permeable outer shell and at least one gas - forming material contained therein such that contact of a liquid with the gas - forming material causes gas release to inflate the deployment unit.

[0155] Typically, since the operating time of the gas - forming material is faster than that of the gel - forming material, the deployment unit is first inflated to at least partially deploy the contracted device, and then the gel - forming material expands to further deploy the device into its unfolded configuration.

[0156] According to some embodiments, the arrangement includes a single deployment unit.

[0157] According to other embodiments, an arrangement includes two or more deployment units. The two or more deployment units may be attached to each other or may not be attached to each other. The two or more deployment units may be the same as each other or may differ from each other in at least one of the liquid permeability of the liquid-permeable shell, the type of gas-forming material, the amount of gas-forming material, size, and / or geometry, etc.

[0158] In some embodiments, at least one deployment unit is attached to a self-expanding device. In other embodiments, at least one deployment unit is not connected to a self-expanding device in the arrangement.

[0159] In some embodiments, a water-decomposable sealing composition provides mechanical stability to a sealed area during the transition of the device from a contracted state to an expanded state and has water solubility and is configured to provide controlled disintegration of the sealed area after the device expands to the expanded state, thereby causing loss of integrity of the compartment and / or the device after its deployment.

[0160] By another of its aspects, the present disclosure provides a method for delivering at least one active agent to the tissue of a subject in need thereof, the method comprising administering to the subject a self-expanding device encapsulated in a biodegradable shell as disclosed herein.

[0161] In another aspect, a method for prolonging or sustaining the delivery of at least one active agent to the tissue of a subject in need thereof is provided, the method comprising administering to the subject a self-expanding device encapsulated in a biodegradable shell as disclosed herein. Thus, the device of the present disclosure forms a reservoir of the active agent that will be delivered to the target site for an extended period of time.

[0162] By a further aspect, a method for delivering at least one active agent to the tissue of a subject in need thereof is provided, the method comprising administering to the subject a self-expanding device encapsulated in a biodegradable shell as disclosed herein.

[0163] By yet a further aspect, a method for attaching an adherent tissue layer to the tissue of a subject in need thereof through a mucosa is provided, the method comprising administering to the subject a self-expanding device encapsulated in a biodegradable shell as disclosed herein.

[0164] As used herein, the term "about" means including a deviation of ±10% from the value of a specifically recited parameter (such as concentration, time, etc.).

[0165] Whenever a numerical range is expressed herein, it is intended to include any recited numeral (fractional or integral) within the recited numerical range. The phrases “ranging between” a first recited numeral and a second recited numeral and “ranging from” a first recited numeral “to” a second recited numeral are used interchangeably herein and are intended to include the first and second recited numerals and all fractional and integral numerals therebetween.

[0166] Unless the context requires otherwise, the term “comprising” and its variations, will be understood to imply the inclusion of the stated integer or step or group of integers or group of steps but not the exclusion of any integer or step or group of integers or group of steps.

[0167] It should generally be noted that when the term “... at least one...” is applied to any component of a device or arrangement of the present disclosure, it should be understood to include one, two, three, four or even more different occurrences of the component in the device or arrangement.

[0168] It should be understood that, for clarity, certain features of the present disclosure described in the context of different embodiments may also be provided in combination in a single embodiment. Conversely, for simplicity, the various features of the present disclosure described in the context of a single embodiment may also be provided separately or in any suitable sub-combination or in any other described embodiment of the invention in a suitable manner. Certain features described in the context of various embodiments will not be considered essential features of those embodiments unless the embodiment does not function without those elements. BRIEF DESCRIPTION OF THE DRAWINGS

[0169] For a better understanding of the subject matter disclosed herein and to illustrate how it may be practiced, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

[0170] Figures 1A to 1C is a schematic representation of an exemplary device according to an embodiment of the present disclosure, wherein the device is configured as a sleeve: Figure 1A is a front perspective view, Figure 1B is a top cross-sectional view along line I-I, Figure 1C showing the expanded form of the device;

[0171] Figures 1D to 1F is a schematic representation of another exemplary device according to an embodiment of the present disclosure, wherein an active agent carrying member is utilized in place of an attachable tissue member: Figure 1D is a front perspective view, Figure 1E is a top cross-sectional view along line II-II, Figure 1F showing the expanded form of the device, wherein the active agent carrying member is held against tissue on the expanded device;

[0172] Figure 2A is a self - expanding compartment considered alone, defined between two sealed regions;

[0173] Figure 2B is a top cross - sectional view of a device according to an embodiment of the present disclosure, showing the sealed regions;

[0174] Figure 3 is a schematic top view of a device according to another embodiment of the present disclosure, where the compartment is formed by different parts of a deformable film;

[0175] Figures 4A to 4B shows a schematic representation of a device according to another example of the present disclosure, where the compartment is formed by different parts of a deformable film;

[0176] Figures 4C to 4D shows a schematic representation of a device according to another example of the present disclosure, where the compartment is formed by different parts of a deformable film;

