Self-dimensioning device for delivery of formulation to lumen wall

Abstract

The present application relates to a self-dimensioned device for delivering a formulation to a lumen wall. A system for delivering a therapeutic agent into a lumen is provided. In one embodiment, a system includes a custom-sizing device including an expandable assembly including at least one non-compliant section configured to resist deformation in an expanded configuration, the expandable assembly further including at least one hinge configured to couple the at least one non-compliant section to the at least one non-compliant section to the at least one non-compliant section to the at least one non-compliant section. The at least one hinge is configured to allow deformation in an expanded configuration, and the expandable assembly is configured to bend around the hinge to accommodate the inner circumference of the lumen upon expansion independent of the inner circumference of the lumen within a selected range. The system includes a therapeutic formulation and a delivery mechanism. The self-sizing device is configured to cause the delivery mechanism to apply a force to the therapeutic formulation when the expandable assembly is expanded, the force being designed to expel the therapeutic formulation from the self-sizing device. The self-sizing device may be disposed within the capsule.

Description

[0001] This application is a divisional application of an application with a filing date of September 30, 2020, application number 202080078229.0, and invention name “Self-sizing device for delivering preparations to lumen walls”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to and the 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 GASTROINTESTINAL TRACT,” which is incorporated herein by reference in its entirety for all purposes. Background Art

[0004] It may be desirable to deliver a material or formulation (e.g., a fluid, slurry, powder, or solid) into a lumen, and it may also be desirable to deliver the material at or within 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 be unpredictable and / or variable together, making it challenging to select a device that effectively delivers a material at or within the inner wall of any given lumen.

[0005] An example of delivery into the lumen of an animal body is delivery of a therapeutic agent into the lumen of the gastrointestinal tract. Because the active agent in the therapeutic agent fails to enter the gastrointestinal wall and therefore fails to reach the vascular system, or because gastric juice or other liquids or substances in the gastrointestinal tract destroy the active agent in the gastrointestinal tract, etc., delivering the therapeutic agent by means of a pill dissolved in the gastrointestinal tract is ineffective for many therapeutic agents. In order to address these problems, some oral delivery devices have been developed, which are designed to be activated in the gastrointestinal tract to deliver the therapeutic agent to the gastrointestinal wall to reach the vascular system. The obstacles faced by such devices include unpredictability and variability between several lumens of the gastrointestinal tract, unpredictability and variability in a single lumen of the gastrointestinal tract, unpredictability and variability between lumens of different species, and unpredictability and variability between lumens of different objects of the same species. These obstacles challenge the device that will effectively deliver the therapeutic agent to the target delivery site in the gastrointestinal tract and adapt to various lumens of the circumference that may be encountered at the target delivery site.

[0006] Similar challenges arise in other lumens in the animal body, and in other types of lumens in general. Summary of the invention

[0007] Embodiments of the present disclosure provide devices, systems, and methods for delivering agents to a lumen wall independent of the lumen's inner circumference.

[0008] In one aspect, a self-sizing device for delivering a therapeutic agent includes a capsule sized and configured to be orally ingestible, and an expandable component disposed within the capsule. The expandable component includes at least one non-compliant segment configured to resist deformation in an expanded configuration, and at least one hinge configured to allow deformation in the expanded configuration. The expandable component is configured to expand within a lumen independently of an inner circumference within a selected range and bend about a hinge to conform to the inner circumference of the lumen.

[0009] In an embodiment, the selected range is about 50 mm to about 150 mm.

[0010] In an embodiment, the selected range is from about 5 mm to about 500 mm.

[0011] In an embodiment, the expandable component is in a folded and / or rolled arrangement when in the capsule and is configured to unfold and / or roll out when released from the capsule to expand to a maximum circumference in the absence of a restraining force and to less than the maximum circumference in the presence of a restraining force.

[0012] In an embodiment, the width or circumference of the hinge is smaller than the corresponding width or circumference of the non-compliant section.

[0013] In embodiments, the lumen is the lumen of the small intestine.

[0014] In an embodiment, the expandable component includes at least two non-compliant sections.

[0015] In an embodiment, the expandable assembly comprises at least two hinges.

[0016] In embodiments, the self-sizing device further comprises a therapeutic agent and a piston, and the self-sizing device is configured such that upon expansion of the expandable component, the piston applies a force to the therapeutic agent designed to expel the therapeutic agent from the device.

[0017] In one aspect, 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, the expandable component including at least one non-compliant section, the at least one non-compliant section being configured to resist deformation in an expanded configuration, and at least one hinge, the at least one hinge being configured to allow deformation in an expanded configuration. The expandable component is configured to bend around the hinge to adapt to the inner circumference of the lumen when expanded, independent of the inner circumference of the lumen within a selected range. The self-sizing device is configured to cause the delivery mechanism to apply a force to the formulation when the expandable component is expanded, the force being designed to expel the formulation from the self-sizing device.

[0018] In an embodiment, the system further comprises a capsule in which the expandable component is disposed. When in the capsule, the expandable component is in a folded and / or rolled arrangement and is configured to unfold and / or spread out when released from the capsule.

[0019] In an embodiment, the expandable component is further configured to expand to a maximum circumference in the absence of a restraining force and to less than the maximum circumference in the presence of a restraining force after being released from the capsule.

