Self-sizing device for delivering preparations to the wall of a body lumen

Abstract

A system for delivering a therapeutic agent into a lumen is provided. The system comprises a self-sizing device including an inflatable component, wherein the inflatable component comprises at least one non-compliant section configured to resist deformation in the inflated configuration, and the inflatable component further comprises at least one hinge configured to allow deformation in the inflated configuration, wherein the inflatable component is configured to bend around the hinge upon inflatation to adapt to the inner circumference of the lumen regardless of the inner circumference of the lumen within a selected range. The system comprises a therapeutic agent and a delivery mechanism. The self-sizing device is configured such that, upon inflatation of the inflatable component, the delivery mechanism applies a force to the therapeutic agent designed to eject the therapeutic agent from the self-sizing device. The self-sizing device may be placed within a capsule.

Description

Technology Field

[0001] Cross-reference of related applications

[0002] This application claims priority and interest in U.S. Provisional Patent Application No. 62 / 909,206, filed on October 1, 2019, under the title INFLATABLE DEVICES, SYSTEMS AND METHODS FOR DELIVERING THERAPEUTIC COMPOUNDS INTO WALL OF THE GASTRO INTESTINAL TRACT, the entirety of which is incorporated herein by reference for all purposes. Background Technology

[0003] It may be desirable to deliver a substance or formulation (e.g., fluid, slurry, powder, or solid) into a lumen, and it may be additionally desirable to deliver the substance to or into the inner wall of the lumen. In many applications, the inner circumference of the lumen may be unpredictable / unpredictable or variable, or the inner circumference of multiple lumens may be collectively unpredictable / unpredictable or variable, so selecting an effective device for delivering the substance to or into the inner wall of any given lumen can be a difficult task.

[0004] An example of delivery into the lumen of the animal body is the delivery of therapeutic agents into the lumen of the gastrointestinal tract. Delivery of therapeutic agents by dissolving pills in the gastrointestinal tract is ineffective for many agents, primarily because the active agent of the therapeutic agent fails to pass through the wall of the gastrointestinal tract and reach the bloodstream, or because the active agent within the gastrointestinal tract is destroyed by gastric juice or other fluids or substances. To address these concerns, some oral delivery devices have been developed designed to be activated within the gastrointestinal tract to deliver the therapeutic agent into the wall of the gastrointestinal tract and reach the bloodstream. The obstacles faced by these devices include unpredictability and variability between multiple lumens of the gastrointestinal tract, unpredictability and variability within a single lumen of the gastrointestinal tract, unpredictability and variability between lumens of different species, and unpredictability and variability between lumens in different subjects of the same species. These obstacles present a challenge in identifying a device effective in delivering the therapeutic agent to a target delivery site within the gastrointestinal tract and accommodating the various lumen perimeters that may be encountered at that target delivery site.

[0005] Similar difficulties arise in relation to other lumens within the animal body, and generally other types of lumens. Prior art literature

[65535] International Patent Publication WO 2018-102799 A1 (June 7, 2018) US Patent Publication US 2018-0279941 A1 (Oct. 4, 2018) US Patent Publication US 2013-0274659 A1 (Oct. 17, 2013) US Patent Publication US 2019-0175881 A1 (June 13, 2019) US Patent Publication US 2016-0015648 A1 (January 21, 2016) US Patent Publication US 2017-0106099 A1 (April 20, 2017) US Patent Publication US 2011-0207998 A1 (2011.08.25.)

[0006] The embodiments of the present disclosure provide an apparatus, system, and method for delivering a formulation to a lumen wall regardless of the inner circumference of the lumen.

[0007] In one embodiment, a self-sizing device for delivering a therapeutic agent comprises a capsule sized and configured for oral intake, and an inflatable component disposed within the capsule. The inflatable component comprises at least one non-compliant section configured to resist deformation in the inflated configuration, and at least one hinge configured to allow deformation in the inflated configuration. The inflatable component is configured to expand within the lumen and bend around the hinge to adapt to the inner circumference of the lumen regardless of the inner circumference within a selected range.

[0008] In one embodiment, the selected range is about 50 mm to about 150 mm.

[0009] In one embodiment, the selected range is about 5 mm to about 500 mm.

[0010] In one embodiment, while in the capsule, the expandable component is in a folded / or rolled arrangement and, when released from the capsule, unfolds / or unwraps to expand to a maximum circumference when unconstrained and to less than a maximum circumference when constrained.

[0011] In one embodiment, the hinge has a width or perimeter smaller than the width or perimeter of each non-compliant section.

[0012] In one embodiment, the lumen is the lumen of the small intestine.

[0013] In one embodiment, the expandable component includes at least two non-compliant sections.

[0014] In one embodiment, the expandable component includes at least two hinges.

[0015] In one embodiment, the self-sizing device further comprises a therapeutic agent and a piston, and the self-sizing device is configured such that the piston applies force to the therapeutic agent when the expandable component expands, and the force is designed to discharge the therapeutic agent from the device.

[0016] In one embodiment, a system for delivering a formulation comprises a self-sizing device, a formulation, and a delivery mechanism. The self-sizing device comprises an inflatable component comprising at least one non-compliant section configured to resist deformation in an extended configuration, and at least one hinge configured to allow deformation in an extended configuration. The inflatable component is configured to bend around the hinge to adapt to the inner circumference of the lumen within a selected range, independent of the inner circumference of the lumen, upon expansion. The self-sizing device is configured to apply a force to the formulation designed so that, upon expansion of the inflatable component, the delivery mechanism ejects the formulation from the self-sizing device.

[0017] In one embodiment, the system further comprises a capsule in which an inflatable component is disposed. While inside the capsule, the inflatable component is arranged in a folded / or rolled-up configuration and is configured to unfold / or unroll when released from the capsule.

[0018] In one embodiment, the expandable component is further configured to expand to a maximum circumference when unconstrained and to expand to less than a maximum circumference when constrained after being released from the capsule.

[0019] In one embodiment, the self-sizing device is configured to be placed in the gastrointestinal tract, and the selected range is about 50 mm to about 150 mm.

[0020] In one embodiment, the hinge has a width or perimeter smaller than the width or perimeter of each non-compliant section.

[0021] In one embodiment, the lumen is the lumen of the small intestine.

[0022] In one embodiment, the expandable component includes at least two non-compliant sections.

[0023] In one embodiment, the expandable component includes at least two hinges.

[0024] In one embodiment, the delivery mechanism includes a piston, and the self-sizing device is configured so that the piston applies force to the formulation when the expandable component expands.

[0025] In one embodiment, a method for delivering a therapeutic agent comprises the step of providing a self-sizing device comprising a therapeutic agent, wherein the self-sizing device further comprises an inflatable component comprising at least one non-compliant section configured to resist deformation in an extended configuration and at least one hinge configured to allow deformation in an extended configuration. The inflatable component is configured to bend around the hinge to adapt to the inner circumference of the lumen within a selected range, independent of the inner circumference of the lumen, upon dislocation. The method further comprises the step of providing instructions for placing the self-sizing device within the body to deliver the therapeutic agent into the lumen.

[0026] In one embodiment, the instructions include instructions for swallowing a self-sizing device.

