Expandable device for delivering activators to tissues

Abstract

The present disclosure relates to expandable devices, particularly self-expanding devices for adhesion to tissue, such as intestinal tissue. The present disclosure also relates to expandable devices, particularly self-expanding devices for delivery of at least one active agent to or across tissue.

Description

Technical Field

[0005] ,

[0001] The present disclosure relates to an expandable device, specifically a self-expanding device, for adhesion to tissue, such as intestinal tissue, and optionally for delivering at least one active agent to or across the tissue.

Background Art

[0002] References considered relevant as background to the presently disclosed subject matter are listed below. · PCT Patent Publication No. WO2016 / 015648 · PCT Patent Publication No. WO2008 / 062440 · PCT Patent Publication No. WO2009 / 125432 · PCT Patent Publication No. WO2013 / 188819 · PCT Patent Publication No. WO2015 / 026552 · PCT Patent Publication No. WO2015 / 120471

[0003] Approval of the above references in this specification should not be inferred to mean that they are relevant in any way to the patentability of the subject matter of the present disclosure.

[0004] Background Art The effective and targeted delivery of various compounds and active agents to tissue (e.g., the inner layer of the intestinal tract) or across tissue has proven to be a challenge over the years. Due to the mucus secretions that cover various tissues to provide a hydrated environment and lubrication of biological surfaces, targeted delivery of active agents often requires the use of mucus adhesion components or other tissue attachment arrangements that can adhere to the tissue over a predefined period, thereby providing a longer contact time between the tissue and the active agent and enabling the tissue to absorb the active agent through and / or across the tissue for a longer time.

[0005] Many of the approaches used involve compositions containing particulate mucoadhesive components (e.g., capsules containing an activator dispersed in mucoadhesive particles, or devices that disperse mucoadhesive particles when exposed to defined conditions). However, such compositions are difficult to disperse near the relevant tissue once, and the location where the mucoadhesive adheres to the tissue cannot be adequately controlled. Furthermore, such systems often suffer from insufficient adhesive strength and / or insufficient residence time at the target site.

[0006] Other approaches propose using various applicators to bring mucosal adhesives into contact with target tissue. Using such applicators is often invasive and therefore not well-suited for delivering activators to internal organs (such as the digestive tract).

[0007] General explanation This disclosure provides a self-expanding device which can be administered to a subject and undergo controlled deployment or adhesion to a tissue of one or more tissue-adherent layers (or patches), such as a mucoadhesive material. The tissue-adherent layers may comprise one or more activators that can be delivered to and / or across the tissue to which the tissue-adherent layers are attached.

[0008] Additionally, achieving good adhesion and sufficient bonding time in the mucous adhesive layer may be useful in blocking the movement of ions, molecules, and / or small particles across the tissue.

[0009] The device of this disclosure is designed to controllably increase in volume in order to drive a tissue-adherent layer or patch, such as a layer of mucosal adhesive material, toward tissue and to temporarily apply force to it in order to adhere or bond the layer or patch to the tissue at a desired location. Thus, once the device is administered, it is exposed to appropriate conditions for deployment, the device expands, and the tissue-adherent layer is delivered to the tissue.

[0010] Accordingly, one aspect of the present disclosure provides a self-expandable device comprising: at least one self-expandable compartment formed from a substantially continuous deformable film having one or more liquid-permeable sections, wherein the compartment is configured to enclose a gel-forming material therein, and the gel-forming material expands upon contact with a liquid; and a tissue-adherent layer coating at least a portion of the outer surface of the compartment, wherein the device is configured to adhere the tissue-adherent layer to a tissue by irreversibly expanding the device from a collapsed state to an expanded state upon contact between the gel-forming material and a liquid.

[0011] In another embodiment, the Disclosure provides a self-expandable device configured to adhere a tissue-adherent layer to tissue, the device having a collapsed state and an expanded state. The device comprises at least one self-expandable compartment formed from a substantially continuous deformable film having one or more liquid-permeable sections, the compartment enclosing a gel-forming material therein, the gel-forming material being configured to expand upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state. The device also comprises a tissue-adherent layer coating at least a portion of the outer surface of the compartment, so that the expansion of the device from a collapsed state to an expanded state causes the expansion of the compartment, thereby driving the tissue-adherent layer toward the tissue to adhere at least a portion of the tissue-adherent layer to the tissue.

[0012] In a further embodiment, the Disclosure provides a self-expandable device for delivering at least one activator to and / or across tissue, the device having a collapsed state and an expanded state. The device comprises at least one self-expandable compartment formed from a substantially continuous deformable film having one or more liquid-permeable sections, the compartment enclosing a gel-forming material therein, the gel-forming material being configured to expand upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state. The device also comprises a tissue-adherent layer coating at least a portion of the outer surface of the compartment, the tissue-adherent layer comprising at least one mucoadhesive material and at least one activator. The expansion of the device from a collapsed state to an expanded state causes the expansion of the compartment, and thus drives the tissue-adherent layer toward the tissue to adhere at least a portion of the tissue-adherent layer to the tissue, thereby enabling delivery of the activator to and / or across the tissue.

[0013] In other words, the device comprises a closed compartment formed from a deformable film having one or more liquid-permeable sections, holding one or more gel-forming materials therein. For administration, the device is in a collapsed state, i.e., has a compact configuration with a given initial volume. Once administered and exposed to suitable conditions, as will be further discussed below, the penetration of liquid through the liquid-permeable sections of the film causes the gel-forming material to expand, thereby increasing its volume and irreversibly unfolding the device into an expanded state. The outer surface of the compartment is at least partially coated with a tissue-adherent layer, e.g., a mucoadhesive layer. Thus, the expansion of the compartment into an expanded state drives and / or extrudes the tissue-adherent layer toward the tissue, allowing it to come into contact with the tissue and adhere or bond to it.

[0014] In another embodiment, a self-expandable device is provided configured to adhere a tissue-adhering layer to tissue, the device having an unexpanded (collapsed) state and an expanded state, and having one or more liquid-permeable sections, and having a collapsed configuration in the unexpanded state of the device, the at least one self-expandable core formed from a substantially continuous, closed, deformable film, the film encloses a volume holding at least one gel-forming material configured to expand upon contact with a liquid, thereby increasing the volume of the core and unfolding the film into an expanded configuration to irreversibly switch the device from an unexpanded state to an expanded state, the expansion of the device from an unexpanded (collapsed) state to an expanded state causes the core to unfold and drives the tissue-adhering layer toward the tissue to adhere at least a portion of the tissue-adhering layer to the tissue.

[0015] The term "tissue-adherent layer" refers to a layer that can self-adhere to tissue, typically mucosal epithelial tissue. Attachment of the tissue-adherent layer to the tissue can be achieved by mechanical means, such as microneedles or microhooks, which can be temporarily fixed within the tissue upon application of pressure by a self-expandable core. Alternatively, the tissue-adherent layer can be a mucoadhesive layer.

[0016] The tissue-adhering layer may contain or support at least one activator to be delivered to the tissue. For example, a mucoadhesive layer may contain at least one mucoadhesive material and at least one activator, in which case the adhesion of the mucoadhesive layer to the tissue allows for the delivery of the activator to or across the tissue. In another embodiment, the microneedle is composed of a polymer material in which at least one activator is embedded.

[0017] In the context of this disclosure, the term "tissue" refers to any organ surface or biological membrane that can typically be coated with mucus or mucous membrane (e.g., mucosal epithelial tissue). For example, tissues may include gastric tissue, intestinal tissue, rectal tissue, vaginal tissue, urinary tract tissue, nasal tissue, etc.

[0018] The term mucoadhesive (or any variant thereof) typically refers to a composition of compounds or substances that can adhere to tissue via mucus or mucous membranes. Mucoadhesive materials typically interact with mucus present on or secreted by tissue (e.g., one or more interactions such as electrostatic interaction, physical entanglement or interpenetration, diffusion, adsorption, or mechanical coupling).

[0019] Mucous adhesive materials are typically polymers that may be natural, semi-synthetic, or synthetic. Non-limiting examples of mucous adhesives include tragacanth, sodium alginate, guar gum, xanthan gum, karaya gum, gelan gum, carrageenan, soluble starch, gelatin, chitosan, cellulose derivatives (methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose (NaCMC)), polyacrylic acid (PAA) polymers (carbomer, polycarbophil, etc.), and polyhydroxyethylmethyl acrylate. These may include phosphates, polyethylene oxide (PEO, typically high molecular weight PEO), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), lectins, pectins, thiolated polymers (e.g., chitosan-iminothiolane), poly(acrylate)-cysteine, poly(acrylate)-homocysteine, polyethylene glycol, chitosan-tricoglycolic acid, chitosan-titanium, alginate-cysteine, poly(methacrylic acid)-cysteine, carboxymethylcellulose-cysteine ​​sodium, and others.

[0020] In some embodiments, the mucous adhesive layer may further contain one or more additional components. Such additional components may be, for example, emulsifiers (surfactants) such as poloxamer or carbomer, stabilizers such as carboxymethylcellulose, suspending agents such as cellulose or talc, acidifying agents such as citric acid or ascorbic acid, viscosity increasers such as carbopol or polyethylene oxide, foaming agents such as sodium bicarbonate or ammonium carbonate, solubilizing agents such as lecithin, antimicrobial and antiseptic agents such as sorbic acid or potassium sorbate, antioxidants such as alpha-tocopherol or butylhydroxyanisole, release modifiers such as tween 80 or sodium lauryl sulfate, coating agents such as ethyl cellulose or cellulose acetate, binders such as hydroxypropylcellulose or polyvinylpyrrolidone, curing agents such as stearic acid or wax, plasticizing agents such as diethylphthalic acid or triethyl crystalline ethyl acetate, and others.