[0020] In embodiments, the self-sizing device is configured to be placed in the gastrointestinal tract and the selected range is about 50 mm to about 150 mm.

[0021] In an embodiment, the width or circumference of the hinge is smaller than the corresponding width or circumference of the non-compliant section.

[0022] In embodiments, the lumen is the lumen of the small intestine.

[0023] In an embodiment, the expandable component includes at least two non-compliant sections.

[0024] In an embodiment, the expandable assembly comprises at least two hinges.

[0025] In embodiments, the delivery mechanism comprises a piston, and the self-sizing device is configured such that the piston applies a force to the formulation when the expandable component is expanded.

[0026] In one aspect, a method for delivering a therapeutic agent includes providing a self-sizing device including a therapeutic agent, the self-sizing device also including an expandable component, the expandable component including at least one non-compliant segment, the at least one non-compliant segment being configured to resist deformation in an expanded configuration, and at least one hinge, the at least one hinge being configured to allow deformation in the expanded configuration. The expandable component is configured to bend around the hinge to conform to the inner circumference of the lumen when expanded, independent of the inner circumference of the lumen within a selected range. The method also includes providing instructions for placing the self-sizing device in vivo to deliver the therapeutic agent into the lumen.

[0027] In embodiments, the instructions include instructions for swallowing the self-sizing device.

[0028] In embodiments, the instructions include instructions for manually inserting the self-sizing device into the lumen. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 , Figure 2 , Figure 3 and Figure 4 Each shows an example of an embodiment of an expandable assembly having at least two non-compliant sections and at least one hinge.

[0030] Figure 5A , Figure 5B , Figure 5C , Figure 5D , Figure 5E and Fig. 5F Each shows an example of an embodiment of an expandable component having at least two non-compliant sections and at least one hinge.

[0031] Figure 6 An example of an embodiment of an expandable assembly having at least two non-compliant sections and at least two hinges is shown.

[0032] Fig. 7A and Figure 7B An example of an embodiment of an expandable assembly having at least one non-compliant section and at least two hinges is shown.

[0033] Fig. 8A and Figure 8B An example of an embodiment of an expandable assembly having at least two non-compliant sections and at least two hinges is shown.

[0034] Fig. 9A and Fig. 9B Each shows an example of an embodiment of a capsule structure.

[0035] Fig. 10A Examples of embodiments of an expandable component prior to being folded and / or rolled up are shown, as well as examples of embodiments of a capsule.

[0036] Fig. 10B Shows that Fig. 10A The expandable component of the embodiment in which the expandable component is in a folded and / or rolled arrangement before being disposed in the capsule.

[0037] Fig. 10C The diagram shows the Fig. 10B in a folded and / or rolled arrangement and arranged in a capsule Fig. 10A expandable component.

[0038] Fig.11A , Fig. 11B and Fig. 11C An example of an embodiment of the device is shown as a swallowable device is passed through a lumen, the device comprising an expandable component within a degradable capsule.

[0039] Fig.11D , Fig.11E and Fig.11F The expandable component is shown as it expands within the lumen. Fig. 11C Progress of the expandable component in a rotating view.

[0040] Fig.12 An example of an embodiment of a self-sizing device including an expandable component in a fully expanded state within a lumen is shown.

[0041] Fig.13A An example of an embodiment of a self-sizing device comprising an expandable component having one non-compliant section and no hinge is shown.

[0042] Fig. 13B An example of an embodiment of a self-sizing device comprising an expandable component having two non-compliant sections and a hinge is shown. DETAILED DESCRIPTION

[0043] The present disclosure relates to self-sizing devices for delivering a formulation into a lumen.Before discussing the details of the self-sizing devices of the present disclosure, some conventions are provided for the convenience of the reader.

[0044] Various abbreviations may be used herein to represent standard units, such as deciliter (dl), milliliter (ml), microliter (μl), international unit (IU), centimeter (cm), millimeter (mm), nanometer (nm), inch (in), kilogram (kg), gram (gm), milligram (mg), microgram (μg), millimole (mM), Celsius (°C), Fahrenheit (°F), millitorr (mTorr), hour (hr), or minute (min).

[0045] When used in the present disclosure, the terms "eg," "such as," "for example," "for an example," "for another example," "examples of," "by way of example," and "etc." mean a list of one or more non-limiting examples preceding or following; it should be understood that other examples not listed are also within the scope of the present disclosure.

[0046] As used herein, the singular terms "a / an" and "the" may include plural referents unless the context clearly indicates otherwise. Unless explicitly stated otherwise, reference to an object in the singular is not intended to mean "one and only one" but rather "one or more."

[0047] The term "in an embodiment" or variations thereof (e.g., "in another embodiment" or "in an embodiment") refers herein to use in one or more embodiments, and in no case limits the scope of the present disclosure to only the embodiments shown and / or described in the figures. Thus, components shown and / or described herein with respect to an embodiment may be omitted or may be used in another embodiment (e.g., in another embodiment shown and described herein, or in another embodiment within the scope of the present disclosure and not shown and / or described herein).