[0027] In one embodiment, the instructions include instructions for manually inserting a self-sizing device into the lumen. Brief explanation of the drawing

[0028] FIGS. 1, FIGS. 2, FIGS. 3, and FIGS. 4 each illustrate examples of embodiments of an expandable component having at least two non-compliant sections and at least one hinge. FIG. 5A, B, C, D, E, and F each illustrate examples of embodiments of an expandable component having at least two non-compliant sections and at least one hinge. FIG. 6 illustrates an example of an embodiment of an expandable component having at least two non-compliant sections and at least two hinges. FIGS. 7a and 7b illustrate examples of embodiments of an expandable component having at least one non-compliant section and at least two hinges. FIGS. 8A and 8B illustrate examples of embodiments of an expandable component having at least two non-compliant sections and at least two hinges. FIGS. 9A and FIGS. 9B each illustrate examples of embodiments of a capsule structure. FIG. 10a illustrates an example of an embodiment of an expandable component and an example of an embodiment of a capsule before being folded and / or rolled up. FIG. 10b illustrates the expandable component of FIG. 10a in an embodiment of an array that is folded and / or rolled up before the expandable component is placed in a capsule. FIG. 10c illustrates a folded / or rolled-up arrangement of FIG. 10b and an expandable component of FIG. 10a placed inside a capsule. FIGS. 11a, FIGS. 11b, and FIGS. 11c illustrate examples of embodiments of a swallowable device comprising an expandable component within a degradable capsule that is degradable when the device crosses a lumen. FIGS. 11d, FIGS. 11e, and FIGS. 11f illustrate the progression of the expandable component of FIG. 11c as it expands within the lumen in a rotated view. FIG. 12 illustrates an example of an embodiment of a self-sizing device comprising an expandable component in a fully expanded state within the lumen. FIG. 13a illustrates an example of an embodiment of a self-sizing device comprising a hinge-free expandable component having one non-compliant section. FIG. 13b illustrates an example of an embodiment of a self-sizing device comprising an expandable component having two non-compliant sections and one hinge. Specific details for implementing the invention

[0029] The present disclosure relates to a self-sizing device for delivering a formulation into a lumen. Before discussing the details of the self-sizing device of the present invention, some conventions are provided for the convenience of the reader.

[0030] Various abbreviations may be used for standard units, such as deciliter (dl), milliliter (ml), microliter (μl), International Unit (IU), centimeter (cm), millimeter (mm), nanometer (nm), inch (in), kilogram (kg), gram (gm), milligram (mg), microgram (μg), millimole (mM), Celsius (°C), Fahrenheit (°F), millitor (mTorr), hour (hr), or minute (min).

[0031] As used in this disclosure, the terms “e.g.,” “same as,” “e.g.,” “e.g.,” “e.g.,” “e.g.,” “another example,” “e.g.,” “e.g.,” “e.g.,” and “etc.” indicate that a list of one or more non-limiting examples precedes or follows; other examples not listed should also be understood to be within the scope of this disclosure.

[0032] Singular terms used herein (corresponding to the English "a," "an," and "the") may include plural referents unless the context clearly indicates otherwise. Unless explicitly stated otherwise, references to singular referents mean "one or more" rather than "one and only one."

[0033] The terms “in an embodiment” or variations thereof (e.g., “in another embodiment” or “in one embodiment”) refer to use in one or more embodiments herein and in no case are the scope of this disclosure limited merely to the illustrative and / or described embodiments. Accordingly, components illustrative and / or described herein in relation to an embodiment may be omitted or used in other embodiments (e.g., other embodiments illustrative and described herein, or other embodiments within the scope of this disclosure that are not illustrative and / or described herein).

[0034] The term “component” refers to one of a set of one or more items that together constitute the device, formulation, or system discussed herein. A component may be a solid, powder, gel, plasma, fluid, gas, or other composition. For example, a device may include a number of solid components assembled together to form the device and may additionally include a fluid component placed in the device. In another example, a formulation may include two or more powder and / or fluid components mixed together to form the formulation.

[0035] The term “design” or its grammatical variations (e.g., “designed” or “designed”) refers to features intentionally included herein based on estimates of tolerances (e.g., component tolerances and / or manufacturing tolerances) and estimates of environmental conditions expected to be faced (e.g., temperature, humidity, external or internal ambient pressure, external or internal mechanical pressure, stress from external or internal mechanical pressure, product life or shelf life, or, in the case of introduction into the body, physiology, body chemistry, biological composition of fluids or tissues, chemical composition of fluids or tissues, pH, species, diet, health, sex, age, ancestry, disease, or tissue damage); it should be understood that actual tolerances and environmental conditions before and / or after delivery may affect the features, and that different components, devices, formulations, or systems of the same design may have different actual values ​​with respect to these features. The design also includes variations or modifications before or after manufacturing.

[0036] The term “manufacture” or its grammatical variations (e.g., “manufactured” or “manufactured”) relating to a component, device, formulation, or system refers to the manufacture or assembly of a component, device, formulation, or system as described herein. Manufacture may be performed wholly or partially by hand and / or wholly or partially by automated means.

[0037] The term “constituted” or its grammatical variations (e.g., “constituted” or “constitutes”) refers herein to a component, device, formulation, or system manufactured according to such concept or design, regardless of whether such concept, design, or variation or modification thereof (regardless of whether such variation or modification occurs before, during, or after manufacture) is captured in writing.

[0038] The term "body" here refers to the body of the animal kingdom.

[0039] The term "subject" refers to a body into which an embodiment of the present disclosure is delivered or is intended to be delivered. For example, in relation to a human being, the subject may be a patient receiving treatment from a medical professional.

[0040] As used herein, the term "fluid" refers to a liquid or gas, including water and humidity. As used herein, the term "fluidic environment" refers to an environment in which one or more fluids are present.

[0041] The term “biological material” herein refers to blood, tissues, fluids, enzymes, interstitial fluid, and other secretions of the body. The term “digestive material” herein refers to biological material present along the gastrointestinal (GI) tract of the animal kingdom and other material traversing the GI tract (e.g., food in an undigested or digested state, such as chime).

[0042] The term "intake" or its grammatical variations (e.g., "intake" or "intaken") refers herein to insertion into the stomach by swallowing or by other means of immersion in the stomach (e.g., immersion into the stomach by endoscopy or immersion into the stomach through a port).

[0043] In this document, the term "lumen" refers to the internal space of a tubular structure. Examples of lumens in the body include arteries, veins, and tubular cavities within organs.

[0044] The term “lumen wall” refers to the wall of the lumen, where the wall includes all layers from the inner circumference to the outer circumference of the lumen, and includes, for example, the mucosa, submucosa, fascia, serosa, and outer wall of the lumen, along with constituent blood vessels and tissues in relation to the lumen of the body.

[0045] The term “gastrointestinal tract” or “GI tract” refers herein to the body’s intake / excretion system, including, for example, the mouth, pharynx, esophagus, stomach, pylorus, small intestine, cecum, large intestine, colon, rectum, anus, and valves or sphincters between them.

[0046] The term "GI lumen" generally refers to the lumen of the GI tract (e.g., the esophagus, stomach, small intestine, large intestine, or colon), and the term "GI lumen wall" refers to the lumen wall of the GI lumen.

[0047] The term “formulation” refers herein to a preparation comprising one or more components. A formulation may consist of a fluid, slurry, powder, or solid (e.g., a condensed or solid form such as tablets or microtablets). Each formulation may comprise one or more components, and a device or system may comprise one or more formulations.