[0177] Figures 5A to 5C shows Figure 1A the various main folding structures of the device;

[0178] Figures 5D to 5F shows the device with the main fold wrapped in an intestinal envelope - top view ( Figure 5D ), side view ( Figure 5E ), and wrapped in a degradable housing ( Figure 5F );

[0179] Figures 6A to 6B shows an exemplary main folding structure of the device, where the device includes a deployment unit in a non - inflated state ( Figure 6A ) and an inflated state ( Figure 6B );

[0180] Figures 6C to 6D shows another exemplary main folding structure of the device, where the device includes a deployment unit in a non - inflated state ( Figure 6C ) and an inflated state ( Figure 6D ). Detailed Description

[0181] Below, an exemplary device according to the present disclosure will be described. Although the specific examples show the device as being substantially symmetric, it should be understood that the device can also be asymmetric or have any other shape. Additionally, for ease of illustration, the components of the device are shown out of proportion. Further, although the exemplary device will be shown having an active agent - carrying component or a tissue - attachable component, it should be understood that similar devices without such components are also included within the scope of the examples.

[0182] Figure 1AShown is a self-expanding device according to an embodiment of the present disclosure, in a contracted (non-expanded) state. Figures 1A to 1C The device 100 in Figures 1A to 1C has an overall cylindrical sleeve-like shape and includes a plurality (six in this example) of self-expanding compartments, uniformly labeled 102, and is formed by a deformable two-layer film 104 that is substantially insoluble in water. Although six compartments are shown in this example, it should be understood that any number of compartments may be utilized, such as 2, 3, 4, 5, 6, 7, 8, or even more compartments.

[0183] In this example, the entire sleeve is constructed of two overlapping layers of a deformable film that is substantially insoluble in water, which has liquid-permeable portions 106 to allow liquid to enter the compartments. The deformable films are interconnected along the periphery of the compartments by a sealing region 108, which also constitutes a connecting region connecting adjacent compartments 102 in this example. However, it should also be understood that the sealing region may be part of a larger connecting region between compartments and separate the compartments from each other (not shown).

[0184] Since the films are attached to each other only within the sealing regions (by a water-decomposable sealing composition, as described below), the compartments define enclosed spaces that enclose a gel-forming material 110. After liquid penetrates into the compartments 102 through the portions 106, the gel-forming material 110 is activated, causing the gel-forming material to expand and switch the device from its contracted state (as Figures 1A to 1B shown) to its expanded state (as Figure 1C shown). An attachable tissue component 112 is located on the outer surface of each compartment 102 (i.e., the surface of the film 104 facing outward from the compartment). For example, the attachable tissue component 112 may be in the form of an attachable tissue layer. As described above, the attachable tissue component 112 may contain one or more active agents to be delivered to the tissue. Also as described above, the device may also not have an attachable tissue component 112, for example, as a device configured to deliver an active agent residing on the surface of the compartment, or a device configured to temporarily apply pressure to the tissue (when the device is in its expanded state).

[0185] The attachable tissue component 112 may be provided as a patch that is applied (e.g., adhered) to the film 104 on the compartment 102. For example, when the attachable tissue component is a mucoadhesive layer, the patch may include a mucoadhesive material that is superimposed on a backing layer (not shown), which enables the patch to adhere or attach to the outer surface of the compartment and provides support for the mucoadhesive material. Alternatively, the mucoadhesive material may first be applied to the film 104 at a specific location, and then the compartment 102 may be formed at a location corresponding to the area of the film containing the mucoadhesive material, thereby forming a multi-layer film structure.

[0186] As Figure 1C shown is the device in its expanded form, 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 attachable tissue member closer to the tissue and abuts against the tissue due to the increase in the compartment volume, thereby attaching the attachable tissue member to the tissue.

[0187] As Figures 1D to 1F shown, another configuration of the device is a device 100' similar to the Figures 1A to 1C device, however, device 100' includes an active agent-carrying member 113 instead of an attachable tissue layer 112.

[0188] As Figure 1D shown is device 100', wherein the active agent-carrying member 113 is attached to a self-expanding compartment 102 formed by a deformable bilayer film 104 that is substantially insoluble in water. Portion 106 is liquid-permeable, allowing liquid to enter compartment 102 to react with the gel-forming material 110, thereby expanding compartment 102 and transitioning the device from its contracted state ( Figure 1E ) to its expanded state ( Figure 1F ). As in device 100, in device 100', the deformable films are interconnected along the periphery of the compartment by a sealing region 108.

[0189] As Figure 1F shown, when the device transitions to the expanded state, its volume increases due to the expansion of compartment 102, thereby driving the active agent-carrying member 113 towards the tissue, e.g., towards the intestinal wall 113. The change in volume brings the active agent-carrying member 113 closer to the tissue 115 until the active agent-carrying member 113 contacts the tissue 115. Due to its volume state, as long as device 100 maintains its integrity in the expanded state, the active agent-carrying member 113 is held against the tissue to allow the active agent carried by member 113 to be delivered to the tissue.

