Self-sizing device for delivering pharmaceutical products to the luminal wall

Abstract

The present invention provides a system for delivering therapeutic formulations into the lumen of a body. [Solution] The system includes a self-sizing device comprising an expandable component having at least one non-conforming section structured to resist deformation in an expanded configuration, the expandable component configured to expand by expansion further comprises at least one hinge structured to allow deformation in an expanded configuration and is structured to flex around the hinge upon expansion to fit the 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 such that, upon expansion of the expandable component, the delivery mechanism applies a force to the therapeutic formulation, which is a force designed to release the therapeutic formulation from the self-sizing device. The self-sizing device can be placed inside a capsule.

Description

Technical Field

[0001] Cross-Reference to Related Applications This application claims the priority and benefit of U.S. Provisional Patent Application No. 62 / 909,206, filed on October 1, 2019, entitled "INFLATABLE DEVICES, SYSTEMS AND METHODS FOR DELIVERING THERAPEUTIC COMPOUNDS INTO WALL OF THE GASTRO INTESTINAL TRACT", the entire content of which is incorporated herein by reference for all purposes. Background Art

[0002] It may be desirable to deliver a material or preparation (e.g., fluid, slurry, powder, or solid) into a lumen, and further, it may be desirable to deliver the 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 may collectively be unpredictable and / or variable. As a result, selecting an effective device for delivering material at or into the inner wall of any given lumen can be challenging.

[0003] An example of delivery into the lumen of an animal body is the delivery of therapeutic drugs into the lumen of the gastrointestinal tract. Delivery of therapeutic drugs by pills that dissolve in the gastrointestinal tract is ineffective for many therapeutic drugs for several reasons, including the inability of the active ingredient in the therapeutic drug to penetrate the gastrointestinal wall and reach the vascular structure, or the destruction of the active ingredient by gastric juice or other fluids or substances within the gastrointestinal tract. To address these concerns, several oral delivery devices have been developed that are activated within the gastrointestinal tract and designed to reach the vascular structure in order to deliver therapeutic drugs into the gastrointestinal wall. The obstacles faced by such devices include the unpredictable and variable nature of the lumen between several lumens of the gastrointestinal tract, the unpredictable and variable nature of a single lumen within the gastrointestinal tract, the unpredictable and variable nature of the lumen between different species, and the unpredictable and variable nature of the lumen between different subjects of the same species. These obstacles present challenges in effectively delivering therapeutic drugs to delivery target sites within the gastrointestinal tract and identifying devices that correspond to the various lumen circumferentialities that may be encountered at those delivery target sites.

[0004] Similar challenges exist for other lumens within animal bodies, and for other types of lumens in general. [Overview of the project]

[0005] Embodiments of this disclosure provide devices, systems, and methods for delivering a formulation to a luminal wall independently of the circumferential aspect of the lumen.

[0006] In one embodiment, a self-sizing device for delivering a therapeutic formulation includes a capsule that is sized and structured for oral ingestion, and an expandable component disposed within the capsule. The expandable component includes at least one non-conforming section structured to resist deformation in the expanded configuration, and at least one hinge structured to allow deformation in the expanded configuration. The expandable component is structured to expand within a lumen and to flex around the hinge to conform to the inner circumference of the lumen, independently of the inner circumference within a selected range.

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

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

[0009] In one embodiment, the expandable components are in a folded and / or rolled arrangement while inside the capsule, and are structured to unfold and / or unwind when released from the capsule, expanding to the maximum circumference if there is no restraining force, and to less than the maximum circumference if there is a restraining force.

[0010] In one embodiment, the hinge has a width or circumference smaller than the width or circumference of each of the non-adaptive 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-conforming 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, the self-sizing device being structured such that when an expandable component expands, the piston applies force to the therapeutic formulation, and the force is designed to release 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 comprising at least one non-conforming 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 flex around the hinge when expanded to fit the inner circumference of a lumen independently of the inner circumference of a lumen within a selected range. The self-sizing device is structured to apply a force to the delivery mechanism, designed to release the formulation from the self-sizing device, when the expandable component is expanded.

[0016] In one embodiment, the system further includes a capsule in which an expandable component is housed. While inside the capsule, the expandable component is in a folded and / or rolled-up configuration, and is structured to unfold and / or roll up when released from the capsule.

[0017] In one embodiment, the expandable component is further structured to expand to its maximum circumference if there is no restraining force, and to less than its maximum circumference if there is a restraining force, after being released from the capsule.

[0018] In one embodiment, the self-sizing device is structured to be positioned in the digestive tract, with a selected range of approximately 50 mm to 150 mm.

[0019] In one embodiment, the hinge has a width or circumference smaller than the width or circumference of each of the non-adaptive 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-conforming 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 configured such that when the expandable component expands, the piston exerts a force on the formulation.

