Self-sizing device for delivering formulation to lumen wall

Abstract

To provide a system for delivering a therapeutic formulation into a lumen.SOLUTION: A system includes a self-sizing device comprising an expandable component that includes at least one non-compliant section structured to resist deformation in an expanded configuration, the expandable component, which is configured to expand through dilation, further including at least one hinge structured to allow deformation in an expanded configuration, the expandable component structured to bend about the hinge upon expansion to adapt to an inner circumference of a lumen within a selected range. The system includes a therapeutic formulation and a delivery mechanism. The self-sizing device is structured to, upon expansion of the expandable component, cause the delivery mechanism to apply a force to the therapeutic formulation, the force designed to expel the therapeutic formulation from the self-sizing device. The self-sizing device may be disposed within a capsule.SELECTED DRAWING: Figure 13B

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Patent Application No. 62 / 909,206, filed October 1, 2019, entitled INFLATABLE DEVICES, SYSTEMS AND METHODS FOR DELIVERING THERAPEUTIC COMPOUNDS INTO WALL OF THE GASTRO INTESTINAL TRACT, the entire contents of which are incorporated herein by reference for all purposes. [Background technology]

[0002] It may be desirable to deliver a material or formulation (e.g., a fluid, slurry, powder, or solid) to a lumen, and further, it may be desirable to deliver a material at or into the inner wall of the lumen. In many applications, the inner circumference of a lumen may be unpredictable and / or variable, or the inner circumferences of multiple lumens collectively may be unpredictable and / or variable, such that selecting a device that is effective for delivering a material at or into the inner wall of any given lumen may be a challenge.

[0003] An example of delivery into a lumen of an animal body is the delivery of a therapeutic formulation into the lumen of the digestive tract. Delivery of a therapeutic formulation by a pill that dissolves in the digestive tract is ineffective for many therapeutic formulations, due to, among other reasons, the inability of the active agent in the therapeutic formulation to penetrate the wall of the digestive tract and reach the vasculature, or the destruction of the active agent in the digestive tract by gastric juices or other fluids or substances in the digestive tract. To address these concerns, several oral delivery devices have been developed that are designed to activate in the digestive tract and reach the vasculature to deliver the therapeutic formulation into the wall of the digestive tract. Obstacles faced by such devices include unpredictable and variable between several lumens of the digestive tract, unpredictable and variable within a single lumen of the digestive tract, unpredictable and variable between lumens of different species, as well as unpredictable and variable between lumens in different subjects of the same species. These obstacles pose a challenge to identify a device that effectively delivers a therapeutic formulation to a delivery target site in the digestive tract and accommodates the circumference of the various lumens that may be encountered at the delivery target site.

[0004] Similar challenges exist with respect to other lumens within animal bodies, and other types of lumens in general. Summary of the Invention

[0005] Embodiments of the present disclosure provide devices, systems, and methods for delivering a formulation to a lumen wall independent of the lumen circumference.

[0006] In one aspect, a self-sizing device for delivering a therapeutic formulation includes a capsule sized and structured to be orally ingested and an expandable component disposed within the capsule. The expandable component includes at least one non-compliant section structured to resist deformation in an expanded configuration and at least one hinge structured to permit deformation in the expanded configuration. The expandable component is structured to expand within a lumen and flex about the hinge to conform to an inner circumference of the lumen, regardless of the inner circumference within a selected range.

[0007] In one embodiment, the selected range is from about 50 mm to about 150 mm.

[0008] In one embodiment, the selected range is from about 5 mm to about 500 mm.

[0009] In one embodiment, the expandable component is in a folded and / or rolled configuration while in the capsule and is structured to unfold and / or unroll upon release from the capsule to expand to a maximum circumference when unconstrained and to expand to less than the maximum circumference when constrained.

[0010] In one embodiment, the hinge has a width or circumference that is less than the width or circumference of each of the non-compliant sections.

[0011] In one embodiment, the lumen is the lumen of the small intestine.

[0012] In one embodiment, the expandable component comprises at least two non-compliant sections.

[0013] In one embodiment, the expandable component comprises at least two hinges.

[0014] In one embodiment, the self-sizing device further comprises a therapeutic formulation and a piston, wherein the self-sizing device is structured to cause the piston to apply a force to the therapeutic formulation upon expansion of the expandable component, the force designed to expel the therapeutic formulation from the device.

[0015] In one embodiment, a system for delivering a formulation includes a self-sizing device, a formulation, and a delivery mechanism. The self-sizing device includes an expandable component including at least one non-compliant section structured to resist deformation in an expanded configuration and at least one hinge structured to allow deformation in an expanded configuration. The expandable component is structured to bend about the hinge upon expansion to conform to the inner circumference of the lumen independent of the inner circumference of the lumen within a selected range. The self-sizing device is structured to apply a force to the formulation to the delivery mechanism upon expansion of the expandable component, the force being designed to release the formulation from the self-sizing device.

[0016] In one embodiment, the system further includes a capsule in which the expandable component is disposed, where while within the capsule, the expandable component is in a folded and / or rolled configuration and is structured to unfold and / or unroll when released from the capsule.

[0017] In one embodiment, the expandable component is further structured to expand to a maximum circumference when unconstrained and to less than a maximum circumference when constrained after being released from the capsule.

[0018] In one embodiment, the self-sizing device is structured to be placed in the digestive tract, the selected range being from about 50 mm to about 150 mm.

[0019] In one embodiment, the hinge has a width or circumference that is less than the width or circumference of each of the non-compliant sections.

[0020] In one embodiment, the lumen is the lumen of the small intestine.

[0021] In one embodiment, the expandable component comprises at least two non-compliant sections.

[0022] In one embodiment, the expandable component comprises at least two hinges.

[0023] In one embodiment, the delivery mechanism comprises a piston and the self-sizing device is structured to apply a force to the piston on the formulation upon expansion of the expandable component.

[0024] In one aspect, a method for delivering a therapeutic compound includes providing a self-sizing device including the therapeutic compound, the self-sizing device further comprising an expandable component including at least one non-compliant section structured to resist deformation in an expanded configuration, and at least one hinge structured to allow deformation in the expanded configuration. The expandable component is structured to flex about the hinge upon expansion to conform to a circumference of the lumen independent of the circumference of the lumen within a selected range. The method further includes providing instructions for placing the self-sizing device within the body to deliver the therapeutic compound into the lumen.

[0025] In one embodiment, the instructions include instructions for swallowing the self-sizing device.