[0021] Depending on the target site and the desired contact time between the mucous adhesive layer and the tissue, a mucous adhesive can be selected to provide a longer (stronger mucous adhesion) or shorter (weaker mucous adhesion) residence time for the tissue. The strength of mucous adhesion can be influenced, among other things, by the molecular weight of the polymer, the degree of crosslinking, the length and flexibility of the chains, the charge and polarity, the pH, and the concentration of the mucous adhesive composition.

[0022] A tissue-adhering layer, such as a mucoadhesive layer, coats at least partially the outer surface of the compartment; that is, the tissue-adhering layer can coat one or more regions of the surface, a plurality of spaced-out surface regions, or a continuous coating of the surface. In other embodiments, the tissue-adhering layer substantially coats the entire outer surface of the compartment.

[0023] In another embodiment, in the collapsed state, the tissue-adhering layer is a sheet of mucous adhesive material, the sheet of mucous adhesive material having a non-extending configuration (e.g., folded or wound) in which a portion of the tissue-adhering layer coats at least one region of the outer surface of the compartment, and having an extending configuration (e.g., unfolded or unwound) that extends beyond the compartment in the expanded state.

[0024] In other words, the tissue-adhering layer may be formed from a sheet of mucoadhesive material having one or more dimensions (i.e., length and / or width) larger than those of the compartment. To enable administration, the sheet is folded and / or rolled up in a non-extending configuration so that a portion of the sheet coats at least one area of ​​the compartment. Once administered, as the compartment expands, the sheet of mucoadhesive material may undergo unfolding and / or unrolling in an extending configuration so that the extending sheet extends beyond the dimensions of the compartment. Such arrangement allows for the delivery and deployment of a tissue-adhering layer having dimensions larger than those of the compartment.

[0025] In some embodiments, when in the extended state of the extended configuration, the tissue - attachable layer comprises a first portion that coats at least one region of the outer surface of the compartment and a second portion that extends beyond the compartment, and the first portion and the second portion are integral with other portions to form a mucous - adhesive material sheet. To provide mechanical support at the second position of the mucous - adhesive material sheet, the tissue - attachable layer may, in some embodiments, include a backing support layer over the second portion. In such embodiments, the tissue - attachable layer can include the backing support layer on one or both of the surface facing the tissue and the surface facing non - tissue on the opposite side of the second portion. The backing support layer can be made of any suitable material, for example, a non - mucous - adhesive material that may be configured to decompose to allow exposure of the tissue - attachable layer during or after extension of the tissue - attachable layer and / or during or after expansion of the device. When the backing support layer covers both the tissue - facing surface and the non - tissue - facing surface of the second portion, the type of layer may be different between the tissue - facing surface and the non - tissue - facing surface.

[0026] Typically, the tissue is generally of a luminal organ or a hollow - cavity organ such as, for example, the gastrointestinal tract (e.g., esophagus, stomach, small intestine, large intestine), paranasal sinuses, nasal cavity, vagina, uterus, fallopian tubes, urinary tract, rectum, etc.

[0027] As described above, the compartment is made of a continuous deformable film. The term "continuous deformable film" means a film constructed as a monolithic film, a film constructed as one seamless film, and a film constructed from film segments welded together to form a continuous structure. The continuous deformable film has one or more liquid-permeable sections to allow the penetration of liquid into the compartment and the expansion of the gel-forming material. Other sections of the deformable film may be impermeable to liquid. Thus, in some embodiments, the deformable film may be made of an impermeable material except for that or more sections of the liquid-permeable material. In other words, the deformable film may be made from two or more different materials integrally formed with each other, one material being liquid-permeable and the other material being impermeable to liquid.

[0028] According to some embodiments, the one or more sections of the deformable film are different from each other in their liquid permeability. For example, the sections may differ in their composition, porosity, thickness, size, and density of perforations.

[0029] According to other embodiments, the entire deformable film is made of a liquid-permeable material, that is, a continuous film of a liquid-permeable material. In such embodiments, the deformable film may be made entirely from a single liquid-permeable material or from two or more segments, the two or more segments being integrally formed with each other to form the deformable film, and each of the segments being made of a different liquid-permeable material.

[0030] In some embodiments, the deformable film and / or gel-forming material is decomposable. Therefore, after the tissue-adhering layer has been expanded and attached to the tissue, the compartment components can be relatively quickly (e.g., mechanically, physically, and / or chemically) decomposed and removed from the deployment site, leaving the tissue-adhering layer attached to the tissue. In some embodiments, the deformable film includes weakened regions configured to allow fragmentation of the film after a predetermined period from the expansion of the device. Weakened regions can be generated, for example, by locally controlling the film's composition, mechanical structure, or structural features (e.g., adhesive and / or welded areas).

[0031] The clearance of the tissue-adherent layer from tissue typically occurs through the shedding of tissue cells and detachment from the target site. For example, intestinal tissue sheds every few hours, and therefore the tissue-adherent layer attached to it is removed from the target site along with the shed tissue. Thus, the residence time of the tissue-adherent layer at the target site is typically, but not exclusively, determined by the properties of the tissue to which it is intended to attach. Alternatively, the residence time and / or detachment of the tissue-adherent layer from tissue may be controlled by the properties of the tissue-adherent layer (i.e., its chemical or physical properties).

[0032] In some embodiments, the deformable film and / or gel-forming material is chemically degradable. In other embodiments, the deformable film and / or gel-forming material is physically degradable. For example, the deformable film and / or gel-forming material may be modified to degrade within 15 minutes to 3 hours so as not to cause prolonged interference within the organ (e.g., the digestive tract) into which the device is deployed.

[0033] In its expanded state, the device may have a circular, polygonal, or irregular shape. In its expanded state, the device may be designed to assume a three-dimensional (3D) shape that generally conforms to the shape of at least one section of the lumen or cavity into which the device expands (or unfolds).

[0034] In other embodiments, the device may have an annular or ring-shaped form when extended.

[0035] In some other embodiments, the device may be configured to define a hollow lumen, assuming a substantially cylindrical shape when in its expanded state. Such a hollow cylindrical shape prevents the formation of an obstruction in the lumen organ or organ cavity when the device is in its expanded state and allows a liquid or solid to pass through the organ while the device is deployed therein and attached to the tissue.

[0036] Since the device is typically deployed within a tubular organ or organ cavity, it can be assumed to have an elongated shape (e.g., cylindrical) when expanded. In some embodiments, when expanded, the device has a length-to-width (W / L) ratio greater than approximately 1.5.

[0037] In some embodiments, the device is in the form of a sleeve, the sleeve wall is composed of a deformable film, a self-expandable compartment is defined along the circumference of the sleeve, and a tissue-adhering layer coats at least a portion of the outer surface of the compartment and faces outward from the surface of the sleeve. Typically, the compartments are elongated along the longitudinal axis of the sleeve and arranged parallel to each other along the perimeter of the sleeve.

[0038] In some embodiments, each of the elongated compartments is horizontally segmented to form two or more subcompartments arranged longitudinally along the longitudinal axis of the sleeve. In such embodiments, each subcompartment may carry a tissue-adhering layer on its outer surface. The horizontal segmentation may provide the device with another degree of flexibility in its collapsed form, allowing the device to be further folded along the horizontal segmentation lines to reduce its volume for encapsulation in a biodegradable shell for ingestion, as further disclosed below.

[0039] A device may have a single compartment, but it is also assumed that a device may have two or more compartments, whether similar or different. Various extended shapes of the device described above can be generated by the use of multiple compartments. For example, a hollow cylindrical shape may be created by forming a ring using several elongated compartments mounted together along their longitudinal axes. Thus, in some embodiments, a device may have two or more compartments that are identical or different from one another (e.g., size, shape, activator, type, size or shape, degradation rate of tissue-adhering layers, etc.). According to some embodiments, a device may include one or more compartments that carry tissue-adhering layers, but other compartments of the device may not contain such tissue-adhering layers.

[0040] When the device has two or more compartments, all compartments can be formed from a continuous deformable film, for example by forming a separating region to define the periphery of the compartments (e.g., by welding). Alternatively, each compartment may be made of a continuous deformable film, and the compartments may be attached to each other (e.g., welded) to form the device.

[0041] By varying the size, shape, and number of compartments, as well as the type of gel-forming material and / or tissue-adhering layer, different expansion rates, expansion shapes, and / or target delivery can be obtained. Changing the size, number, and geometric shape of the compartments can also be used to obtain symmetrical or asymmetrical expansion shapes of the device. Varying the properties of the gel-forming material and / or deformable film also allows for control of the force applied to the tissue by the device to adhere the tissue-adhering layer to the tissue in its expanded state. Furthermore, by folding the device to obtain a collapsed state and / or controlling the number and / or position of the liquid-permeable sections of the deformable film, the exposure of the gel-forming material to liquid can be controlled, and therefore the overall expansion rate of the device can be controlled.

[0042] The compartment is made from a closed, continuous, deformable film, thus defining a closed volume that holds the gel-forming material. In other words, the continuous film completely encloses the gel-forming material. The film is typically flexible and / or deformable, thereby allowing it to be folded in various ways to reduce the size of the device and obtain a disintegrated state, so that it can be easily administered to the patient who needs the device and into a target organ or organ cavity. In some embodiments, the device is encapsulated in its disintegrated state in a self-administerable capsule and swallowed by the patient.

[0043] In some embodiments, when the configuration is collapsed, the distance between adjacent compartments is about 10 mm or less, for example, about 1 to 5 mm.