[0024] In one aspect, a method for delivering a therapeutic formulation comprises providing a self-sizing device containing the therapeutic formulation, wherein the self-sizing device further comprises: 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 permit deformation in the expanded configuration. The expandable component is structured to bend around the hinge during expansion so as to conform to the inner circumference of a lumen within a selected range independently of the inner circumference of the lumen. The method further comprises providing instructions for placing the self-sizing device in the body to deliver the therapeutic formulation 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 a lumen. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] [Figure 1-4] Examples of embodiments of an expandable component comprising at least two non-compliant sections and at least one hinge, respectively, are shown. [Figure 5] It is a diagram showing directions. [Figures 5A-5F] Examples of embodiments of an expandable component comprising at least two non-compliant sections and at least one hinge, respectively, are shown. [Figure 6]Shows an example of an embodiment of an expandable component comprising at least two non-compliant sections and at least two hinges. [Figures 7A-7B] Shows an example of an embodiment of an expandable component comprising at least one non-compliant section and at least two hinges. [Figure 8A-8B] Shows an example of an embodiment of an expandable component comprising at least two non-compliant sections and at least two hinges. [Figure 9A-9B] Each shows an example of an embodiment of a capsule structure. [Figure 10A] Shows an example of an embodiment of an expandable component before being folded and / or rolled, and an example of an embodiment of a capsule. [Figure 10B] Shows the expandable component of Fig. 10A in an embodiment of a folded and / or rolled arrangement prior to placement of the expandable component within the capsule. [Figure 10C] Shows the expandable component of Fig. 10A disposed within a capsule, in the folded and / or rolled arrangement of Fig. 10B. [Figure 11A-11C] Shows an example of an embodiment of an ingestible device comprising an expandable component within a degradable capsule when the device traverses a lumen. [Figure 11D-11F] Shows, from a rotated view, the progression of the expandable component of Fig. 11C when the expandable component expands within a lumen. [Figure 12] Shows an example of an embodiment of a self-sizing device comprising the expandable component in a fully expanded state within a lumen. [Figure 13A] Shows an example of an embodiment of a self-sizing device comprising an expandable component that has one non-compliant section and no hinges. [Figure 13B] Shows an example of an embodiment of a self-sizing device comprising an expandable component that has two non-compliant sections and one hinge. DETAILED DESCRIPTION OF EMBODIMENTS

[0028] This disclosure relates to a self-sizing device for delivering a pharmaceutical product into a lumen. Before discussing the details of the self-sizing device of this disclosure, some rules are provided for the reader's convenience.

[0029] This specification uses various abbreviations 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), millimoles (mM), degrees Celsius (°C), degrees Fahrenheit (°F), millitorr (mTorr), hour (hr), or minute (min).

[0030] Where used in this disclosure, the terms “e.g.,” “such as,” “for example,” “for example,” “for another example,” “example,” “as an example,” and “etc.” indicate that they precede or follow a list of one or more non-limiting examples, and it should be understood that other examples not listed are also within the scope of the invention.

[0031] As used herein, the singular terms “a,” “an,” and “the” may refer to multiple objects unless otherwise evident from the context. A reference to a singular object is not intended to mean “only,” but rather “one or more,” unless explicitly stated otherwise.

[0032] The term “in an embodiment” or its variations (e.g., “in another embodiment” or “in one embodiment”) means, in this specification, to be used in one or more embodiments, and in no case is the scope of the invention limited to the illustrated and / or described embodiments. Accordingly, components illustrated and / or described herein with respect to embodiments may be omitted or used in another embodiment (e.g., another embodiment illustrated and described herein, or another embodiment not illustrated and / or described herein within the scope of this disclosure).

[0033] The term “component” as used herein refers to one item in a set of one or more items that together constitute a device, formulation, or system under consideration. A component may be a solid, powder, gel, plasma, fluid, gas, or other composition. For example, a device may include several solid components assembled together to structure the device, and further include fluid components placed within the device. Another example is a formulation which may include two or more powder and / or fluid components mixed together to produce the formulation.

[0034] The term “design” or its grammatical variations (e.g., “design” or “designed”) refers to properties intentionally incorporated based on, for example, estimated tolerances (e.g., part tolerances and / or manufacturing tolerances) and expected environmental conditions 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, product age, 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). It should be understood that different components, devices, formulations, or systems of the same design may have different actual values ​​with respect to their properties, as actual tolerances and environmental conditions before and / or after delivery may affect the properties. Design also includes variations or modifications before or after manufacturing.

[0035] The term “manufacture” or its grammatical variations (e.g., “manufactured” or “manufactured”) relating to components, devices, formulations, or systems, as used herein, means the act of making or assembling components, devices, formulations, or systems. Manufacturing may be carried out entirely or partially manually and / or entirely or partially automated.

[0036] The term “structured” or its grammatical variations (e.g., “structure” or “structured”) means, in this specification, a component, device, formulation, or system manufactured in accordance with a concept or design, or a variation thereof, or a modification thereof (whether such change or modification occurs before, during, or after manufacture), regardless of whether such concept or design is incorporated into the documentation.

[0037] In this specification, the term "body" refers to the body of an animal.

[0038] In this specification, the term “Subject” refers to the body to which the embodiments of this disclosure are delivered or intended to be delivered. For example, with respect to a human being, 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 moisture 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 substance” as used herein refers to blood, tissues, body fluids, enzymes, interstitial fluid, and other bodily secretions. The term “digested material” as used herein refers to biological substance along the gastrointestinal (GI) tract of an animal body, and other substances that cross the digestive tract (e.g., undigested or digested food).

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

[0042] In this specification, 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.

[0043] The term "luminal wall" refers to the wall of a lumen, where the wall includes all layers from the inner to the outer periphery of the lumen, such as the mucosa, submucosa, muscular layer, serosal membrane, and outer wall of the lumen, along with the constituent blood vessels and tissues.

[0044] The term “gastrointestinal tract” or “GI tract” as used herein refers 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 the valves or sphincters between them.

[0045] The term "GI lumen" generally refers to the lumen of any of the GI ducts (e.g., the lumen of the esophagus, stomach, small intestine, large intestine, or colon), while the term "GI lumen wall" refers to the lumen wall of the GI lumen.

[0046] The term “formulation” as used herein refers to a preparation comprising one or more components. A formulation may consist of a fluid, slurry, powder, or solid (e.g., a condensed or solidified form such as a tablet or micropill). 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. Components of a therapeutic formulation may include, for example, pharmacologically active agents, DNA or siRNA transcripts, cells, cytotoxic agents, vaccines or other prophylactic agents, nutritional supplements, vasodilators, vasoconstrictors, delivery enhancers, delays, excipients, diagnostic agents, or substances for cosmetic enhancement.