[0026] In one embodiment, the instructions include instructions for manually inserting the self-sizing device into the lumen. [Brief description of the drawings]

[0027] [Figure 1-4] 1A-1C each show an example of an embodiment of an expandable component with at least two non-compliant sections and at least one hinge. [Figure 5A-5F] 1A-1C each show an example of an embodiment of an expandable component with at least two non-compliant sections and at least one hinge. [Figure 6] 1 shows an example embodiment of an expandable component with at least two non-compliant sections and at least two hinges. [Figure 7A-7B] 1 illustrates an example embodiment of an expandable component with at least one non-compliant section and at least two hinges. [Figure 8A-8B] 1 shows an example embodiment of an expandable component with at least two non-compliant sections and at least two hinges. [Figure 9A-9B] Each represents an example embodiment of a capsule structure. [Figure 10A] 1 illustrates an example embodiment of an expandable component and an example embodiment of a capsule before being folded and / or rolled. [Figure 10B] 10B illustrates the expandable component of FIG. 10A in an embodiment in a folded and / or rolled configuration prior to placement of the expandable component within a capsule. [Figure 10C] FIG. 10B shows the expandable component of FIG. 10A disposed within a capsule in a folded and / or rolled configuration. [Figures 11A-11C] 1 shows an example of an embodiment of a swallowable device that includes an expandable component within a degradable capsule as the device traverses an internal lumen. [Fig. 11D-11F] 11D shows a rotated view of the progression of the expandable component of FIG. 11C as it expands within the lumen. [Figure 12] 1 shows an example of an embodiment of a self-sizing device that includes an expandable component in a fully extended state within a lumen. [Figure 13A] 1 shows an example of an embodiment of a self-sizing device that includes an expandable component with one non-conforming section and no hinges. [Figure 13B] 1 shows an example of an embodiment of a self-sizing device that includes an expandable component with two non-conforming sections and a hinge. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] The present disclosure relates to a self-sizing device for delivering a pharmaceutical agent into a lumen. Before discussing the details of the self-sizing device of the present disclosure, some rules are provided for the convenience of the reader.

[0029] In this specification, various abbreviations are used for standard units such as deciliter (dl), milliliter (ml), microliter (μl), international units (IU), centimeter (cm), millimeter (mm), nanometer (nm), inch (in), kilogram (kg), gram (gm), milligram (mg), microgram (μg), millimole (mM), degrees Celsius (°C), degrees Fahrenheit (°F), millitorr (mTorr), hours (hr), or minutes (min).

[0030] As used in this disclosure, the terms "eg," "such as," "for example," "for example," "for another example," "example," "for example," and "etc." indicate preceding or following a list of one or more non-limiting examples, with it being understood that other examples not listed are within the scope of the invention.

[0031] As used herein, the singular terms "a," "an," and "the" may include plural referents unless otherwise clear from the context. Reference to a singular object is not intended to mean "the only one," but rather "one or more," unless expressly stated.

[0032] The term "in an embodiment" or variations thereof (e.g., "in another embodiment" or "in one embodiment") is used herein to refer to use in one or more embodiments and does not in any way limit the scope of the invention to only the embodiments shown and / or described. Thus, elements illustrated and / or described herein with respect to an embodiment may be omitted or used in another embodiment (e.g., in another embodiment illustrated and described herein, or in another embodiment not illustrated and / or described herein within the scope of the present disclosure).

[0033] The term "component" as used herein refers to one item of a set of one or more items that together constitute the device, formulation, or system under consideration. A component may be a solid, powder, gel, plasma, fluid, gas, or other configuration. For example, a device may include multiple solid components that are assembled together to structure the device, and may further include a fluid component disposed within the device. As another example, a formulation may include two or more powder and / or fluid components that are mixed together to create the formulation.

[0034] The term "design" or grammatical variations thereof (e.g., "designed" or "engineered") refers to properties that are intentionally built in based on, for example, estimates of tolerances (e.g., component tolerances and / or manufacturing tolerances) and environmental conditions expected to be encountered (e.g., temperature, humidity, external or internal ambient pressure, external or internal mechanical pressure, stress due to external or internal mechanical pressure, age of the product, or shelf life, or if introduced into the body, physiology, body chemistry, biological composition of body fluids or tissues, chemical composition of body fluids or tissues, pH, species, diet, health, sex, age, ancestry, disease, or tissue damage), with it being understood that different components, devices, formulations, or systems of the same design may have different actual values ​​for those properties because actual tolerances and environmental conditions before and / or after delivery may affect the properties. Design also includes pre- or post-manufacturing variations or modifications.

[0035] The term "manufacture" or grammatical variations thereof (e.g., "production" or "manufactured"), as used herein in connection with a component, device, formulation, or system, refers to making or assembling the component, device, formulation, or system. Manufacturing can be performed wholly or partially manually and / or in wholly or partially automated processes.

[0036] The term "structured" or grammatical variations thereof (e.g., "structure" or "structured"), as used herein, refers to a component, device, formulation, or system that is produced according to a concept or design, or variations or modifications thereto (whether such changes or modifications occur before, during, or after production), whether or not such concept or design is incorporated in a document.

[0037] The term "body" as used herein refers to an animal body.

[0038] The term "subject" as used herein refers to a body to which an embodiment of the present disclosure is delivered or intended to be delivered. For example, with respect to a human, the subject may be a patient receiving treatment from a medical professional.

[0039] The term "fluid" as used herein refers to a liquid or gas, and includes water and humidity. The term "fluid environment" as used herein refers to an environment in which one or more fluids are present.

[0040] The term "biological material" as used herein refers to blood, tissues, bodily fluids, enzymes, interstitial fluid, and other secretions of the body. The term "digestion" as used herein refers to the biological material along the gastrointestinal (GI) tract of an animal body, and other material that traverses the digestive tract (e.g., food, either undigested or digested).

[0041] The term "ingest" or grammatical variations thereof (e.g., "ingesting" or "ingested"), as used herein, refers to taking into the stomach, whether by swallowing or by other means of deposition in the stomach (e.g., by depositing in the stomach via an endoscope or by depositing in the stomach via a port).

[0042] The term "lumen," as used herein, refers to the interior space of a tubular structure. Examples of lumens in the body include arteries, veins, and tubular cavities within organs.

[0043] The term "lumen wall" refers to the wall of a lumen, where wall, in relation to a lumen within the body, includes all layers from the inner periphery of the lumen to the outer periphery, such as the mucosa, submucosa, muscularis, serosa, and the outer wall of the lumen, along with their constituent blood vessels and tissues.

[0044] The term "digestive tract" or "GI tract," as used herein, refers to the intake / excretion system of the body including, for example, the mouth, pharynx, esophagus, stomach, pylorus, small intestine, cecum, large intestine, colon, rectum, anus, and the valves or sphincters between them.

[0045] The term "GI lumen" generally refers to any lumen of the GI tract (eg, the lumen of the esophagus, stomach, small intestine, large intestine, or colon), and the term "GI lumen wall" refers to the luminal wall of the GI lumen.

[0046] The term "formulation" as used herein refers to a preparation that contains one or more components. A formulation may consist of a fluid, a slurry, a powder, or a solid (e.g., a compacted or solidified form such as a tablet or microtablet). Each formulation may contain one or more components, and a device or system may contain one or more formulations.

