Intragastric expandable device

Abstract

The present disclosure provides a biodegradable device that is administered to a patient in the form of a compact, ingestible package. The device is self-expandable within the stomach upon contact with liquid to assume an expanded bulk structure within the stomach. The device has a folded configuration that facilitates ingestion by the patient and is designed to unfold and self-expand within the stomach upon ingestion due to expansion of a plurality of expandable cells comprising one or more gel-forming materials. The present disclosure provides such a device, methods of manufacturing the same, and building blocks thereof.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to ingestible intragastric devices, in particular expandable, self-deploying devices. BACKGROUND

[0002] The following references are believed to be relevant as background to the presently disclosed subject matter.

[0003] WO 2006 / 092789

[0004] WO 2007 / 136735

[0005] WO 2013 / 183058

[0006] WO 2015 / 083171

[0007] Acknowledgement herein of the above references is made solely for the purpose of providing a context for the presently disclosed subject matter. Nothing in this acknowledgement is, or should be taken as, a confirmation that these references are prior art.

[0008] BACKGROUND

[0009] Obesity and overweight have become one of the major risk factors for morbidity and mortality. Due to the medical and psychosocial implications of being overweight, as well as the difficulty of changing eating habits, patients often find it difficult to maintain the rules of life of diet and physical activity.

[0010] One of the approaches to induce weight loss is by reducing the stomach volume and / or increasing satiety, either by invasive surgery (e.g. bariatric surgery) or by administering a device that deploys in the stomach. Ingestible devices that deploy in the stomach temporarily reduce the stomach volume and increase satiety by exerting pressure on the stomach wall, thereby inducing a fuller sensation of the stomach with less amount of food consumed. These devices are designed to reside in the stomach for a predetermined period of time, following which they degrade to allow passage of the device through the pylorus (the barrier between the stomach and the intestine) into the intestine for natural elimination from the body. SUMMARY

[0011] The present disclosure provides biodegradable devices to be administered to a patient in a compact, ingestible package. The devices are self-expandable upon contact with a liquid (e.g. water, gastric fluid) in the stomach, and assume an expanded, large volume structure inside the stomach. The expanded form of the devices is designed to reside in the stomach for a predetermined period of time before undergoing degradation. The devices are designed for rapid and efficient expansion, controlled by the folded arrangement of the device in its compact, folded form. Thus, the devices of the present disclosure assume a compact, folded structure that can be easily swallowed by the patient, and can significantly change shape and increase volume inside the stomach to induce increased satiety.

[0012] Thus, in one aspect of the disclosure, there is provided a biodegradable, self-expandable device having a first, folded state and an expanded state. The device comprises a thin annular base unit divided into a plurality of consecutive (i.e. contiguous) segments along its peripheral portion. The annular base unit comprises a plurality of first and second fold axes, such that each segment is defined between a pair of consecutive first fold axes, and each segment comprises one second fold axis. The first and second fold axes are alternately arranged along the peripheral portion of the unit.

[0013] One or more of the plurality of segments comprises one or more cells comprising at least one gel-forming material, the gel-forming material being substantially encapsulated in each cell between at least two liquid-permeable layers;

[0014] In the first, folded state of the device, the segments are folded such that the first fold axes extend along a common axis, and each folded segment assumes a loop-like conformation, the second fold axis defining the apex of the loop-like conformation, and the folded segments are substantially stacked one on top of the other (i.e. the loops are arranged one on top of the other and substantially parallel to each other, with respect to the thickness dimension of the film). In the expanded state of the device, the first fold axes are spaced apart from each other.

[0015] The gel-forming material is configured to swell upon contact with a liquid (e.g. intragastric liquid permeating through the liquid-permeable layers upon ingestion of the device) to irreversibly transform the device from the first, folded state to the expanded state.

[0016] In other words, in the first, folded state, the device is folded such that the loops formed by the folded segments are stacked one on top of the other, the first fold axes are substantially co-axial, the apex of the loop-like folded segments defined by the second fold axes (each second fold axis defines the apex of the loop-like folded segment) extends opposite the first fold axes, resulting in a fan- or flower-like structure, while the loops are stacked one on top of the other.

[0017] Upon ingestion of the device, liquid permeates through the liquid-permeable material layers to contact the gel-forming material encapsulated within the cells of the device, thereby causing swelling (i.e. expansion) of the gel-forming material. Thus, contact of the liquid with the cells causes an increase in volume of the gel-forming material, pushing the loop-like folded segments away from each other and causing the loop-like folded segments to unfold, thereby obtaining the expanded state of the device. In its expanded state, the device generally assumes its base annular shape, thus reducing the volume of the stomach and / or exerting pressure on the stomach wall to increase satiety.

[0018] By varying the type, number, geometry, distribution, etc. of the cells, as well as the size of the segments, different expansion rates and shapes after expansion can be obtained. Furthermore, by folding the device along the alternating first and second axes and obtaining a collar-like folded segment, control of the exposure of the gel-forming material in the cells to the liquid in the stomach can be obtained, thereby controlling the overall expansion rate of the device inside the stomach.

[0019] It is emphasized that the first folding axis does not overlap the second folding axis. In other words, the first and second folding axes are arranged alternately along the peripheral portion (or perimeter) of the annular base unit and are spaced apart from each other along the peripheral portion.

[0020] The term "thin" as used throughout this disclosure is intended to mean an element whose thickness dimension (T) is substantially smaller than its length (L) and width (W) (T < L, T < W). For example, a thin annular base unit is intended to mean a base unit whose thickness is substantially smaller than the other dimensions of the unit.

[0021] In some embodiments, the annular base unit has a width-to-thickness ratio of at least 6 (W / T > 6), sometimes of at least 10 (W / T > 10), and even of at least 20 (W / T > 20). In other embodiments, the annular base unit has a length-to-thickness ratio of at least 6 (L / T > 6), sometimes of at least 10 (L / T > 10), and even of at least 20 (L / T > 20). In some other embodiments, the annular base unit has both a width-to-thickness ratio and a length-to-thickness ratio of at least 6 (W / T > 6 and L / T > 6).

[0022] The term "strip" refers to an elongated thin strip of material (i.e. a strip whose length is greater than its width and whose width is greater than its thickness (L > W > T)) defined between two end portions and extending along a longitudinal axis. The strip can have a substantially uniform width along its entire length or can have a varying width.