[0048] The term “therapeutic agent” refers herein to a preparation intended for therapeutic, diagnostic, or other biological purposes. The components of a therapeutic agent may be, for example, pharmacological active agents, DNA or SiRNA transcripts, cells, cytotoxic agents, vaccines or other prophylactic agents, nutraceutical agents, vasodilators, vasoconstrictors, delivery enhancers, retardants, excipients, diagnostic agents, or cosmetic enhancers.

[0049] The pharmacological active agent may be, for example, an antibiotic, a non-steroidal anti-inflammatory drug (NSAID), angiogenesis inhibitor, a neuroprotective agent, a chemotherapy agent, a peptide, a protein, an immunoglobulin (e.g., a TNF-alpha antibody), an interleukin of the IL-17 family, an anti-eosinophil antibody, another antibody, a nanobody, a large molecule, a small molecule, or a hormone, or a biologically active variant or derivative of the foregoing.

[0050] Cells may be, for example, stem cells, red blood cells, white blood cells, neurons, or other viable cells. Cells may be produced by or from a living organism, or may contain components of a living organism. Cells may be allogeneic or autologous.

[0051] Vaccines can be, for example, against influenza, coronavirus, meningitis, human papillomavirus (HPV), or chickenpox. Vaccines can respond to attenuated viruses.

[0052] The functional food preparation may be, for example, vitamin A, thiamine, niacin, riboflavin, vitamin B-6, vitamin B-12, other B-vitamins, vitamin C (ascorbic acid), vitamin D, vitamin E, folic acid, phosphorus, iron, calcium, or magnesium.

[0053] Vasodilators may be, for example, l-arginine, sildenafil, nitrates (e.g., nitroglycerin), or epinephrine.

[0054] Vasoconstrictors can be, for example, stimulants, amphetamines, antihistamines, epinephrine, or cocaine.

[0055] Delivery enhancers may be, for example, permeability enhancers, enzyme blockers, peptides that penetrate through the mucosa, antiviral agents such as protease inhibitors, disintegrants, superdisintegrants, pH regulators, surfactants, bile salts, fatty acids, chelating agents, or chitosan. Delivery enhancers may serve, for example, as a delivery medium for the delivery of components of a therapeutic agent or to improve the absorption of components of a therapeutic agent into the body. Delivery enhancers may prime the intestinal epithelium (e.g., fluidize the outer layer of cells) to improve the absorption and / or bioavailability of one or more other components contained in the delivery device.

[0056] The retardant may be, for example, poly(lactic acid) (PLA), poly(glycolic acid) (PGA), polyethylene glycol (PEG), poly(ethylene oxide) (PEO), poly(l-lactic acid) (PLLA), poly(d-lactic acid) (PDLA), other polymers, or hydrogels. The retardant may be included in the therapeutic formulation along with one or more other component(s) to slow the release rate of other component(s) from the therapeutic formulation (e.g., mixed with them or provided with a structure around them).

[0057] Excipients may be, for example, binders, disintegrants, superdisintegrants, buffers, antioxidants, or preservatives. Excipients may be provided to provide a medium for the components of the therapeutic formulation (e.g., to aid in manufacturing) or to preserve the integrity of the components of the therapeutic formulation (e.g., during manufacturing, during storage, or after ingestion before dispersion in the body).

[0058] Diagnostic agents may be, for example, detectors, contrast agents, radionuclides, fluorescent materials, luminescent materials, radiopaque materials, or magnetic materials.

[0059] The term “degrade” or its grammatical variations (e.g., “degrading,” “degraded,” “degradable,” and “degradation”) refers to being weakened, partially degraded, or completely degraded herein by, for example, dissolution, chemical degradation (including biodegradation), decomposition, chemical modification, mechanical degradation, or disintegration—which also, without limitation, include dissolution, fracture, deformation, shrinkage, or contraction. The term “non-degradable” refers to the expectation that degradation will be minimized or within a certain acceptable design ratio for at least an expected period in the expected environment.

[0060] The terms "substantially" and "about" are used herein to describe and explain small variations. For example, when used with numerical values, the terms may refer to a variation of ±10% or less, e.g., ±5% or less, ±4% or less, ±3% or less, ±2% or less, ±1% or less, ±0.5% or less, ±0.1% or less, or ±0.05% or less.

[0061] The range of numbers used herein includes any number within the range, or any sub-range where the minimum and maximum numbers of the sub-range fall within the range. Thus, for example, “< 9” may refer to any number less than 9, or any sub-range of numbers where the minimum value of the sub-range is greater than or equal to 0 and the maximum value of the sub-range is less than 9. Ratios may also be presented in the form of ranges in this application. For example, ratios in the range of about 1 to about 200 should be understood to include the explicitly stated limits of about 1 and about 200, as well as individual ratios such as about 2, about 35, and about 74, and sub-ranges such as about 10 to about 50, about 20 to about 100, etc.

[0062] The discussion now continues with respect to self-sizing devices. The embodiments of this description provide a device, a system, and a method for manufacturing a self-sizing device.

[0063] In one embodiment, the self-sizing device is a device designed to deliver a therapeutic agent to or into the lumen wall. In one embodiment, the self-sizing device is an ingestible device designed to deliver a therapeutic agent to or into the GI lumen wall; such a device may be delivered within a capsule.

[0064] The self-sizing device includes a component configured to be inflated—hereinafter referred to as the "inflatable component" for convenience. The self-sizing device includes at least one inflatable module that causes the inflatable component to inflate from a first non-inflated configuration to a second inflated configuration when triggered.

[0065] An expandable component comprises multiple sections. In the expanded configuration of the expandable component, at least one of the sections is non-compliant and one or more of the sections are compliant. Compliant refers to a state in which a section can be easily deformed, while non-compliant refers to a state in which a section resists deformation.

[0066] If there are no constraints, each section will be fully expanded and the expandable component will reach its maximum dimensions, which may vary, for example, depending on the material used to form the expandable component and / or the capacity of the expansion module being implemented (for example, in the case of expansion by inflation, the maximum dimensions may be affected by limitations on the expansion force available from the expansion module, or by the material of the expandable component or the stretch factor of the materials).

[0067] Each conforming section operates in a manner similar to a hinge and will therefore be referred to as a hinge for convenience. In the fully extended state of the expandable component (when each section is fully extended), each hinge has at least one design dimension (width, length, and / or perimeter) that is substantially smaller than the corresponding design dimension of each non-conforming section.

[0068] As the expandable component expands, it will achieve a shape that reflects the equilibrium between the force the expandable component exerts on the lumen and the force of the lumen on the expandable component. In other words, the expandable component may not expand fully and, if limited by the lumen, will tend to bend around the hinge. This bending is due to the smaller dimension(s) of the hinge compared to the corresponding dimension(s) of the non-compliant section(s), which leads to lower stiffness of the hinge compared to the stiffness of the non-compliant section(s) in the expanded configuration of the expandable component.

[0069] In this manner, the expandable component expands for at least a sufficient amount of time to achieve delivery until the non-compliant section (hereinafter referred to as NCS) is pressurized against the lumen wall to maintain the expandable component in a position suitable for delivering the formulation to the lumen wall. The expandable component can then be deflated automatically or manually.