[0044] In some embodiments, when the configuration is collapsed, the width of the compartment is approximately 25 mm or less, for example, approximately 8 to 20 mm.

[0045] In some embodiments, when in a collapsed state, the device is configured to fold into a primary folded configuration and undergo unfolding during the transition from the collapsed state to the expanded state. In other words, the device may fold to assume its collapsed state, which has an overall reduced size or overall reduced volume. As the liquid penetrates the liquid-permeable film, the gel-forming material begins to expand and its volume increases. This then applies force to the deformable film, and due to its flexibility and / or deformability, the film unfolds to assume the expanded state of the device.

[0046] In some embodiments, the device is folded at least once along its longitudinal axis or along an axis angled with respect to the longitudinal axis of the device (e.g., along the horizontal midline) to obtain a primary folded configuration. In other embodiments, the device is folded at least once along both its longitudinal axis and an axis angled with respect to the longitudinal axis of the device to obtain a primary folded configuration.

[0047] In the case of a primary folded configuration, the folded device may be enclosed by an enteric envelope according to some embodiments. According to some embodiments, the enteric envelope is formed from an enteric film. According to such embodiments, the enteric film comprises or is composed of one or more enteric polymers. The term enteric polymer means a polymer material (i.e., a single polymer or a composition of polymers) configured to decompose or solubilize by liquids only within a specified pH range. For example, preferably, the enteric polymer is stable (i.e., maintains its physical and chemical structure) when exposed to an acidic environment (e.g., in the stomach) and is solubilized by more alkaline liquids (such as those in the intestines).

[0048] According to some embodiments, the enteric envelope is configured to hold the device in its primary folded configuration by, for example, shaping the enteric envelope to have dimensions similar to those of the device when it is in its primary folded configuration. In some embodiments, the enteric envelope is securely attached to the device in its primary folded configuration with virtually no space formed between the enteric envelope and the device.

[0049] In some embodiments, the enteric-coated film includes one or more additives, such as film-forming compounds, plasticizers, stabilizers, and fillers.

[0050] The enteric-coated envelope functions to maintain the device in its folded configuration until the gastrointestinal tract reaches suitable conditions (e.g., appropriate pH) within the GI tube, allowing the enteric-coated envelope to break down after ingestion, exposing the device and enabling its unfolding and expansion.

[0051] In some embodiments, in addition to the device, the enteric envelope encapsulates at least one antibuoyancy element having a density higher than about 1 g / ml to prevent the device from floating on the surface of the fluid in the stomach and to improve the delivery of the encapsulated device to the intestines. In some embodiments, the antibuoyancy element may consist of one or more regions of greater thickness in the enteric envelope. In other embodiments, the antibuoyancy element may be one or more mass units attached to the enteric envelope or placed within the space formed by the enteric envelope. In some other embodiments, the space defined by the enteric envelope is divided into a primary space enclosing the folded device and one or more auxiliary spaces containing the antibuoyancy element.

[0052] To achieve further compactness in the collapsed state, the device, in some embodiments, has a secondary wound configuration, thereby configuring the folded device to be further wound around its axis and to undergo simultaneous unwinding and unfolding during the transition from the collapsed state to the expanded state.

[0053] According to some embodiments, the device may be encased in an enteric envelope when in its secondary folded configuration. Alternatively, the device may be encased by a first enteric envelope when in its primary folded configuration and by a second enteric envelope when in its secondary folded configuration. In other words, the device can be folded into its primary folded configuration, then encased in a first enteric envelope, then folded or wound into its secondary folded configuration, and then encased in a second enteric envelope to maintain the device in its secondary folded configuration.

[0054] According to other embodiments, the device may first be wound up and then folded to represent a collapsed state.

[0055] In some other embodiments, in the collapsed state, the device is wound around its axis and is configured to undergo unwinding during the transition from the collapsed state to the extended state (i.e., without unfolding).

[0056] According to some embodiments, one or more isolation layers are positioned between one or more of the device's folds to prevent the outer layers of the device from adhering to themselves when the device is in its primary and / or secondary folded configuration. These one or more isolation layers may be attached to one or more attachment positions on the device to maintain their position and function when the device is folded into its primary and / or secondary folded configuration. Alternatively, the isolation layers may be positioned between folds without being fixed to the device (for example, by placing such layers on the device before folding and then folding the device together with the isolation layers to form the primary and / or secondary folded configuration).

[0057] As described above, the compartment is formed from a deformable film having one or more liquid-permeable sections. The sections (or, in some embodiments, the entire deformable film) are made of a liquid-permeable material. In the context of this disclosure, the term liquid-permeable material means a material (a compound or composition of a substance) that allows the diffusion or passage of a liquid through it. For example, a liquid-permeable material may be perforating or porous. According to some embodiments, the liquid-permeable material may include one or more compounds selected from hypromellose phthalate, cellulose acetate phthalate, hypromellose succinate acetate, cellulose acetate, cellulose butyrate acetate, ethylcellulose, polymethyl methacrylate, polyethyl acrylate, polyvinyl acrylate phthalate, polyvinyl acetate, shellac, carboxymethyl ethylcellulose (CMEC), and any combination thereof.

[0058] According to some embodiments, the liquid-permeable material may further include at least one binder, a plasticizer, a pore-forming agent, an emulsifier, a film-forming agent, and any combination thereof.

[0059] To allow for the disassembly of the device's expanded compartments, the liquid-permeable material is typically biodegradable, and preferably enterogradable.

[0060] The term biodegradable means any type of disintegration of a device caused by exposure to suitable biological conditions after administration and expansion. This term encompasses mechanical damage, chemical or physical degradation, chemical or physical disintegration, or any other type of destruction of the device's integrity as it passes through the digestive tract for elimination from the body.

[0061] The term "gel-forming material" refers to a compound or composition that can absorb a liquid and thereby form a three-dimensional volume network of molecules. A gel-forming material can form a physical gel (i.e., a gel in which molecules are held within a 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 comprises one or more gel-forming compounds. In other embodiments, the gel-forming material comprises one or more additives.

[0062] According to some embodiments, the gel-forming material comprises one or more polymers. According to other embodiments, the gel-forming material may be charged or neutral.

[0063] According to some other embodiments, the gel-forming material is crosslinked or crosslinkable. While we do not wish to be bound by theory, the molecular weight and degree of crosslinking of the gel-forming material significantly affect the gel's consistency (e.g., hardness or stiffness) as well as its rheological properties (e.g., viscosity). Therefore, various molecular weights and degrees of crosslinking are parameters that can be used to control the behavior of the zones and thereby control the device's deployment speed and / or expansion size.

[0064] 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 malean anhydride, polyethylene oxide, polyacrylic acid, polyethylene glycol, carboxymethylcellulose, polyvinylpyrrolidone, sodium polyacrylate, hydroxypropyl methylcellulose, or any combination or composition thereof.

[0065] In some embodiments, the gel-forming material is a composition comprising at least one charged gel-forming compound that constructs a PEC (polyelectrolyte complex) formation upon liquid adsorption, and at least one compound having the opposite charge. In some embodiments, the at least one charged gel-forming compound is selected from polyvinyl acetate diethylaminoacetate (AEA), polylysine, chitosan, polymethacrylate (Eudragit E), and polyarginine. In other embodiments, the oppositely charged compound is selected from gelatin, hyaluronic acid, sodium polyacrylate, heparin, polyacrylic acid (carbomer), alginate, pectin, and carboxymethylcellulose.

[0066] In some other embodiments, the gel-forming material is at least one superabsorbent polymer (SAP). The term superabsorbent polymer refers to a polymer (typically crosslinked) or polymer composition that can absorb and retain a large amount of liquid, such as water (or a liquid containing water), relative to the dry mass of the polymer. Non-limiting examples of SAPs include polyethylene glycol (PEG), polyglutamic acid (PGA), polyacrylamide, alginic acid, dextran, polyacrylic acid, carboxymethylcellulose (CMC), pullulan, starch, and any combination thereof.

[0067] In some other embodiments, the gel-forming material has an expansion rate of approximately 10 to 100 times (w / w) (under gastrointestinal pH conditions at 37°C for 1 hour).

[0068] The term expansion coefficient refers to the degree of expansion of a gel-forming material between its state before adsorbing a liquid (i.e., in a dry or semi-dry form) and its state after adsorbing the maximum possible amount of liquid. The expansion coefficient is determined based on weight and calculated according to the following equation: [(wet weight) - (dry weight)] / [(dry weight)].

[0069] The gel-forming material may be in the form of a gel film (i.e., a substantially continuous layer of gel). According to some embodiments, the gel-forming material is in the form of gel particles. According to other embodiments, the gel-forming particles are in the form of a gel film, where the gel particles are embedded in a matrix to form a film. In some embodiments, the gel-forming particles within the gel film are arranged in substantially a single layer of gel particles.

[0070] In further embodiments, the gel-forming material may be in the form of a powder. In some embodiments, when the gel-forming material is in the form of gel particles, the average diameter of the gel-forming material particles may be in the range of about 100 μm to about 300 μm.

[0071] According to some additional embodiments, the compartment may enclose a gas-forming composition in addition to the gel-forming material.

[0072] As described above, the device may have two or more compartments. In such a device, each compartment may contain a different gel-forming material. In some other embodiments, all compartments may contain the same gel-forming material.

[0073] As can be understood, the device is composed of structural layers, i.e., layers that form the structure of the device, or layers that are part of the structure of the device. Such layers include, for example, one or more layers that make up a continuous deformable film, or an inner envelope that encloses the device in its primary folded state. Furthermore, the device includes functional layers, i.e., layers that have a desired functionality and are integrated with structural layers, such as tissue-adhering layers.