[0023] In some embodiments, when referring to a thin strip, the thin strip has a width-to-thickness ratio of at least 10 (W / T > 10), sometimes of at least 20 (W / T > 20), and a length-to-width ratio of at least 3 (L / W > 3), sometimes of at least 6 (L / W > 6), and even of at least 10 (L / W).

[0024] By some embodiments, the device can additionally have a second folded state in which the device is coiled in a direction from the common axis towards the apical end. The device in its second state can be encapsulated in a gastro-degradable shell.

[0025] According to another aspect of the present disclosure, there is provided a packaged biodegradable self-expandable device having a primary folded state, a secondary folded state and an expanded state, and a gastro-degradable shell packaging the device in the secondary folded state. The device comprises: a thin annular base unit divided into a plurality of consecutive segments along a circumference of the unit; alternating first and second fold axes, each segment being defined between a pair of consecutive first fold axes and each segment comprising one second fold axis; and one or more segments of the plurality of segments comprising one or more pockets comprising at least one gel-forming material, the gel-forming material in each pocket being packaged between at least two layers of liquid-permeable material. In the primary folded state of the device, the segments are folded such that the first fold axes extend along a common axis, and each folded segment assumes a collar-like configuration, the second fold axis defining an apex of the collar-like configuration, the folded segments being substantially stacked one on top of another. In the secondary folded state of the device, the device is further rolled in a direction from the common axis towards the apex. In the expanded state, the first fold axes are spaced apart from one another. The gel-forming material is configured for thickening upon contact with liquid, such that swelling of the gel-forming material upon contact with intragastric liquid after ingestion irreversibly transforms the device from the secondary folded state to the expanded state, at least partially through the primary folded state.

[0026] When the packaged device is ingested, the gastro-degradable shell is first degraded to expose the device. Upon contact with intragastric liquid, swelling of the gel-forming material in the pockets causes the device to at least partially unfold from its secondary folded state. Subsequently, the device can assume its expanded state upon further swelling of the gel-forming material in the pockets, as described above.

[0027] In the expanded state, the device can have an annular shape, a polygonal shape or an irregular shape. Typically, in its expanded state in the stomach, the device can assume a three-dimensional (3D) shape substantially conforming to a shape of at least one section of the stomach.

[0028] In some embodiments, the annular base unit is formed from a thin strip having a longitudinal axis, the first and second fold axes being alternately arranged along and perpendicular to the longitudinal axis.

[0029] Typically, the strip has a substantially uniform thickness along its length, except for the pockets (typically thicker).

[0030] In some embodiments, the strip extends between matching end portions configured for attachment to one another to form the annular base unit. The matching end portions can be configured, in some embodiments, to form an attachment region upon attachment to one another, the attachment region having a thickness substantially identical to the thickness of the strip.

[0031] In other embodiments, the annular base unit is planar, i.e. an object of substantially 2D annular shape, whose width is delimited by two concentric borders.

[0032] The term "annular" is intended to mean a base unit having a continuous closed shape / profile that surrounds a void. The annular base unit does not necessarily have to be circular, by some embodiments, the annular base unit can be circular (i.e. ring-shaped), polygonal (e.g. triangular, rectangular, trapezoidal, trihedral, pentahedral, hexahedral, heptahedral, etc.) or irregularly shaped. The annular base unit shape can be symmetrical or asymmetrical.

[0033] As previously mentioned, the cells are formed substantially of a single layer of gel-forming material sandwiched between at least two layers of liquid-permeable material. According to some embodiments, other areas of the annular base unit (e.g. non-cell areas of the annular base unit) can be formed of liquid-permeable material. In the context of the present disclosure, the term "liquid-permeable material" is intended to mean a material (compound or composition of matter) that allows liquid to diffuse or pass through it. In order to allow the device to degrade after a predetermined period of time, the liquid-permeable material is typically biodegradable, preferably enterically degradable. For example, the liquid-permeable material can be perforated or porous.

[0034] According to some embodiments, the liquid-permeable material can comprise one or more compounds selected from the group consisting of hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, hypromellose acetate succinate, cellulose acetate, ethyl cellulose, polymethyl methacrylate, polymethyl acrylate, polyethyl acrylate, polyvinyl acrylate phthalate, polyvinyl acetate, lacquer, carboxymethyl cellulose, carboxyethyl cellulose, carboxymethyl ethyl cellulose (CMEC) and any combination thereof.

[0035] According to some embodiments, the liquid-permeable material can further comprise at least one binder, plasticizer, pore-forming agent, film-forming agent and any combination thereof.

[0036] The term "biodegradable" is intended to mean any type of decomposition of the device caused by exposure to biological conditions after ingestion of the device. This term encompasses mechanical breakage, chemical or physical degradation, chemical or physical disintegration or any other type of destruction of its integrity during its passage through the gastrointestinal tract and out of the body.

[0037] The annular base unit has spatially separated areas, herein referred to as "cells", which comprise gel-forming material and are distributed along segments of the unit, as described hereinabove.

[0038] In some embodiments, the gel-forming material in the cells is present 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. By other embodiments, the gel-forming particles are present in a gel film, the gel particles being embedded in a matrix to form the film. In some embodiments, the gel-forming particles are arranged in the gel film as a substantially monolayer of gel particles.

[0039] According to other embodiments, the gel-forming material is a composition comprising a matrix embedded with a monolayer of swellable particles. Also according to other embodiments, the gel-forming material can be in the form of a powder. The average diameter of the gel-forming material particles can range between about 100 μm and about 300 μm.

[0040] According to some embodiments, each of the cells comprises a different gel-forming material. In other embodiments, at least some of the cells comprise a gel-forming material that is different from the gel-forming material of other cells. In some other embodiments, all of the cells comprise the same gel-forming material.

[0041] The term "gel-forming material" is intended to mean a compound or composition capable of absorbing a liquid thereby forming a three-dimensional, bulk volume network of molecules. The gel-forming material can form a physical gel, i.e., a gel in which the molecules are held in the network by physical forces, or a chemical gel, i.e., a gel in which the molecules are chemically bonded to one another to form the network structure.

[0042] According to some embodiments, the gel-forming material comprises one or more gel-forming compounds. According to other embodiments, the gel-forming material comprises one or more additives.

[0043] According to some embodiments, the gel-forming material comprises one or more polymers. According to some embodiments, the gel-forming material can be charged or neutral.

[0044] According to some other embodiments, the gel-forming material is cross-linked or cross-linkable. Without wishing to be bound by theory, the molecular weight and degree of cross-linking of the gel-forming material have a significant effect on the consistency (e.g., hardness or stiffness) and rheological properties (e.g., viscosity) of the gel. Thus, the various molecular weights and degrees of cross-linking are some of the parameters that can be used to control the behavior of the cells, and thereby control the deployment rate and / or expanded size of the device within the stomach.