[0070] The inflatable component may be removed after contraction, left to decompose in situ, or allowed to pass out of the lumen. For example, when used in an application within the GI lumen, the inflatable component may be allowed to pass through the GI tube after contraction. The inflatable component may be composed of a degradable material such that it decomposes after a designed period following exposure to the environment at the target site.

[0071] Self-sizing devices are particularly suitable for preventing delivery affected by material present in the lumen. For example, a self-sizing device has the ability to push out and / or compress material against the lumen wall so as not to interfere with the material due to the rapid expansion of the expandable component, allowing it to expand to a degree suitable for the desired delivery rate for the formulation to be delivered without delivery techniques or additional expansion. In the case of a self-sizing device configured to deliver into the GI lumen, the device can perform such delivery regardless of whether the subject is in a feeding or fasting state (i.e., delivery is achieved regardless of whether there is digested material in the GI lumen).

[0072] FIGS. 1 through 4 illustrate examples of embodiments of an inflatable component in a fully extended state, in which the inflatable component is expanded without constraints on maximum dimensions (which may depend, for example, on the material(s) used in the inflatable component and the capacity of the expansion module, among other considerations). An arbitrarily assigned xyz reference frame is indicated for convenience of discussion, and the inflatable components of FIGS. 1 through 4 are illustrated in the xy reference plane. Each inflatable component includes two NCS and one hinge in the illustrated xy plane.

[0073] Referring to FIG. 1, the expandable component (100) comprises NCS (105) and NCS (106) separated by a hinge (110). In this drawing of the embodiment as illustrated in FIG. 1a, the dimension x1 of NCS (105) is greater than the dimension x3 of NCS (106), and both x1 and x3 are greater than the dimension x2 of the hinge (110). In other words, x1 / x3 > 1, x1 / x2 > 1, and x3 / x2 > 1. Also, in this drawing of the embodiment, the dimension y1 of NCS (105) is greater than the dimension y2 of NCS (106). Then, in this drawing, NCS (105) is larger and longer than NCS (106).

[0074] Often, the extended shape of an expandable component (e.g., expandable component (100)) will result in an expandable component having a long dimension (e.g., length L) aligned with the central axis of the cavity where the expandable component is located.

[0075] In the embodiment illustrated in FIG. 1, the hinge (110) is NCS (105) and NCS (106) (each x2< <x1 및 x2<<x3)보다 훨씬 좁기 때문에, NCS(105) 및 NCS(106)는 A 및 B로 지시된 화살표에 의해 표시된 바와 같이 힌지(110) 주위의 x-y 평면에서 서로를 향해 또는 서로 멀어지도록 구부러질 수 있으며, 이는 팽창 가능한 구성요소(100)가 불균일한 내강 표면 및 / 또는 불일치한 내강 직경을 수용할 수 있게 한다.

[0076] Referring to FIG. 2, the expandable component (200) comprises NCS (205) and NCS (206) separated by a hinge (210). In this figure, the expandable component (200) is similar to the expandable component (100) as shown in FIG. 1. The x4 dimension of NCS (205) is larger than the x6 dimension of NCS (206), and both x4 and x6 are larger than the x5 dimension of the hinge (210); and the dimension y3 of NCS (205) is larger than the dimension y4 of NCS (206). However, the x5 shown in FIG. 2 is approximately three times larger than the x2 shown in FIG. 1; Therefore, NCS (205) and NCS (206) can have the ability to bend toward each other or away from each other in the xy plane—which is less than the ability of NCS (105) and NCS (106) to bend toward each other or away from each other in the xy plane—while still maintaining some flexibility that allows the expandable component (200) to accommodate an uneven lumen surface and / or inconsistent lumen diameter.

[0077] As can be seen by comparing FIG. 1 and FIG. 2, the dimensions of the hinge (e.g., hinge (110) or hinge (210)) can be designed to have a desired width. The width and other dimensions of the expandable component can be designed, for example, to suit a specific application, thereby minimizing the amount of material used to construct the expandable component, reducing manufacturing costs, or increasing manufacturing speed.

[0078] Referring to FIG. 3, the expandable component (300) comprises NCS (305) and NCS (306) separated by a hinge (310). The dimension x7 of NCS (305) is greater than the dimension x9 of NCS (306), and both x7 and x9 are greater than the dimension x8 of the hinge (310). In this embodiment, the dimension y5 of NCS (305) is approximately the same as the dimension y6 of NCS (306), which exemplifies a different variation of the dimension.

[0079] Referring to FIG. 4, the expandable component (400) comprises NCS (405) and NCS (406) separated by a hinge (410). In this embodiment, the dimension x10 of NCS (405) is smaller than the dimension x12 of NCS (406), and both x10 and x12 are somewhat larger than the dimension x11 of the hinge (410), and the dimension y7 of NCS (405) is approximately twice as large as the dimension y8 of NCS (406), which exemplifies other variations of the dimension.

[0080] Other comparative dimensions of the NCS and hinge are within the scope of the present disclosure. For example, the dimensions of the hinge in the xy plane may be larger than the dimensions of the NCS in that plane. Additionally, the dimensions may vary in the z direction within a specific section (NCS or hinge).

[0081] FIGS. 5A through F illustrate examples of embodiments of expandable components such as those that may appear when one or more of the expandable components (100, 200, 300, or 400) of FIGS. 1, 2, 3, and 4 are each rotated (here, rotated in the yz plane). For convenience, with respect to FIGS. 5A through F, non-compliant sections are referred to as NCS (505, 506) and compliant sections are referred to as hinges (510).

[0082] NCS (505) and NCS (506) can be bent toward or away from each other in the yz plane around the hinge (510), which allows the expandable component to accommodate various lumen diameters and shapes.

[0083] As can be seen in FIGS. 5A through F, the shape of the expandable component may change in a rotated (e.g., side) drawing as in a non-rotated (e.g., front) drawing. For example, one (or both) of the NCS (505, 506) may have a surface that is substantially flat, somewhat rounded, significantly rounded, or of a different curvature.

[0084] It will be evident from the above discussion that each of the various sections (each NCS and each hinge) can be designed to have not only desired dimensions but also desired absolute dimensions compared to other sections. For example, a hinge may have a width in the xy plane equal to or greater than the width of a specific NCS in the same xy plane, while having a width in the yz plane substantially smaller than the width of the specific NCS in the yz plane.

[0085] With reference to FIGS. 1 through 4 and FIGS. 5 A through F in relation to some examples of embodiments of an inflatable component, it will be apparent that various designs for an inflatable component having two non-compliant sections (NCS) and one compliant section (hinge) may exist according to the present disclosure. In various embodiments, the inflatable component according to the present disclosure more generally has one or more NCS and one or more hinges.

[0086] The expandable component of the self-sizing device may be configured to have one or more sections in each of two or more planes. For example, the expandable component (100) illustrated in the first xy plane of FIG. 1 may be configured to have additional NCS and / or hinge sections in the second xy plane so that when viewed in the yz plane, the expandable component (100) forms a Y-shape, an X-shape, or other multi-pronged shape. The prongs may include one or more NCS or may not include NCS, or may include one or more hinges or may not include hinges.

[0087] The expandable component may include a weakening feature to make it more compliant in the hinge area.