[0074] The device may also comprise one or more auxiliary functional layers to enable various additional functions, such as a controlled release layer, a separation layer, or a non-mucosal adhesive layer. The one or more auxiliary functional layers may be continuous or separated layer segments. The one or more auxiliary functional layers may be integral with the structural and / or functional layers, partially attached to the structural and / or functional layers, or not attached to the structural and / or functional layers. In some embodiments, at least one auxiliary functional layer is sandwiched between the tissue-adhering layer and the outer surface of the compartment (e.g., a backing layer to maintain / retain the integrity of the tissue-adhering layer). In some embodiments, the auxiliary functional layer functions as a separation layer.

[0075] It should be understood that any type of layer containing a device (e.g., structural layer, functional layer, auxiliary functional layer) itself can be constructed from a multilayer structure or from sublayers formed integrally with the other.

[0076] The device is typically designed to deliver at least one activator to a target site through and / or across tissue. Thus, as described above, the tissue-adherent layer may contain or support one or more such activators. Depending on the type of activator to be delivered (e.g., polarity, hydrophobic / hydrophilicity, size, etc.), the drug may be contained within or on the surface of the tissue-adherent layer (the outer surface facing the tissue, and / or the inward surface facing the gel-forming material).

[0077] In some embodiments, when the tissue-adhering layer is a mucous adhesive layer, the activator is embedded within the mucous adhesive material. For example, the activator can be dispersed or dissolved in the mucous adhesive material.

[0078] In other embodiments, the activator may be encapsulated within various microparticle or nanoparticle structures such as liposomes, microparticles, microcapsules, nanoparticles, or nanocapsules, and the structures are distributed within the mucous adhesive material.

[0079] In another embodiment, the active material coats at least a portion of the surface of the tissue-adhering layer. For example, the active material can coat at least a portion of one or both of the surface facing the tissue or the surface facing the deformable film of the tissue-adhering layer.

[0080] According to further embodiments, the activator may be linked to the mucous adhesive material by one or more linker sites that are susceptible to defined biological conditions, thereby allowing the release of the activator therefrom once exposed to such conditions.

[0081] In some embodiments, if the tissue-adhering layer includes microneedles, the activator can be embedded within the microneedles, for example, within the polymer on which the microneedles are interpreted.

[0082] Activators are typically pharmaceutical activators. The term pharmaceutical activator refers to a molecule, compound, or composition that is safe and effective for pharmaceutical use, typically in mammals, and possesses the desired biological activity. Activators may be selected from, for example, antibiotics, proteins, peptides, polypeptides, lipids, nucleic acids, hormones, steroids, antibodies, vitamins, anti-inflammatory drugs, antihistamines, antiemetics, analgesics, chemotherapeutic agents, prophylactic agents, coagulation factors, radiopharmaceuticals, contrast agents, electrolytes, nutritional supplements, and small molecules (molecular weight less than approximately 1,000 Da or less than approximately 500 Da).

[0083] In other embodiments, the activator comprises microorganisms (e.g., gut-friendly bacteria) and / or viruses.

[0084] In other embodiments, the activator may be a nutritional supplement compound.

[0085] The activator may be in the form of a salt, an acid addition salt, a free base, a hydrate, a solvate, or a prodrug.

[0086] The activator may be suitable for administration to humans. In other embodiments, the activator may be a veterinary activator.

[0087] The activator is typically present in a therapeutically effective amount in the tissue-adherent layer. The effective amount for the purposes of this specification may be determined by considerations known in the art. This amount must be effective in achieving the desired therapeutic effect, depending, among other things, on the type and severity of the disease being treated and the treatment regime. The effective amount is typically determined in a well-designed clinical trial (dose-range study), and those skilled in the art will know how to properly conduct such a trial to determine the effective amount. As is generally known, the effective amount depends on various factors, including various pharmacological parameters such as the ligand's affinity for the receptor, its distribution profile in the body, and its half-life in the body, as well as factors such as age and sex, in case of undesirable side effects.

[0088] A pharmaceutical activator may be selected to induce a therapeutic effect, such that by treating or preventing an undesirable condition or disease in a subject, it can induce, enhance, suspend, or reduce at least one effect, for example, at least one effect. At least one agent (substance, molecule, element, compound, entity, or combination thereof) may be selected from among therapeutic agents, i.e., agents that can induce or modulate a therapeutic effect when administered in a therapeutically effective dose.

[0089] In other embodiments, the activator may be a diagnostic agent, i.e., a drug that enables the diagnosis of one or more conditions or disorders. The diagnostic effective dose refers to the amount of activator, radiopharmaceutical, or diagnostic composition that enables efficient molecular imaging, depending on the type of imaging technique used (e.g., PET, SPECT, etc.), the acquisition parameters of the specific imaging technique used, the area of ​​the body scanned, the physical condition of the subject, the purpose of the test, or any other factors that are apparent to those skilled in the art.

[0090] In some embodiments, the device may include at least one additional active substance different from the at least one activator. The additional active substance may have the same pharmaceutically active substance as the activator, or it may have a pharmaceutically active substance different from the activator.

[0091] In some embodiments, the mucoadhesive layer includes additional active substances. In such embodiments, the activator and the additional active substances may have a co-therapeutic effect, i.e., an additional or synergistic effect. For example, the additional active substances may function to increase the permeability or bioavailability of the activator, or to increase or improve the therapeutic effect or biological activity of the activator.

[0092] In other embodiments, additional active substances may be contained within the compartment, for example, associated with a deformable film, associated with a gel-forming material, or mixed (or dispersed) in the gel-forming material. In such cases, the additional active substances may be selected to have an immediate or short-term therapeutic effect, while the activator may be selected to have a long-term or sustained therapeutic effect.

[0093] In other embodiments, the activator and additional active substances may be selected from drugs having similar or identical therapeutic effects. For example, the activator and additional active substances may be the same, but one may be contained within the tissue-adherent layer and the other within a compartment. Such an arrangement can be used to divide the required dose of the drug so that a portion of the drug is released immediately after the expansion and / or breakdown of the gel-forming material, and the remainder is slowly absorbed from the tissue-adherent layer once it has adhered to the tissue. In another embodiment, the activator and additional active substances may have similar effects, with the additional active substance having an immediate effect and the activator having a long-lasting or sustained effect.

[0094] In other words, the device can be used to administer two or more pharmaceutical activators simultaneously, i.e., one at a time. Simultaneous administration may allow one drug in a combination to be administered within a specific time interval (e.g., 5 minutes, 10 minutes, or even several hours) after another drug, provided that the circulating half-life concentration of the first drug in the combination is present at a therapeutically effective level at the same time as the other drug to be administered. The time delay between drug administrations may vary depending on the exact properties of the drugs, interactions between individual drugs, their respective half-lives, and other factors readily recognizable by a skilled technician.

[0095] In further embodiments, the activators and additional substances may have different effects, and the device is designed for continuous administration, meaning there is a time lag between the administration of one drug and the other. Such a time lag may be short or significant. That is, the first administered drug may no longer be present in the bloodstream at a therapeutically effective amount (or clinically substantive amount) when the second (or subsequent) drug is administered.

[0096] In some additional embodiments, the device may include two or more types of tissue-adhering layers. Different areas of the outer surface of compartments and / or different compartments may be coated with different types of tissue-adhering layers. These different types of tissue-adhering layers may contain different types of activators.

[0097] In some additional embodiments, the tissue-facing surface of the tissue-adhering layer (or part thereof) may be covered with a non-muco-adhesive material (layer) which may be configured to decompose in order to allow exposure of the muco-adhesive layer during or after the extension of the tissue-adhering layer and / or the expansion of the device.

[0098] To prevent undesirable or premature deployment of the device and / or to enable delivery of the device to a suitable organ lumen or cavity, the device may be provided with a biodegradable shell that encapsulates the device in its disintegrated state. Therefore, the biodegradable shell is selected to degrade upon exposure to suitable biological conditions (e.g., pH, presence of specific chemical compounds).

[0099] If the device is intended for oral administration and designed to deploy into the intestines, the biodegradable shell may be made from or coated with an enteric coating.

[0100] In some embodiments, the device is an ingestible device and is intended to be deployed, for example, in the stomach or intestines. Therefore, such a device is typically encapsulated within a digestive track-degradable shell, encapsulating the device in its disintegrated state. For intestinal deployment, the shell may be designed or selected to provide a safe first passage through the stomach and to biodegrade only when exposed to defined conditions within the intestines. By some embodiments, the digestive track-degradable shell is designed to degrade as a function of the pH of the environment, thereby deploying to a desired portion of the intestine. For example, it is known that different parts of the digestive tract have different pH values. On the one hand, the stomach typically has a pH of 1.5–3.5, while the duodenum has a pH of typically 6, gradually increasing to about 7.4 in the small intestine (until reaching the terminal ileum). In the cecum, the pH drops to 5.7, but gradually increases again, reaching a pH of 6.7 in the rectum. Therefore, by utilizing a digestive track-degradable shell that degrades at a predetermined pH value (or range of values), deployment of the device in a desired portion of the digestive track can be obtained.

[0101] A biodegradable shell could be, for example, a capsule.