[0190] Figure 2A is a close-up cross-sectional view of one of the compartments (of devices 100 and 100'), showing the structure of the sealing region. Compartment 102 is defined between portions of film 104, and the portions of the film are attached to each other at the sealing region 108 along the periphery of the compartment. The sealing region 108 includes at least one water-decomposable sealing composition 114, and the water-decomposable sealing composition 114 is positioned as a layer between the peripheral portions of film 104, thereby forming a closed space that defines the interior of the compartment and encloses the gel-forming material 110.

[0191] The water-decomposable sealing composition includes at least one first hydrophilic material and at least one second hydrophilic material that differ in hydrophilicity and water solubility.

[0192] The hydrophilicity and solubility of the first hydrophilic material are lower than those of the second hydrophilic material. The first hydrophilic material is selected such that, due to its lower hydrophilicity, it is chemically and / or thermodynamically compatible with the water-insoluble deformable film. This compatibility allows the peripheral portions of the water-insoluble deformable film to be adhered to each other by a water-decomposable 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 the formation of the sealed area (e.g., by heat welding, ultrasonic welding, solvent bonding, etc.), thereby allowing a continuous contact surface to exist between the water-insoluble deformable film portion and the water-decomposable sealing composition. Thus, this compatibility enables the formation of a closed compartment with a sealed area that maintains its mechanical integrity during changes in the volume of the compartment when the compartment is converted between a contracted state and an expanded state.

[0193] When exposed to appropriate pH conditions in the intestine, typically at a pH of about 6 - 7, the first hydrophilic material generally undergoes chemical or physical decomposition. When the first hydrophilic material is selected to react under defined conditions in the intestine, this selection provides further control over the disintegration of the device after ingestion, thus preventing undesired disintegration when the device passes through the stomach but allowing disintegration under the pH conditions in the intestine.

[0194] However, due to its lower solubility and the limited exposure to water due to the structure of the sealed area (i.e., the limited surface area of the water-decomposable sealing composition layer exposed to water), a suitable decomposition environment is required.

[0195] To obtain such a suitable decomposition environment, the water-decomposable sealing composition includes a second hydrophilic material having a higher hydrophilicity. The second hydrophilic material is used to rapidly absorb and capture water diffusing into the sealed area, thereby forming an environment that supports the solubilization of the first hydrophilic material to allow the disintegration of the sealed area and the loss of integrity of the device. Due to its higher hydrophilicity, the second hydrophilic material also allows for the controlled delivery of water to the sealed area after deployment, thereby controlling the exposure of the first hydrophilic material to water and further controlling the onset of its decomposition.

[0196] The combination of the first hydrophilic material and the second hydrophilic material allows for a high degree of controllability of the disintegration rate of the sealed area: due to the water-insoluble films sandwiching a water-decomposable sealing composition therebetween, and due to the limited diffusibility of water through the films, a relatively small amount of water can penetrate into the sealed area. The second hydrophilic material allows for the rapid absorption and capture of the water diffusing into the sealed area, thereby enabling the control of the exposure of the first hydrophilic material to water for its solubilization. Since the first hydrophilic material is used to form an adhesion between two water-insoluble films, the increased absorption of water by the second hydrophilic material provides appropriate conditions for the solubilization of the first hydrophilic material, thereby causing the disintegration of the sealed area and the loss of integrity of the compartment and / or device. By balancing and selecting the first hydrophilic material and the second hydrophilic material, different disintegration start times and disintegration rates can be obtained.

[0197] As Figure 2B shown in Figures 1A to 1B the cross-section of the device, which shows the formation of compartments between the sealed areas. It should be understood that the same construction of compartments and sealed areas is applied to Figures 1D to 1E the device. Since the device has a typical closed form, the layer of the water-decomposable sealing composition 114 is sandwiched between the films 104, significantly limiting the exposure of the water-decomposable sealing composition to liquids; thus, the second hydrophilic material that promotes water absorption into the sealed area allows for an increased water absorption into the sealed area so that the first hydrophilic material can dissolve to decompose the sealed area.

[0198] In operation, due to being exposed to appropriate conditions after ingestion, the device undergoes a series of transformations. Generally, the device is encapsulated in a biodegradable shell in its folded structure, such as encapsulated in a capsule 118 (as Figure 5F illustrated). After, for example, orally administering the device, the biodegradable capsule 118 passes through the stomach and decomposes when exposed to appropriate conditions in the intestine, thereby exposing the device 100. As described, in some configurations, the biodegradable capsule 118 degrades in the stomach and the device is encapsulated / coated with an enteric layer 122 ( Figures 5E to 5F ), and the enteric layer 122 protects the device as it passes through the stomach and is designed to decompose when exposed to appropriate conditions in the intestine. However, it should be noted that in other structures, the enteric layer 122 may not be present. The enteric layer generally comprises or is formed of one or more enteric polymers.