[0088] FIG. 6 illustrates an expandable component (600) having two NCS, NCS (605) and NCS (606), in the illustrated drawing. The expandable component (600) defines an opening (615), illustrated as elliptical in this embodiment. In other words, the expandable component (600) includes a weakening feature illustrated as the opening (615). The omission of material in the opening (615) leaves two hinges, hinge (610) and hinge (611). The fully expanded hinges (610, 611) each have at least one design dimension (width, length, and / or perimeter) that is substantially smaller than the corresponding design dimensions of NCS (605) and NCS (606), which provides an increase in the conformability of the hinges (610, 611) compared to NCS (605, 606). The expandable component (600) in this embodiment will tend to bend around the hinge (610, 611). The hinge (610, 611) may have similar or different dimensions. When rotated to a different drawing, the expandable component (600) may have various shapes, including the shapes illustrated in FIG. 5 A through F.

[0089] FIGS. 7A and 7B illustrate an expandable component (700) having a single NCS (705) and two hinges, a hinge (710) and a hinge (711). The expandable component (700) is illustrated in the xy plane of FIG. 7A and in the yz plane of FIG. 7B, with the hinge (711) hidden behind the hinge (710). In this embodiment, the hinges (710, 711) themselves act to apply pressure to the inner surface of the lumen while also providing conformity.

[0090] FIGS. 8A and FIG. 8B illustrate an expandable component (800) having three NCS, NCS (805), NCS (806) and NCS (807), and two hinges, hinge (810) and hinge (811). The expandable component (800) is illustrated in the xy plane of FIG. 8A and in the yz plane of FIG. 8B, so that hinge (811) is hidden behind hinge (810) and NCS (807) is hidden behind NCS (806).

[0091] As can be seen from FIGS. 7a and FIGS. 8a, the expandable component (700) and the expandable component (800) appear similar in the illustrated xy plane. However, when rotated 90 degrees (e.g., as illustrated in FIGS. 7b and FIGS. 8b, illustrated in the yz plane, respectively), it can be seen that NCS (806) and NCS (807) ( FIG. 8b) expand to have dimensions in the z-direction that are substantially larger than the corresponding dimensions of hinge (710) and hinge (711) ( FIG. 7b).

[0092] In one embodiment of a self-sizing device according to the present disclosure, an inflatable component is disposed within a capsule.

[0093] FIGS. 9a and 9b illustrate examples of embodiments of a capsule. In FIG. 9a, the capsule (900) comprises a cylindrical body (905) and two end caps (910) fitted on or within the body (905). At least one of the three components of the capsule (900) (cylindrical body (905), first end cap (910), and / or second end cap (910)) is detachable. The end cap (910) may be adhered to the body (905) or press-fitted on or within the body (905) to hold the end cap (910) in place. In FIG. 9b, the capsule (950) comprises a portion (920) and a portion (921) that are fitted together. At least one of the portions (920, 921) is detachable. The portions (920, 921) may be adhered together or press-fitted. Examples of capsule sizes include 000, 00, and 0 capsule sizes. Capsule shapes other than those exemplified in FIGS. 9a and 9b, such as spherical or oval shapes, or irregular shapes, or shapes symmetric with respect to a first axis and asymmetric with respect to a second axis perpendicular to the first axis (e.g., egg shape), or shapes having at least one flat surface may be used.

[0094] In one embodiment, the self-sizing device includes a degradable coating on an expandable component and / or a capsule (if a capsule is included).

[0095] In one embodiment, a coating is applied directly onto an expandable component to complete the manufacture of a self-sizing device (e.g., instead of placing the expandable component inside a capsule). The coating may completely cover and seal the expandable component, or it may cover a portion of the expandable component. For example, the coating may decompose under certain conditions to expose one or more decomposable components of the self-sizing device. In turn, the one or more decomposable components decompose after exposure to initiate, for example, the expansion of the expandable component, or, in an embodiment where gas is used to expand the expandable component, to contract the expandable component after delivery of the formulation by releasing gas.

[0096] The coating on the expandable device and / or capsule is or may comprise a material comprising an opaque material (e.g., to prevent the contents from being visible), a colored material (e.g., to provide color coding for identifying the formulation contained in the self-sizing device), and / or a prominent flavor or odor (e.g., an undesirable flavor or odor that diminishes interest, or a desirable flavor or odor that arouses interest), each of which is sufficiently dissolved or decomposed so that the self-sizing device can deliver the formulation at the target delivery site.

[0097] All or part of the coating and / or capsule may be designed to decompose after a specific length of time under expected conditions at the target site, for example, after a design period following placement, or in the presence of a specific chemical, or under a specific value or range of pH, temperature, or pressure applied to the capsule, or a combination of the foregoing. In one embodiment, the capsule is designed to be destroyed by an external trigger, for example, a wireless transmission trigger that causes a mechanism within the capsule to tear or destroy the capsule.

[0098] As mentioned, embodiments of a self-sizing device according to the present disclosure may be used to deliver a therapeutic agent to or into the GI lumen wall by ingestion (e.g., by manual positioning of the self-sizing device or by swallowing). The self-sizing device may comprise a capsule. The self-sizing device may comprise a coating (e.g., the coating described above) on the capsule and / or an expandable component designed to decompose at a specific location within the GI tract, such as in the stomach or intestine. In one embodiment, all or part of the capsule and / or coating is designed to decompose after a specific length of time in the presence of a specific chemical or under conditions expected at a target site within the GI tract (e.g., under a specific value or range of pH, temperature, pressure applied to the capsule, or a combination thereof). In one embodiment, the coating comprises a substance to improve swallowability, such as guar gum or xanthan gum.

[0099] FIGS. 10a through 10c illustrate examples of assembling a self-sizing device (1050). FIG. 10a illustrates an embodiment of an inflatable component (1000) and an embodiment of a capsule (1010). The external dimensions of the inflatable component (1000) may be several times larger than the internal dimensions of the capsule (1000). For example, the longest dimension of an embodiment of the inflatable component (1000) may be 2 to 5 times larger than the internal length of the capsule (1010). Other ratios of the external dimensions of the inflatable component to the internal dimensions of the capsule are within the scope of this disclosure. FIG. 10b illustrates an inflatable component (1000) that is folded and / or rolled into an array (1001) smaller than the internal dimensions of the capsule (1010). As illustrated, the array (1001) is folded and / or rolled into a complex origami-style array in this embodiment. FIG. 10c illustrates an array (1001) placed within a capsule (1010) and a capsule (1010) assembled together (e.g., as in FIG. 9a, where the end cap (910) is fitted over or within the body (905), or as in FIG. 9b, where the parts (920, 921) are fitted together). The device (1050) comprises an inflatable component (1000) (in the array (1001)) and a capsule (1010), and may include other components not illustrated, such as an inflatable module, a delivery component, one or more coatings, and a shrink valve.

[0100] FIGS. 11a through 11f illustrate an example of a method in which a device (1050) is provided at a target delivery site of a GI tube and an expandable component (1000) is positioned to deliver a therapeutic agent into the lumen wall (1111) of the GI lumen (1110). Referring again to FIGS. 11a through 11c, the device (1050) is depicted in a drawing approximately perpendicular to the direction of movement of the device (1050) (indicated by an arrow), whereas the device (1050) in FIGS. 11d through 11f is depicted as if looking into the lumen (1110) (e.g., approximately 90 degrees from the drawing in FIGS. 11a through 11c).