[0045] In some embodiments, the gel-forming material can be selected from the group consisting of gelatin, alginate, chitosan, dextran, collagen, hyaluronic acid, polyglutamic acid, elastin, polycarbophil calcium, acrylamide, styrene maleic anhydride, polyethylene oxide, polyacrylic acid, polyethylene glycol, carboxymethylcellulose, polyvinylpyrrolidone, sodium polyacrylate, hypromellose, or any combination or composition thereof.

[0046] By some embodiments, the gel-forming material is a composition comprising at least one charged gel-forming compound and at least one compound having an opposite charge, which upon absorption of liquid, constructs a PEC (polyelectrolyte complex). In some embodiments, the at least one charged gel-forming compound is selected from the group consisting of polyvinyl acetate aminoacetate diethyl ester (AEA), polylysine, chitosan, polymethacrylate (Ultresol E), polyarginine, and any mixture thereof. In other embodiments, the compound having an opposite charge is selected from the group consisting of gelatin, hyaluronic acid, sodium polyacrylate, heparin, polyacrylic acid (carbomer), alginate, pectin, hydroxymethylcellulose, and any mixture thereof.

[0047] In some other embodiments, the gel-forming material is at least one superabsorbent polymer (SAP). The term "superabsorbent polymer" refers to a polymer (typically cross-linked) or a polymer composition that can absorb and retain large amounts of liquid, e.g. water (or aqueous liquid), relative to the dry mass of the polymer, non-limiting examples of SAPs are polyethylene glycol (PEG), polyglutamic acid (PGA), polyacrylamide, alginic acid, dextran, polyacrylic acid, carboxymethylcellulose (CMC), pullulan, starch, and any combination thereof.

[0048] In some other embodiments, the gel-forming material has a swelling ratio (under gastric acid pH, 37°C for 1 hour) of about 10 to 100 times (w / w).

[0049] The term "swelling ratio" denotes the extent of expansion between the state of the gel-forming material before absorption of liquid (i.e. dry or semi-dry form) and the state after absorption of the maximum possible amount of liquid. The swelling ratio is calculated on a weight basis and according to the following formula:

[0050] [(wet weight) - (dry weight)] / [(dry weight)]

[0051] As mentioned above, the annular base unit is divided into a plurality of consecutive (contiguous) segments. The segments can have the same length or different lengths. At least some of the segments comprise one or more of the said cells; when a segment comprises one or more cells, the cells are arranged within the segment in a spatially spaced apart manner (i.e. spaced apart from each other). The cells can be uniformly distributed (i.e. equidistant) in each segment; alternatively, the distance between the cells can be different between segments, or even between cells within a single segment.

[0052] As mentioned above, first and second folding axes are defined in the strip, which are arranged alternately along the peripheral portion of the annular base unit. The term "folding axis" (or any linguistic variant thereof) denotes a line, typically perpendicular to the longitudinal axis of the strip or directed towards the center point of the planar annular base unit, around which portions of the unit can be folded as will now be explained. The folding axis can be a physical line marked or formed on the annular base unit, or it can be virtual (i.e. marked on and / or physically formed on the unit).

[0053] The first folding axis is defined between segments; in other words, two consecutive segments define a first folding axis therebetween (an alternative definition is that each segment is defined between a pair of consecutive first folding axes). For each of the segments, the second folding axis is defined as the folding axis within the segment span, i.e. between a pair of consecutive first folding axes.

[0054] In the primary folded state, each of the segments forms a loop-like configuration, the first axes defining the segments being stacked one on top of the other, typically forming a common axis of the primary folded state. The second folding axis formed within the segments, the top end of the loop-like configuration.

[0055] The term "loop-like configuration" denotes a substantially closed shape, having a substantially closed contour. Depending on the position of the second folding axis, the loop-like configuration can be mirror-symmetrical about a plane extending between the common axis and the second folding axis, or it can be non-symmetrical.

[0056] In addition, in the primary folded state, the folded segments are arranged such that all the first folding axes extend along the common axis of the folded device (indeed, the first folding axes can be seen as substantially coextensive around the common axis). The folded segments are thus stacked one on top of the other. In some embodiments, the folded segments are arranged in the primary folded state parallel to a plane defined between the common axis and the second folding axis.

[0057] Once the folded segments are stacked one on top of the other, the device can be easily further folded into one or more secondary folded states, to further compact the device. According to some embodiments, the device in its primary folded state can be further rolled in a direction from the common axis towards the top end of the loop-like folded segments, thereby obtaining a secondary folded state. Such secondary folded state allows for a further reduction in the size of the device when the device is folded to enable packaging of the folded device in a gastro-degradable shell, such as a capsule.

[0058] Gastric degradable shells are typically of a size suitable for expansion, such as about "Elongated 000" capsules or 000 capsules 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 provides below non-limiting capsule sizes suitable for use as gastric degradable shells.

[0059] Table 1: Degradable shell (capsule) size

[0060]

[0061] As mentioned above, devices according to some embodiments are formed from an annular base unit member formed from a thin strip. The strip, also referred to herein as a "primary unit", is also an aspect of the present disclosure. Thus, in another aspect there is provided a primary unit in the form of a thin strip having a longitudinal axis, the base unit being constructed from a porous material encapsulating regions of at least one gel-forming material, the regions being spatially separated along the longitudinal axis, each region defining a cell, the gel-forming material in each cell being encapsulated between at least two layers of liquid permeable material, the gel-forming material being configured to swell upon contact with liquid, and the primary unit being configured to form an annular base unit of a foldable biodegradable self-expandable device.

[0062] In some embodiments, the strip extends between matching end portions, the end portions being configured for attachment to each other to form the annular base unit. By some embodiments, the matching end portions can be configured to form an attachment region having a thickness substantially the same as the thickness of the strip upon attachment of the end portions to each other.

[0063] In some embodiments, the matching end portions are connected to each other by overlapping the matching end portions on top of each other, followed by joining the overlapped regions to each other. In other embodiments, the matching end portions are connected to each other by overlapping the matching end portions side by side.

[0064] In some other embodiments, each of the end portions comprises at least two layers of liquid permeable material, one layer extending shorter along the end portion than the other layer, such that the longer layer forms a single-layer end section of the end portion. In such embodiments, the end portions are connectable to each other by overlapping the single-layer end sections side by side or on top of each other to obtain a joint section having a total thickness of two layers.