[0048] Pharmacologically active agents may include, for example, antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), angiogenesis inhibitors, neuroprotective agents, chemotherapeutic agents, peptides, proteins, immunoglobulins (e.g., TNF-α antibodies), interleukins of the IL-17 family, anti-eosinophil antibodies, other antibodies, nanobodies, macromolecules, small molecules, or hormones, or any biologically active variants or derivatives of any of the aforementioned.

[0049] Cells can be, for example, stem cells, red blood cells, white blood cells, neurons, or other living cells. Cells can be produced by or from an organism, or may contain components of an organism. Cells can be homogeneous or autologous.

[0050] Vaccines can be for, for example, influenza, coronavirus, meningitis, human papillomavirus (HPV), or chickenpox. Vaccines can target attenuated viruses.

[0051] Nutritional supplements may include, 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] Vasodilators may include, for example, L-arginine, sildenafil, nitrates (e.g., nitroglycerin), or epinephrine.

[0053] Vasoconstrictors may include, for example, stimulants, amphetamines, antihistamines, epinephrine, or cocaine.

[0054] Delivery enhancers may include, for example, osmotic enhancers, enzyme blockers, mucosal-penetrating peptides, antiviral drugs such as protease inhibitors, disintegrants, hyperdisintegrants, pH modifiers, surfactants, bile salts, fatty acids, chelating agents, or chitosan. Delivery enhancers can, for example, serve as delivery vehicles for delivering components of therapeutic formulations or help improve the absorption of components of therapeutic formulations into the body. Delivery enhancers can 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.

[0055] The retarder 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), another polymer, or a hydrogel. The retarder may be included together with one or more other components in the therapeutic formulation (e.g., mixed or providing a structure around them) to slow down the release rate of the other components in the therapeutic formulation.

[0056] Excipients may be, for example, binders, disintegrants, superdisintegrants, buffers, antioxidants, or preservatives. Excipients may provide a medium for the components of a therapeutic formulation (e.g., to aid in manufacturing) or may be preserved to maintain the integrity of the components of a therapeutic formulation (e.g., during manufacturing, storage, or after ingestion before dispersion in the body).

[0057] Diagnostic agents may include, for example, detection agents, contrast agents, radionuclides, fluorescent substances, luminescent substances, radiopaque substances, or magnetic substances.

[0058] The term “degrade” or its grammatical variations (e.g., “degrading,” “degraded,” “degradable,” and “degradation”) as used herein means weakening by dissolution, chemical degradation (including biodegradation), partial degradation, or complete degradation, disintegration, chemical modification, mechanical degradation, or collapse, including but not limited to dissolution, collapse, deformation, deflation, or shrinkage. The term “non-degradable” means the expectation that degradation will be minimal or within a certain acceptable design percentage, at least over the expected period in the 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 number, these terms may refer to a range of variation of that number of ±10%, such as ±5%, ±4%, ±3%, ±2%, ±1%, ±0.5%, ±0.1%, or ±0.05%.

[0060] Where used herein, a numerical range includes any number within the range, or any subrange if the minimum and maximum numbers within the subrange are within the range. Thus, for example, "<9" may refer to any number less than 9, or a numerical subrange where the minimum value of the subrange is greater than or equal to zero and the maximum value of the subrange is less than 9. Ratios may also be presented in range form herein. For example, a ratio in the range of about 1 to about 200 includes the explicitly stated limits of about 1 and about 200, but should be understood to also include 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 still under consideration. Embodiments described here provide devices, systems, and manufacturing methods for self-sizing devices.

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

[0063] A self-sizing device includes components structured to expand, which are hereafter referred to as "expandable components" for convenience. The self-sizing device includes at least one expansion module, which, when triggered, expands the expandable component from a first unexpanded configuration to a second expanded configuration.

[0064] An expandable component includes multiple sections. In the expanded configuration of the expandable component, at least one of the sections is non-conformable and at least one of the sections is conformable. Conformability refers to a state in which a section can be easily deformed, while non-conformability refers to a state in which a section resists deformation.

[0065] In the absence of constraints, each section will expand to its fully stretched state, and the expandable component will reach its maximum dimensions. This may depend, for example, 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 the limitations of the expansion force available from the expansion module, or by the expansion coefficients of one or more materials of the expandable component).

[0066] Each adaptable section behaves like a hinge and is therefore referred to as a hinge for convenience. When the expandable component is fully extended (each section fully extended), each hinge has at least one design dimension (width, length, and / or circumference) that is substantially smaller than the corresponding design dimension of each non-adaptable section.

[0067] As an 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 stretch and, if constrained by the lumen, tends to bend around the hinge. This bending is due to the smaller dimensions of the hinge compared to the corresponding dimensions of the non-adaptive section, and in the expanded configuration of the expandable component, the stiffness of the hinge is lower compared to the stiffness of the non-adaptive section.

[0068] In this way, the expandable component expands until the non-adaptive section (hereinafter referred to as NCS) is pressed against the inner wall of the lumen, and the expandable component is maintained in a position suitable for delivering the formulation to the lumen wall for at least a time sufficient to achieve such delivery. The expandable component can then be deflated automatically or manually.

[0069] Expandable components can be removed after deflation, left to decompose in place, or allowed to pass through the lumen. For example, when used in applications within a GI lumen, expandable components may be allowed to pass through the GI tube after deflation. Expandable components can be constructed from decomposable materials, so that they decompose after a designed period of time after being exposed to the environment of the target site.

[0070] Self-sizing devices are particularly well-suited to avoid delivery being affected by substances present in the lumen. For example, self-sizing devices have the ability to rapidly expand expandable components to extrude and / or compress substances in contact with the lumen wall, and can expand to a degree appropriate to the delivery technique and the desired delivery rate for the formulation to be delivered without further expansion. In the case of a self-sizing device structured for delivery to a GI lumen, the self-sizing device can achieve such delivery regardless of whether the subject is feeding or fasting (i.e., delivery is achieved regardless of whether digested material is present in the GI lumen).