[0047] The term "therapeutic formulation" as used herein refers to a formulation intended for therapeutic, diagnostic or other biological purposes.The components of a therapeutic formulation may be, for example, a pharmacologically active agent, a DNA or siRNA transcript, a cell, a cytotoxic agent, a vaccine or other preventative agent, a dietary supplement, a vasodilator, a vasoconstrictor, a delivery enhancer, a retardant, an excipient, a diagnostic agent, or a cosmetic enhancement agent.

[0048] The pharmacologically active agent can be, for example, an antibiotic, a nonsteroidal anti-inflammatory drug (NSAID), an angiogenesis inhibitor, a neuroprotective agent, a chemotherapeutic agent, a peptide, a protein, an immunoglobulin (e.g., a TNF-α antibody), an interleukin of the IL-17 family of interleukins, an anti-eosinophil antibody, another antibody, a nanobody, a macromolecule, a small molecule, or a hormone, or a biologically active variant or derivative of any of the foregoing.

[0049] The cells may be, for example, stem cells, red blood cells, white blood cells, neurons, or other living cells. The cells may be generated by or from an organism, or may contain components of an organism. The cells may be allogeneic or autologous.

[0050] The vaccine can be, for example, against influenza, coronavirus, meningitis, human papillomavirus (HPV), or chickenpox. The vaccine can correspond to an attenuated virus.

[0051] The dietary supplement can be, for example, vitamin A, thiamine, niacin, riboflavin, vitamin B-6, vitamin B-12, another B vitamin, vitamin C (ascorbic acid), vitamin D, vitamin E, folic acid, phosphorus, iron, calcium, or magnesium.

[0052] The vasodilator can be, for example, l-arginine, sildenafil, a nitrate (eg, nitroglycerin), or epinephrine.

[0053] The vasoconstrictor can be, for example, a stimulant, an amphetamine, an antihistamine, epinephrine, or cocaine.

[0054] The delivery enhancer may be, for example, a penetration enhancer, an enzyme blocker, a peptide that penetrates mucous membranes, an antiviral drug such as a protease inhibitor, a disintegrant, a superdisintegrant, a pH modifier, a surfactant, a bile salt, a fatty acid, a chelating agent, or chitosan. The delivery enhancer may, for example, serve as a delivery vehicle for delivering a component of the therapeutic formulation or may serve to improve the absorption of a component of the therapeutic formulation into the body. The delivery enhancer 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 included in the delivery device.

[0055] The retarding agent can 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), another polymer, or a hydrogel. The retarding agent can be included with (e.g., mixed with or provide structure around) one or more other components in the therapeutic formulation to slow the release rate of the other components in the therapeutic formulation.

[0056] An excipient can be, for example, a binder, disintegrant, superdisintegrant, buffer, antioxidant, or preservative. An excipient can provide a vehicle for the components of a therapeutic formulation (e.g., to aid in manufacturing) or can preserve the integrity of the components of a therapeutic formulation (e.g., during manufacturing, storage, or after ingestion prior to distribution in the body).

[0057] The diagnostic agent can be, for example, a detection agent, a contrast agent, a radionuclide, a fluorescent material, a luminescent material, a radiopaque material, or a magnetic material.

[0058] The term "degrade" or grammatical variations thereof (e.g., "degrading," "degraded," "degradable," and "degradation"), as used herein, refers to weakening, partial or complete degradation, breakdown, chemical modification, mechanical degradation, or disintegration, such as by dissolution, chemical degradation (including biodegradation), including, but not limited to, dissolving, disintegrating, deforming, shrinking, or shrinking. The term "non-degradable" refers to an expectation that degradation will be minimal or within a certain acceptable design percentage, at least for an expected period of time in an expected environment.

[0059] As used herein, the terms "substantially" and "about" are used to describe and convey small variations. For example, when used in conjunction with a numerical value, these terms can refer to a variation range of ±10% or less of that numerical value, such as ±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.

[0060] As used herein, a range of numerical values ​​includes any numerical value within the range, or any subrange where the minimum and maximum numbers within the subrange are within the range. Thus, for example, "<9" may refer to any numerical value less than 9, or a subrange of numerical values ​​where the minimum of the subrange is equal to or greater than zero, and the maximum of the subrange is less than 9. Ratios may also be presented herein in range format. For example, a ratio in the range of about 1 to about 200 should be understood to include the explicitly stated limits of about 1 and about 200, but also individual ratios such as about 2, about 35, and about 74, and subranges such as about 10 to about 50, about 20 to about 100, etc.

[0061] Self-sizing devices are an ongoing topic of research. The embodiments of the present description provide devices, systems, and methods of manufacture for self-sizing devices.

[0062] In one embodiment, the self-sizing device is a device designed to deliver a therapeutic formulation at or into the lumen wall. In one embodiment, the self-sizing device is an ingestible device designed to deliver a therapeutic formulation at or into the GI lumen wall, and such a device may be delivered in a capsule.

[0063] A self-sizing device includes a component structured to expand, hereinafter referred to for convenience as an “expandable component.” A self-sizing device includes at least one expansion module that, when triggered, expands the expandable component from a first, unexpanded configuration to a second, expanded configuration.

[0064] The expandable component includes a plurality of sections, where in an expanded configuration of the expandable component, at least one of the sections is non-compliant and at least one of the sections is compliant, where compliant refers to a state in which the section may be easily deformed and non-compliant refers to a state in which the section resists deformation.

[0065] In the absence of constraints, each section will expand to a fully extended state and the expandable component will reach a maximum dimension, which may depend, for example, on the materials used to form the expandable component and / or the capacity of the expansion modules implemented (e.g., in the case of expansion by inflation, the maximum dimension may be affected by limitations on the expansion force available from the expansion modules or the stretch coefficient of one or more materials of the expandable component).

[0066] Each compliant section operates similarly to a hinge and is therefore conveniently referred to as a hinge, and when the expandable component is in a fully extended state (each section is fully extended), each hinge has at least one design dimension (width, length, and / or circumference) that is substantially less than the corresponding design dimension of each non-compliant section.

[0067] As the expandable component expands, it achieves a shape that reflects the balance between the forces exerted by the expandable component on the interior of the lumen and the forces of the lumen in contact with the expandable component. In other words, the expandable component may not fully extend and, if constrained by the lumen, will tend to bend about the hinge. This bending is due to the smaller dimensions of the hinge compared to the corresponding dimensions of the non-compliant sections, resulting in a lower stiffness of the hinge compared to the stiffness of the non-compliant sections in the expanded configuration of the expandable component.

[0068] In this manner, the expandable component expands until the non-compliant section (hereinafter, NCS) presses against the inner luminal wall, maintaining the expandable component in a suitable position to deliver the formulation to the luminal wall for at least a period of time sufficient to accomplish such delivery. The expandable component can then be automatically or manually deflated.