[0065] In some embodiments, the primary unit (or strip) can be divided into a plurality of contiguous segments along the longitudinal axis, with alternating first and second fold axes, each of the first fold axes being defined between adjacent segments and each segment including one second fold axis, one or more of the plurality of segments including one or more pockets.

[0066] A biodegradable self-expandable device having a primary folded state and an expanded state is provided by another aspect, the device comprising a thin annular base unit formed from a strip having a longitudinal axis, first and second fold axes being arranged alternately along and perpendicular to the longitudinal axis, the strip being divided into a plurality of contiguous segments such that each pair of contiguous first fold axes defines a segment therebetween and each segment includes a second fold axis, and one or more of the plurality of segments including one or more pockets including at least one gel-forming material, the gel-forming material in each pocket being encapsulated between at least two layers of liquid-permeable material; in the primary folded state of the device, the segments are folded such that the first fold axes extend along a common axis and each folded segment assumes a collar-like configuration, the second fold axis defining an apex of the collar-like configuration, the folded segments being stacked substantially one on top of the other, the gel-forming material being configured to swell upon contact with a liquid to irreversibly transform the device from the primary folded state to the expanded state, in which the first fold axes are spaced apart from each other.

[0067] A biodegradable self-expandable device having a primary folded state and an expanded state is provided by another aspect, the device comprising a thin annular base unit formed from a strip having a longitudinal axis, first and second fold axes being arranged alternately along and perpendicular to the longitudinal axis, the strip being divided into a plurality of contiguous segments such that each pair of contiguous first fold axes defines a segment therebetween and each segment includes a second fold axis, and one or more of the plurality of segments including one or more pockets including at least one gel-forming material, the gel-forming material in each pocket being encapsulated between at least two layers of liquid-permeable material; in the primary folded state of the device, the segments are folded such that the first fold axes extend along a common axis and each folded segment assumes a collar-like configuration, the second fold axis defining an apex of the collar-like configuration, the folded segments being stacked substantially one on top of the other, the gel-forming material being configured to swell upon contact with a liquid to irreversibly transform the device from the primary folded state to the expanded state, in which the first fold axes are spaced apart from each other.

[0068] By another of its aspects, the present disclosure provides a method for producing a biodegradable self-expandable device as described herein. The method comprises:

[0069] (a) joining two opposite matching ends of a thin strip to form a thin annular base unit, the strip having a longitudinal axis and being divided into a plurality of consecutive segments along the longitudinal axis, one or more segments of the plurality of segments comprising one or more zones, each zone comprising at least one gel-forming material configured to swell upon contact with a liquid, the gel-forming material in each zone being encapsulated between at least two layers of liquid-permeable material; and

[0070] (b) folding the annular base unit along first and second folding axes, the first and second folding axes being alternately arranged along the longitudinal axis of the strip, each of the first folding axes being defined between adjacent segments and each segment comprising one second folding axis, thereby obtaining a primary folded state in which the segments are folded such that the first folding axes extend along a common axis, and each folded segment assumes a grommet-like configuration, the second folding axis defining the top end of the grommet-like configuration, the folded segments being substantially stacked one on top of the other.

[0071] By another aspect, the present disclosure provides an alternative method of producing a biodegradable self-expandable device as described herein. The method comprises:

[0072] (a') folding a thin strip, the thin strip having a longitudinal axis and being divided into a plurality of consecutive segments along the longitudinal axis defined between two opposite matching ends of the strip, the folding being along first and second folding axes alternately arranged along the longitudinal axis of the strip, each of the first folding axes being defined between adjacent segments and each second folding axis being defined within a segment, one or more segments of the plurality of segments comprising one or more zones, each zone comprising at least one gel-forming material configured to swell upon contact with a liquid, and the gel-forming material in each zone being encapsulated between at least two layers of liquid-permeable material; and

[0073] (b') joining two opposite matching ends of the strip, thereby obtaining a primary folded state of a thin annular base unit formed by the strip, in which the segments are folded such that the first folding axes extend along a common axis, and each folded segment assumes a grommet-like configuration, the second folding axis defining the top end of the grommet-like configuration, the folded segments being substantially stacked one on top of the other.

[0074] Joining the two opposite matching ends of the strip to obtain an annular base unit can be performed by any suitable joining method, such as mechanical interlocking, adhesion, heat welding, solvent welding, stitching, etc.

[0075] By yet another aspect, there is provided a method of manufacturing a biodegradable self-expandable device, the method comprising folding a thin annular base unit along first and second folding axes, the first and second folding axes being arranged alternately along a circumference of the unit, the unit being divided into a plurality of consecutive segments along said circumference, such that each segment is defined between a pair of consecutive first folding axes and each segment comprises one second folding axis, thereby obtaining a primary folded state in which the segments are folded such that the first folding axes extend along a common axis and each folded segment assumes a collar-like configuration, the second folding axis defining an apex of the collar-like configuration, the folded segments being substantially stacked one on top of the other, one or more segments of the plurality of segments comprising one or more pockets, each pocket comprising at least one gel-forming material configured to swell upon contact with a liquid, and the gel-forming material in each pocket being encapsulated between at least two layers of liquid-permeable material.

[0076] According to some embodiments, the method of the present disclosure can further comprise winding the device in its primary folded state around the common axis in a direction from the common axis towards the apex, thereby obtaining a secondary folded state of the device.

[0077] According to another embodiment, the method of the present disclosure comprises encapsulating the device in its secondary folded state within a gastro-degradable shell.

[0078] By another aspect, there is provided a method of producing an encapsulated biodegradable self-expandable device as described herein. The method comprises:

[0079] (i) joining two opposite mating ends of a thin strip to form a thin annular base unit, the strip having a longitudinal axis and being divided into a plurality of consecutive segments along said longitudinal axis, one or more segments of the plurality of segments comprising one or more pockets, each pocket comprising at least one gel-forming material configured to swell upon contact with a liquid, the gel-forming material in each pocket being encapsulated between at least two layers of liquid-permeable material;

[0080] (ii) folding the annular base unit along first and second folding axes, the first and second folding axes being arranged alternately along the longitudinal axis of the strip, each of the first folding axes being defined between adjacent segments and each segment comprising one second folding axis, thereby obtaining a primary folded state in which the segments are folded such that the first folding axes extend along a common axis and each folded segment assumes a collar-like configuration, the second folding axis defining an apex of the collar-like configuration, the folded segments being substantially stacked one on top of the other;

[0081] (iii) winding the device in its primary folded state around the common axis to obtain a secondary folded state of the device; and

[0082] (iv) packaging the device in its second folded state in a gastro-degradable shell to obtain said packaged biodegradable self-expandable device.