[0102] If the device is an ingestible device, the biodegradable capsules typically have a swallowable size of, for example, about “extended 000” or 000 or 00 capsules or less (i.e., an outer diameter of about 9.97 mm or less, a height or locked length of about 30.0 mm or less, and an actual volume of about 1.68 ml or less). Table 1 below provides a non-limiting list of capsule sizes suitable for use as digestible track biodegradable shells. [Table 1]

[0103] If the device is ingestible, it may have two types of shells, one enclosing the other. There may be an outer shell in the form of a capsule to facilitate swallowing the device, which is designed to be disintegrable in the gastric environment. The second inner shell may be a coating or encapsulation layer that coats / encapsulates the device, configured to maintain the device in its disintegrated state for a predetermined period before deployment. For example, the inner shell may be made from an enteric-coated material, thus preventing the device from deploying in the stomach and allowing its deployment only upon entry into the intestines.

[0104] The device can be used to deliver at least one activator to a target site, but the device may also be excluding the activator or may contain only the activator within its compartment. For example, the device can be used to deliver a patch to the wall of tissue to temporarily block the passage of substances through, for example, mucosal / epithelial tissue (both in and / or into the lumen), or to cover a perforation or ulcer within the tissue.

[0105] As described above, in some embodiments, the tissue-adhering layer may not contain an active agent, but the compartment and / or gel-forming material may contain an active substance / agent such as an analgesic or anti-inflammatory agent, which can be released during the degradation of the gel-forming material to provide the desired local effect relatively quickly after administration.

[0106] In another aspect, the Disclosure provides a self-expandable device configured to deliver at least one activator to tissue, the device having a collapsed state and an expanded state, and being encapsulated in a decomposable shell when in the collapsed state, the device comprising at least one self-expandable compartment formed from a substantially continuous deformable film having one or more liquid-permeable sections, the compartment being configured to enclose a gel-forming material therein, the gel-forming material expanding upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state, and a tissue-adherent layer coating at least a portion of the outer surface of the compartment, the tissue-adherent layer comprising at least one muco-adhesive material and at least one activator, the expansion of the device from a collapsed state to an expanded state causing the expansion of the compartment to drive the tissue-adherent layer toward the tissue in order to deliver the activator to the tissue and to adhere at least a portion of the muco-adhesive layer to the tissue.

[0107] In a further embodiment, a self-expandable device is provided configured to adhere a tissue-adhering layer to tissue, the device having a collapsed state and an expanded state, and being encapsulated in a decomposable shell when in the collapsed state, the device comprising: at least one self-expandable compartment formed from a substantially continuous deformable film having one or more liquid-permeable sections, the compartment being configured to enclose a gel-forming material therein, the gel-forming material expanding upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state; and a tissue-adhering layer coating at least a portion of the outer surface of the compartment, the expansion of the device from a collapsed state to an expanded state causing the expansion of the compartment to drive the tissue-adhering layer toward the tissue in order to adhere at least a portion of the mucoadhesive layer to the tissue.

[0108] In yet another embodiment, a self-expanding device is provided configured to adhere a tissue-adhering layer to tissue, the device having a collapsed state and an expanded state, wherein a substantially continuous, deformable film is formed on a sleeve, defining at least one self-expanding compartment, the compartment having one or more liquid-permeable sections, therein enclosing a gel-forming material, the gel-forming material being configured to expand upon contact with a liquid, thereby expanding the compartment to irreversibly switch the device from a collapsed state to an expanded state. The tissue-adhering layer coats at least a portion of the outer surface of the compartment such that the expansion of the device from a collapsed state to an expanded state drives the tissue-adhering layer toward the tissue to adhere at least a portion of the mucoadhesive layer to the tissue.

[0109] In another embodiment, a kit is provided comprising a self-expandable device, such as one described herein, encapsulated in a biodegradable shell, and instructions for use.

[0110] In another embodiment, the Disclosure provides a method for delivering at least one activator to a target tissue in need thereof, the method comprising administering to the target a self-expandable device such as one disclosed herein, encapsulated in a biodegradable shell.

[0111] In a further embodiment, a method is provided for delivering at least one activator to a target tissue in need for an extended period or continuously, the method comprising administering to the subject a self-expandable device, such as one disclosed herein, encapsulated in a biodegradable shell. Thus, the device of the disclosure forms a reservoir of activators delivered to the target site for an extended period.

[0112] In yet another embodiment, a method is provided for attaching a tissue-adherent layer to a target tissue requiring it, via a mucous membrane, the method comprising administering to the target a self-expandable device, such as one disclosed herein, encapsulated in a biodegradable shell.

[0113] Embodiment Hereafter, embodiments of the present disclosure will be described by numbered embodiments. These numbered embodiments are intended to be an addition to the above disclosure.

[0114] 1. A self-expandable device configured to attach a tissue-adhering layer to tissue, wherein the device has a collapsed state and an expanded state, At least one self-expandable compartment formed from a substantially continuous deformable film having one or more liquid-permeable sections, wherein the compartment is configured to enclose a gel-forming material therein, and the gel-forming material expands upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state. A tissue-adhering layer that coats at least a portion of the outer surface of the compartment, As a result, the device's expansion from a collapsed state to an expanded state causes the expansion of compartments to drive the tissue-adherent layer toward the tissue, thereby causing at least a portion of the tissue-adherent layer to adhere to the tissue.

[0115] 2. The device according to Embodiment 1, wherein the tissue-adhering layer comprises a plurality of microneedles.

[0116] 3. The device according to Embodiment 1, wherein the tissue-adhering layer is a mucous adhesive layer.

[0117] 4. The device according to Embodiment 3, wherein the mucous adhesive layer comprises at least one mucous adhesive material.

[0118] 5. The device according to Embodiment 3, wherein the mucous adhesive layer comprises at least one mucous adhesive material and at least one activator.

[0119] 6. The device according to Embodiment 2, wherein the microneedles are made of a polymer material in which at least one activator is embedded.

[0120] 7. The device of Embodiment 6, wherein the activator is embedded in the mucous adhesive material.

[0121] 8. The device according to Embodiment 7, wherein the activator is dispersed or dissolved in the mucous adhesive material.

[0122] 9. The device according to Embodiment 8, wherein the activator is encapsulated within liposomes, microparticles, microcapsules, nanoparticles, or nanocapsules distributed within the mucous adhesive material.

[0123] 10. The device according to Embodiment 6, wherein the active material coats at least a surface portion of the mucous adhesive layer.

[0124] 11. The device according to Embodiment 10, wherein the active material coats at least a portion of one or both of the surfaces facing the tissue of the mucous adhesive layer or the surfaces facing the deformable film.

[0125] 12. The device according to any one of Embodiments 5 to 11, wherein the activator is a pharmaceutical activator.

[0126] 13. The device according to any one of embodiments 5 to 11, wherein the device comprises at least one additional active substance different from the at least one activator.

[0127] 14. The device according to Embodiment 13, wherein the mucous adhesive layer contains an additional active substance.

[0128] 15. The device according to Embodiment 14, wherein an additional active substance is contained within the compartment.

[0129] 16. The device according to any one of embodiments 13 to 15, wherein the additional active substance is a pharmaceutical activator.

[0130] 17. The device according to any one of Embodiments 1 to 16, wherein one or more sections of the deformable film differ from one another in their liquid permeability.

[0131] 18. The device according to Embodiment 17, wherein a deformable film is made of an impermeable material to store the section, or more sections, of a liquid-permeable material.

[0132] 19. The device according to Embodiment 17 or 18, wherein the deformable film is made from two or more different materials integrally formed with each other, one material being liquid-permeable and the other material being impermeable to liquid.

[0133] 20. The device according to any one of embodiments 1 to 19, wherein the entire deformable film is made from a liquid-permeable material.

[0134] 21. The device according to Embodiment 20, wherein a deformable film is made from two or more different liquid-permeable materials and is integrally formed with respect to one another.

[0135] 22. The device according to any one of embodiments 1 to 21, wherein the deformable film is detachable.

[0136] 23. The device according to Embodiment 22, wherein the deformable film is chemically or biologically degradable.

[0137] 24. The device according to Embodiment 22, wherein the deformable film is mechanically disassembled.

[0138] 25. The device according to any one of embodiments 1 to 24, wherein the deformable film includes a weakening region that allows the film to be fragmented.

[0139] 26. A device according to any one of Embodiments 1 to 25, wherein the gel-forming material is detachable.

[0140] 27. The device according to any one of Embodiments 1 or 26, wherein the tissue is selected from gastric tissue, intestinal tissue, rectal tissue, vaginal tissue, urinary tract tissue, and nasal tissue.

[0141] 28. The device according to any one of embodiments 1 to 27, wherein when in a collapsed state, the device is folded in a primary folded configuration and is configured to undergo unfolding during a transition from a collapsed state to an extended state.

[0142] 29. The device according to Embodiment 28, wherein the device is encased in an enteric envelope when in the primary folded configuration.

[0143] 30. The device according to Embodiment 29, wherein the enteric envelope comprises at least one antibuoyancy element having a density higher than approximately 1 g / ml.

[0144] 31. The device according to any one of embodiments 28 to 30, wherein, when in a collapsed state, the device has a secondary wound configuration, thereby the folded device is further wound around its axis and is configured to undergo simultaneous unwinding and unfolding during the transition from a collapsed state to an extended state.

[0145] 32. The device according to Embodiment 31, wherein in the secondary wound configuration, the device is enclosed by an enteric envelope.

[0146] 33. The device according to Embodiment 31, wherein in the primary folded configuration, the device is wrapped by a first enteric envelope, and in the secondary wound configuration, the device is wrapped by a second enteric envelope.

[0147] 34. The device according to any one of embodiments 1 to 33, wherein when in a collapsed state, the device is wound around its axis and is configured to undergo unwinding during a transition from a collapsed state to an expanded state.

[0148] 35. A device according to any one of embodiments 1 to 34, comprising a biodegradable shell that encapsulates the device in its disintegrated state.