[0069] The expandable component can be removed after deflation, left to degrade in situ, or passed from the lumen. For example, when used in applications within the GI lumen, the expandable component can be allowed to pass through the GI tract after deflation. The expandable component can be constructed from a degradable material such that the expandable component degrades after a designed period of time after exposure to the environment of the target site.

[0070] Self-sizing devices are particularly suitable for avoiding delivery being affected by material present in the lumen. For example, self-sizing devices have the ability to rapidly expand the expandable component to push out material and / or compress material against the lumen wall, and can expand to an extent appropriate for the delivery technique and the desired delivery rate for the formulation to be delivered without further expansion. In the case of self-sizing devices structured for delivery to the GI lumen, the self-sizing devices can achieve such delivery whether the subject is in a fed or fasted state (i.e., delivery is achieved whether or not digestive material is present in the GI lumen).

[0071] Figures 1-4 show example embodiments of expandable components in a fully extended state in which the expandable components are unconstrained and extended to their maximum dimensions (which may depend, for example, on the materials used for the expandable components and the capabilities of the expansion modules, among other considerations). For ease of discussion, an arbitrarily assigned xyz coordinate system is shown, with the expandable components of Figures 1-4 shown in the xy reference plane. Each expandable component includes two NCSs and one hinge in the xy plane shown.

[0072] Referring to FIG. 1, the expandable component 100 includes NCS105 and NCS106 separated by a hinge 110. In this figure of this embodiment shown in FIG. 1A, the dimension x1 of NCS105 is greater than the dimension x3 of NCS106, 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. Further, in this figure of this embodiment, the dimension y1 of NCS105 is greater than the dimension y2 of NCS106. Thus, in this figure, NCS105 is taller and longer than NCS106.

[0073] Often, the elongated shape of an expandable component (e.g., expandable component 100) results in an expandable component having a long dimension (e.g., length L) aligned with the central axis of the lumen in which the expandable component is positioned.

[0074] In the embodiment shown in FIG. 1, since the hinge 110 is much narrower than NCS105 and NCS106 (x2<<x1 and x2<<x3, respectively), NCS105 and NCS106 can bend towards or away from each other in the x-y plane around the hinge 110, as indicated by the arrows labeled A and B, which may enable the expandable component 100 to accommodate a non-uniform lumen surface and / or an inconsistent lumen diameter.

[0075] Referring to FIG. 2, expandable component 200 includes NCS 205 and NCS 206 separated by hinge 210. In this figure, expandable component 200 is similar to expandable component 100 as shown in FIG. 1. Dimension x4 of NCS 205 is larger than dimension x6 of NCS 206, and both x4 and x6 are larger than dimension x5 of hinge 210. Also, dimension y3 of NCS 205 is larger than dimension y4 of NCS 206. However, x5 shown in FIG. 2 is about three times larger than x2 shown in FIG. 1. Thus, NCS 205 and NCS 206 have the ability to bend toward or away from each other in the xy plane, which is less than the ability of NCS 105 and NCS 106 to bend toward or away from each other in the xy plane. Still, some flexibility is maintained to allow expandable component 200 to accommodate uneven luminal surfaces and / or inconsistent luminal diameters.

[0076] As can be seen by comparing Figures 1 and 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 minimize the amount of material used to structure the expandable component, reduce manufacturing costs, or increase manufacturing speed to suit a particular application.

[0077] 3, expandable component 300 includes NCS 305 and NCS 306 separated by hinge 310. Dimension x7 of NCS 305 is greater than dimension x9 of NCS 306, and both x7 and x9 are greater than dimension x8 of hinge 310. In this embodiment, dimension y5 of NCS 305 is approximately equal to dimension y6 of NCS 306, illustrating another variation in dimensions.

[0078] 4, expandable component 400 includes NCS 405 and NCS 406 separated by hinge 410. In this embodiment, dimension x10 of NCS 405 is smaller than dimension x12 of NCS 406, both x10 and x12 are somewhat larger than dimension x11 of hinge 410, and dimension y7 of NCS 405 is approximately twice as large as dimension y8 of NCS 406, illustrating further variations in NCS 406 dimensions.

[0079] Other comparative dimensions of the NCS and hinge are within the scope of the present invention. For example, the dimensions of the hinge in the xy plane may be greater than the dimensions of the NCS in that plane. Furthermore, the dimensions may vary in the z direction within a particular section (NCS or hinge).

[0080] 5A-5F show examples of embodiments of expandable components such as how one or more of expandable components 100, 200, 300, or 400 of FIGS. 1, 2, 3, 4, respectively, look when the field of view is rotated (here, rotated in the yz plane). For convenience with respect to FIGS. 5A-5F, the non-compliant sections are referred to as NCSs 505, 506 and the compliant sections are referred to as hinges 510.

[0081] NCS 505 and NCS 506 can bend towards or away from each other in the yz plane about hinge 510, allowing the expandable component to accommodate various lumen diameters and shapes.

[0082] 5A-5F, the shape of the expandable component can vary in a rotated (e.g., side) view as it does in a non-rotated (e.g., front) view. For example, one (or both) of the NCSs 505, 506 can have a surface that is substantially flat, somewhat rounded, significantly rounded, or of other curvature.

[0083] From the above discussion, it will be apparent that each of the various sections (each NCS and each hinge) can be designed to have a desired absolute dimension as well as a desired dimension relative to the other sections. For example, a hinge can have a width in the xy plane that is greater than or equal to the width of a particular NCS in the same xy plane, while having a width in the yz plane that is substantially less than the width of that particular NCS in that yz plane.

[0084] 1-4 and 5A-5F for some examples of expandable component embodiments, it will be apparent that there can be a wide variety of designs for an expandable component having two non-compliant sections (NCS) and one compliant section (hinge) according to the present disclosure. In various embodiments, expandable components according to the present disclosure more generally have one or more NCSs and one or more hinges.

[0085] The expandable component of a self-sizing device can be structured to have one or more sections in each of two or more planes. For example, the expandable component 100 shown in a first xy plane in FIG. 1 can be structured to have additional NCS and / or hinge sections in a second xy plane such that the expandable component 100 forms a Y-shape, X-shape, or other multi-sided shape as viewed in the yz plane. The prongs may include one or more NCSs or no NCSs and / or include one or more hinges or no hinges.

[0086] The expandable component may include weakening features to allow for increased compliance at the hinge area.

[0087] FIG. 6 illustrates an expandable component 600 having two NCSs, NCS 605 and NCS 606 in the illustrated view. Expandable component 600 defines an opening 615, shown as an oval in this embodiment. Stated differently, expandable component 600 includes a weakening feature, shown as opening 615. Omission of material within opening 615 leaves two hinges, hinge 610 and hinge 611. Fully extended hinges 610 and 611 have at least one design dimension (width, length, and / or circumference) that is substantially smaller than the corresponding design dimension of NCS 605 and NCS 606, respectively, which provides increased compliance of hinges 610, 611 relative to NCS 605, 606. Expandable component 600, in this embodiment, tends to bend around hinges 610, 611. Hinges 610, 611 may have similar or different dimensions. When rotated to another view, the expandable component 600 can have a variety of shapes, including those shown in Figures 5A-5F.