[0083] By yet another aspect, there is provided a method of producing a packaged biodegradable self-expandable device as described herein. The method comprises:

[0084] (i') folding a thin strip, the thin strip having a longitudinal axis and being divided into a plurality of consecutive segments along the longitudinal axis defined between two opposite mating ends of the strip, said folding being along first and second folding axes arranged alternately along the longitudinal axis of the strip, each of the first folding axes being defined between adjacent segments and each of the second folding axes being defined within a segment, one or more segments of the plurality of segments comprising one or more sub-segments, each sub-segment comprising at least one gel-forming material configured to swell upon contact with a liquid, the gel-forming material in each sub-segment being encapsulated between at least two layers of liquid-permeable material;

[0085] (ii') joining the two opposite mating ends of the strip, thereby obtaining a primary folded state of a thin annular base unit formed by the strip, wherein the segments are folded such that the first folding axes extend along a common axis, and each folded segment assumes a grommet-like configuration, the second folding axes defining the top end of the grommet-like configuration, the folded segments being substantially stacked one on top of the other;

[0086] (iii') winding the device in its primary folded state around the common axis to obtain a second folded state of the device; and

[0087] (iv') packaging the device in its second folded state in a gastro-degradable shell to obtain said packaged biodegradable self-expandable device.

[0088] By yet another aspect, there is provided a method of producing a packaged biodegradable self-expandable device as described herein. The method comprises:

[0089] (i") folding the thin planar annular base unit along first and second folding axes, the first and second folding axes being arranged alternately along the unit's peripheral portion, the unit being divided into a plurality of consecutive segments along said peripheral portion, such that each segment is defined between a pair of consecutive first folding axes, and each segment comprises one second folding axis, thereby obtaining a primary folded state in which the segments are folded such that the first folding axes extend along a common axis, and each folded segment assumes a collar-like configuration, the second folding axis defining the top end of the collar-like configuration, the folded segments being substantially stacked one on top of the other, one or more segments of the plurality of segments comprise one or more sub-segments, each sub-segment comprising at least one gel-forming material configured to swell upon contact with a liquid, and the gel-forming material in each sub-segment is encapsulated between at least two layers of liquid-permeable material;

[0090] (ii") winding the device in its primary folded state around the common axis to obtain a secondary folded state of the device; and

[0091] (iii") encapsulating the device in its secondary folded state within a gastro- degradable shell to obtain said encapsulated biodegradable self-expandable device.

[0092] By another aspect, the present disclosure provides a method of reducing the gastric volume of a subject, the method comprising administering to the subject an encapsulated biodegradable self-expandable device as described herein.

[0093] By yet another aspect of the present disclosure, there is provided a method of increasing the satiety of a subject, the method comprising administering to the subject an encapsulated biodegradable self-expandable device as described herein.

[0094] By still another aspect of the present disclosure, there is provided a method of promoting weight loss in a subject, the method comprising administering to the subject an encapsulated biodegradable self-expandable device as described herein.

[0095] Without wishing to be bound by theory, it is stipulated that the device of the present application is capable of stimulating the mechanoreceptors on the gastric wall, thereby simulating the sensation of gastric satiation (as after a typical meal) in the treated patient, thereby suppressing the patient's appetite for a predetermined, limited period of time. It is further stipulated that the simulation of the sensation of gastric satiation is achieved by using the device of the present disclosure, thereby inducing gastric stasis and slowing down the gastric emptying period (thereby also prolonging the interval between meal periods).

[0096] In all of the methods described herein, the device can be administered concomitantly, sequentially or simultaneously with any other therapeutic method for suppressing the patient's appetite, promoting satiety and / or weight loss in the patient (including, but not limited to, administering additional active agents, the patient's participation in exercise and / or diet programs, and participation of the patient in psychological therapy).

[0097] In another of its aspects, the present disclosure provides a kit (set) comprising an encapsulated biodegradable self-expandable device as defined herein and instructions for use.

[0098] In another aspect, a kit is provided comprising an encapsulated biodegradable self-expandable device as defined herein, and an ingestible degradation formulation for accelerating degradation of the device in the stomach. The ingestible degradation formulation can be a slow release or delayed release formulation administered concomitantly with the device, such that degradation in the stomach is initiated after a predetermined period of time. Alternatively, the degradation formulation can be administered after a predetermined period of time from ingestion of the device. BRIEF DESCRIPTION OF DRAWINGS

[0099] For a better understanding of the subject matter disclosed herein, and to show how it can be implemented in practice, embodiments will now be described, by way of non-limiting examples only, with reference to the accompanying drawings, in which:

[0100] Figures 1A-1C Schematic depiction of a top view Figure 1A ) and side view Figure 1B , 1C ) of a section of a ring-shaped base unit constituting a device according to an embodiment of the present disclosure.

[0101] Figures 1D-1E Schematic depiction of a top view Figure 1D ) and side view Figure 1E ) of a primary unit (strip) for forming a ring-shaped base unit of a device and of a structure for joining the "ends" of the strips according to an embodiment of the present disclosure.

[0102] Figures 1F(i)-1F(iii) Various structures of detail F in Figure 1D are shown, demonstrating different structures of strip end portions when the strips comprise two layers of liquid permeable material.

[0103] Figures 1G(i)-1G(iv) Various connection structures of strip end portions of Figures 1F(i)-1F(iii) are shown.

[0104] Figures 1H(i)-1H(ii) Various structures of detail H in Figure 1D are shown, demonstrating different structures of strip end portions when the strips comprise a single layer of liquid permeable material as the terminal section of the strip end portion.

[0105] Figures 1I(i)-1I(iv) Various connection structures of strip end portions of Figures 1F(i)-1F(iii) are shown.

[0106] Figure 1Jfor an exemplary annular base unit, wherein the strip ends are joined by the structure of Figure III(ii).

[0107] Figures 2A-2C is a schematic depiction (top view) of a planar annular base unit according to some embodiments of the disclosure.

[0108] Figures 3A-3B is a schematic depiction of an annular base unit prior to being folded into a primary folded state according to an embodiment of the disclosure.

[0109] Figures 4A-4B is a schematic depiction of exemplary consecutive steps of folding Figure 3A the annular base unit of Figure 3 into a primary folded state.