[0101] FIG. 11a illustrates a device (1050) within a lumen (1110) shown in a relaxed state (e.g., between peristaltic contractions). In this embodiment, the outer diameter of the device (1050) is smaller than the inner diameter of the lumen (1110) at this point of the GI tube. The device (1050) crosses the lumen (1110) through the operation of, for example, peristalsis, hydrodynamics, and / or gravity.

[0102] FIG. 11b illustrates that after reaching a designed target site or after encountering conditions (e.g., pH) indicating a designed target site, the capsule (1010) is decomposed (or triggered to be broken open or decomposed) as the device (1050) continues to traverse the lumen (1110). For example, in relation to intestinal delivery, the target site may be in a general area (e.g., small intestine), a more specific area (e.g., jejunum), or a specific tissue area (e.g., a tissue area having a known or detected pathological condition indicated or to be treated).

[0103] FIG. 11c illustrates that after the capsule (1010) is disassembled (or simultaneously), the expandable component (1000) begins to unfold from a folded and / or rolled-up arrangement.

[0104] FIG. 11d illustrates an expandable component (1000) that is mostly unfolded, and FIG. 11e illustrates an expandable component (1110) that is expanded (e.g. by an expansion module).

[0105] FIG. 11f illustrates an expandable component (1000) after expansion. In this embodiment, the expandable component (1000) could have expanded until the baseline (1120) was approximately straight, provided it was not restricted by the lumen (1110). However, the lumen (1110) applies force to the expandable component (1000), causing the expandable component (1000) to bend at the hinge (1002). Then, the NCS (1003) and NCS (1004) of the expandable component (1000) press against the lumen wall of the lumen (1110) (e.g., on opposite sides of the lumen) and position the expandable component (1000) to deliver a therapeutic agent to or into the lumen wall. The hinge (1002) may also press against the lumen wall. In one embodiment, peristalsis can move the expandable component (1000) through the lumen (1110) in an expanded state. In one embodiment, the expandable component (1000) may have sufficient internal pressure (combined with surface tension) to firmly maintain the expandable component (1000) in approximately the same position even during peristalsis. In one embodiment, the expandable component (1000) includes surface roughness or surface protrusions to help maintain the position of the expandable component (1000).

[0106] The expansion of an expandable component may be performed by any suitable expansion module. In one embodiment, a spring mechanism is released from a compressed state to unfold a piece of filler made of a hard or soft material and push it outward to expand the expandable component. In one embodiment, two or more reactants are mixed together to form a gas and thereby expand the expandable component. In one embodiment, the material is rapidly combusted to produce a gas and thereby expand the expandable component. Other expansion modules are within the scope of this disclosure.

[0107] FIG. 12 illustrates a lumen (1200) in which a self-sizing device (1210) comprising an expandable component (1250) is located. In this embodiment, the force of the lumen (1200) on the expandable component (1250) is not sufficient to cause the hinge (1251) of the expandable component (1250) to bend substantially, and thus the expandable component (1250) is in a roughly fully expanded state. In other words, the bending of the hinge (1251) of the expandable component (1250) can be ignored at this position in the lumen (1200).

[0108] The expandable component (1250) expands by the generation of gas and includes a valve (1255) that releases gas from within the expandable component (1250) into the lumen (1200) to contract the expandable component (1250). The valve (1255) may include one or more components. In one embodiment, the valve (1255) is a pinch valve that decomposes in the presence of a fluid (e.g., biological material) to reveal a port or opening defined by the expandable component (1250). In one embodiment, the valve (1255) is a piece of material or coating over the port or opening in the expandable component (1250), and the piece of material or coating is designed to decompose after a certain period in which the expandable component (1250) has delivered a therapeutic agent. In one embodiment, the valve (1255) is opened manually.

[0109] A therapeutic agent (or multiple therapeutic agents) may be stored in an expandable component (1250) in any composition (e.g., as a solid, fluid, slurry, or powder). The therapeutic agent(s) may be delivered in any composition (e.g., as a solid, fluid, slurry, or powder). In one embodiment, two or more components of a therapeutic agent are mixed within the expandable component (1250) prior to delivery. In one embodiment, the expandable component (1250) includes a portal, such as a portal (1260), which defines an opening (1261) through which the therapeutic agent passes and is delivered.

[0110] In one embodiment, the therapeutic agent is passively released so that the therapeutic agent is applied to the inner surface of the lumen (1200) (e.g., for absorption through the mucous membrane); in this embodiment, the therapeutic agent may be released through a portal such as a portal (1260) or through a number of holes (not shown) in the expandable component (1250) which are not covered by the unfolding of the expandable component (1250), are created during the unfolding, or are not covered by the breakdown of the coating over the holes.

[0111] In one embodiment, the therapeutic agent is actively released so that the therapeutic agent is forcibly discharged from the expandable component (1250) through or beyond one or more layers of the lumen (1200) (e.g., into or through the mucosa, through the submucosa, through the muscle, through the serosa, or through the outer wall of the lumen (1200), or through the peritoneal wall into the mesentery or abdominal cavity); in this embodiment, the therapeutic agent may be discharged through one or more portals such as a portal (1260), or through a hole (not shown) below the expandable component (1250)—which is not covered by the expansion of the expandable component (1250), is created during expansion, or is not covered by the breakdown of the coating over the hole.

[0112] The therapeutic agent may be forcibly ejected from the expandable component (1250) by a delivery mechanism. For example, with respect to a solid composition (e.g., tablet, pellet, or pointed form), the therapeutic agent may be ejected by a spring mechanism that is released to rapidly eject the solid composition from the expandable component (1250), or by a piston mechanism in which a piston is moved by a spring mechanism or gas expansion to rapidly push the solid composition out of the expandable component (1250). For example, with respect to a fluid, slurry, or powder of the therapeutic agent, a bladder may be compressed to forcibly squeeze the fluid, slurry, or powder out of the expandable component (1250).

[0113] In one embodiment, the surface of the expandable component (1250) through which the therapeutic agent is delivered comes into contact with the wall of the lumen (1200) along an elongation of approximately 5 mm to 20 mm.

[0114] In one embodiment, the therapeutic agent is delivered from multiple surfaces or from an expandable component (1250) along them.

[0115] FIG. 13a illustrates an embodiment of a self-sizing device (1300) comprising an expandable component (1305) that includes one NCS (1310) and does not include a hinge. FIG. 13b illustrates an embodiment of a self-sizing device (1350) comprising two NCS, NCS (1360) and NCS (1361), and an expandable component (1355) that includes a hinge (1365) between them. In relation to these embodiments, the width (W1) of the expandable component (1305) is similar to the width (W2) of the expandable component (1355), while the height (H1) of the expandable component (1305) is smaller than the height (H2) of the expandable component (1355).

[0116] Multiple devices (1300) (Fig. 13a) constructed according to the same design have approximately the same maximum circumference of the NCS (1310) (in the yz plane) when fully inflated in the lumen due to the non-conforming nature of the NCS (1310), so that the expandable component (1305) does not adapt significantly to various different internal lumen circumferences. Thus, different sizes of the devices (1300) may be suitable for different animal species and / or different subjects within the species. In contrast, multiple devices (1350) (Fig. 13b) constructed according to the same design are unlikely to have the same maximum circumference (in the yz plane) when fully inflated in the lumen because, even when each device (1350) is inflated, it will be adjusted to the size of the inflated lumen due to the flexibility (non-conforming, bending) of the hinge (1365). The maximum circumference for the device (1350) within the lumen refers to the maximum circumference of the shape (e.g., partially extended shape or fully extended shape) that the device (1350) takes within the lumen.