[0048] The term "component" refers to an item in a group of one or more items in this article, which together constitute the device, preparation or system in question. Components can be solid, powder, gel, plasma, fluid, gas or other structures. For example, a device can include a plurality of solid components assembled together to constitute the device, and can also include a fluid component arranged in the device. For another example, a preparation can include two or more powders and / or fluid components, which are mixed together to prepare a preparation.

[0049] The term "design" or grammatical variations thereof (e.g., "designing" or "designed") refers herein to estimates based on, for example, tolerances (e.g., component tolerances and / or manufacturing tolerances) and environmental conditions expected to be encountered (e.g., temperature, humidity, external or internal environmental pressures, external or internal mechanical pressures, stresses from external or internal mechanical pressures, product age or shelf life, or, in the case of introduction 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 is understood that actual tolerances and environmental conditions before and / or after delivery will affect the properties, and therefore different components, devices, formulations, or systems with the same design may have different actual values ​​for these properties. Design also includes changes or modifications before or after manufacture.

[0050] The term "manufacture" or its grammatical variations (e.g., "manufacturing" or "manufactured") in connection with a component, device, formulation, or system refers herein to the manufacture or assembly of a component, device, formulation, or system. Manufacturing can be performed in whole or in part by hand and / or in whole or in part in an automated manner.

[0051] The term "structured" or its grammatical variations (e.g., "structure" or "structuring") as used herein refers to a component, device, formulation or system manufactured according to a concept or design, or variations or modifications thereto (whether such changes or modifications occur before, during or after manufacture), whether or not such concept or design is recorded in written form.

[0052] The term "body" as used herein refers to the animal body.

[0053] The term "subject" herein refers to the body into which embodiments of the present disclosure are delivered or intended to be delivered. For example, in the case of humans, a subject may be a patient being treated by a healthcare professional.

[0054] The term "fluid" herein refers to a liquid or a gas, and includes water and moisture. The term "fluid environment" herein refers to an environment in which one or more fluids are present.

[0055] The term "biological matter" as used herein refers to blood, tissues, body fluids, enzymes, interstitial fluids, and other secretions of the body. The term "digestive matter" as used herein refers to biological matter along the gastrointestinal (GI) tract of an animal, as well as other matter that passes through the GI tract (e.g., food in an undigested or digested state, such as chyme).

[0056] The term "ingest" or grammatical variations thereof (e.g., "ingestign" or "ingested") refers herein to ingestion into the stomach, whether by swallowing or by other means of deposition into the stomach (e.g., endoscopic deposition into the stomach or deposition into the stomach through a port).

[0057] The term "lumen" herein refers to the interior space of a tubular structure. Examples of lumens in the body include arteries, veins, and tubular cavities within organs.

[0058] The term "luminal wall" refers to the wall of a lumen, wherein the wall includes all layers from the inner circumference to the outer circumference of the lumen, for example, in the case of a lumen in the body, the mucosa, submucosa, muscularis, serosa, and outer wall of the lumen, as well as constituent blood vessels and tissues.

[0059] The term "gastrointestinal tract" or "GI tract" refers herein to the body's ingestion / excretion system including, for example, the mouth, pharynx, esophagus, stomach, pylorus, small intestine, cecum, large intestine, colon, rectum, anus, and valves or sphincters therebetween.

[0060] 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.

[0061] The term "preparation" refers to a formulation comprising one or more components in this article. A preparation can be composed of a fluid, a slurry, a powder or a solid (e.g., in a concentrated or combined form, such as a tablet or microtablet). Each preparation can include one or more components, and a device or system can include one or more preparations.

[0062] The term "therapeutic agent" as used herein refers to an agent intended for therapeutic, diagnostic or other biological purposes. The components of a therapeutic agent can be, for example, a pharmacologically active agent, a DNA or siRNA transcript, a cell, a cytotoxic agent, a vaccine or other prophylactic agent, a nutrient, a vasodilator, a vasoconstrictor, a delivery enhancer, a delay agent, an excipient, a diagnostic agent, or a substance for cosmetic enhancement.

[0063] The pharmacologically active agent can be, for example, an antibiotic, a nonsteroidal anti-inflammatory drug (NSAID), an angiogenesis inhibitor, a neuroprotectant, a chemotherapeutic agent, a peptide, a protein, an immunoglobulin (e.g., a TNF-α antibody), an interleukin in the IL-17 interleukin family, 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.

[0064] The cell can be, for example, a stem cell, a red blood cell, a white blood cell, a neuron or other living cell. The cell can be produced by a living organism or produced by a living organism or contain a component of a living organism. The cell can be allogeneic or autologous.

[0065] For example, the vaccine may be against influenza, coronavirus, meningitis, human papillomavirus (HPV) or varicella. The vaccine may correspond to an attenuated virus.

[0066] The nutrient 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.

[0067] The vasodilator may be, for example, L-arginine, sildenafil, a nitrate (eg, nitroglycerin), or epinephrine.

[0068] The vasoconstrictor may be, for example, a stimulant, an amphetamine, an antihistamine, or epinephrine.

[0069] Delivery enhancers can be, for example, penetration enhancers, enzyme blockers, peptides that penetrate through the mucosa, antiviral drugs such as protease inhibitors, disintegrants, super disintegrants, pH regulators, surfactants, bile salts, fatty acids, chelating agents or chitosan. For example, delivery enhancers can be used as delivery media for delivering components of therapeutic preparations, or for improving the absorption of components of therapeutic preparations in vivo. Delivery enhancers can start intestinal epithelium (for example, fluidizing the outer layer of cells) to improve absorption and / or bioavailability of one or more other components included in the delivery device.