[0149] 36. A device according to any one of Embodiments 1 to 35, which is an ingestionable device.

[0150] 37. The device according to embodiment 36, comprising a digestable track biodegradable shell that encapsulates the device in its disintegrated state.

[0151] 38. The device according to embodiment 37, wherein the digestive track biodegradable shell is a gastric biodegradable shell.

[0152] 39. The device according to Embodiment 36, comprising an outer shell configured to be biodegradable in the gastric environment, enclosing an inner shell coating or encapsulating the device and maintaining the device in its biodegraded state for a predetermined period before deployment.

[0153] 40. The device according to embodiment 39, wherein the outer shell is in the form of a gastric-degradable capsule.

[0154] 41. The device according to embodiment 39 or 40, wherein the inner shell is made from an enteric-coated material.

[0155] 42. The device according to any one of Embodiments 1 to 41, wherein the gel-forming material is in the form of a gel film.

[0156] 43. The device according to any one of Embodiments 1 to 42, wherein the gel-forming material is in the form of gel particles.

[0157] 44. The device according to embodiment 43, wherein gel particles are embedded in a matrix to form a substantially continuous gel film.

[0158] 45. The device according to Embodiment 43 or 44, wherein the gel-forming particles in the gel film are substantially in the form of a single layer of gel particles.

[0159] 46. ​​The device according to any one of Embodiments 1 to 45, wherein the gel-forming material comprises one or more gel-forming compounds.

[0160] 47. The device according to Embodiment 46, wherein the gel-forming material comprises one or more additives.

[0161] 48. The device according to any one of Embodiments 1 to 47, wherein the gel-forming material comprises a superabsorbent polymer (SAP).

[0162] 49. The device according to Embodiment 48, wherein the gel-forming material has an expansion coefficient in the range of approximately 1:10 to 1:100 (v / v).

[0163] 50. The device according to any one of embodiments 1 to 49, wherein the device has an L / W ratio of at least about 1.5 when the device is in its extended state.

[0164] 51. The device according to any one of Embodiments 1 to 50, wherein in an extended state, the device has an annular or ring-shaped form.

[0165] 52. The device according to any one of embodiments 1 to 51, wherein, in an expanded state, the compartment is configured to assume a substantially cylindrical shape defined around a hollow lumen.

[0166] 53. The device according to embodiment 52, comprising two or more of the compartments that are attached to each other to form the cylindrical shape.

[0167] 54. The device according to any one of Embodiments 1 to 53, wherein, in a collapsed state, the tissue-adhering layer is a sheet of mucoadhesive material, and the sheet of mucoadhesive material has a non-extending (e.g., folded or wound) configuration in which a portion of the tissue-adhering layer coats at least one region of the outer surface of the compartment, and in an expanded state, has an extending configuration that extends beyond the compartment (e.g., unfolded or unwound).

[0168] 55. The device according to Embodiment 54, wherein in the extended configuration of the tissue-adhering layer, the sheet has one or more dimensions (i.e., length and / or width) that are larger than the dimensions of the compartment.

[0169] 56. The device according to Embodiment 54 or 55, wherein, when in an extended configuration, the tissue-adhering layer comprises a first portion that coats at least one area of ​​the outer surface of a compartment, and a second portion that extends beyond the compartment, the first portion and the second portion being integral with the other portion to form a sheet of mucoadhesive material.

[0170] 57. The device according to embodiment 56, wherein the tissue-adhering layer includes a backing support layer on the second portion.

[0171] 58. The device according to embodiment 56 or 57, wherein the tissue-adhering layer includes the backing support layer on one or both of the surface facing the tissue and the non-tissue surface opposite the second portion.

[0172] 59. A kit comprising an ingestible, self-expandable device as described in any one of Embodiments 1 to 58, encapsulated in a biodegradable shell, and instructions for use.

[0173] 60. A method for attaching a tissue-adherent layer to a target tissue requiring it, via a mucous membrane, the method comprising administering to the target a self-expandable device according to any one of embodiments 1 to 58, encapsulated in a biodegradable shell.

[0174] 61. A method for delivering at least one activator to a target tissue in need thereof, the method comprising administering to the target a self-expandable device described in any one of embodiments 5 to 58, encapsulated in a biodegradable shell.

[0175] 62. A method for delivering at least one activator to a target tissue in need thereof over a long period of time, the method comprising administering to the target a self-expandable device described in any one of embodiments 5 to 58, encapsulated in a biodegradable shell.

[0176] 63. A self-expandable device configured to attach a mucoadhesive layer to tissue, wherein the device has a collapsed state and an expanded state, A substantially continuous deformable film formed in a sleeve and defining at least one self-expandable compartment, wherein the compartment has one or more liquid-permeable sections and encloses a gel-forming material therein, and the gel-forming material expands upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state; The compartment comprises a viscous adhesive layer that coats at least a portion of the outer surface of the compartment, As a result, the device's expansion from a collapsed state to an expanded state causes the expansion of compartments to drive the mucoadhesive layer toward the tissue, thereby causing at least a portion of the mucoadhesive layer to adhere to the tissue.

[0177] 64. A self-expandable device for delivering at least one activator to tissue, wherein the device has a collapsed state and an expanded state, At least one self-expandable compartment formed from a substantially continuous deformable film having one or more liquid-permeable sections, wherein the compartment is configured to enclose a gel-forming material therein, and the gel-forming material expands upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state. A tissue-adhering layer that coats at least a portion of the outer surface of a compartment, comprising a tissue-adhering layer containing at least one mucolytic adhesive material and at least one activator, As a result, the expansion of the device from a collapsed state to an expanded state causes the expansion of compartments to drive the tissue-adherent layer toward the tissue, thereby causing at least a portion of the tissue-adherent layer to adhere to the tissue for delivery of the activator to the tissue.

[0178] 65. A self-expandable device for delivering at least one activator to tissue, wherein the device has a collapsed state and an expanded state, At least one self-expandable compartment formed from a substantially continuous deformable film having one or more liquid-permeable sections, wherein the compartment is configured to enclose a gel-forming material therein, and the gel-forming material expands upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from a collapsed state to an expanded state. A tissue-adhering layer coating at least a portion of the outer surface of a compartment, comprising a tissue-adhering layer having a plurality of microneedles containing at least one activator, As a result, the expansion of the device from a collapsed state to an expanded state causes the expansion of compartments to drive the tissue-adherent layer toward the tissue, thereby causing at least a portion of the tissue-adherent layer to adhere to the tissue for delivery of the activator to the tissue.

[0179] 66. Use of a self-expandable device according to any one of Embodiments 1 to 58 in a method for attaching a tissue-adherent layer to a target tissue requiring it, wherein the self-expandable device is encapsulated in a biodegradable shell.

[0180] 67. Use of a self-expandable device according to any one of embodiments 5 to 58 in a method for delivering at least one activator to a target tissue in need thereof, wherein the self-expandable device is encapsulated in a biodegradable shell.

[0181] 68. Use of a self-expandable device according to any one of embodiments 5 to 58 in a method for delivering at least one activator to a target tissue in need therefor over a long period of time, wherein the self-expandable device is encapsulated in a biodegradable shell.

[0182] 69. A self-expandable device according to any one of Embodiments 1 to 58 for use in a method of attaching a tissue-adherent layer to a target tissue requiring it, wherein the self-expandable device is encapsulated in a biodegradable shell.

[0183] 70. A self-expandable device according to any one of embodiments 5 to 58 for use in a method of delivering at least one activator to a target tissue in need thereof, wherein the self-expandable device is encapsulated in a biodegradable shell.

[0184] 71. A self-expandable device according to any one of embodiments 5 to 58 for use in a method of delivering at least one activator to a target tissue in need therefor over a long period of time, wherein the self-expandable device is encapsulated in a biodegradable shell.

[0185] To better understand the subject matter disclosed herein and to illustrate how it may be put into practice, embodiments are described herein by reference only as non-limiting examples. [Brief explanation of the drawing]

[0186] [Figure 1A-1G] This is a schematic diagram of a device according to some exemplary embodiments of the present disclosure. [Figure 2A-2F] This is a schematic diagram of the sequence of device operation after administration to the target. [Figure 2G] This is a schematic diagram of an asymmetric device according to an embodiment of the present disclosure. [Figure 2H] This is a schematic diagram of the device according to the present disclosure, showing the asymmetric adhesion state of the tissue-adhering layer to the tissue. [Figure 3A-3D] This is an illustrative cross-sectional view of the device in its extended state. [Figure 3E-3F] These are longitudinal cross-sectional views passing through the devices shown in Figures 3A and 3B, respectively. [Figure 3G-3H] The cross-sectional view shows a device designed to fit lumens or cavities with various cross-sectional shapes. [Figure 3I] The device has compartments of different sizes, as shown in the cross-sectional view. [Figure 4A-4B] This is an illustrative cross-sectional view of a further configuration of the device in its extended state. [Figure 5A-5B] This is a schematic diagram of a device according to some further embodiments of the present disclosure. [Figure 6A-6C] This is a schematic diagram of a device according to an additional embodiment of the present disclosure, in which the device is configured as a sleeve. Figure 6A is a front perspective view, Figure 6B is a top section view across line VV, and Figure 6C shows the device in an extended form. [Figure 6D-6F] Figures 6A and 6B show various folding configurations of the device. [Figure 6G-6H] The folded configuration of the device shown in Figure 6E, encased in an enteric-coated envelope, is shown in a top view (Figure 6G) and a side view (Figure 6H). [Figures 7A-7B] These are schematic diagrams of some modified versions of the device shown in Figures 6A and 6B. [Figure 7C-7D] Figure 7A or Figure 7B shows the device in a possible primary folded configuration. [Figures 7E-7F] Figures 7C and 7D show the devices covered with an enteric-coated envelope, respectively. [Modes for carrying out the invention]

[0187] The following describes exemplary devices according to this disclosure. While certain embodiments demonstrate that the devices are substantially symmetrical, it should be understood that the devices may also be asymmetrical or of any other shape. Furthermore, the elements of the devices are not shown to a constant scale for the sake of clarity.