[0071] Figures 1–4 show examples of embodiments of expandable components in a fully stretched state, where the expandable component is stretched unconstrained to its maximum dimensions (this may depend, for example, on the materials used for the expandable component and the capabilities of the expansion module, among other considerations). For convenience of consideration, an arbitrarily assigned xyz coordinate system is shown, and the expandable components in Figures 1–4 are shown in the xy reference plane. Each expandable component includes two NCSs and one hinge in the shown xy plane.

[0072] Referring to FIG. 1, the expandable component 100 comprises NCS 105 and NCS 106 separated by a hinge 110. In this view of the embodiment shown in FIG. 1A, the dimension x1 of NCS 105 is larger than the dimension x3 of NCS 106, and both x1 and x3 are larger than the dimension x2 of the hinge 110. In other words, x1 / x3>1, x1 / x2>1, and x3 / x2>1. Furthermore, in this view of the embodiment, the dimension y1 of NCS 105 is larger than the dimension y2 of NCS 106. Accordingly, in this drawing, NCS 105 is taller and longer than NCS 106.

[0073] In many cases, the elongated shape of an expandable component (e.g., expandable component 100) results in the 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, the hinge 110 is much narrower than NCS 105 and NCS 106 (x2<<x1 and x2<<x3, respectively), so that NCS 105 and NCS 106 can bend toward 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 allow the expandable component 100 to accommodate uneven lumen surfaces and / or inconsistent lumen diameters.

[0075] Referring to Figure 2, the expandable component 200 includes NCS205 and NCS206 separated by a hinge 210. In this figure, the expandable component 200 is similar to the expandable component 100 as shown in Figure 1. The dimension x4 of NCS205 is larger than the dimension x6 of NCS206, and both x4 and x6 are larger than the dimension x5 of the hinge 210. Also, the dimension y3 of NCS205 is larger than the dimension y4 of NCS206. However, x5 shown in Figure 2 is approximately three times larger than x2 shown in Figure 1. Thus, NCS205 and NCS206 have the ability to bend toward or away from each other in the xy plane, which is less than the ability of NCS105 and NCS106 to bend toward or away from each other in the xy plane. Still, some degree of flexibility is maintained so that the expandable component 200 can accommodate non-uniform lumen surfaces and / or inconsistent lumen diameters.

[0076] As can be seen by comparing Figure 1 and Figure 2, the dimensions of the hinges (e.g., hinge 110 or hinge 210) can be designed to have a desired width. The width and other dimensions of the expandable components can be designed, for example, to suit a particular application, to minimize the amount of material used to structure the expandable components, thereby reducing manufacturing costs or increasing manufacturing speed.

[0077] Referring to Figure 3, the expandable component 300 includes NCS305 and NCS306 separated by a hinge 310. Dimension x7 of NCS305 is greater than dimension x9 of NCS306, and both x7 and x9 are greater than dimension x8 of hinge 310. In this embodiment, dimension y5 of NCS305 is approximately equal to dimension y6 of NCS306, demonstrating another variation of dimensions.

[0078] Referring to Figure 4, the expandable component 400 includes NCS405 and NCS406 separated by a hinge 410. In this embodiment, dimension x10 of NCS405 is smaller than dimension x12 of NCS406, both x10 and x12 are somewhat larger than dimension x11 of hinge 410, and dimension y7 of NCS405 is about twice as large as dimension y8 of NCS406, showing another variation of the NCS406 dimensions.

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

[0080] Figures 5A–5F show examples of embodiments of the expandable components, such as how one or more of the expandable components 100, 200, 300, or 400 in Figures 1, 2, 3, and 4 appear when the field of view is rotated (here, rotated to the yz plane). For convenience, in Figures 5A–5F, the non-adaptive sections are referred to as NCS505, 506 and the adaptable sections are referred to as hinge 510.

[0081] NCS505 and NCS506 can be bent toward or away from each other in the yz plane around the hinge 510, thereby allowing the expandable components to accommodate various lumen diameters and shapes.

[0082] As can be seen in Figures 5A-5F, the shape of the expandable component can change in a rotated (e.g., side) view as it does in an unrotated (e.g., front) view. For example, one (or both) of the NCS505, 506 may have a surface that is substantially flat, somewhat rounded, quite rounded, or has other curvatures.

[0083] From the above considerations, it will be clear that each of the various sections (each NCS and each hinge) can be designed to have desired absolute dimensions and desired dimensions in relation to other sections. For example, a hinge may 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 smaller than the width of that particular NCS in the yz plane.

[0084] Looking at Figures 1–4 and 5A–5F with respect to some examples of embodiments of the expandable component, it will be clear that there can be a wide variety of designs for the expandable component having two non-adaptive sections (NCS) and one adaptable section (hinge) according to the present disclosure. In various embodiments, the expandable component according to the present disclosure more generally has one or more NCS and one or more hinges.

[0085] The expandable components 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 the first xy plane of Figure 1 may be structured to have additional NCS and / or hinge sections in the second xy plane, as seen in the yz plane, such that the expandable component 100 forms a Y-shape, X-shape, or other polyhedral shape. The prongs may include or not include one or more NCSs, and / or include or not include one or more hinges.

[0086] Expandable components may include weakening features to enhance adaptability in the hinge area.

[0087] Figure 6 shows an expandable component 600 having two NCSs, NCS605 and NCS606, in the shown figure. The expandable component 600 defines an opening 615, shown as an ellipse in this embodiment. In other words, the expandable component 600 includes a weakening function shown as the opening 615. The omission of material within the opening 615 leaves two hinges, hinge 610 and hinge 611. Fully stretched hinges 610 and 611 each have at least one design dimension (width, length, and / or circumference) substantially smaller than the corresponding design dimensions of NCS605 and NCS606, which provides increased adaptability of hinges 610, 611 to NCS605, 606. In this embodiment, the expandable component 600 tends to bend around hinges 610, 611. Hinges 610, 611 may have similar or different dimensions. When rotated to a different view, the expandable component 600 can have various shapes, including those shown in Figures 5A to 5F.