[0110] Figure 4C is a schematic depiction of the primary folded state of Figure 4B , viewed from the direction marked "V", showing the stacking of the collars.

[0111] Figures 5A-5C is a schematic depiction of alternative exemplary consecutive steps of folding the annular base unit of Figure 3 into a primary folded state.

[0112] Figures 6A-6B is a schematic depiction of exemplary folding of the device of Figure 4B (or Figure 5C ) into a secondary folded state Figure 6A and into a packaged form Figure 6B .

[0113] Figures 7A-7D is a schematic depiction of exemplary folding of the device of Figure 2B into a primary folded state. DETAILED DESCRIPTION

[0114] In the following, exemplary devices according to the disclosure will be described. While specific examples show the devices as substantially symmetrical and having a certain number of rectangular cells, it will be understood that any number and shape of cells can be used, distributed in any way along the segments. The devices need not necessarily exhibit the originally folded shape as symmetrical, as described herein above. Furthermore, for ease of illustration, the elements of the devices are not shown to scale.

[0115] Firstly, Figure 1A(i) shows a schematic depiction of a segment of an annular base unit of the device. Figures 1A-1C Figure 1A(ii) provides a top view of the segment, Figure 1A Figure 1A(iii) provides a side view of Figures 1B-1C Figure 1A(iv) provides a perspective view of Figure 1Aa side view of a cross-section A-A. The section 100 is made of a liquid permeable degradable material, a plurality of cells 102 are distributed along the length of the section 100. The annular base unit is typically made of two or more layers of liquid permeable material, attached, stitched or welded to each other at the edges 109 (not shown in the remaining figures for the sake of convenience) and to the section 100 at the edges 109. The cells 102 are typically formed by a layer of liquid permeable material 111 sandwiching a film of gel-forming material 113 at discrete areas. Alternatively, the section can be made of a liquid permeable material in one piece, forming a pocket in which the gel-forming material is encapsulated at discrete areas forming the cells. Figure 1A The cells 102 are typically formed by a layer of liquid permeable material 111 sandwiching a film of gel-forming material 113 at discrete areas. Alternatively, the section can be made of a liquid permeable material in one piece, forming a pocket in which the gel-forming material is encapsulated at discrete areas forming the cells.

[0116] The annular base unit is in the form of a thin strip. That is, the length (L) of the thin strip is significantly larger than its width (W) (e.g. L / W>3, 6, 10) and the thickness (T) of the thin strip is significantly smaller than its width (e.g. W / T>10, 20).

[0117] The section 100 is divided into a plurality of consecutive segments 104, defining a first fold axis 106 between each two adjacent segments. Each segment also includes a second fold axis 108. Since each segment 104 includes only one second fold axis 108, the first and second axes are alternately arranged along the length of the section.

[0118] As seen in Figure 1B and 1C The section 100 of the annular base unit does not need to have a uniform thickness. For example, as shown in Figure 1B the section 100 can have a given thickness at the location of the first fold axis 106 and a larger thickness in the cells 102. In the example of Figure 1C at the location of the first fold axis 106, the layers of liquid permeable material are attached to each other, forming a spacer segment 107 including one or more cells.

[0119] Figures 1D-1E A schematic view of a primary unit in the form of a strip 100' (comprised of a section 100) from which an annular base unit according to an embodiment of the present disclosure of a device can be comprised is shown in Figures 1F(i)-1I(iv) The strip 100' has an elongated shape extending along a longitudinal axis 110 between two opposite mating end portions 112. Cells 102 are distributed along the length of the strip 100'. The end portions 112 can be designed in different structures as shown in the example presented in

[0120] Figures 1F(i)-1F(iii) A schematic view of a primary unit in the form of a strip 100' (comprised of a section 100) from which an annular base unit according to an embodiment of the present disclosure of a device can be comprised is shown in Figure 1DThe structure in detail F illustrates the different structures at the ends of the strip when it comprises two layers of liquid-permeable material. As shown, the two layers are typically welded together at different locations to form the strip. Welding can be performed along the entire length of the strip, leaving the end edges unwelded (Fig. 1F(iii)), or welding can be performed so that the end segments of the strip are not connected to each other ( Figures 1F(i)-1F(ii) The end portions 112 of the strips can be interconnected by various structures. This can be achieved by overlapping (e.g., as shown in Figures 1G(1) and 1G(ii)) or by juxtaposing (e.g., like...) Figure 1G(iii) and 1G(iv) (As seen in the text).

[0121] Figures 1H(i)-1H(ii) It shows Figure 1E The structure of detail H shows another structure of the strip end portion. When the strip includes two layers of liquid-permeable material of different lengths at the end portion 112, it results in a single-layer end segment at the end portion 112 (such as...). Figure 1H(i) and 1H(ii) As shown, the two layers can be welded together along their overlapping area, leaving the end monolayer exposed, allowing it to be joined to the opposing strip end portion 112, as seen in Figure 1H(ii). To join the opposing strip ends, the two monolayer end segments of the end portions can overlap each other (as shown in Figures 1I(i)-1I(II)) or be placed side by side (as seen in Figures H(iii)-1H(iv)), and the monolayer end segments of the end portions are welded together.

[0122] Once folded in the direction of arrow 114, the matching end portions 112 are joined together and further engaged / attached / connected to each other, for example... Figure 1J As shown. The primary unit at this time forms an annular base unit of the device according to one embodiment of the present disclosure, wherein segments, sub-segments, a first folding axis, and a second folding axis are arranged along the periphery of the annular base unit.

[0123] In another implementation, the ring-shaped base unit can have a planar structure, i.e., be formed as a substantially 2D thin ring-shaped object, the width of which is defined by two concentric boundaries, such as... Figures 2A-2C As shown. Planar annular base elements 1100, 1100' and 1100" (respectively...) Figure 2A , 2B Units 1102 and 2C are constructed as planar annular objects, wherein subunits 1102, segments 1104, the first folding axis 1106, and the second folding axis 1108 are arranged along the periphery of the annular base unit. The annular base unit is typically made of two or more layers of liquid-permeable material and is attached, stitched, or welded together at the edges 1109. A detailed description of the folding method of these planar base units will be provided below.