[0188] Figure 1A shows a collapsed (non-expanded) self-expandable device according to an embodiment of the present disclosure. Device 100 includes a self-expandable compartment, indicated as 102 overall, formed from a continuous deformable film 104. In this particular embodiment, the entire deformable film is made of a liquid-permeable material, but it should be understood that, as described herein, the deformable film may have one or more sections (not shown) that are liquid-permeable and other sections that are not liquid-permeable. At least a portion of the volume of the compartment is filled with a gel-forming material 106. A tissue-adhering layer 108 in this embodiment, for example, a mucoadhesive layer, or a layer containing microneedles or microhooks, substantially coats the outer surface of the compartment 102 (i.e., the surface of the film 104 facing outward from the compartment). If the device is intended to deliver one or more activators to tissue, the tissue-adhering layer 108 contains activators. For example, to enable oral administration for intestinal deployment, the device is encapsulated in a biodegradable (e.g., gastric-degradable) capsule 110, so that the device can pass through the stomach intact and undeployed.

[0189] Another embodiment of the device is shown in Figure 1B, where the tissue-adhering layer coats separate zones on the outer surface of the compartment.

[0190] The device may further include, for example, one or more additional active substances contained within a compartment, such as a mixture with a gel-forming material 106.

[0191] In an embodiment of Figure 1C, another device for oral ingestion is shown, designed to deliver a tissue-adherent layer to the intestines. In this embodiment, the device 100 is shown in a disintegrated and encapsulated state. In addition to the capsule 110, which is designed to facilitate swallowing of the device and is intended to disintegrate in the stomach, a second inner shell 116 is an enteric envelope that coats or encapsulates the device. The enteric envelope is configured to maintain the device in its disintegrated state as long as it is in the stomach, and to disintegrate upon exposure to suitable conditions in the intestines, thus allowing the device to unfold in the intestines rather than the stomach.

[0192] In another embodiment shown in Figure 1D, the mucous adhesive layer 108 coats the compartment region in a partially asymmetrical manner.

[0193] In another embodiment, the compartment may be formed from at least two different deformable films 104 and 105, as shown in Figure 1E, to cause asymmetrical development of the tissue-adhering layer. For example, film 104 may be made of a liquid-permeable material, and film 105 may be made of a non-liquid-permeable film. Alternatively, films 104 and 105 may differ in their degree of liquid permeability.

[0194] In another embodiment shown in Figures 1F and 1G, the device is shown in a disintegrated and encapsulated state, and the capsule 110 further includes an antibuoyancy element 111 located within an enteric envelope 116. The element 111 typically has a density higher than that of gastric fluid, for example, a density higher than about 1 g / ml, to ensure immersion of the capsule in gastric fluid and delivery of the device to the intestine.

[0195] In the embodiment shown in Figure 1F, element 111 is attached to the inner surface of the enteric envelope. Alternatively, element 111 may be composed of a region of the enteric envelope having a greater thickness than other regions of the enteric envelope.

[0196] In the embodiment shown in Figure 1G, the enteric envelope 116 defines an internal space that is divided into a main space 115 in which the folded device 102 is enclosed, and two auxiliary spaces 113 that house the antibuoyancy elements 111.

[0197] Figures 2A–2E show exemplary sequences of operation of the device of this disclosure. While this embodiment demonstrates deployment of the device in the intestine, it should be understood that the device can be administered and deployed into any other suitable body cavities or cavities. For example, the device may be administered into other organs such as the urinary tract, vagina, rectum, or nasal cavity. If the target organ or cavity is relatively user-accessible, the device may be administered by utilizing a dedicated applicator (not shown) to insert the device into the organ or cavity.

[0198] After the device is administered orally, for example, the biodegradable capsule 110 passes through the stomach and undergoes degradation upon exposure to favorable conditions in the intestines, thus exposing the device 100. As described above, in some configurations, as shown in Figure 2A, the biodegradable capsule 110 is degraded in the stomach, and the device is encapsulated / coated with an enteric layer (coating) 116 that protects the device as it passes through the stomach and is designed to degrade when exposed to favorable conditions in the intestines. However, it should be noted that in other configurations, the layer 116 may be absent. The enteric layer typically contains one or more enteric polymers or is formed from one or more enteric polymers.

[0199] When the capsule 110 (or the enteric coating 116 as shown in Figure 2A) disintegrates, the fluid in the intestine penetrates the liquid-permeable section of the deformable film 104 of the compartment 102, causing the gel-forming material 106 contained therein to expand. The expansion of the gel-forming material causes the compartment to expand and the film to deform, as shown in Figure 2B, causing the device to assume its expanded state. In the expanded state, the expansion of the gel-forming material causes a force to be applied to the film 104 in the direction of arrow 112, bringing the tissue-adhering layer 108 into contact with and adhering to the tissue 114. Thus, the transition of the device from the disintegrated state to the expanded state drives the muco-adhering layer associated with the compartment toward the tissue and brings it into close contact with it under the application of force (applied by the expanded gel-forming material).

[0200] As shown in Figures 2G and 2H, the mucous adhesive layer 108 does not need to symmetrically coat the deformable film and / or can adhere to the tissue in an asymmetrical manner.

[0201] As shown in Figures 2C and 2D, the deformable film 104 and / or gel-forming material 106 undergo decomposition and are removed from the target site by the natural movement of the intestine, causing the tissue-adherent layer to adhere to or remain attached to the tissue. Therefore, if the tissue-adherent layer 108 contains an activator, the activator contained within the muco-adherent layer is delivered to the tissue during the period that the tissue-adherent layer remains attached to the tissue, as seen in Figure 2E.

[0202] Because tissue is routinely shed from the intestinal wall every few hours, this tissue shedding also results in the separation and breakdown of the tissue-adherent layer, as well as its clearance from the intestine, as seen in Figure 2F.

[0203] In some other embodiments, in the collapsed state, the device is wound around its axis and is configured to be unwound during the transition from the collapsed state to the extended state (i.e., without folding).

[0204] In its expanded state, the device may have a circular, polygonal, or irregularly shaped cross-section. Typically, in its expanded state, the device can be assumed to have a three-dimensional (3D) shape that generally conforms to the shape of at least one section of the lumen or cavity into which the device expands (unfolds). In certain exemplary embodiments, the compartment is assumed to be substantially cylindrical with a circular cross-section, as shown in Figure 3A. However, it is also possible to assume different shapes with different cross-sections when the device is in its expanded state, as shown in Figure 3B. As seen in Figure 3B, the device can be assumed to be cylindrical in its expanded state with a hollow lumen. Such a hollow cylindrical shape prevents the formation of an obstruction in the organ cavity when the device is in its expanded state and allows fluids or solids to pass through the organ while the device is unfolded within it and adheres to the tissue.

[0205] Typically, the device has a single compartment, but it should also be noted that, as shown in Figures 3C and 3D, for example, the device may include two or more similar or different compartments, arranged to form a hollow lumen between them, allowing fluids and solids to pass through the organ after the device is expanded (thus preventing organ obstruction).

[0206] Figures 3E to 3H show examples of cross-sections of the device perpendicular to those shown in Figures 3A to 3D. Figures 3E and 3F correspond to Figures 3A and 3B, respectively. Figures 3F and 3G show cross-sections in which the device is designed to fit lumens or cavities with various cross-sections. The device may also be designed to fit cavities with non-cylindrical shapes.

[0207] Figure 3I shows a cross-section of the device in the same direction as Figures 3E-3H, consisting of compartments of different lengths.

[0208] As shown in Figures 4A and 4B, the device may have other extended shapes. For example, the device may include compartments of different sizes and configurations, resulting in three-dimensional (3D) shapes with different mechanical strengths. Furthermore, some of the compartments may be mounted to one or more mounting locations to limit the expansion of the device and form a desired 3D configuration. For example, in the device shown in Figures 3C and 3D, each compartment is mounted to two adjacent compartments to form a hollow, closed shape when extended, whereas in the device of Figure 4A, some of compartments 102B are mounted to two adjacent compartments, while some of compartments 102A are mounted to three or more adjacent compartments, thereby forcing the extended device to assume an hourglass shape. Such shapes can improve the rigidity and stability of the device. In such a configuration, not all compartments typically carry a tissue-adhering layer; for example, compartment 102A may be used to provide mechanical properties to the device, while compartment 102B may carry a tissue-adhering layer (not shown) and be able to come into contact with tissue.

[0209] Alternatively, the compartment may be constrained by one or more constraint elements 120, and when in an expanded state, the compartment is forced to assume a desired shape, as shown in Figure 4B.

[0210] Furthermore, to obtain a compact device in its collapsed (non-expanded) state, the device may be folded into various folded configurations (i.e., a primary folded configuration (not shown)) and / or wound configurations (i.e., a secondary wound configuration) to allow its unfolding (and / or unwinding) during the transition from the collapsed state to the expanded state. In other words, the device may be folded to assume its collapsed state, having an overall reduced size or overall reduced volume. When the liquid penetrates the deformable film, the gel-forming material begins to expand and its volume increases. This then applies force to the deformable film, and due to its flexibility and / or deformability, the film unfolds to assume the expanded state of the device.