[0070] The delay 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 delay agent can include one or more other components in the therapeutic formulation (e.g., to mix or provide structure) to slow the release rate of the other components from the therapeutic formulation.

[0071] Excipients can be, for example, binders, disintegrants, super disintegrants, buffers, antioxidants or preservatives. Excipients can provide a medium for the components of the therapeutic formulation (e.g., to aid in manufacturing), or maintain the integrity of the components of the therapeutic formulation (e.g., after ingestion during manufacturing, during storage, or before dispersion in the body).

[0072] The diagnostic agent can be, for example, a sensor agent, a contrast agent, a radionuclide, a fluorescent substance, a luminescent substance, a radiopaque substance, or a magnetic substance.

[0073] The term "degrade" or its grammatical variants (e.g., "degrading," "degraded," "degradable," and "degradation") herein refers to weakening, partial degradation, or complete degradation, such as by dissolution, chemical degradation (including biodegradation), decomposition, chemical modification, mechanical degradation, or disintegration, which also includes, but is not limited to, dissolution, fragmentation, deformation, shrinkage, or contraction. The term "non-degradable" means that the expected degradation will be minimal, or within some acceptable design percentage, for at least the expected duration in the expected environment.

[0074] As used herein, the terms "substantially" and "about" are used to describe and illustrate small variations. When used in conjunction with a numerical value, the terms may refer to a range of variation of less than or equal to ±10% of the numerical value, such as less than or equal to ±5%, less than or equal to ±4%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1%, less than or equal to ±0.5%, less than or equal to ±0.1%, or less than or equal to ±0.05%.

[0075] As used herein, a numerical range includes any number within the range, or any subrange in which the minimum and maximum numbers in the subrange fall within the range. Thus, for example, "<9" may refer to any number less than 9, or any subrange of numbers in which the minimum value of the subrange is greater than or equal to 0 and the maximum value of the subrange is less than 9. Ratios may also be presented in this article in a range format. For example, a ratio within the range of about 1 to about 200 should be understood to include the explicit enumerated limits of about 1 and about 200, but also includes 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.

[0076] The discussion of self-sizing devices is now continued. Embodiments of the present specification provide devices, systems, and methods of manufacture for self-sizing devices.

[0077] In embodiments, the self-sizing device is a device designed to deliver a therapeutic agent at or into the lumen wall. In embodiments, the self-sizing device is an ingestible device designed to deliver a therapeutic agent at or into the lumen wall of the GI lumen; such devices may be delivered within a capsule.

[0078] The self-sizing device includes a component configured to expand, which for convenience is hereinafter referred to as an "expandable component". The self-sizing device includes at least one expansion module that, when triggered, causes the expandable component to expand from a first unexpanded configuration to a second expanded configuration.

[0079] The expandable component includes a plurality of segments. In the expanded configuration of the expandable component, at least one of the segments is non-compliant and at least one of the segments is compliant. Compliant refers to a state in which a segment can be easily deformed, while non-compliant refers to a state in which a segment resists deformation.

[0080] In the absence of restraint, each segment will expand to a fully extended state and the expandable component will reach its maximum size, which may depend on, for example, the materials used to form the expandable component and / or the capacity of the expansion module implemented (e.g., for expansion by inflation, the maximum size may be limited by the inflation force available from the expansion module, or by the stretch factor of one or more materials of the expandable component).

[0081] Each compliant segment operates in a manner similar to a hinge and will therefore be referred to as a hinge for convenience. In the fully extended state of the expandable assembly (wherein each segment is 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-compliant segment.

[0082] As the expandable component expands, the expandable component will reach a certain shape that reflects the balance between the force applied by the expandable component on the interior of the lumen and the force of the lumen resisting 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 size of the hinge compared to the corresponding size of the non-compliant section, which results in a lower stiffness of the hinge compared to the stiffness of the non-compliant section in the expanded configuration of the expandable component.

[0083] In this manner, the expandable component is expanded until the non-compliant segment (hereinafter referred to as NCS) is pressed against the inner wall of the lumen to maintain the expandable component in a position suitable for delivering the agent to the lumen wall for at least a time sufficient to complete such delivery. The expandable component can then be deflated automatically or manually.

[0084] The expandable component can be removed after deflation, can be left in place to degrade, or can be allowed to pass through the lumen. For example, when used in an application within a GI lumen, the expandable component can be allowed to pass through the GI tract after deflation. The expandable component can be composed of a degradable material such that the expandable component degrades after a designed period of time after exposure to the environment at the target site.

[0085] Self-sizing devices are particularly useful for avoiding delivery being affected by the presence of material in the lumen. For example, the self-sizing device may have the ability to push material out of the way and / or press material against the lumen wall through rapid expansion of the expandable component, thereby expanding to a degree suitable for the delivery technique and the desired delivery rate of the formulation to be delivered without further expansion. For self-sizing devices configured for delivery into the GI lumen, the self-sizing device can accomplish such delivery regardless of whether the subject is in a fed state or a fasted state (that is, such delivery is accomplished regardless of whether there is digestive material in the GI lumen).