[0124] Figure 3A A side view of a toroidal base unit 200 made of a strip 100' is shown, according to an embodiment of the present disclosure, along with the first folding axes 106A-106C and the second folding axes 108A-108D, respectively. The attachment region of the end portion 112 of the strip constitutes a first folding axis 106D. A plurality of cells 102 are distributed along the length of the strip 100'. It will be appreciated that each of the cells is constructed as described herein, i.e. comprising a gel-forming material encapsulated between at least two layers of liquid permeable material. For ease of observation, in this figure, as well as in all subsequent figures, the layers are not shown. It will be appreciated that while eight cells, four first folding axes and four second folding axes are shown in this particular example, the device of the present disclosure can comprise other arrangements (i.e. comprising different numbers of cells and axes), as long as the first and second folding axes alternate arrangement and folding principle described herein are maintained. For example, Figure 3B A toroidal base unit comprising six cells, three first folding axes and three second folding axes is drawn.

[0125] Figure 4A and 4B are exemplary stages of a folding sequence of the toroidal base unit 200 to obtain a first folded state of the device. For example, as shown in Figure 4A , the toroidal base unit can be first folded along the first folding axis 106B, and then along the first folding axes 106A and 106C (as shown in Figure 4B ). Once so folded, the first folding axes 106A-106D are mutually adjacent and substantially coaxial along a common axis 202. This folding causes each segment 104 defined between two consecutive first folding axes 106 to assume a collar-like configuration, with its respective second folding axis 108 defining the top end of the collar. By this folding, the collars are mutually adjacent, with the first folding axes 106 mutually adjacent (sometimes coaxial) forming the common axis 202 and the second folding axes 108 extending in an opposite direction to the common axis, so that the collars are stacked one on top of the other. This structure constitutes a first folded state 300 of the device. Figure 4C A view is provided from the direction of arrow V in Figure 4B . In this view, the collars and, respectively, the folded segments can be seen stacked one on top of the other along the thickness / dimension of the strip.

[0126] As can be seen, due to the folding, the cells 102 are distributed along the collar-like folded segments and are positioned between adjacent collars.

[0127] An alternative folding sequence is found in Figures 5A-5C and follows Figures 4A-4BThe folding principle is similar to that shown.

[0128] The first-stage folding device 300 can be further, for example, as... Figure 6A As shown, the fold is a two-stage fold. Figure 6A As shown, in the second-order folded state, the device is wound from the common axis 202 toward the top end 304 in the direction of arrow 302, thereby transforming the device into a wound cylindrical structure. It should be noted that the winding direction can also be from the top end 304 toward the common axis 202.

[0129] like Figure 6A As shown, once the secondary folded state is achieved, the secondary folded device 306 can be encapsulated in a digestible encapsulation shell, such as capsule 308, which can be administered to a patient for ingestion.

[0130] Upon administration, the capsule is ingested and degrades in the stomach to expose the device in its second folded state. Once exposed to the liquid in the stomach, the gel-forming material within the cell (exposed to the liquid) begins to absorb the liquid and swell. This swelling begins to unfold the second-folded device, and the unfolding process pushes the loop-like folded segments apart and causes the device to expand into its extended state, in which the device typically takes on a shape corresponding to its ring-shaped base.

[0131] In its expanded shape, the expanded cells cause the device to increase in volume within the stomach, thereby reducing the stomach's capacity and / or exerting pressure on the stomach wall to increase satiety.

[0132] We will now demonstrate a method for folding a planar toroidal basic unit. Although Figures 7A-7D The specific example shown is about a triangular toroidal base element. It should be understood that the same folding principle can also be applied to other planar toroidal base elements, such as circular, rectangular, hexagonal, etc.

[0133] Planar triangular ring base element 1100' ( Figure 7A It can first be folded along the first folding axis 1106C in the direction of arrow 1120, so that axes 1106A and 1106C overlap each other. Figure 7B The device is then folded about the coupling shafts 1106A and C in the direction of arrow 1122 to obtain... Figure 7C The structure is shown in the diagram. The first folding axis 1106B is then folded toward the joining axes 1106A and C, such that the first folding axis 1106B is coaxial along the common axis 1202. This folding results in each segment defined between the two consecutive first folding axes 1106 exhibiting a loop-like structure, with each respective second folding axis 1108 defining the apex of the loop. Through this folding, a substantially planar structure is obtained. Figure 7D), the collar-like folded segments are arranged substantially parallel to each other along a plane defined between the common axis and the second folding axis. The planar structure constitutes a primary folded state 1300 of the device.

[0134] As can be seen, due to the folding, the cells 1102 are distributed along the collar-like folded segments, and are positioned between adjacent collars.

[0135] The primary folded device 300 can be further folded into a secondary folded state by rolling the device from the direction of the common axis 1202 towards the top end.

Claims

1. An ingestible, biodegradable, self-expanding device having a primary folded state and an expanded state, the device comprising: The thin annular base unit is divided into multiple continuous segments along the periphery of the unit. Each segment is defined between a pair of successive first folding axes, and each segment includes a second folding axis, the first and second folding axes being arranged alternately along the periphery of the unit. One or more of the plurality of segments include one or more cells, the one or more cells including at least one gel-forming material, the gel-forming material being encapsulated in each cell between at least two layers of liquid-permeable material; In the first-stage folded state of the device, the segment folding is such that the first folding axis extends along a common axis, each folded segment presents a loop-like structure, the second folding axis defines the apex of the loop-like structure, and the folded segments are substantially stacked vertically. The gel-forming material is configured to expand upon contact with a liquid to irreversibly transform the device from the first-order folded state to the extended state, in which the first fold axes are spaced apart from each other.

2. The device according to claim 1, having a two-stage folded state, wherein the device in the first-stage fold is further wound in a direction from the common axis toward the top end.

3. The device according to claim 2, further comprising a gastrodegradable shell, the shell encapsulating the device in its secondary folded state.

4. The apparatus of claim 1, wherein the liquid-permeable material and / or the gel-forming material is enterodegradable.

5. The apparatus of claim 1, wherein the gel-forming material is in the form of a gel film.

6. The apparatus of claim 1, wherein the gel-forming material is in the form of gel particles.

7. The apparatus of claim 6, wherein the gel particles are embedded within a matrix to form a substantially continuous gel film.

8. The apparatus of claim 1, wherein the gel-forming material comprises a superabsorbent polymer (SAP).

9. The apparatus of claim 1, wherein each segment comprises one or more cells.

10. The apparatus of claim 1, wherein the number of cells in each segment may be the same or different.

11. The apparatus of claim 1, wherein one or more of the plurality of segments comprise a plurality of spatially spaced cells.

12. The apparatus of claim 1, wherein in the extended state, the apparatus has a circular shape, a polygonal shape, or an irregular shape.