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

[0089] Figures 8A and 8B show an expandable component 800 having three NCSs, NCS805, NCS806, and NCS807, as well as two hinges, hinge 810 and hinge 811. The expandable component 800 is shown in the xy plane in Figure 8A and in the yz plane in Figure 8B, such that hinge 811 is hidden behind hinge 810 and NCS807 is hidden behind NCS806.

[0090] As can be seen from Figures 7A and 8A, expandable components 700 and 800 appear similar in the shown xy-plane. However, when rotated by 90 degrees (for example, as shown in the yz-plane, as shown in Figures 7B and 8B, respectively), NCS806 and NCS807 (Figure 8B) are found to expand to have dimensions in the z-direction, which are substantially larger than the corresponding dimensions of hinges 710 and 711 (Figure 7B).

[0091] In embodiments of the self-sizing device according to this disclosure, expandable components are arranged within a capsule.

[0092] Figures 9A and 9B show examples of capsule embodiments. In Figure 9A, capsule 900 includes a cylindrical body 905 and two end caps 910 mounted on or inside the body 905. At least one of the three components of capsule 900 (the cylindrical body 905, the first end cap 910, and / or the second end cap 910) is disassembled. To hold the end caps 910 in place, they can be glued or press-fitted onto or inside the body 905. In Figure 9B, capsule 950 includes fitted parts 920 and 921. At least one of parts 920 and 921 is disassembled. Parts 920 and 921 can be glued or press-fitted together. Examples of capsule sizes include capsule sizes 000, 00, and 0. Capsule shapes other than those shown in Figures 9A and 9B, such as spherical or oval shapes, or irregular shapes, or shapes that are symmetrical with respect to a first axis and asymmetrical with respect to a second axis perpendicular to the first axis (e.g., oval), or shapes having at least one flat surface, can also be used.

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

[0094] In one embodiment, the coating is applied directly to an expandable component to complete the fabrication of a 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 may degrade under certain conditions, exposing one or more degradable components of the self-sizing device. The one or more degradable components then decompose after exposure, initiating the expansion of the expandable component, or, in embodiments where gas is used to expand the expandable component, releasing the gas to cause the expandable component to deflate after the delivery of the formulation, and so on.

[0095] The coating on the expandable device and / or capsule may be or may include materials containing opaque materials (e.g., to conceal the contents), colored materials (e.g., to provide color coding for identifying the formulation contained in the self-sizing device), and / or distinctive flavors or odors (e.g., an undesirable flavor or odor to pique interest, or a desirable flavor or odor to stimulate 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 part of the coating and / or capsule may be designed to decompose under expected conditions at the target site, for example, after a design period following placement, or in the presence of a specific chemical, or a specific value or range of pH, temperature, or pressure applied to the capsule, or a combination thereof. In one embodiment, the capsule is designed to decompose with an external trigger, for example, a trigger transmitted wirelessly to cause a mechanism inside the capsule to tear or break the capsule.

[0097] As described above, embodiments of self-sizing devices according to this disclosure may be used to deliver therapeutic formulations in or into 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 components, designed to decompose at a specific location in the GI tubule, such as in the stomach or intestines. In one embodiment, all or part of the capsule and / or coating is designed to decompose in the presence of a specific chemical or after a specific time period under conditions expected at a target site in the GI tubule (e.g., pH, temperature, pressure applied to the capsule, or a specific value or range of the aforementioned combinations). In one embodiment, the coating includes a material to improve swallowability, such as guar gum or xanthan gum.

[0098] Figures 10A–10C show examples of assembling the self-sizing device 1050. Figure 10A shows embodiments of the expandable component 1000 and the capsule 1010. The external dimensions of the expandable component 1000 may be several times larger than the internal dimensions of the capsule 1010. For example, the longest dimension of the embodiment of the expandable 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 expandable component to the internal dimensions of the capsule are within the scope of the present invention. Figure 10B shows the expandable component 1000 folded and / or rolled into an arrangement 1001 smaller than the internal dimensions of the capsule 1010. As shown, in this embodiment, the arrangement 1001 is folded and / or rolled into an origami-style complex arrangement. Figure 10C shows arrangement 1001 positioned in capsule 1010, and capsule 1010 assembled together (for example, as in Figure 9A with the end cap 910 mounted on or inside the body 905, or as in Figure 9B with parts 920, 921 fitted in). Device 1050 includes the expandable component 1000 (located in arrangement 1001) and capsule 1010, and may include other components not shown, such as expansion modules, delivery components, one or more coatings, and a shrink valve.

[0099] Figures 11A–11F illustrate an example of how device 1050 is provided to a delivery target site within the GI tubule, positioning the expandable component 1000 to deliver the therapeutic formulation into the luminal wall 1111 of the GI lumen 1110. Returning to Figures 11A–11C, device 1050 is shown from a field of view nearly perpendicular to the direction of device 1050's movement (indicated by the arrow), whereas in Figures 11D–11F, device 1050 is shown looking at the lumen 1110 (for example, about 90 degrees from the view in Figures 11A–11C).

[0100] Figure 11A shows the device 1050 within the lumen 1110 in a relaxed state (e.g., during peristaltic contraction). In this embodiment, the outer diameter of the device 1050 is smaller than the inner diameter of the lumen 1110 at this point in the GI tube. The device 1050 traverses the lumen 1110, for example, through the action of peristalsis, hydrodynamics, and / or gravity.