[0086] Figures 1 to 4 An example of an embodiment of an expandable component is illustrated in a fully expanded state, wherein the expandable component is expanded without being limited to a maximum size (which may depend on, for example, the material or materials used for the expandable component and the capabilities of the expansion module, etc.). For ease of discussion, an arbitrarily assigned xyz reference frame is indicated, and Figures 1 to 4The inflatable components are shown in the xy reference plane. Each inflatable component includes two NCSs and one hinge in the shown xy plane.

[0087] Referring Figure 1 , the inflatable component 100 includes NCS 105 and NCS 106 separated by hinge 110. In this view of this embodiment, as Figure 1 shown, the dimension x1 of NCS 105 is greater than the dimension x3 of NCS 106, and both x1 and x3 are greater than the dimension x2 of hinge 110. In other words, x1 / x3>1, x1 / x2>1, x3 / x2>1. Additionally, in this view of this embodiment, the dimension y1 of NCS 105 is greater than the dimension y2 of NCS 106. Then, in this view, NCS 105 is taller and longer than NCS 106.

[0088] Generally, the elongated shape of the inflatable component (e.g., inflatable component 100) will result in the inflatable component having a long dimension (e.g., length L) aligned with the central axis of the lumen in which the inflatable component is located.

[0089] In Figure 1 the shown embodiment, because hinge 110 is much narrower than NCS 105 and NCS 106 (x2 << x1 and x2 << x3 respectively), NCS 105 and NCS 106 can bend towards or away from each other around hinge 110 in the xy plane, as indicated by the arrows marked A and B, which can allow the inflatable component 100 to adapt to uneven lumen surfaces and / or inconsistent lumen diameters.

[0090] Referring Figure 2 , the inflatable component 200 includes NCS 205 and NCS 206 separated by hinge 210. In this view, the inflatable component 200 is similar to Figure 1 the inflatable component 100 shown. The dimension x4 of NCS 205 is greater than the dimension x6 of NCS 206, and both x4 and x6 are greater than the dimension x5 of hinge 210; the dimension y3 of NCS 205 is greater than the dimension y4 of NCS 206. However, as Figure 2 shown, x5 is approximately three times x2 as Figure 1 shown; thus, NCS 205 and NCS 206 may have a lesser ability to bend towards or away from each other in the xy plane than NCS 105 and NCS 106 in the xy plane, while still maintaining a certain flexibility to allow the inflatable component 200 to adapt to uneven lumen surfaces and / or inconsistent lumen diameters.

[0091] By comparing Figure 1 and Figure 2As can be seen, the dimensions of a hinge (e.g., hinge 110 or hinge 210) can be designed to have a desired width. The width and other dimensions of an expandable component can be designed, for example, to be suitable for a particular application, to minimize the amount of material used to construct the expandable component, to reduce manufacturing costs, or to increase manufacturing speed.

[0092] refer to Figure 3 , expandable assembly 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, thereby illustrating another variation in size.

[0093] refer to Figure 4 , expandable assembly 400 includes NCS 405 and NCS 406 separated by hinge 410. In this embodiment, dimension x10 of NCS 405 is less than dimension x12 of NCS 406, both x10 and x12 are slightly greater than dimension x11 of hinge 410, and dimension y7 of NCS 405 is approximately twice dimension y8 of NCS 406, thereby illustrating another variation in size.

[0094] Other comparative dimensions of the NCS and hinge are within the scope of the present disclosure. For example, the dimensions of the hinge in the xy plane may be greater than the dimensions of the NCS in this plane. In addition, the dimensions in the z direction may be different within a particular section (NCS or hinge).

[0095] FIG. 5A to FIG. 5F Examples of embodiments of expandable components are shown, such as Figure 1 , Figure 2 , Figure 3 , Figure 4 One or more of the expandable components 100, 200, 300, or 400 may appear as they are rotated (herein, rotated to the yz plane). For ease of reference FIG. 5A to FIG. 5F , the non-compliant sections are referred to as NCS 505 , 506 , and the compliant section is referred to as hinge 510 .

[0096] NCS 505 and NCS 506 can bend toward or away from each other about hinge 510 in the yz plane, which can allow the expandable assembly to accommodate a variety of lumen diameters and shapes.

[0097] like FIG. 5A to FIG. 5FAs can be seen in the , the shape of the expandable component can vary in a rotated (e.g., side) view as well as in an unrotated (e.g., front) view. For example, one (or both) of NCS 505, NCS 506 can have a surface that is substantially flat, slightly rounded, fairly rounded, or other curvature.

[0098] As will be apparent from the above discussion, each of the various segments (each NCS and each hinge) can be designed to have desired absolute dimensions as well as desired dimensions relative to the other segments. For example, a hinge may have a width in the xy plane that is equal to or greater than 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 the particular NCS in the yz plane.

[0099] For some examples of implementations of expandable components see Figures 1 to 4 and FIG. 5A to FIG. 5F It is apparent that, according to the present disclosure, there are a variety of designs for an expandable assembly having two non-compliant sections (NCS) and one compliant section (hinge). In various embodiments, an expandable assembly according to the present disclosure more generally has one or more NCSs and one or more hinges.