[0088] Figures 7A and 7B show an expandable component 700 having a single NCS 705 and two hinges, hinge 710 and hinge 711. Expandable component 700 is shown in the xy plane in Figure 7A and in the yz plane in Figure 7B, such that hinge 711 is hidden behind hinge 710. In this embodiment, the hinges 710, 711 themselves act to apply pressure against the inner surface of the lumen while providing compliance.

[0089] 8A and 8B show an expandable component 800 having three NCSs, NCS 805, NCS 806, and NCS 807, and two hinges, hinge 810 and hinge 811. Expandable component 800 is shown in the xy plane in FIG. 8A and in the yz plane in FIG. 8B, such that hinge 811 is hidden behind hinge 810 and NCS 807 is hidden behind NCS 806.

[0090] As can be seen in Figures 7A and 8A, expandable components 700 and 800 appear similar in the xy plane shown. However, upon rotation 90 degrees (e.g., as shown in the yz plane, as shown in Figures 7B and 8B, respectively), NCSs 806 and 807 (Figure 8B) are seen to expand to have a z-dimension that is substantially larger than the corresponding dimension of hinges 710 and 711 (Figure 7B).

[0091] In an embodiment of a self-sizing device according to the present disclosure, the expandable component is disposed within a capsule.

[0092] 9A and 9B show examples of capsule embodiments. In FIG. 9A, capsule 900 includes a cylindrical body 905 and two end caps 910 attached on or in the body 905. At least one of the three components of capsule 900 (cylindrical body 905, first end cap 910, and / or second end cap 910) is disassembled. End cap 910 can be glued or press-fitted on or in the body 905 to hold it in place. In FIG. 9B, capsule 950 includes a portion 920 and a portion 921 that are fitted together. At least one of portions 920, 921 is disassembled. Portions 920, 921 can be glued or press-fitted together. Examples of capsule sizes include 000, 00, and 0 capsule sizes. Capsule shapes other than those shown in Figures 9A and 9B can also be used, such as spherical or ovoid, or irregular shapes, or shapes that are symmetrical about a first axis and asymmetrical about a second axis perpendicular to the first axis (e.g., ovoid), or shapes having at least one flat side.

[0093] In one embodiment, the self-sizing device includes a degradable coating on the expandable component and / or on the capsule (if a capsule is included).

[0094] In one embodiment, the coating is applied directly to the expandable component to complete the manufacture of the self-sizing device (e.g., instead of placing the expandable component in a capsule). The coating can completely cover and seal the expandable component, or it can cover a portion of the expandable component. For example, the coating can degrade under certain conditions to expose one or more degradable components of the self-sizing device. The one or more degradable components then degrade after exposure and initiate expansion of the inflatable component, or, in embodiments where a gas is used to inflate the inflatable component, release the gas to cause the inflatable component to deflate after delivery of the formulation, etc.

[0095] The coating on the expandable device and / or capsule may be or may include an opaque material (e.g., to prevent the contents from being seen), a colored material (e.g., to provide color coding to identify the formulation contained in the self-sizing device), and / or a material that has a noticeable flavor or odor (e.g., an undesirable flavor or odor to discourage interest, or a desirable flavor or odor to encourage interest), each having sufficient solubility or degradability to enable the self-sizing device to deliver the formulation to the delivery target site.

[0096] All or a portion of the coating and / or capsule may be designed to degrade under the conditions expected at the target site, for example, after a designed period of time after placement, or in the presence of a particular chemical, or a particular 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 degrade upon an external trigger, for example, a trigger wirelessly transmitted that causes a mechanism within the capsule to rupture or break the capsule.

[0097] As previously described, embodiments of the self-sizing device according to the present disclosure may be used to deliver therapeutic formulations at or within the GI lumen wall via ingestion (e.g., by manual positioning or swallowing of the self-sizing device). The self-sizing device may include a capsule. The self-sizing device may include a coating (e.g., a coating as described above) on the capsule and / or expandable component designed to degrade at a specific location within the GI tract, such as within the stomach or intestines. In one embodiment, all or a portion of the capsule and / or coating is designed to degrade in the presence of a specific chemical or after a specific length of time under conditions (e.g., specific values ​​or ranges of pH, temperature, pressure applied to the capsule, or combinations of the foregoing) expected at a target site within the GI tract. In one embodiment, the coating includes a material to improve swallowability, such as guar gum or xanthan gum.

[0098] 10A-10C show examples of assembling a self-sizing device 1050. FIG. 10A shows an embodiment of an expandable component 1000 and an embodiment of a capsule 1010. The outer dimensions of the expandable component 1000 may be several times larger than the inner dimensions of the capsule 1010. For example, the longest dimension of an embodiment of the expandable component 1000 may be 2-5 times larger than the inner length of the capsule 1010. Other ratios of the outer dimensions of the expandable component to the inner dimensions of the capsule are within the scope of the invention. FIG. 10B shows the expandable component 1000 folded and / or rolled into an arrangement 1001 that is smaller than the inner dimensions of the capsule 1010. As shown, the arrangement 1001 is folded and / or rolled into a complex arrangement in an origami style in this embodiment. 10C shows the arrangement 1001 disposed on the capsule 1010, and the capsule 1010 assembled together (e.g., as in FIG. 9A where the end cap 910 is attached on or in the body 905, or as in FIG. 9B where the portions 920, 921 are fitted). The device 1050 includes the expandable component 1000 (in arrangement 1001) and the capsule 1010, and may include other components not shown, such as an expansion module, a delivery component, one or more coatings, and a deflation valve.

[0099] 11A-11F show an example of how device 1050 may be provided to a delivery target site within the GI tract to position expandable component 1000 to deliver a therapeutic formulation into the luminal wall 1111 of the GI lumen 1110. Returning to FIGS. 11A-11C, device 1050 is shown from a perspective that is approximately perpendicular to the direction of travel of device 1050 (indicated by the arrow), whereas device 1050 in FIGS. 11D-11F is shown looking into lumen 1110 (e.g., approximately 90 degrees from the views of FIGS. 11A-11C).

[0100] 11A shows device 1050 within lumen 1110 shown in a relaxed state (e.g., during a peristaltic contraction). In this embodiment, the outer diameter of device 1050 is smaller than the inner diameter of lumen 1110 at this point in the GI tract. Device 1050 traverses lumen 1110 via, for example, peristaltic, hydrodynamic, and / or gravitational action.