[0199] After the capsule 118 (or enteric layer) decomposes, the fluid in the intestine penetrates into the liquid-permeable part of the deformable film 104 of the compartment 102, causing the gel-forming material 110 contained therein to swell. The swelling of the gel-forming material causes the swelling of the compartment and the deformation of the film, making the device assume an expanded state. In the expanded state, the swelling of the gel-forming material causes a force to be applied to the film 104 against the tissue at the target site, forcing the tissue-adherable component 112 to contact and adhere to the tissue ( Figure 1C ), or fixing the active-agent-carrying component 113 against the tissue 115 as long as the device maintains its integrity in the expanded state ( Figure 1F ). Thus, the transition of the device from its contracted state to its expanded state drives the tissue-adherable component 112 (e.g., the mucosal adhesive layer) or the active-agent-carrying component 113 associated with the compartment towards the tissue and brings it into close contact with the tissue under the application of a force (applied by the swollen gel-forming material).

[0200] After expansion, the water-decomposable sealing composition in the sealing region 108 absorbs water from the environment and causes the controlled disintegration of the sealing region 108, resulting in the loss of integrity of the compartment (i.e., splitting or disintegration) and the fragmentation of the device, leading to its withdrawal from the target site. After the compartment loses its integrity, the gel-forming material 110 is removed from the target site by the natural movement of the intestine, leaving the tissue-adherable component attached or adhered to the tissue. When the tissue-adherable component 112 contains an active agent, the active agent contained in the mucosal adhesive component is delivered to the tissue during the period when the tissue-adherable component remains adhered to the tissue.

[0201] Since the tissue detaches from the intestinal wall every few hours, the detachment of the tissue also causes the detachment and disintegration of the tissue-adherable component and the removal of the tissue-adherable layer from the intestine.

[0202] Alternatively, when the device includes the active-agent-carrying component 113, the loss of integrity of the compartment will result in the cessation of contact between the active-agent-carrying component 113 and the tissue, followed by the withdrawal of the device fragments from the target site.

[0203] Figure 3Another exemplary structure of the device according to an embodiment of the present disclosure is provided. The device 200 is composed of respective portions 204 of a water-insoluble deformable film, which are arranged in an overlapping pair-wise manner to form compartments and are attached to each other along their peripheral portions to form a sealed area 208 and a space (not labeled) of the compartment for accommodating the gel-forming material. Each film portion 204 includes at least one liquid-permeable portion 206 that allows water to penetrate into the compartment to activate the gel-forming material at the target site, thereby switching the device from its contracted state to its expanded state (due to the expansion of the gel-forming material in the compartment), to allow the attachable tissue component 212 to attach to the tissue at the target site. In this embodiment, after expansion, the device will begin to decompose along the peripheral sealed area 208 after the second hydrophilic material absorbs sufficient water to dissolve the first hydrophilic material in the water-decomposable sealing composition.

[0204] It should be noted again that an active agent-carrying component (not shown) can be used instead of the attachable tissue component 212, keeping the active agent-carrying component against the tissue to form contact with the tissue (but not adhering to the tissue), to allow the delivery of the active agent to the tissue, as long as the device maintains its integrity in its expanded state.

[0205] The water-insoluble film portions are arranged in different configurations and connection regions are constructed to obtain the device as shown in Figures 4A to 4B and Figures 4C to 4D In these examples, the connection region consists of the sealed areas of adjacent compartments, and the sealed areas are stacked on top of each other.

[0206] In Figures 4A to 4B configuration, the compartments are attached to each other such that two films of each compartment are attached to adjacent compartments - for example, compartment 102A is attached to two adjacent compartments 102B and 102C; compartment 102B is attached through the upper film portion 104t of the sealed area 108AB, while the other compartment 102C is attached through the lower film 104b of the sealed area 108AC of compartment 102A.

[0207] In Figures 4C to 4D configuration, the compartments are attached to each other such that only one film in each compartment is attached to an adjacent compartment - for example, compartment 102A' is attached to two adjacent compartments 102B' and 102C'; both compartments 102B' and 102C' are attached through their upper film portions 104t' to the lower film portion 104b' of compartment 102A' in the sealed areas 108AB' and 108AC' respectively.

[0208] The attachment of one compartment to another is generally made using a water-decomposable sealing composition.

[0209] In Figures 4A to 4DIn an embodiment, the sealed areas of adjacent compartments are stacked on top of each other to form a connection area. By stacking the sealed areas, the connection area includes multiple alternating layers, namely layers of the peripheral part of a deformable film that is substantially insoluble in water, with layers of a water-decomposable sealing composition arranged therebetween. This layered arrangement allows the water-decomposable sealing composition to serve both as a structural component of the device that can attach one compartment to another during device production and to provide mechanical integrity during the transitions of the device between its folded and unfolded configurations and between its contracted and expanded states.