[0101] Figure 11B shows that after reaching the designed target site or encountering conditions representing the designed target site (e.g., pH), the capsule 1010 disintegrates (or is triggered to break down or disintegrate) as the device 1050 continues to traverse the lumen 1110. For example, with respect to intestinal delivery, the target site may be a general area (e.g., small intestine), a more specific area (e.g., jejunum), or a specific tissue area (e.g., a marked or tissue area with a known or detected condition to be treated).

[0102] Figure 11C shows that following (or simultaneously with) the disassembly of capsule 1010, the expandable component 1000 begins to unfold from its folded and / or rolled-up position.

[0103] Figure 11D shows the expandable component 1000 in its fully extended state, and Figure 11E shows the expandable component 1000 when it has been extended (e.g., by an expansion module).

[0104] Figure 11F shows the expandable component 1000 after expansion. In this embodiment, the expandable component 1000 could have expanded if it had not been constrained by the lumen 1110 until the reference line 1120 was nearly straight. However, the lumen 1110 exerts a force on the expandable component 1000, causing it to bend at the hinge 1002. The NCS 1003 and NCS 1004 of the expandable component 1000 then press against the luminal wall of the lumen 1110 (e.g., the opposite side of the lumen) to position the expandable component 1000 and deliver the therapeutic formulation to or into the luminal wall. The hinge 1002 may also compress the luminal wall. In one embodiment, peristaltic movement can move the expandable component 1000 through the lumen 1110 into its expanded state. In one embodiment, the expandable component 1000 may have sufficient internal pressure (combined with surface tension) to firmly hold the expandable component 1000 in substantially the same position, even during peristalsis. In one embodiment, the expandable component 1000 includes surface roughness or surface protrusions, which help maintain the position of the expandable component 1000.

[0105] The expansion of an expandable component can be achieved by any suitable expansion module. In one embodiment, a spring mechanism is released from a compressed state, unfolding and pushing out a filler piece of rigid or flexible material, 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 is rapidly combusted to generate a gas, thereby expanding the expandable component. Other expansion modules are within the scope of the present invention.

[0106] Figure 12 shows a lumen 1200 in which a self-sizing device 1210, including an expandable component 1250, is positioned. 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. In other words, the bending of the hinge 1251 of the expandable component 1250 is negligible at this position within the lumen 1200.

[0107] The expandable component 1250 expands by the generation of gas and includes a valve 1255 for deflating the expandable component 1250 by releasing the gas from within the expandable component 1250 into the lumen 1200. 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., a biological substance) to expose a port or opening defined by the expandable component 1250. In one embodiment, the valve 1255 is part of a material or coating on the port or opening of the expandable component 1250, and that part of the material or coating is designed to decompose after a certain period of time after the expandable component 1250 has delivered a therapeutic formulation. In one embodiment, the valve 1255 is opened manually.

[0108] A therapeutic formulation (or multiple therapeutic formulations) can be stored within an 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 the expandable component 1250 before 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 formulation is delivered.

[0109] In one embodiment, the therapeutic formulation is passively released so that the therapeutic formulation is applied to the inner surface of the lumen 1200 (for example, for absorption via the mucosa), in such an embodiment the therapeutic formulation may be released through a portal such as a portal 1260, or through a plurality of holes exposed by the deployment of an expandable component 1250, a plurality of holes within the expandable component 1250 created during deployment, or a plurality of holes (not shown) exposed by the decomposition of a coating thereon.

[0110] In one embodiment, the therapeutic formulation is actively released from the expandable component 1250 so as to be forcibly released through (penetrating) the lumen 1200 or one or more layers thereon (for example, through or within the mucosa, through the submucosa, through the muscular layer and through the serosa, or through the outer wall of the lumen 1200, or through the peritoneal wall into the mesentery or peritoneal cavity). In such embodiments, the therapeutic formulation 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 through holes exposed by the deployment of the expandable component 1250, holes created during deployment, or holes exposed by the decomposition of the coating over the holes.

[0111] The therapeutic formulation can be forcibly released from the expandable component 1250 by a delivery mechanism. For example, with respect to a solid composition (e.g., a tablet, pellet, or pointed form), the therapeutic formulation can be released by means of a spring mechanism that is released to rapidly inject 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, with respect to a fluid, slurry, or powder 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 an expandable component 1250 through which the therapeutic formulation is delivered is in contact with the wall of the lumen 1200 along a length of approximately 5 mm to 20 mm.

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

[0114] Figure 13A shows an embodiment of a self-sizing device 1300 that includes one NCS 1310 and an expandable component 1305 without a hinge. Figure 13B shows an embodiment of a self-sizing device 1350 that includes two NCSs, NCS 1360 and NCS 1361, and an expandable component 1355 with a hinge 1365 between them. With respect to 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 smaller than the height H2 of the expandable component 1355.

[0115] Multiple devices 1300 (Figure 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 misfit of the NCS 1310, and as a result, the expandable components 1305 will not fit significantly around a variety of different internal lumen circumferences. Therefore, devices 1300 of different sizes may be suitable for different animal species and / or different subjects within a species. In contrast, multiple devices 1350 (Figure 13B) structured according to the same design are unlikely to have the same maximum circumference when fully expanded within the lumen, because each device 1350 will adjust to the size of the expanded lumen due to the flexibility (misfit, bending) of the hinge 1365, even when expanded. The maximum circumference with respect to the device 1350 within the lumen refers to the maximum circumference of the shape that the device 1350 takes within the lumen (e.g., partially stretched shape or fully stretched shape).

[0116] Trial device designs similar to those shown in Figures 1300 and 1350 were prepared, and multiple trial devices were manufactured based on each trial device design. For convenience of reference, the identification numbers used in Figures 13A and 13B are used to describe these test devices in the following discussion. In the case of these trial devices, the expansion module contained two reactants (sodium bicarbonate and citric acid) and a biodegradable pinch valve 1370 to separate the two reactants. The valve 1370 was designed to decompose, allowing the reactants to mix and produce carbon dioxide, thereby inflating expandable components 1305 and 1355.