[0101] 11B shows that after reaching the designed target site or encountering conditions (e.g., pH) representative of the designed target site, the capsule 1010 degrades (or is triggered to break down or degrade) as the device 1050 continues to traverse the lumen 1110. For example, for intestinal delivery, the target site can 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 that has been marked or has a known or detected condition to be treated).

[0102] FIG. 11C shows that following (or simultaneously with) the degradation of the capsule 1010, the expandable component 1000 begins to unfold from its folded and / or rolled configuration.

[0103] FIG. 11D shows the expandable component 1000 mostly unfolded, and FIG. 11E shows the expandable component 1000 when expanded (eg, with an expansion module).

[0104] FIG. 11F shows the expandable component 1000 after expansion. In this embodiment, the expandable component 1000 would have been able to expand if not constrained by the lumen 1110 until the reference line 1120 was approximately straight. However, the lumen 1110 exerts a force on the expandable component 1000, which causes the expandable component 1000 to bend at the hinge 1002. The NCS 1003 and NCS 1004 of the expandable component 1000 then press against the lumen wall of the lumen 1110 (e.g., on opposite sides of the lumen) to position the expandable component 1000 to deliver the therapeutic compound at or within the lumen wall. The hinge 1002 may also compress the lumen wall. In one embodiment, peristaltic motion may move the expandable component 1000 through the lumen 1110 to its expanded state. In one embodiment, the expandable component 1000 can have sufficient internal pressure (combined with surface tension) to hold the expandable component 1000 firmly 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.

[0105] Expansion of the expandable component can be accomplished by any suitable expansion module. In one embodiment, a spring mechanism is released from a compressed state to deploy and push filler pieces of hard or soft material outward, thereby expanding the expandable component. In one embodiment, two or more reactants are mixed together to form a gas, thereby expanding the expandable component. In one embodiment, a material combusts rapidly to produce a gas, thereby expanding the expandable component. Other expansion modules are within the scope of the present invention.

[0106] 12 shows a lumen 1200 in which a self-sizing device 1210 is positioned that includes an expandable component 1250. In this embodiment, the force of the lumen 1200 on the expandable component 1250 is not sufficient to substantially bend the hinge 1251 of the expandable component 1250, so that the expandable component 1250 is in a nearly fully extended state. Stated another way, bending of the hinge 1251 of the expandable component 1250 is negligible at this location within the lumen 1200.

[0107] The expandable component 1250 is expanded by the production of gas and includes a valve 1255 for releasing 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 degrades 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 part of a material or coating on the port or opening of the expandable component 1250, which part of the material or coating is designed to degrade over a period of time after the expandable component 1250 delivers the therapeutic compound. In one embodiment, the valve 1255 is manually opened.

[0108] The therapeutic formulation (or multiple therapeutic formulations) can be stored within expandable component 1250 in any configuration (e.g., as a solid, fluid, slurry, or powder). The therapeutic formulation can be delivered in any configuration (e.g., as a solid, fluid, slurry, or powder). In one embodiment, two or more components of the therapeutic formulation are mixed within expandable component 1250 prior to delivery. In one embodiment, expandable component 1250 includes a portal, such as portal 1260, which defines an opening 1261 through which the therapeutic formulation is delivered.

[0109] In one embodiment, the therapeutic compound is released passively as the therapeutic compound is applied to the inner surface of lumen 1200 (e.g., for absorption via the mucosa), and in such embodiments, the therapeutic compound may be released through a portal, such as portal 1260, or through multiple holes exposed by the deployment of expandable component 1250, multiple holes in expandable component 1250 created during deployment, or multiple holes exposed as a coating thereon degrades (not shown).

[0110] In one embodiment, the therapeutic compound is actively released from the expandable component 1250 such that it is forced out through (through) the lumen 1200 or one or more layers thereon (e.g., into or through the mucosa, through the submucosa, through the muscularis layer through the serosa, or through the outer wall of the lumen 1200, or through the peritoneal wall into the mesenteric or peritoneal cavity). In such an embodiment, the therapeutic compound may be released through one or more portals, such as portal 1260, or through one or more holes (not shown) in the expandable component 1250, or holes exposed by deployment of the expandable component 1250, holes created during deployment, or holes exposed by degradation of a coating over the holes.

[0111] The therapeutic formulation may be forcefully released from the expandable component 1250 by a delivery mechanism. For example, for a solid composition (e.g., in the form of a tablet, pellet, or point), the therapeutic formulation can be released by means of a spring mechanism that is released to rapidly eject the solid composition from the expandable component 1250, or by means of 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, for a fluid, slurry, or powder of the therapeutic formulation, a bladder can be compressed to push the fluid, slurry, or powder out of the expandable component 1250.

[0112] In one embodiment, the surface of the expandable component 1250 through which the therapeutic compound is delivered contacts the wall of the lumen 1200 along a length of about 5 mm to 20 mm.

[0113] In one embodiment, the therapeutic compound is delivered from the expandable component 1250 from or along multiple surfaces.

[0114] 13A shows an embodiment of a self-sizing device 1300 that includes an expandable component 1305 that includes one NCS 1310 and no hinge. FIG. 13B shows an embodiment of a self-sizing device 1350 that includes an expandable component 1355 that includes two NCSs, NCS 1360 and NCS 1361, and a hinge 1365 therebetween. For these embodiments, the width W1 of the expandable component 1305 is similar to the width W2 of the expandable component 1355, but the height H1 of the expandable component 1305 is less than the height H2 of the expandable component 1355.

[0115] Multiple devices 1300 (FIG. 13A) structured according to the same design will have approximately the same maximum circumference (yz plane) of the NCS 1310 when fully expanded within the lumen due to the incompatibility of the NCS 1310, such that the expandable component 1305 does not significantly conform to the various different internal lumen circumferences. Thus, different sized devices 1300 may be suitable for different animal species and / or different subjects within a species. In contrast, multiple devices 1350 (FIG. 13B) structured according to the same design will likely not have the same maximum circumference when fully expanded within the lumen, because each device 1350, even when expanded, will adjust to the size of the expanded lumen due to the flexibility (incompatibility, bending) of the hinge 1365. The maximum circumference for the device 1350 within the lumen refers to the maximum circumference of the shape the device 1350 assumes within the lumen (e.g., a partially extended shape or a fully extended shape).

[0116] Trial device designs similar to those shown in Figures 1300, 1350 were prepared and multiple trial devices were manufactured based on each trial device design. For ease of reference, the identification numbers used in Figures 13A and 13B will be used to describe these test devices in the following discussion. For these trial devices, the expansion module contained two reactants (baking soda and citric acid) and a biodegradable pinch valve 1370 that separated the two reactants. The valve 1370 was designed to decompose and allow the reactants to mix and produce carbon dioxide, which expands the expandable component 1305 and the expandable component 1355.

[0117] For the trial devices, each expandable component was constructed of similar materials and did not stretch significantly during inflation.