[0100] The expandable component of the self-sizing device can be configured to have one or more sections in each of two or more planes. Figure 1 The expandable assembly 100 shown in the first xy plane in FIG. 1 can be configured to have additional NCS and / or hinge segments in the second xy plane so that the expandable assembly 100 forms a Y-shape, an X-shape, or other multi-pronged shape as viewed in the yz plane. The prongs can include one or more NCSs or no NCSs, and / or one or more hinges or no hinges.

[0101] The expandable component may include weakening features to make it more compliant in the articulation area.

[0102] Figure 6An expandable component 600 is shown having two NCSs (NCS 605 and NCS 606) in the perspective shown. The expandable component 600 defines an opening 615, which is shown as an ellipse in this embodiment. In other words, the expandable component 600 includes a weakened feature shown as opening 615. The omission of material in opening 615 leaves two hinges, hinge 610 and hinge 611. The fully extended hinges 610 and 611 each have at least one design dimension (width, length and / or circumference) that is substantially smaller than the corresponding design dimensions of NCS 605 and NCS 606, which provides an increase in the compliance of the hinges 610, 611 relative to the NCS 605, NCS 606. In this embodiment, the expandable component 600 will tend to bend about the hinges 610, 611. The hinges 610, 611 can have similar or different sizes. When rotated to different perspectives, the expandable component 600 can have a variety of shapes, including FIG. 5A to FIG. 5F The shape shown in .

[0103] Fig. 7A and Figure 7B An expandable assembly 700 is shown having a single NCS 705 and two hinges (hinge 710 and hinge 711). Fig. 7A is shown in the xy plane and in Figure 7B 710, 711 are shown in the yz plane in FIG. 7 so that hinge 711 is hidden behind hinge 710. In this embodiment, hinges 710, 711 themselves operate to apply pressure to the inner surface of the lumen while also providing compliance.

[0104] Fig. 8A and Figure 8B An expandable assembly 800 is shown having three NCSs (NCS 805, NCS 806, and NCS 807) and two hinges (hinge 810 and hinge 811). Fig. 8A is shown in the xy plane and in Figure 8B 806 .

[0105] As from Fig. 7A and Fig. 8A As can be seen in FIG. 1 , expandable assembly 700 and expandable assembly 800 appear similar in the xy plane shown. However, when rotated 90 degrees (e.g., as shown in FIG. 1 , respectively), expandable assembly 700 and expandable assembly 800 appear similar in the xy plane shown. Figure 7B and Figure 8B As shown in the yz plane shown in FIG. 1 , it can be seen that NCS 806 and NCS 807 ( Figure 8B ) expands to have a dimension in the z direction that is substantially larger than the hinges 710 and 711 ( Figure 7B ) of the corresponding size.

[0106] In an embodiment of a self-sizing device according to the present disclosure, an expandable component is disposed within a capsule.

[0107] Fig. 9A and Fig. 9B An example of an embodiment of a capsule is shown. Fig. 9A In the present invention, the capsule 900 includes a cylindrical body 905 and two end caps 910 mounted on or in the body 905. At least one of the three components of the capsule 900 (cylindrical body 905, first end cap 910 and / or second end cap 910) is degradable. The end caps 910 can be adhered or press-fitted on or in the body 905 to hold the end caps 910 in place. Fig. 9B In the embodiment, capsule 950 includes a portion 920 and a portion 921 assembled together. At least one of portions 920, 921 is degradable. Portions 920, 921 may be adhered or press-fitted together. Examples of capsule sizes include 000, 00, and 0 capsule sizes. Shapes different from Fig. 9A , Fig. 9B Capsules of the shapes shown in may also be used, such as spherical or oval, 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., egg-shaped), or shapes having at least one flat side.

[0108] In embodiments, the self-sizing device comprises a degradable coating on the expandable component and / or on the capsule when a capsule is included.

[0109] In an 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 may degrade under certain conditions to expose one or more degradable components of the self-sizing device. Subsequently, one or more degradable components degrade after exposure, such as causing the expansion of the expandable component, or in an embodiment where a gas is used to expand the expandable component, the gas is released and the expandable component is deflated after the delivery of the formulation.

[0110] The coating on the expandable device and / or capsule can be or include an opaque material (e.g., so that the contents are not visible), a colored material (e.g., to provide color coding for identifying the formulation contained in the self-sizing device), and / or a material including a noticeable taste or odor (e.g., an undesirable taste or odor to discourage interest, or a desired taste or odor to stimulate interest), each of which dissolves or degrades sufficiently to allow the self-sizing device to deliver the formulation to the target delivery site.

[0111] All or part of the coating and / or capsule may be designed to degrade after a certain length of time under conditions expected at the target site, such as after a designed period of time after placement, or in the presence of a specific chemical, or at certain values ​​or ranges of pH, temperature, or pressure applied to the capsule, or a combination of the foregoing. In an embodiment, the capsule is designed to rupture upon an external trigger, such as a wirelessly transmitted trigger that causes a mechanism within the capsule to tear or destroy the capsule.