[0117] In the trial device, each expandable component was made of the same material and did not stretch significantly during expansion.

[0118] Human clinical trials were conducted to compare the delivery rates of device 1300 and device 1350 when delivering solid composition formulations to the luminal wall of human GI.

[0119] Three trial device designs were used: Device A, Device B, and Device C. Devices A and B were similar to Device 1300 (Figure 13A), and Device C was similar to Device 1350 (Figure 13B). Each device during testing contained a capsule swallowed by the subject (not shown in Figures 13A and 13B).

[0120] Device A, when fully inflated and unconstrained, had a maximum circumference (in the yz plane) of approximately 65 mm. Device B, when fully inflated and unconstrained, had a maximum circumference (in the yz plane) of approximately 68 mm. For clarity, devices A and B had similar shapes and widths (the width of both devices was approximately equal to W1), but device B was taller than device A (for example, the height of device A was equal to H1, while the height of device B was greater than H1). Device C, when fully inflated and unconstrained, had a maximum circumference (in the yz plane) of approximately 80 mm.

[0121] When expanded, the internal volume V1 of the expandable component 1305 of device A was approximately 8 cubic centimeters (cc), while the internal volume V2 of the expandable component 1355 of device C was approximately 4 cc. The reduction in volume of the expandable component 1355 is partly attributable to NCS1360 and NCS1361 of device 1350, respectively, and collectively, it has a smaller circumference (in the yz plane) than NCS1310 of device 1300. Despite the total height H2 of the expandable component 1355 being greater than the total height H1 of the expandable component 1305 of device A, a reduction in volume of the expandable component 1355 of device C was achieved. Increasing the height of the expandable component 1355 allowed for expansion into 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 required for the 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 carbon dioxide pressure on the piston, causing the piston to move rapidly and inject the solid composition of the formulation into the wall of the lumen.

[0123] In the trial devices, radiopaque markers were included in the therapeutic formulation and other locations within the trial device. Imaging was performed throughout each trial to track the location 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 lumen wall of the small intestine.

[0124] result Device A delivered the therapeutic agent to the GI lumen wall in 25% of 12 subjects. Device B delivered the therapeutic agent to the GI lumen wall in 50% of 20 subjects. Device C delivered the therapeutic agent to the GI lumen wall in 80% of 20 subjects. While delivery rates of 25% to 50% (e.g., for devices A and B) are acceptable, a delivery rate of 80% or higher (device C) is naturally 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 entire set of subjects. However, the trial results suggest that the delivery rate in a particular individual may be influenced by the maximum circumference (in the yz plane) of a hingeless device. Therefore, for some therapeutic procedures, it may be possible to test multiple devices (each with a different maximum circumference) per individual before or at the start of the procedure to determine which device size is most appropriate for that individual.

[0126] In contrast, the trial results suggested that a single size and design of an expandable component including a hinge (e.g., device C) could be successfully used for a high percentage of targets. In particular, the results achieved by device C were achieved using an early version of the hinged design, and it is expected that further improvements to the hinged design will yield even higher delivery rates.

[0127] Furthermore, it is noteworthy that multiple lots of self-sizing devices structured similarly to device 1350 (e.g., similar to device C) with an expandable component 1355 having a hinge 1365, all having the same design and dimensions as the expandable component 1355, were tested in various animal species, including humans, pigs, and dogs. As a result, high delivery rates were obtained in each species, even when the size of the intestinal lumen varied considerably across different species. In comparison, for devices structured similarly to device 1300 with an expandable component 1305 without a hinge, multiple sizes of the expandable component 1305 were used across different animal species to accommodate specific species-specific lumen sizes, in order to avoid discomfort caused by excessive stretching of the intestine.

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

[0129] Prior to conceiving the hinge structure of the expandable component, concerns arose regarding the number of available device sizes and how to determine the appropriate device size for an individual. Clinical trial results have shown that the novel concept of adding a hinge to the expandable component addresses these and other concerns. A single design of the hinged expandable component according to this disclosure can deliver a formulation into a lumen with high delivery rates over a selected range of the inner wall of the lumen. In one embodiment, the device is designed for delivery into the human small intestine, with a selected range of approximately 10 mm to 100 mm, or approximately 20 mm to 80 mm. In one embodiment, a self-sizing device suitable for use in any of the various locations along the GI tubule (e.g., stomach, small intestine, large intestine, colon) across various animal species is designed to have a selected range of approximately 5 mm to 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 visible from a first viewing angle and multiple hinges visible from a second viewing angle rotated from the first viewing angle, so that each of 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 multiple hinges, enabling the expandable component to fit a wider selected range of lumen circumferences.

[0131] Another advantage of the hinge-based design concept is that, compared to expandable components without hinges, it can reduce the total surface area of ​​the expandable components while allowing a single self-sizing device design to be used for a wide variety of applications in diverse lumens across a wide range of animal species and diverse targets within those species. Therefore, the amount of material required can be reduced. This reduction in material, along with a 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 in a particular area 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 material to a particular area of ​​the expandable component. Examples of materials that can be used to structure the expandable component include polyester, PET, HDPE, crosslinked 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 a forwarding device (e.g., a piston or rod) that is operably coupled directly or otherwise to the solid composition and applies force to the surface of the solid composition to advance it into the lumen wall. The delivery mechanism may be operably in contact with the lumen wall when an expandable component is expanded, or otherwise closely positioned, so that the solid composition is injected 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 includes a solid composition detachably coupled to a piston, so that the solid composition advances against the lumen wall and then separates from the piston.