[0118] A human clinical trial was conducted to compare the delivery rates of device 1300 and device 1350 in delivering a solid composition formulation to the wall of the GI lumen in humans.

[0119] Three trial device designs were used: Device A, Device B, and Device C. Device A and Device B were similar to Device 1300 (FIG. 13A), and Device C was similar to Device 1350 (FIG. 13B). Each device under test contained a capsule that was swallowed by the subject (not shown in FIGS. 13A, 13B).

[0120] Device A had a maximum circumference (in the yz plane) of about 65 mm when fully inflated and unconstrained. Device B had a maximum circumference (in the yz plane) of about 68 mm when fully inflated and unconstrained. For clarity, Device A and Device B were similar in shape and width (the width of Device A and the width of 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 circumference (in the yz plane) of about 80 mm when fully inflated and unconstrained.

[0121] When expanded, the internal volume V1 of expandable component 1305 of device A was approximately 8 cubic centimeters (cc), while the internal volume V2 of expandable component 1355 of device C was approximately 4 cc. The reduction in volume of expandable component 1355 is due in part to NCS 1360 and NCS 1361, respectively, of device 1350, which collectively have a smaller circumference (in the yz plane) than NCS 1310 of device 1300. The reduction in volume of expandable component 1355 of device C was achieved even though the overall height H2 of expandable component 1355 is greater than the overall height H1 of expandable component 1305 of device A. The increased height of expandable component 1355 allowed for deployment into a larger diameter lumen. The smaller volume of expandable component 1355 allowed for a reduction in the amount of reactant required compared to the amount of reactant required for expandable component 1305 to achieve the same internal pressure.

[0122] In the trial device, the delivery mechanism 1375 included a piston that delivered the therapeutic formulation by pressure of carbon dioxide against a piston, causing the piston to move rapidly and eject the solid composition of the formulation into the wall of the lumen.

[0123] The trial devices contained radiopaque markers in the therapeutic formulation and elsewhere within the trial device. Imaging was performed throughout each trial to track the position of each trial device, to track whether each expandable component separated from the capsule, and to track whether the therapeutic formulation was delivered into the luminal wall of the small intestine.

[0124] result Device A delivered the therapeutic formulation to the GI lumen wall in 25% of 12 subjects. Device B delivered the therapeutic formulation to the GI lumen wall in 50% of 20 subjects. Device C delivered the therapeutic formulation to the GI lumen wall in 80% of 20 subjects. Delivery rates of 25% to 50% (e.g., for Devices A and B) are acceptable, but of course delivery rates of 80% or greater (Device C) are desirable.

[0125] The trial results showed that increasing the circumference of the expandable component (Device A compared to Device B) resulted in better delivery rates across the range of subjects. However, the trial results suggest that the delivery rate in a particular person may be affected by the maximum circumference (in the yz plane) of the unhinged device, and therefore, for some treatment procedures, it may be possible to test multiple devices (each with a different maximum circumference) per person prior to or at the start of the treatment procedure to identify which device size is most appropriate for use with that person.

[0126] In contrast, trial results suggested that a single size and design of the expandable component, including the hinge (e.g., Device C), could be used successfully in a high percentage of subjects. Notably, the results achieved by Device C were achieved using an early version of the hinged design, and improvements to the hinged design are expected to result in even higher delivery rates.

[0127] It is further noted that multiple lots of self-sizing devices (e.g., similar to device C) structured similarly to device 1350 with expandable component 1355 having hinge 1365, all with the same design and dimensions of expandable component 1355, have been tested in various animal species, including humans, pigs, and dogs. As a result, high delivery rates are obtained in each species, even though the intestinal lumen sizes of the various species vary significantly. In comparison, for devices structured similarly to device 1300 with expandable component 1305 not having a hinge, multiple sizes of expandable component 1305 were used across different animal species to match the lumen size of each specific species to avoid discomfort caused by overstretching the intestine.

[0128] For devices structured similarly to Device C, delivery rates were shown to be consistent whether subjects were fed or fasted for several hours before ingesting the device.

[0129] Prior to the conception of the hinged structure of the expandable component, concerns arose over the number of device sizes available and how to determine the appropriate device size for an individual. Clinical trial results show that the novel concept of adding a hinge to the expandable component solves these and other concerns. A single design of a hinged expandable component according to the present disclosure can deliver a formulation to a lumen at a high delivery rate over a selected range of circumference of the inner wall of the lumen. In one embodiment, the device is designed for delivery into the small intestine of a human, the selected range being from about 10 mm to about 100 mm, or from about 20 mm to about 80 mm. In one embodiment, a self-sizing device suitable for use in any of a variety of locations along the GI tract (e.g., stomach, small intestine, large intestine, colon) across a variety of animal species is designed to have a selected range of from about 5 mm to about 500 mm. Other ranges can be selected, and different ranges can be selected for different types of lumens in the body, or for other types of lumens.

[0130] In one embodiment, the expandable component is designed with at least one hinge that is visible from a first viewing angle and multiple hinges that are visible from a second viewing angle rotated from the first viewing angle, such that each of the three or more sections (NCS and / or hinges) of the expandable component contacts the lumen in which the expandable component is located. This structure allows for compliance of the multiple hinges to accommodate a wider selected range of lumen circumferences.

[0131] Another advantage of the hinge design concept is that it allows a single self-sizing device design to be used for applications in a wide variety of lumens across a wide variety of species in the animal kingdom, and a wide variety of subjects within a species, while reducing the total surface area of ​​the expandable component compared to expandable components that do not use hinges. Thus, the amount of material required can be reduced. This reduction in material, along with the reduction in the amount of reactants, can lead to cost savings.

[0132] In one embodiment, the expandable component is structured using one type of material throughout. In one embodiment, the expandable component is structured using two or more different materials. In one embodiment, the level of compliance of the expandable component can be adjusted based on the thickness of the material at specific regions of the expandable component. In one embodiment, the level of compliance of the expandable component can be adjusted by adding layers of the same or different materials to specific regions of the expandable component. Examples of materials that can be used to structure the expandable component include polyester, PET, HDPE, cross-linked polymers, silicone, polyurethane, or other elastomers or polymers.

[0133] In one embodiment, the formulation is a solid composition. The delivery mechanism (e.g., delivery mechanism 1375) includes an advancement device (e.g., a piston or rod) that is directly or otherwise operably coupled to the solid composition and applies a force to the surface of the solid composition to advance it into the lumen wall. The delivery mechanism may be in operative contact with or otherwise closely positioned to the lumen wall when the expandable component is expanded, such that the solid composition is ejected directly into the lumen wall with minimal or no gap between the delivery surface and the lumen wall. This may improve the delivery rate of the self-sizing device.

[0134] In one embodiment, the self-sizing device comprises a solid composition removably coupled to a piston such that after the solid composition advances to the lumen wall, the solid composition separates from the piston.