[0117] Test device designs similar to the examples of devices (1300, 1350) were prepared, and a number of test devices were manufactured based on each of the test device designs. For convenience of reference, the identification numbers used in FIG. 13a and FIG. 13b are used to describe these test devices in the following discussion. For these test devices, the expansion module included two reactants (sodium bicarbonate and citric acid) and a biodegradable pinch valve (1370) that separates the two reactants. The valve (1370) was designed to decompose and mix the reactants to generate carbon dioxide, thereby expanding the expandable component (1305) and the expandable component (1355).

[0118] In the case of the test device, all of the individual expandable components were composed of similar materials, and they did not expand significantly during expansion.

[0119] A human clinical trial was conducted to compare the percentage delivery rates for the device (1300) and the device (1350) when delivering a solid composition formulation to the human GI lumen wall.

[0120] Three test device designs, device A, device B, and device C, were used. Devices A and B were similar to device (1300) (Fig. 13a), and device C was similar to device (1350) (Fig. 13b). In the test, each device contained a capsule swallowed by a subject (not illustrated in Fig. 13a, 13b).

[0121] Device A had a maximum perimeter of approximately 65 mm (in the yz plane) when fully expanded and unconstrained. Device B had a maximum perimeter of approximately 68 mm (in the yz plane) when fully expanded and unconstrained. For clarity, Device A and Device B had similar shapes and similar widths (the widths of Device A and Device B were approximately equal to W1), but Device B was taller than Device A (e.g., the height of Device A was equal to H1, and the height of Device B was greater than H1). Device C had a maximum perimeter of approximately 80 mm (in the yz plane) when fully expanded and unconstrained.

[0122] When expanded, the internal volume (V1) of the expandable component (1305) of device A was approximately 8 cubic centimeters (cc), whereas the internal volume (V2) of the expandable component (1355) of device C was approximately 4 cc. The reduced volume of the expandable component (1355) was partly due to the NCS (1360) and NCS (1361) of device (1350) and had a smaller circumference (in the yz plane) overall than the NCS (1310) of device (1300). The reduced volume of the expandable component (1355) of device C was achieved even though the total height (H2) of the expandable component (1355) was greater than the total height (H1) of the expandable component (1305) of device A. The greater height of the expandable component (1355) allowed for placement in a larger diameter lumen. The smaller volume of the expandable component (1355) allowed for a reduction in the amount of reactant required compared to the amount of reactant required for the expandable component (1305) to achieve the same internal pressure.

[0123] In the test apparatus, the delivery mechanism (1375) includes a piston that delivers a therapeutic agent by the pressure of carbon dioxide against the piston, causing the piston to move rapidly and release a solid composition of the agent into the wall of the lumen.

[0124] In the test apparatus, radiopaque markers were included in the therapeutic agent and at other locations within the test apparatus. Imaging was performed throughout each test to track the location of each test apparatus, to track whether each expandable component separated from the capsule, and to track whether the therapeutic agent was delivered to the lumen wall of the small intestine.

[0125] result.Device A delivered therapeutic agents to the GI lumen wall in 25% of 12 subjects; Device B delivered therapeutic agents to the GI lumen wall in 50% of 20 subjects; and Device C delivered therapeutic agents to the GI lumen wall in 80% of 20 subjects. A delivery rate of 25% to 50% (e.g., for Devices A and B) is acceptable, but a delivery rate of 80% or more (for Device C) is, of course, desirable.

[0126] The test results showed that increasing the circumference of the expandable component (Device A compared to Device B) resulted in better delivery rates across the subject group. However, the test results suggested that delivery rates in specific individuals may be influenced by the maximum circumference of the hingeless device (in the yz plane), and that for some therapeutic treatments, each person may be tested with multiple devices (each with a different maximum circumference) before or at the start of the treatment to determine the most suitable device size for that person.

[0127] In contrast, test results suggested that a single size and design of an expandable component including a hinge (e.g., Device C) could be successfully used across a high proportion of subjects. Notably, the results achieved by Device C were achieved using an initial version of the hinge design; it is expected that improvements to the hinge design would result in even higher delivery rates.

[0128] Additionally, multiple lots of self-sizing devices configured similarly to the device (1350) having an expandable component (1355) having a hinge (1365) (e.g., similar to device C) (all having the same design and dimensions of the expandable component (1355)) were tested in various animal species including humans, pigs, and dogs, and as a result, high delivery rates were shown in each species despite the fact that the intestinal lumen sizes of the various species differed significantly; in contrast, it is noted that in the case of the device configured similarly to the device (1300) having an expandable component (1305) without a hinge, various sizes of the expandable component (1305) were used across various animal species to avoid discomfort caused by excessive stretching of the intestine and were adapted to the lumen size of each specific species.

[0129] For a device configured similarly to Device C, it was found that the delivery rate was consistent regardless of whether the subject ate food or fasted for several hours prior to ingesting the device.

[0130] Prior to the concept of a hinge structure for an inflatable component, there were concerns regarding how many device sizes were available and how to determine the appropriate device size for an individual. Clinical trial results demonstrate that the new concept of adding a hinge to an inflatable component resolves these and other concerns. A single design of a hinged inflatable component according to the present disclosure can deliver a formulation into the lumen with a high delivery rate over a selected range of the circumference of the lumen wall. In one embodiment, the device is designed for delivery within the human small intestine, and the selected range is about 10 mm to about 100 mm, or about 20 mm to about 80 mm. In one embodiment, a self-sizing device suitable for use at any various location along the GI tract (e.g., stomach, small intestine, large intestine, colon) across various animal species is designed to have a selected range of about 5 mm to about 500 mm. Other ranges may be selected, and different ranges may be selected for different types of lumens or different types of lumens within the body.

[0131] In one embodiment, the expandable component is designed to have at least one hinge visible in a first viewing angle and a plurality of hinges visible in a second viewing angle rotated from the first viewing angle, such that each of three or more sections (NCS and / or hinge sections) of the expandable component contacts the lumen in which the expandable component is placed. This structure may allow for the conformability of the plurality of hinges to adapt the expandable component to a wider selected range of the lumen perimeter.

[0132] Another advantage of the hinged design concept is that, compared to hinged inflatable components, the total surface area of ​​the inflatable component can be reduced, allowing a single self-sizing device design to be used for applications in various lumens, various animal species, and various subjects within the species. Consequently, a reduced amount of material may be required; this reduction in material, along with a reduced amount of reactants, can lead to cost savings.

[0133] In one embodiment, the inflatable component is constructed using one type of material throughout. In one embodiment, the inflatable component is constructed using two or more different materials. In one embodiment, the conformability level of the inflatable component may be adjusted based on the thickness of the material in a specific area of ​​the inflatable component. In one embodiment, the conformability level of the inflatable component may be adjusted by adding a layer of the same material or a different material to a specific area of ​​the inflatable component. Examples of materials that may be used to construct the inflatable component include polyester, PET, HDPE, cross-linked polymer, silicone, polyurethane, or other elastomers or polymers.