[0210] Note that the water-decomposable sealing composition that connects the sealed areas to each other in the connection area can be the same as the water-decomposable sealing composition within the sealed area or a different water-decomposable sealing composition. This possible variation in the water-decomposable sealing composition allows for different onset and / or rates of disintegration of the connection area and the sealed area; in other words, by choosing different water-decomposable sealing compositions within and between the sealed areas, a gradual disintegration can be obtained - first disassembling the device into individual compartments and then disassembling the individual compartments themselves.

[0211] To obtain compactification of the device in its contracted (non-expanded) state, the device can be folded into various folded configurations (i.e., various main folded configurations as Figures 5A to 5C shown) and / or rolled-up configurations (not shown) to allow it to unfold (and / or unroll) during the transition from the contracted state to the expanded state. In other words, the device can be folded to present its contracted state, with an overall reduced size or an overall reduced volume. After a liquid penetrates through the permeable part of the deformable film, the gel-forming material begins to expand and increase in volume. This in turn applies a force to the deformable film, and due to its flexibility and / or deformability, the film unfolds to present the expanded state of the device.

[0212] Figures 5A to 5C Various configurations for folding the device to give it a more compact ingestion form are shown. For ease of visualization, only the attachable tissue component 112 is shown on the film 104. Additionally, it should be understood that an active-agent carrying component 113 can be used instead of the attachable tissue component 112 (not shown in Figures 5A - 5F ). When the device is in the contracted state, the device can be folded into one of the main folded configurations as Figures 5A - 6C shown and encapsulated in a biodegradable capsule (not shown). After the biodegradable capsule is ingested and decomposes, exposure to the liquid in the gastrointestinal tract causes the gel-forming material in the compartment to expand, thereby expanding the compartment and causing at least partial expansion and unfolding to the expanded state.

[0213] After being folded into the main folded configuration, the folded device can be wrapped by an intestinal envelope 122, for example asFigures 5D to 5E As shown, the intestinal envelope 122 is used to maintain the device in its primary folded structure until the appropriate conditions for deployment within the digestive tract are reached. The device can be further encapsulated within a biodegradable capsule 118.

[0214] To achieve further compactification in the contracted state, in some embodiments, the device can have a secondary rolled-up structure (not shown), whereby the folded device is further rolled up around its axis and is configured to simultaneously deploy and unroll during the transition from the contracted state to the expanded state. It should be noted that the intestinal envelope can wrap the device in its secondary folded structure (not shown), instead of or in addition to the intestinal envelope 122 wrapping the device in its primary folded structure. In the case where the device includes two intestinal envelopes, the first envelope and the second envelope can be configured to have the same decomposition / dissolution properties or different decomposition / dissolution properties.

[0215] Figures 6A to 6B Shown is a device or arrangement according to another embodiment of the present disclosure, which further includes a deployment unit. For ease of viewing, only the overall outline of the device is shown. An arrangement 300 including a device 100' (similar to Figure 5A 's folded device) in its contracted and folded structures is associated with a deployment unit 302 located between the folds of the device ( Figure 6A ). The deployment unit 302 includes a liquid-permeable outer shell 304 and at least one gas-forming material 306 contained therein, such that contact of the liquid with the gas-forming material causes the release of gas 308 to inflate the deployment unit (illustrated by arrow 310) to assist in switching the device 100' to its deployed structure (as Figure 6B shown). Generally, the reaction rate of the gas-forming material encapsulated in the outer shell 304 is faster than the expansion rate of the gel-forming material in the compartment. In other words, the operating time of the gas-forming material is faster than the operating time of the gel-forming material. The initial deployment of the device is facilitated by the inflation of the deployment unit, while further deployment and expansion from the contracted state to the expanded state are achieved by the expansion of the gel-forming material encapsulated in the compartments of the device.

[0216] As Figures 6C to 6D shown is an arrangement 400 for a device similar to Figure 5B 's folded device 100'', where the functional features are similar to those in Figures 6A to 6B (converted by 100). Figures 6A to 6B 's device and Figures 6C to 6D 's device have different primary folded structures.

[0217] Although the examples provided herein discuss the deployment of the device in the intestine, it is to be understood that the device can be administered and deployed in any other suitable body lumen or cavity. For example, the device can be administered to other organs such as the urinary tract, vagina, rectum, intranasally, etc. When the target organ or cavity is relatively accessible to the user, the device can be administered by using a dedicated applicator (not shown) to insert the device into the organ or cavity. The properties of the water-degradable sealant composition are then adjusted to accommodate the specific conditions of the desired target site.