[0112] As noted, embodiments of self-sizing devices according to the present disclosure can be used to deliver therapeutic agents to or in the GI luminal wall by ingestion (e.g., by manual positioning or by swallowing the self-sizing device). The self-sizing device may include a capsule. The self-sizing device may include a coating (e.g., as described above) on the capsule and / or expandable component, which is designed to degrade at a specific location in the GI tract (e.g., in the stomach or intestine). In an embodiment, all or part of the capsule and / or coating is designed to degrade after a certain length of time in the presence of a specific chemical substance or under conditions expected at a target site in the GI tract (e.g., at certain values ​​or ranges of pH, temperature, or pressure applied to the capsule, or a combination of the foregoing). In an embodiment, the coating includes a material that improves swallowability, such as guar gum or xanthan gum.

[0113] FIG. 10A to FIG. 10C An example of assembling a self-sizing device 1050 is shown. Fig. 10A An embodiment of an expandable component 1000 and an embodiment of a capsule 1010 are shown. The outer dimension of the expandable component 1000 can be several times larger than the inner dimension of the capsule 1000. For example, the longest dimension of an embodiment of the expandable component 1000 can be two to five times the inner length of the capsule 1010. Other ratios of the outer dimension of the expandable component to the inner dimension of the capsule are within the scope of the present disclosure. Fig. 10B The expandable assembly 1000 is shown folded and / or rolled into an arrangement 1001 that is smaller than the interior dimensions of a capsule 1010. As shown, the arrangement 1001 is folded and / or rolled in this embodiment in a complex arrangement in the style of origami. Fig. 10C An arrangement 1001 disposed in a capsule 1010 and an assembled capsule 1010 (e.g., Fig. 9A wherein the end cap 910 is mounted on or in the body 905, or as Fig. 9B , where portions 920, 921 are assembled together). Device 1050 includes expandable component 1000 (in arrangement 1001) and capsule 1010, and may include other components not shown, such as an inflation module, a delivery component, one or more coatings, and a deflation valve.

[0114] FIG. 11A to FIG. 11F An example of how the device 1050 may be provided to a target delivery site in the GI tract and the expandable component 1000 may be positioned to deliver the therapeutic agent into the lumen wall 1111 of the GI lumen 1110 is shown. Return to Reference FIG. 11A to FIG. 11C , the device 1050 is shown from a perspective generally perpendicular to the direction of travel of the device 1050 (indicated by the arrow), and FIG. 11A to FIG. 11C The device 1050 in FIG. 1 is shown as if looking into the lumen 1110 (e.g., with FIG. 11A to FIG. 11C The viewing angle is approximately 90 degrees).

[0115] Fig.11A Device 1050 is shown within lumen 1110, shown in a relaxed state (e.g., between peristaltic contractions). 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 is passed through lumen 1110, for example, by manipulation of peristalsis, fluid dynamics, and / or gravity.

[0116] Fig. 11B The capsule 1010 is shown degrading (or being triggered to rupture or degrade) as the device 1050 continues through the lumen 1110 after reaching the designed target site or after encountering conditions (e.g., pH) representative of the designed target site. 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., one that has been marked or has a known or perceived condition to be treated).

[0117] Fig. 11C It is shown that after (or concurrently with) the degradation of the capsule 1010, the expandable assembly 1000 begins to unfold from its folded and / or rolled arrangement.

[0118] Fig.11D The expandable assembly 1000 is shown mostly deployed, and Fig.11E Expandable assembly 1110 is shown while expanded (eg, by an expansion module).

[0119] Fig.11FThe expandable component 1000 is shown after expansion. In this embodiment, if not constrained by the lumen 1110, the expandable component 1000 will be able to expand until the reference line 1120 is approximately straight. However, the lumen 1110 applies a force to 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) and position the expandable component 1000 to deliver the therapeutic agent at or into the lumen wall. The hinge 1002 may also press against the lumen wall. In an embodiment, peristalsis may cause the expandable component 1000 in its expanded state to move through the lumen 1110. In an embodiment, the expandable component 1000 may have sufficient internal pressure (combined with surface tension) to firmly hold the expandable component 1000 in approximately the same position, even during peristalsis. In an embodiment, the expandable component 1000 includes surface roughness or surface protrusions to help maintain the position of the expandable component 1000.

[0120] The expansion of the expandable component can be accomplished by any suitable expansion module. In an embodiment, a spring mechanism is released from a compressed state to unfold a filler of a solid or soft material to push outward and thereby expand the expandable component. In an embodiment, two or more reactants are mixed together to form a gas and thereby expand the expandable component. In an embodiment, the material burns quickly to produce a gas and thereby expands the expandable component. Other expansion modules are also within the scope of the present disclosure.

[0121] Fig.12 A lumen 1200 is shown in which a self-sizing device 1210 including an expandable component 1250 is positioned. In this embodiment, the force of the lumen 1200 against the expandable component 1250 is insufficient to substantially bend the hinge 1251 of the expandable component 1250, and thus the expandable component 1250 is in a substantially fully extended state. In other words, the bending of the hinge 1251 of the expandable component 1250 is negligible at this location in this lumen 1200.