[0135] Specific 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 contains or is coated with a biodegradable material such as sucrose, maltose, or other sugars to enhance the tip's hardness and tissue-penetrating properties. Once positioned within the lumen wall, the solid composition is disintegrated by the interstitial fluid in the tissue, resulting in the dissolution of the therapeutic formulation and potential absorption into the bloodstream. The properties of the solid composition, such as size, shape, and chemical composition, can be selected to enable drug dissolution and absorption in seconds, minutes, or hours. The dissolution rate can be controlled via various excipients, such as disintegrants (e.g., cross-linked polymers such as starch, sodium starch glycolate, or carboxymethylcellulose). The selection of disintegrants can be specifically tailored to the environment within the lumen wall (e.g., blood flow and average number of peristaltic contractions).

[0136] Solid compositions can be manufactured entirely from formulations, or they can define cavities containing formulations. Self-sizing devices can contain and deliver one or more solid compositions, each of which may contain the same or different formulations as another solid composition. Each solid composition may have different properties. For example, two solid compositions may be designed to deliver their respective formulations simultaneously (e.g., two instances of one formulation, or one instance each of two formulations), or they may be designed to deliver their respective formulations at different times (e.g., to provide a subsequent dose of the same formulation, or to provide a different formulation afterward).

[0137] While the present invention has been described and illustrated with reference to its specific embodiments, these descriptions and illustrations are not intended to limit the invention. It is clearly understood that various modifications can be made and equivalent components can be replaced within embodiments without departing from the true spirit and scope of this disclosure as defined by the appended claims. Elements, features, or actions from one embodiment can be readily recombined or substituted with one or more elements, characteristics, or actions from other embodiments to structure numerous additional embodiments within the scope of the invention. Furthermore, elements shown or described as being combined with other elements may exist as independent elements in various embodiments. In addition, with respect to any positive description of elements, characteristics, components, features, actions, steps, etc., embodiments of the invention specifically intend to exclude such elements, values, characteristics, components, features, actions, steps, etc. Illustrations are not necessarily drawn to a constant scale. There may be distinctions between artistic representations in this disclosure and actual apparatus due to variability such as manufacturing processes. There may be other embodiments of this disclosure that are not specifically shown. Specifications and drawings should be considered illustrative, not limiting. Modifications can be made to suit specific circumstances, materials, substance compositions, methods, or processes to the purposes, spirit, and scope of this disclosure. All such modifications are intended to fall within the scope of the claims appended herein. While the methods disclosed herein have been described with reference to specific operations performed in a particular order, it can be understood that these operations can be combined, subdivided, or rearranged into equivalent methods without departing from the direction of the invention. Thus, unless specifically indicated herein, the order and grouping of operations are not limitations of this disclosure.

Claims

1. A self-sizing device for delivering therapeutic formulations, Capsules that are sized and structured for oral administration, The capsule comprises an expandable component disposed within the capsule, A device wherein the expandable component comprises at least one non-conforming section structured to resist deformation in an expanded configuration, the expandable component further comprises at least one conforming section structured as a hinge that is easily deformable and allows deformation in an expanded configuration, and the expandable component is structured to expand by expansion within a lumen and to bend around the hinge to conform to the circumference of the inner wall of the lumen.

2. The device according to claim 1, wherein the selected range is approximately 50 mm to approximately 150 mm.

3. The device according to claim 1 or 2, wherein the expandable component is in a folded and / or rolled configuration while inside the capsule, and is structured to be unfolded and / or unwound when released from the capsule to expand to a maximum circumference if there is no restraining force, and to less than a maximum circumference if there is a restraining force.

4. The device according to any one of claims 1 to 3, wherein the hinge has a width or circumference smaller than the width or circumference of each of the non-adaptive sections.

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

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

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

8. The device according to any one of claims 1 to 7, further comprising the therapeutic formulation and a piston, wherein the self-sizing device is structured to cause the piston to apply force to the therapeutic formulation when the expandable component expands, the force being designed to release the therapeutic formulation from the device.

9. A system for delivering pharmaceutical products, A self-sizing device comprising an expandable component configured to expand by expansion, which includes at least one non-conformable section structured to resist deformation in the expanded configuration, wherein the expandable component further includes at least one conformable section structured as a hinge that is easily deformable and allows deformation in the expanded configuration, and the pre-expandable component is structured to bend around the hinge upon expansion by expansion to fit the inner circumference of a lumen within a selected range, The aforementioned formulation, A system comprising: a delivery mechanism, the self-sizing device being structured to apply force to the formulation when the expandable components expand, the force being designed to release the formulation from the self-sizing device.

10. The system according to claim 9, further comprising a capsule in which the expandable component is disposed, wherein the expandable component is in a folded and / or rolled arrangement while inside the capsule and is structured to unfold and / or unroll when released from the capsule.

11. The system according to claim 10, wherein the expandable component is further structured to expand to a maximum circumference if there is no restraining force, and to less than a maximum circumference if there is a restraining force, after being released from the capsule.

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

13. The system according to any one of claims 9 to 12, wherein the hinge has a width or circumference smaller than the width or circumference of each of the non-adaptive 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 according to any one of claims 9 to 14, wherein the expandable component comprises at least two of the non-adaptive sections.

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

17. The system according to 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 when the expandable component is expanded.

18. A self-sizing device used for delivering therapeutic formulations into the internal lumen of a target body, The device further comprises an expandable component configured to expand by expansion, comprising the therapeutic formulation and at least one non-conformable section structured to resist deformation in an expanded configuration, the expandable component further comprises at least one conformable section structured as a hinge that is easily deformable and allows deformation in an expanded configuration, the expandable component is structured to bend around the hinge when expanded to fit the inner circumference of the lumen of the body of the object within a selected range.

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

20. The device according to claim 18, wherein the device is configured to be administered by manually inserting it into the lumen of the body of the target.

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