Claims

1. An ingestible self - expanding device, the device having a contracted state and an expanded state, and comprising: Two or more self - expanding compartments interconnected by a connecting region, each compartment formed by two substantially water - insoluble deformable film portions, the two film portions being adhesively bonded to each other at the peripheral portion of the compartment by at least one water - decomposable sealing composition to define a sealing region, each sealing region being a layered structure composed of the water - insoluble deformable films, with at least one water - decomposable sealing composition layer sandwiched between the water - insoluble deformable films, the water - decomposable sealing composition layer adhesively bonding the water - insoluble deformable films to each other at the peripheral portion, The two film portions define a closed space of the compartment at the region surrounded by the peripheral portion therebetween, Each compartment has one or more liquid - permeable portions and a gel - forming material within the closed space, the gel - forming material being configured to expand upon contact with liquid, thereby causing the compartment to expand to irreversibly switch the device from the contracted state to the expanded state, The water - decomposable sealing composition provides mechanical stability to the sealing region during the transition of the device from the contracted state to the expanded state, and is water - soluble, being configured to provide controlled disintegration of the sealing region after the device expands to the expanded state, thereby causing loss of integrity of the compartment and / or the device after its deployment.

2. The device according to claim 1, wherein the connecting region includes the sealing region.

3. The device according to claim 1, wherein adjacent compartments are interconnected by adhesively bonding one or more of their respective sealing regions with a water - decomposable sealing composition.

4. The device according to claim 3, wherein the compartments are interconnected by stacking the sealing regions of adjacent compartments one on top of the other, such that the connecting region is composed of the stacked sealing regions to form a layered structure of alternating layers of the water - insoluble deformable films and the water - decomposable sealing composition.

5. The device according to claim 3, wherein the sealing region includes a first water - decomposable sealing composition, and adjacent compartments are interconnected by adhesively bonding one or more of their respective sealing regions with a second water - decomposable sealing composition, the first water - decomposable sealing composition and the second water - decomposable sealing composition being different from or the same as each other.

6. The device according to any one of claims 1 to 5, wherein the water - decomposable sealing composition includes at least one first hydrophilic material and at least one second hydrophilic material; The hydrophilicity of the first hydrophilic material is lower than that of the second hydrophilic material; and The water - solubility of the first hydrophilic material is less than that of the second hydrophilic material.

7. The device according to claim 6, wherein the first hydrophilic material is chemically and / or thermodynamically compatible with the water - insoluble deformable film for the water - insoluble deformable films to be adhesively bonded to each other at the sealing region.

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

9. The device according to any one of claims 6 to 8, wherein the weight ratio between the first hydrophilic material and the second hydrophilic material is between about 4:1 and 3:

2.

10. The device according to any one of claims 1 to 9, wherein the water-decomposable sealing composition is located within the area of the sealing region.

11. The device according to claim 10, wherein each sealing region comprises one or more of said areas.

12. The device according to any one of claims 1 to 11, comprising at least one tissue attachable member connected to at least a portion of the outer surface of at least one of the compartments such that expansion of the device from the contracted state to the expanded state causes expansion of the compartment to drive the tissue attachable member towards the tissue of the gastrointestinal tract for attaching at least a portion of the tissue attachable member to the tissue.

13. The device according to claim 12, wherein the tissue attachable member comprises at least one mucoadhesive material.

14. The device according to claim 12, wherein the tissue attachable member is a tissue attachable layer.

15. The device according to claim 14, wherein the tissue attachable layer is a mucoadhesive layer.

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

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

18. The device according to claim 17, wherein the active agent is a pharmaceutical active agent.

19. The device according to any one of claims 1 to 11, comprising at least one active agent carrying member connected to at least a portion of the outer surface of at least one of the compartments such that expansion of the device from the contracted state to the expanded state causes expansion of the compartment to drive the active agent carrying member towards the tissue of the gastrointestinal tract and maintain the active agent carrying member in contact with the tissue when the device is in the expanded state.

20. The device according to claim 19, wherein the active agent carrying member is in the form of a layer comprising at least one active agent and coating at least a portion of the outer surface of the compartment.

21. The device according to claim 19, wherein the active agent carrying member is a solid composition comprising at least one active agent.

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

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

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

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

26. The device according to any one of claims 1 to 25, wherein, when in the contracted state, the device is folded in a primary folded structure and is configured to be deployed during the transition from the contracted state to the expanded state.

27. The device according to claim 26, comprising at least one deployment unit that is positioned between the folded portions of the device when in the primary folded structure and is configured to expand upon contact with liquid to assist in the deployment of the device.

28. The device according to claim 27, wherein the deployment unit comprises a liquid-permeable outer shell forming a closed structure and at least one gas-forming material contained therein.

29. The device according to claim 27 or 28, wherein when in the primary folded structure, the device is wrapped in an intestinal membrane.

30. The device according to any one of claims 27 to 29, wherein, when in the contracted state, the device has a secondary rolled-up structure whereby the folded device is further rolled up about its axis and is configured to be deployed and unrolled simultaneously during the transition from the contracted state to the expanded state.

31. The device according to claim 30, wherein when in the secondary rolled-up structure, the device is wrapped in an intestinal membrane.

32. The device according to claim 31, wherein when in the primary folded structure, the device is wrapped in a first intestinal membrane and when in the secondary rolled-up structure, the device is wrapped in a second intestinal membrane.