[0211] In some additional embodiments, as shown in Figures 5A and 5B, the tissue-adhering layer extends beyond the outer surface of the compartment. In such embodiments, an additional backing layer 118 is typically used to provide support for the tissue-adhering layer.

[0212] In some embodiments, the device can take the form of a sleeve, as shown in Figures 6A to 7B, similar to the device in Figures 3C and 3D. The device 200 in Figures 6A and 6B has an overall cylindrical sleeve shape and is formed from a continuous deformable film 204, comprising multiple, in this case six, self-expandable compartments, collectively shown as 202. Although six compartments are shown in this embodiment, it should be understood that any number of compartments, e.g., two, three, four, five, six, seven, eight, or even more, can be utilized.

[0213] In this embodiment, the entire sleeve constitutes a deformable film, and the compartments 202 are defined as pockets (made of a liquid-permeable material, each surrounding a gel-forming material 206). The tissue-adhering layer 208 is located on the outer surface of each compartment 202 (i.e., the surface of the film 204 facing outward from the compartment). The tissue-adhering layer 208 may contain one or more activators to be delivered to the tissue, as described above.

[0214] The tissue-adhering layer 208 may be provided as a patch applied to (e.g., bonded to) the film 204 on the compartment 202. For example, if the tissue-adhering layer is a mucoadhesive layer, the patch may include a mucoadhesive material superimposed on a backing layer (not shown) that allows the patch to be bonded or attached to the outer surface of the compartment and provides support for the mucoadhesive material. Alternatively, the mucoadhesive layer may be applied first to specific locations on the film 204, and then the compartment 202 may be formed at locations corresponding to the areas of the film containing the mucoadhesive layer, thus forming a multilayer film structure.

[0215] Figure 6C shows the expanded form, i.e., the device in a state where it has expanded after being exposed to a liquid that causes the gel-forming material to expand.

[0216] Figures 6D–6F show various configurations for folding the device in Figures 6A–6C to render the device in a more compact form for ingestion. For ease of visualization, only the tissue-adhering layer 208 is shown on the film 204. When in the collapsed state shown in Figure 6A, the device can be folded into one of the primary folded configurations shown in Figures 6D–6F and housed in a biodegradable capsule (not shown). After ingestion and decomposition of the biodegradable capsule, exposure to the liquid in the GI track causes expansion of the gel-forming material in the compartment, thereby expanding the compartment and causing at least partial accompanying expansion and unfolding into the expanded state.

[0217] Once folded into its primary folded configuration, the folded device may be wrapped by an enteric envelope 209, for example, as shown in Figures 6G and 6H, which functions to maintain the device in its primary folded configuration until suitable conditions for deployment within the GI tube are reached.

[0218] To achieve further compactness in the collapsed state, the device may, in some embodiments, have a secondary wound configuration (not shown) so that the folded device is further wound around its axis and undergoes simultaneous unwinding and unfolding during the transition from the collapsed state to the expanded state. Note that the enteric envelope may instead, or in addition to, the enteric envelope 209 that encloses the device in its primary folded configuration, enclose the device in its secondary folded configuration (not shown). If the device includes two enteric envelopes, the first and second envelopes may be configured to have the same or different decomposition / dissolution properties.

[0219] Figures 7A and 7B show alternative arrangements of the devices in Figures 6A and 6B. In the device 200' shown in Figure 7A, each compartment 202' includes two regions coated with a layer 208' of the mucous adhesive material. While two regions are shown in the embodiments of Figures 7A and 7B, it should be noted that three or more regions, e.g., 3, 4, 5, 6, or even more such regions, can be utilized across each compartment, and the devices described herein are not limited by the number of such regions.

[0220] Alternatively, as seen in Figure 7B, the device 200" may include a pair of compartments 202"A, 202"B, where each pair of compartments is arranged continuously along the longitudinal axis 210 of the device, and each compartment 202A, 202B carries a mucoadhesive layer 208" on its outer surface. The arrangements shown in Figures 7A and 7B allow for further folding of the device along line 212, thereby enabling the device to be envisioned in a further compacted form suitable for ingestion. For example, as shown in Figure 7C, the device of Figure 7B can be flattened and then folded along line 212 to obtain a folded collapsed device. The device of Figure 7C can be further folded, for example, in the direction of arrow 214 to further reduce the size of the device and obtain the primary folded configuration shown in Figure 7D. As can be seen in Figures 7E and 7F, the devices in their primary folded configurations may be wrapped by at least one enteric envelope 209''.

[0221] The device may also include at least one additional active substance distinct from the activator. The additional active substance may have similar pharmaceutically active properties to the activator, or different pharmaceutically active properties from those of the activator. For example, the additional active substance may be contained in a mucous adhesive layer released simultaneously with or in succession to the activator. In another embodiment, the additional active substance may function to increase the permeability or bioavailability of the activator, or to increase or enhance the therapeutic effect or biological activity of the activator.

[0222] In further embodiments, additional active substances may be contained within the compartment, for example, associated with a deformable film, associated with a gel-forming material, or mixed (or dispersed) in the gel-forming material. In such cases, the additional active substances may be selected to have an immediate or short-term therapeutic effect, while the activators may be selected to have a long-term or sustained therapeutic effect.

[0223] The device of this embodiment can be used to deliver at least one activator to a target site, but the device may also be excluding activators or may contain only activators in its compartment. For example, the device may be used to deliver a patch to the wall of tissue, for example, to temporarily cover a perforation or ulcer in the tissue.

Claims

1. A self-expandable device configured to attach a tissue-adhering layer to tissue, wherein the device has a collapsed state and an expanded state, At least one self-expandable compartment formed from a substantially continuous deformable film having one or more liquid-permeable sections, wherein the compartment encloses a gel-forming material therein, and the gel-forming material expands upon contact with a liquid, thereby expanding the compartment and irreversibly switching the device from the collapsed state to the expanded state; The compartment comprises a tissue-adhering layer that coats at least a portion of the outer surface, the tissue-adhering layer comprising at least one activator delivered to the tissue, As a result, the expansion of the device from the collapsed state to the expanded state causes the expansion of the compartment to drive the tissue-adherent layer toward the tissue, thereby causing at least a portion of the tissue-adherent layer to adhere to the tissue.

2. The device according to claim 1, wherein the tissue-adhering layer comprises a plurality of microneedles.

3. The device according to claim 1, wherein the tissue-adhering layer is a mucous adhesive layer.

4. The device according to claim 3, wherein the mucous adhesive layer comprises at least one mucous adhesive material.

5. The device according to claim 3, wherein the mucous adhesive layer comprises at least one mucous adhesive material and at least one activator.

6. The device according to claim 2, wherein the microneedle is made of a polymer material in which the at least one activator is embedded.

7. The device according to claim 5, wherein the activator is a pharmaceutical activator.

8. The device according to claim 5, wherein the device comprises at least one additional active substance different from the at least one activator.

9. The device according to claim 1, wherein one or more sections of the deformable film differ from one another in their liquid permeability.

10. The device according to claim 1, wherein the deformable film is detachable.

11. The device according to claim 10, wherein the deformable film is mechanically, chemically, or biologically degradable.

12. The device according to claim 1, wherein the deformable film includes a weakening region that enables fragmentation of the film.

13. The device according to claim 1, wherein the gel-forming material is decomposable.

14. The device according to claim 1, wherein when in the collapsed state, the device is folded in a primary folded configuration and is configured to undergo unfolding during the transition from the collapsed state to the extended state.

15. The device according to claim 14, wherein the device is enclosed by an enteric envelope when in the aforementioned primary folded configuration.

16. The device according to claim 14, wherein, when in the collapsed state, the device has a secondary wound configuration, which is configured such that the folded device is further wound around its axis and simultaneously undergoes unwinding and unfolding during the transition from the collapsed state to the extended state.

17. The device according to claim 16, wherein in the secondary wound configuration, the device is enclosed by an enteric envelope.

18. The device according to claim 16, wherein in the primary folded configuration, the device is wrapped by a first enteric envelope, and in the secondary wound configuration, the device is wrapped by a second enteric envelope.

19. The device according to claim 1, wherein when in the collapsed state, the device is wound around its axis and is configured to be unwound during the transition from the collapsed state to the expanded state.

20. The device according to claim 1, comprising a biodegradable shell that encapsulates the device in its disintegrated state.

21. The device according to claim 1, which is an ingestible device.

22. The device according to claim 1, wherein the gel-forming material is in the form of a gel film.

23. The device according to claim 1, wherein the gel-forming material is in the form of gel particles.

24. The device according to claim 1, wherein the gel-forming material comprises one or more gel-forming compounds.

25. The device according to claim 1, wherein in the collapsed state, the tissue-adhering layer has a non-extending configuration such that a portion of the tissue-adhering layer coats at least a portion of the outer surface of the compartment, and in the extended state, the sheet has an extending configuration such that it extends beyond the compartment.

26. A kit comprising an ingestible, self-expandable device according to any one of claims 1 to 25, encapsulated in a biodegradable shell, and instructions for use.

27. A self-expandable device according to any one of claims 1 to 25, for use in attaching a tissue-adhering layer containing at least one activator to a target tissue requiring such adhesion, via a mucous membrane, wherein the self-expandable device is encapsulated in a biodegradable shell.

28. A self-expandable device according to any one of claims 5 to 25 for use in delivering at least one activator to a target tissue in need thereof, wherein the self-expandable device is encapsulated in a biodegradable shell.

29. A self-expandable device according to any one of claims 5 to 25 for use in delivering at least one activator to a target tissue in need therefor over a long period of time, wherein the self-expandable device is encapsulated in a biodegradable shell.

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