[0135] Particular materials can be selected to impart desired structural and material properties to the solid composition (e.g., column strength for insertion into the lumen wall, or porosity and / or hydrophilicity to control the disintegration of the solid composition and thus the release of the therapeutic formulation). In one embodiment, the tip of the solid composition includes or is coated with a degradable material, such as sucrose, maltose, or other sugars, to increase the hardness and tissue-penetrating properties of the tip. Once positioned within the lumen wall, the solid composition is degraded by interstitial fluid within the tissue, which may result in the dissolution of the therapeutic formulation and absorption into the bloodstream. The properties of the solid composition, such as size, shape, and chemical composition, can be selected to allow for dissolution and absorption of the drug in seconds, minutes, or hours. The rate of dissolution can be controlled through various excipients, such as disintegrants (e.g., cross-linked polymers such as starch, sodium starch glycolate, or carboxymethylcellulose). The choice of disintegrant can be specifically tailored to the environment within the lumen wall (e.g., blood flow and average number of peristaltic contractions).

[0136] The solid composition can be made entirely of the formulation or can define a cavity that contains the formulation. The self-sizing device can contain and deliver one or more solid compositions, each of which can contain the same or different formulation as another solid composition. Each solid composition can have different properties. For example, two solid compositions can be designed to deliver each formulation simultaneously (e.g., two instances of one formulation, or one instance each of two formulations), or can be designed to deliver each formulation at different times (e.g., to provide a subsequent dose of the same formulation, or to provide a different formulation at a later time).

[0137] Although the present invention has been described and illustrated with reference to specific embodiments thereof, these descriptions and illustrations are not intended to limit the present invention. It can be clearly understood that various modifications can be made and equivalent elements can be substituted within the embodiments without departing from the true spirit and scope of the present disclosure as defined by the appended claims. Elements, features, or acts from one embodiment can be easily recombined or substituted with one or more elements, properties, or acts from other embodiments to structure numerous additional embodiments within the scope of the present invention. Furthermore, an element shown or described as being combined with other elements can exist as an independent element in various embodiments. Furthermore, for any positive description of an element, property, component, feature, act, step, etc., an embodiment of the present invention specifically contemplates the exclusion of that element, value, property, component, feature, act, step, etc. Illustrations are not necessarily drawn to scale. There may be distinctions between the artistic representations in the present disclosure and the actual devices due to variability in manufacturing processes, etc. There may be other embodiments of the present disclosure that are not specifically shown. The specification and drawings are to be considered as illustrative and not restrictive. Modifications may be made to adapt a particular situation, material, composition of matter, method, or process to the objective, spirit, and scope of the present disclosure. All such modifications are intended to be within the scope of the claims appended hereto. Although the methods disclosed herein have been described with reference to certain operations performed in a particular order, it will be understood that these operations can be combined, sub-divided, or rearranged in an equivalent manner without departing from the teachings of the invention. Thus, unless otherwise indicated herein, the order and grouping of the operations are not limitations of the present disclosure.

Claims

1. 1. A self-sizing device for delivering a therapeutic formulation, comprising: a capsule sized and structured to be taken orally; an expandable component disposed within the capsule, The device, wherein the expandable component includes at least one non-compliant section structured to resist deformation in an expanded configuration, the expandable component further includes at least one compliant section structured as a hinge to readily deform and allow deformation in the expanded configuration, the expandable component being structured to expand upon inflation within an internal lumen and bend around the hinge to conform to the circumference of the internal wall of the lumen.

2. The device of claim 1 , wherein the selected range is from about 50 mm to about 150 mm.

3. 3. The device of claim 1 or 2, wherein the expandable component is in a folded and / or rolled configuration while within the capsule and is structured to unfold and / or unroll upon release from the capsule to expand to a maximum circumference when unconstrained and to expand to less than a maximum circumference when constrained.

4. A device according to any preceding claim, wherein the hinge has a width or circumference less than a width or circumference of each of the non-compliant sections.

5. The device of any one of claims 1 to 4, wherein the lumen is the lumen of the small intestine.

6. The device of any one of claims 1 to 5, wherein the expandable component comprises at least two of the non-compliant sections.

7. The device of any one of claims 1 to 6, wherein the expandable component comprises at least two of the hinges.

8. 8. The device of any one of claims 1-7, further comprising the therapeutic compound and a piston, the self-sizing device being structured to cause the piston to apply a force to the therapeutic compound upon expansion of the expandable component, the force designed to expel the therapeutic compound from the device.

9. 1. A system for delivering a pharmaceutical formulation, comprising: a self-sizing device comprising an expandable component configured to expand by inflation, the expandable component including at least one non-compliant section structured to resist deformation in an expanded configuration, the expandable component further including at least one compliant section structured as a hinge to readily deform and permit deformation in the expanded configuration, the pre-expandable component structured to flex about the hinge upon expansion by inflation to conform to a circumference of a lumen within a selected range; The formulation, The self-sizing device comprises a delivery mechanism structured to apply a force to the formulation upon expansion of the expandable component, the force designed to expel the formulation from the self-sizing device.

10. 10. The system of claim 9, further comprising a capsule in which the expandable component is disposed, the expandable component being in a folded and / or rolled configuration while within the capsule and structured to unfold and / or unroll when released from the capsule.

11. 11. The system of claim 10, wherein the expandable component is further structured to expand to a maximum circumference in the absence of a constraining force and to expand to less than a maximum circumference in the presence of a constraining force after being released from the capsule.

12. The system of any one of claims 9 to 11, wherein the self-sizing device is structured for placement in the digestive tract, and the selected range is from about 50 mm to about 150 mm.

13. A system according to any one of claims 9 to 12, wherein the hinge has a width or circumference that is smaller than a width or circumference of each of the non-compliant sections.

14. The system according to any one of claims 9 to 13, wherein the lumen is the lumen of the small intestine.

15. The system of any one of claims 9 to 14, wherein the expandable component comprises at least two of the non-compliant sections.

16. The system of any one of claims 9 to 15, wherein the expandable component comprises at least two of the hinges.

17. 17. The system of any one of claims 9 to 16, wherein the delivery mechanism comprises a piston, and the self-sizing device is structured such that the piston applies the force to the formulation upon expansion of the expandable component.

18. 1. A self-sizing device for use in delivery of a therapeutic compound into a body lumen of a subject, comprising: The device further comprises an expandable component configured to expand upon inflation, the expandable component comprising the therapeutic formulation and including at least one non-compliant section structured to resist deformation in an expanded configuration, the expandable component further comprising at least one compliant section structured as a hinge to readily deform and allow deformation in the expanded configuration, the expandable component being structured to bend about the hinge upon expansion to conform, within a selected range, to the inner circumference of the body lumen of the subject.

19. The device of claim 18 , wherein the device is configured to be administered by swallowing.

20. 20. The device of claim 18, wherein the device is configured to be administered by manual insertion into the body lumen of the subject.

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