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

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

35. The device according to 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 attach a tissue-attachable component to tissue, the device having a contracted state and an expanded state, and comprising: two or more self-expanding compartments interconnected by a connecting region, each compartment being formed by two substantially water-insoluble deformable film portions that are adhesively bonded to each other at the peripheral portion of the compartment by at least one water-decomposable sealing composition to define a sealing region, each sealing region being a layered structure composed of the water-insoluble deformable films with at least one water-decomposable sealing composition layer sandwiched between the water-insoluble deformable films, the water-decomposable sealing composition layer adhesively bonding the water-insoluble deformable films to each other at the peripheral portion. The two film portions define a closed space of the compartment therebetween at a region surrounded by the peripheral portion. Each compartment has one or more liquid-permeable portions and a gel-forming material within the closed space, the gel-forming material being configured to swell upon contact with liquid so as to cause the compartment to expand to irreversibly switch the device from the contracted state to the expanded state. The water-decomposable sealing composition provides mechanical stability to the sealed region during the transition of the device from the contracted state to the expanded state and is water-soluble and configured to provide controlled disintegration of the sealed region after the device expands to the expanded state, thereby resulting in the loss of integrity of the compartment and / or the device after its deployment, and at least one tissue attachable member attached to at least a portion of the outer surface of at least one of the compartments. such that expansion of the device from the contracted state to the expanded state causes expansion of the compartment to drive the tissue attachable member towards the tissue for attaching at least a portion of the tissue attachable member to the tissue.

37. An ingestible self-expanding device configured to deliver at least one active agent to tissue, the device having a contracted state and an expanded state, and comprising: Two or more self-expanding compartments interconnected by a connecting region, each compartment being formed by two substantially water-insoluble deformable film portions, the two film portions being adhesively bonded to each other at the peripheral portion of the compartment by at least one water-decomposable sealing composition to define a sealed region, each sealed region being a layered structure composed of the water-insoluble deformable films, with at least one water-decomposable sealing composition layer sandwiched between the water-insoluble deformable films, the water-decomposable sealing composition layer adhesively bonding the water-insoluble deformable films to each other at the peripheral portion. The two film portions define a closed space of the compartment therebetween at a region surrounded by the peripheral portion, each compartment having one or more liquid-permeable portions and a gel-forming material within the closed space, the gel-forming material being configured to swell upon contact with liquid so as to cause the compartment to expand to irreversibly switch the device from the contracted state to the expanded state. The water-decomposable sealing composition provides mechanical stability to the sealed region during the transition of the device from the contracted state to the expanded state and is water-soluble and configured to provide controlled disintegration of the sealed region after the device expands to the expanded state, thereby resulting in the loss of integrity of the compartment and / or the device after its deployment, and at least one active agent carrying member attached to at least a portion of the outer surface of at least one of the compartments. Expansion of the device from the contracted state to the expanded state causes expansion of the compartment to drive the active agent carrying member towards the tissue and hold the active agent carrying member against the tissue for a predefined period of time to allow delivery of the active agent from the active agent carrying member to the tissue.

38. An ingestible self-expanding arrangement comprising: an ingestible self-expanding device having a contracted state and an expanded state, and at least one deployment unit having a non-inflated state and an inflated state; The ingestible self-expanding device comprises: two or more self-expanding compartments interconnected by a connecting region, each compartment being formed by two substantially water-insoluble deformable film portions, the two film portions being adhesively bonded to each other at the peripheral portion of the compartment by at least one water-decomposable sealing composition to define a sealing region, each sealing region being a layered structure composed of the water-insoluble deformable films, with at least one water-decomposable sealing composition layer sandwiched between the water-insoluble deformable films, the water-decomposable sealing composition layer adhesively bonding the water-insoluble deformable films to each other at the peripheral portion, the two film portions defining a closed space of the compartment at the region surrounded by the peripheral portion therebetween, each compartment having one or more liquid-permeable portions within the closed space and enclosing a gel-forming material configured to expand upon contact with liquid, thereby expanding the compartment to irreversibly switch the device from the contracted state to the expanded state; and when in the contracted state, the device is folded in a primary folded configuration, and when in the primary folded configuration the at least one deployment unit is positioned between the folded portions of the device and is configured to switch from the non-inflated state to the inflated state upon contact with liquid to assist in the deployment of the device.