13. The apparatus of claim 1, wherein the annular base unit is formed of a thin strip having a longitudinal axis, and the first and second folded axes are arranged alternately along and perpendicular to the longitudinal axis.

14. The apparatus of claim 13, wherein the strip extends between mating end portions, the end portions being configured to attach to each other to form the annular base unit.

15. The apparatus of claim 14, wherein the mating end portions are configured to form an attachment region when attached to each other, the attachment region having a thickness substantially the same as the thickness of the strip.

16. The apparatus of claim 14, wherein the mating end portions are connected to each other by placing them side by side or overlapping them vertically.

17. The apparatus of claim 14, wherein each of the mating end portions comprises at least two layers of liquid-permeable material, wherein one layer extends along the end portion in a shorter manner than the other, such that the longer layer forms a single-layer end segment of the end portion.

18. The apparatus of claim 17, wherein the mating end portions are connected to each other by aligning the end segments side-by-side or overlapping them vertically.

19. The apparatus of claim 1, wherein the annular base unit is planar.

20. An encapsulated, biodegradable, self-expanding device, comprising: The ingestible, biodegradable, self-expanding device according to claim 1, having a primary folded state, a secondary folded state, and a gastrodegradable shell encapsulating the device in its secondary folded state, In the first-stage folded state of the device, the segment folding is such that the first folding axis extends along a common axis, and each folded segment presents a loop-like structure, the second folding axis defining the apex of the loop-like structure, and the folded segments are substantially stacked vertically. In the secondary folded state of the device, the device is further wound in a direction from the common axis toward the top end, and The gel-forming material is configured to expand upon contact with a liquid to irreversibly transform the device from the secondary folded state to the primary folded state, and from the primary folded state to the extended state, wherein the first folded axes are spaced apart from each other.

21. A kit comprising an encapsulated, ingestible, biodegradable, self-expanding device according to claim 20 and instructions for use.

22. The kit of claim 21, further comprising an ingestible degradation formulation for accelerating the degradation of the ingestible biodegradable self-expanding device in the stomach.

23. A primary unit in the form of a thin strip having a longitudinal axis, the primary unit being configured to form the thin annular base unit of the ingestible, biodegradable, self-expanding device according to claim 1, the primary unit being constructed of a porous material encapsulating regions of at least one gel-forming material, the regions being spatially spaced along the longitudinal axis, each region defining a cell, the gel-forming material in each cell being between at least two layers of liquid-permeable material, the gel-forming material being configured to expand upon contact with a liquid, and the primary unit being configured to form an annular base unit foldable into a biodegradable, self-expanding device.

24. The primary unit of claim 23, wherein the strips extend between mating end portions configured to attach to each other to form the annular base unit.

25. The primary unit of claim 24, wherein the mating end portions are configured to form an attachment region when attached to each other, the attachment region having a thickness substantially the same as the thickness of the strip.

26. The primary unit of claim 23, wherein the strip is divided into a plurality of coherent segments along the longitudinal axis having alternating first and second folding axes, each of the first folding axes defining a space between adjacent segments and each segment including a second folding axis, one or more of the plurality of segments including one or more small cells.

27. A thin annular planar base unit for an ingestible, biodegradable, self-expanding device according to claim 1, the thin annular planar base unit being constructed of a porous material encapsulating regions of at least one gel-forming material, the regions being spatially spaced along the periphery of the unit, each region defining a cell, the gel-forming material in each cell being encapsulated between at least two layers of liquid-permeable material, the gel-forming material being configured to expand upon contact with a liquid, and the thin annular planar base unit being configured to fold into the ingestible, biodegradable, self-expanding device.

28. A method for producing an ingestible, biodegradable, self-expanding device, the method comprising: Two opposing matching ends of a thin strip are joined to form a thin annular base unit, the strip having a longitudinal axis and being divided into a plurality of coherent segments along the longitudinal axis, one or more of the plurality of segments comprising one or more small cells, each small cell comprising at least one gel-forming material configured to expand upon contact with a liquid, the gel-forming material in each small cell being encapsulated between at least two layers of liquid-permeable material; as well as The annular base unit is folded along first and second folding axes, which are alternately arranged along the longitudinal axis of the strip. Each of the first folding axes is defined between adjacent segments and each segment includes a second folding axis, thereby obtaining a first-order folded state, wherein the segments are folded such that the first folding axes extend along a common axis and each folded segment presents a loop-like structure, the second folding axis defining the top of the loop-like structure, and the folded segments are substantially stacked vertically.

29. A method for producing an ingestible, biodegradable, self-expanding device, the method comprising: A thin strip having a longitudinal axis and divided into a plurality of coherent segments along the longitudinal axis is folded, the segments being defined between two opposing mating ends of the strip, the folding being carried out along first and second folding axes, the first and second folding axes being arranged alternately along the longitudinal axis of the strip, each of the first folding axes being defined between adjacent segments and each of the second folding axes being defined within a segment, one or more of the plurality of segments comprising one or more small cells, each cell comprising at least one gel-forming material configured to expand upon contact with a liquid, and the gel-forming material in each cell being encapsulated between at least two layers of liquid-permeable material; By joining the two opposing matching ends of the strip, a first-order folded state of a thin annular base unit formed by the strip is obtained, wherein the segments are folded such that the first folding axis extends along a common axis and each folded segment presents a loop-like structure, the second folding axis defining the top of the loop-like structure, and the folded segments are substantially stacked vertically.

30. A method of producing an ingestible, biodegradable, self-expanding device, the method comprising folding a thin annular base unit along first and second folding axes, the first and second folding axes being alternately arranged along a periphery of the unit, the unit being divided into a plurality of coherent segments along the periphery such that each segment is defined between a pair of successive first folding axes, and each segment includes a second folding axis, thereby obtaining a first-order folded state, wherein the segments are folded such that the first folding axes extend along a common axis, and each folded segment presents a loop-like structure, the second folding axis defining the apex of the loop-like structure, the folded segments being substantially stacked vertically. One or more of the plurality of segments include one or more cells, each cell including at least one gel-forming material configured to expand upon contact with a liquid, and the gel-forming material in each cell being encapsulated between at least two layers of liquid-permeable material.

31. The method of claim 30, further comprising winding the ingestible, biodegradable, self-expanding device in its first-order folded state in a direction from the common axis toward the apex, thereby obtaining a second-order folded state of the device.

32. The method of claim 31, further comprising encapsulating the device in its secondary folded state within a gastrodegradable shell.

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