[0134] In one embodiment, the formulation is a solid composition. A delivery mechanism (e.g., delivery mechanism (1375)) comprises a forwarding device (e.g., a piston or rod) directly or otherwise operablely coupled to the solid composition to apply force to the surface of the solid composition to advance the solid composition into the lumen wall. The delivery mechanism may be operablely in contact with or closely adjacent to the lumen wall when the expandable component is expanded, so that the solid composition is ejected directly into the lumen wall with or without a gap between the surface of the delivery mechanism and the lumen wall, which can improve the delivery rate of the self-sizing device.

[0135] In one embodiment, the self-sizing device includes a solid composition detachably coupled to a piston such that the solid composition is detached from the piston after the solid composition has advanced to the inner wall.

[0136] Specific materials may be selected to impart desired structural and material properties to the solid composition (e.g., column strength for insertion into a lumen wall, or porosity and / or hydrophilicity to control the disintegration of the solid composition and the subsequent release of the therapeutic agent). In one embodiment, the tip of the solid composition comprises or is coated with a degradable material, such as sucrose, maltose, or other sugars, to increase the hardness and tissue penetration properties of the tip. Once positioned within the lumen wall, the solid composition is degraded by the interstitial fluid within the tissue, allowing the therapeutic agent to dissolve and be absorbed into the bloodstream. Properties of the solid composition, such as size, shape, and chemical composition, may be selected to allow the dissolution and absorption of the drug within seconds, minutes, or hours. The dissolution rate may be controlled through various excipients, such as disintegrants (e.g., starch, sodium starch glycolate, or cross-linked polymers such as carboxymethyl cellulose). The selection of the disintegrant can be specifically adjusted according to the environment within the lumen wall (e.g., blood flow and average number of peristaltic contractions).

[0137] The solid composition may be manufactured entirely from a formulation or may define a cavity containing the formulation. A self-sizing device may contain and deliver one or more solid compositions, each of which may contain the same or different formulation as the other solid composition. Each solid composition may have different characteristics; for example, two solid compositions may be designed to deliver each formulation simultaneously (e.g., two cases of one formulation, or one case of each of two formulations), or to deliver each formulation at different times (e.g., to provide a subsequent administration of the same formulation or to subsequently provide a different formulation).

[0138] Although the present disclosure has been described and illustrated with reference to specific embodiments thereof, such description and illustration are not to limit the present disclosure. It will be apparent that various modifications may be made and equivalent components may be substituted within the embodiments without departing from the true spirit and scope of the present disclosure as defined by the appended claims. Furthermore, components, properties, or operations of one embodiment may be readily recombined or replaced with one or more components, properties, or operations of other embodiments to constitute numerous additional embodiments within the scope of the present invention. Moreover, components illustrated or described as being combined with other components may exist as standalone components in various embodiments. Additionally, regarding any positive description of components, properties, components, features, steps, etc., the embodiments of the present invention particularly take into account the exclusion of such components, values, properties, components, features, steps, etc. Illustrations may not necessarily be drawn to scale. Due to variables such as manufacturing processes, there may be differences between the artistic representation in the present disclosure and the actual device. There may be other embodiments of the present disclosure that are not specifically illustrated. The specification and drawings should be regarded as exemplary rather than restrictive. Specific situations, materials, compositions of materials, methods, or processes may be modified to fit the purpose, spirit, and scope of the present disclosure. All such modifications are intended to be within the scope of the claims appended herein. Although the methods disclosed herein have been described with reference to specific operations performed in a specific order, it is understood that these operations may be combined, subdivided, or rearranged in equivalent ways without departing from the teachings of the present disclosure. Accordingly, unless specifically indicated herein, the order and grouping of operations are not a limitation of the present disclosure.

Claims

Claim 1 A self-sizing device for delivering a therapeutic agent, comprising: a capsule sized and configured for oral intake; and an inflatable component disposed within the capsule, comprising at least one non-compliant section configured to resist deformation in the inflated configuration and further comprising at least one hinge configured to allow deformation in the inflated configuration, and comprising an inflatable component configured to expand within a body lumen and bend around the hinge to adapt to the circumference of the inner wall of the body lumen within a selected circumference range. Claim 2 A self-sizing device according to claim 1, wherein the selected perimeter range is 50 mm to 150 mm. Claim 3 A self-sizing device according to claim 1, wherein, while in the capsule, the expandable component is in a folded / or rolled arrangement and is configured to unfold / or unravel when released from the capsule, expanding to a maximum circumference when unconstrained and expanding to a smaller circumference when constrained. Claim 4 In claim 1, the hinge is a self-sizing device having a width or perimeter smaller than the width or perimeter of each non-compliant section. Claim 5 In paragraph 1, the body lumen is a self-sizing device, the lumen of the small intestine. Claim 6 A self-sizing device according to claim 1, wherein the expandable component comprises at least two non-compliant sections. Claim 7 In claim 1, the expandable component is a self-sizing device comprising at least two hinges. Claim 8 A self-sizing device according to any one of claims 1 to 7, further comprising a therapeutic agent and a piston, wherein the self-sizing device is configured such that the piston applies force to the therapeutic agent upon expansion of an expandable component, and the force is designed to discharge the therapeutic agent from the device. Claim 9 A system for delivering a formulation, the system comprising a self-sizing device including an inflatable component, wherein the inflatable component comprises at least one non-compliant section configured to resist deformation in the inflated configuration, and the inflatable component further comprises at least one hinge configured to allow deformation in the inflated configuration, wherein the inflatable component is configured to bend around the hinge upon inflatation to adapt to the inner circumference of a body cavity within a selected circumference range, the self-sizing device; a formulation; and a delivery mechanism, wherein the self-sizing device is configured such that, upon inflatation of the inflatable component, the delivery mechanism applies a force to the formulation designed to discharge the formulation from the self-sizing device. Claim 10 A system for delivering a formulation according to claim 9, further comprising a capsule sized and configured to accommodate the expandable component and to be taken orally, wherein the expandable component is arranged in a folded / or rolled configuration while inside the capsule and is configured to unfold / or unravel when released from the capsule. Claim 11 A system for delivering a formulation according to claim 10, wherein the expandable component is further configured to expand to a maximum circumference when unbound and to expand to a smaller circumference when bound. Claim 12 A system for delivering a formulation, wherein the self-sizing device is configured to be placed in the gastrointestinal tract, and the selected circumference range is 50 mm to 150 mm. Claim 13 In claim 9, the hinge has a width or perimeter smaller than the width or perimeter of each non-compliant section, a system for delivering a formulation. Claim 14 In claim 9, the above body lumen is the lumen of the small intestine, a system for delivering a preparation. Claim 15 In claim 9, the expandable component comprises at least two non-compliant sections, a system for delivering a formulation. Claim 16 In claim 9, the expandable component comprises at least two hinges, a system for delivering a formulation. Claim 17 In claim 9, the delivery mechanism comprises a piston, and the self-sizing device is configured such that the piston applies force to the formulation when the expandable component expands, a system for delivering a formulation. Claim 18 A system for delivering a formulation, wherein, in any one of claims 9 to 17, the formulation is a therapeutic formulation. Claim 19 delete Claim 20 delete

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