39. An ingestible arrangement for delivering at least one active agent to tissue, the arrangement comprising: an ingestible self-expanding device having a contracted state and an expanded state, and at least one deployment unit having a non-inflated state and an inflated state; The ingestible self-expanding device comprises: two or more self-expanding compartments interconnected by a connecting region, each compartment being formed by two substantially water-insoluble deformable film portions, the two film portions being adhesively bonded to each other at the peripheral portion of the compartment by at least one water-decomposable sealing composition to define a sealing region, each sealing region being a layered structure composed of the water-insoluble deformable films, with at least one water-decomposable sealing composition layer sandwiched between the water-insoluble deformable films, the water-decomposable sealing composition layer adhesively bonding the water-insoluble deformable films to each other at the peripheral portion, the two film portions defining a closed space therebetween at the region surrounded by the peripheral portion Each compartment has one or more liquid-permeable portions and a gel-forming material within the enclosed space, the gel-forming material being configured to swell upon contact with liquid so that the compartment swells to irreversibly switch the device from the contracted state to the expanded state, and at least one active agent-carrying member attached to at least a portion of the outer surface of at least one of the compartments, such that expansion of the device from the contracted state to the expanded state causes expansion of the compartment to drive the active agent-carrying member toward the tissue and hold the active agent-carrying member against the tissue for a predefined period to allow delivery of the active agent from the active agent-carrying member to the tissue; and when in the contracted state, the device is folded in a primary folded configuration, and when in the primary folded configuration the at least one deployment unit is positioned between the folded portions of the device and is configured to switch from the non-inflated state to the inflated state upon contact with liquid to assist in the deployment of the device.

40. An ingestible arrangement for attaching an attachable tissue component to tissue, the arrangement comprising: an ingestible self-expanding device having a contracted state and an expanded state, and at least one deployment unit having a non-inflated state and an inflated state; the ingestible self-expanding device comprising: two or more self-expanding compartments interconnected by a connecting region, each compartment formed by two substantially water-insoluble deformable film portions, the two film portions being adhesively bonded to each other at the peripheral portion of the compartment by at least one water-decomposable sealing composition to define a sealed region, each sealed region being a layered structure composed of the water-insoluble deformable films, with at least one water-decomposable sealing composition layer sandwiched between the water-insoluble deformable films, the water-decomposable sealing composition layer adhesively bonding the water-insoluble deformable films to each other at the peripheral portion, the two film portions defining an enclosed space of the compartment at a region surrounded by the peripheral portion, each compartment having one or more liquid-permeable portions and a gel-forming material within the enclosed space, the gel-forming material being configured to swell upon contact with liquid so that the compartment swells to irreversibly switch the device from the contracted state to the expanded state, and an attachable tissue component attached to at least a portion of the outer surface of at least one of the compartments, such that expansion of the device from the contracted state to the expanded state causes expansion of the compartment to drive the attachable tissue component toward the tissue for attaching at least a portion of the attachable tissue component to the tissue; and when in the contracted state, the device is folded in a primary folded configuration, and when in the primary folded configuration the at least one deployment unit is positioned between the folded portions of the device and is configured to switch from the non-inflated state to the inflated state upon contact with liquid to assist in the deployment of the device.

41. The arrangement according to any one of claims 38 to 40, wherein the deployment unit comprises a liquid-permeable outer shell and at least one gas-forming material contained therein, such that contact of the liquid with the gas-forming material causes release of gas to inflate the deployment unit.

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

43. The arrangement according to claim 42, wherein the two or more deployment units are attached to each other.

44. The arrangement according to claim 42, wherein the two or more deployment units are not attached to each other.

45. The arrangement according to claim 43 or 44, wherein the two or more deployment units differ from each other in at least one of the liquid permeability of the liquid-permeable outer shell, the type of gas-forming material, the amount of gas-forming material, the size, and / or the geometry.

46. The arrangement according to claim 43 or 44, wherein the two or more deployments are identical to each other.

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

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

49. The arrangement according to any one of claims 38 to 48, wherein the water-decomposable sealing composition provides mechanical stability to the sealed area during the transition of the device from the contracted state to the expanded state, and is water-soluble and configured to provide controlled disintegration of the sealed area after the device expands to the expanded state, thereby causing loss of integrity of the compartment and / or the device after its deployment.

50. The arrangement according to any one of claims 38 to 49, wherein when the device is in the main folded structure and the deployment unit is in its non-inflated state, the arrangement is wrapped by an intestinal envelope.

51. The arrangement according to any one of claims 38 to 50, wherein when the device is in the contracted state and the deployment unit is in its non-inflated state, the arrangement has a secondary rolled-up structure, whereby the folded device is further rolled up around its axis and is configured to be deployed and spread out simultaneously during the transition from the contracted state to the expanded state.

52. The arrangement according to claim 51, wherein when the arrangement is in the secondary rolled-up structure, the arrangement is wrapped by an intestinal envelope.

53. The arrangement according to claim 52, wherein when the device is in the main folded structure and the deployment unit is in its non-inflated state, the arrangement is wrapped by a first intestinal envelope, and when in the secondary rolled-up structure, the arrangement is wrapped by a second intestinal envelope.

54. The arrangement according to any one of claims 38 to 53, comprising a biodegradable housing that encapsulates the arrangement in its main folded structure.

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

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

57. The arrangement according to any one of claims 39 and 41 to 54, wherein the active agent carrying component is in the form of a layer comprising at least one active agent and coating at least a part of the outer surface of the compartment.

58. The device according to claim 57, wherein the active agent carrying component is a solid composition comprising at least one active agent.

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

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

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

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

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