[0122] The expandable component 1250 expands by generating gas and includes a valve 1255 to release gas from within the expandable component 1250 into the lumen 1200 to deflate the expandable component 1250. The valve 1255 may include one or more components. In an embodiment, the valve 1255 is a pinch valve that degrades in the presence of a fluid (e.g., a biological substance) to expose a port or opening defined by the expandable component 1250. In an embodiment, the valve 1255 is a piece of material or coating on a port or opening in the expandable component 1250, and the piece of material or coating is designed to degrade within a period of time after the expandable component 1250 delivers the therapeutic agent. In an embodiment, the valve 1255 is opened manually.

[0123] The therapeutic agent (or agents) can be stored in any configuration (e.g., as a solid, fluid, slurry, or powder) within the expandable component 1250. The therapeutic agent can be delivered in any configuration (e.g., as a solid, fluid, slurry, or powder). In an embodiment, two or more components of the therapeutic agent are mixed within the expandable component 1250 prior to delivery. In an embodiment, the expandable component 1250 includes an inlet, such as inlet 1260, defining an opening 1261 through which the therapeutic agent is delivered.

[0124] In an embodiment, the therapeutic agent is passively released such that the therapeutic agent is applied to the inner surface of lumen 1200 (e.g., for absorption through the mucosa); in such embodiments, the therapeutic agent can be released through an inlet (e.g., inlet 1260), or can be released through multiple holes (not shown) in expandable component 1250 that are exposed by expansion of expandable component 1250, created during expansion, or exposed by degradation of a coating on the holes.

[0125] In an embodiment, the therapeutic agent is actively released such that the therapeutic agent is forced out of the expandable component 1250 and through one or more layers of the lumen 1200 or beyond (e.g., into or through the mucosa, through the submucosa, through the muscularis, 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 embodiments, the therapeutic agent can be released through one or more inlets (e.g., inlet 1260) or through one or more holes (not shown) in the expandable component 1250 that are exposed by the expansion of the expandable component 1250, created during expansion, or exposed by degradation of a coating on the holes.

[0126] The therapeutic agent can be forced out of the expandable component 1250 by a delivery mechanism. For example, for a solid composition (e.g., in the form of a tablet, pill, or tip), the therapeutic agent can be expelled by a spring mechanism that is released to quickly expel the solid composition from the expandable component 1250, or by way of a piston mechanism, where the piston is moved by a spring mechanism or gas expansion to quickly push the solid composition out of the expandable component 1250. For example, for a fluid, slurry, or powder of the therapeutic agent, the bladder can be squeezed to force the fluid, slurry, or powder out of the expandable component 1250.

[0127] In an embodiment, the surface of the expandable component 1250 through which the therapeutic agent is delivered contacts the wall of the lumen 1200 along a stretch of approximately 5 mm to 20 mm.

[0128] In an embodiment, the therapeutic agent is delivered from the expandable component 1250 from or along multiple surfaces.

[0129] Fig.13A An embodiment of a self-sizing device 1300 is shown that includes an expandable component 1305 that includes one NCS 1310 and no hinges. Fig. 13B An embodiment of a self-sizing device 1350 is shown that includes an expandable component 1355 that includes two NCSs (NCS 1360 and NCS 1361) and a hinge 1365 therebetween. With respect to these embodiments, the width W1 of the expandable component 1305 is similar to the width W2 of the expandable component 1355, while the height H1 of the expandable component 1305 is less than the height H2 of the expandable component 1355.

[0130] Due to the non-compliance of NCS 1310, multiple devices 1300 ( Fig.13A ) will have substantially the same maximum circumference (in the yz plane) of NCS 1310 when fully inflated in a lumen, such that expandable assembly 1305 cannot significantly accommodate a variety of different lumen circumferences. Thus, devices 1300 of different sizes may be suitable for different animal species and / or different subjects within a species. In contrast, multiple devices 1350 ( Fig. 13B ) may not have the same maximum circumference (in the yz plane) when fully inflated in a lumen because each device 1350, even when inflated, will adjust to the size of the lumen being inflated due to the flexibility (non-compliance, bending) of the hinges 1365. The maximum circumference of a device 1350 relative to the lumen refers to the maximum circumference of the shape that the device 1350 assumes within the lumen (e.g., a partially extended shape or a fully extended shape).

[0131] Test device designs similar to the illustrations of devices 1300, 1350 were prepared, and multiple test devices were manufactured based on each test device design. For ease of reference, Fig.13A and Fig. 13B The reference numerals used in the following discussion are used to describe these test devices. For these test devices, the expansion module includes two reactants (sodium bicarbonate and citric acid) and a biodegradable pinch valve 1370 that separates the two reactants. Valve 1370 is designed to degrade the reactants and allow the reactants to mix to produce carbon dioxide, thereby inflating expandable component 1305 and expandable component 1355.

[0132] For the test device, all corresponding inflatable components were constructed of similar materials that did not stretch significantly during inflation.

[0133] Human clinical trials were conducted to compare the percent delivery rates of device 1300 and device 1350 in delivering solid composition formulations into the lumen wall of the human GI tract.

[0134] Three experimental apparatus designs were used, apparatus A, apparatus B, and apparatus C. Apparatus A and apparatus B are similar to apparatus 1300 ( Fig.13A ), while device C is similar to device 1350 ( Fig. 13B Each device in the trial consisted of a capsule ( Fig.13A , Fig. 13B not shown).

[0135] Device A has a maximum circumference (in the yz plane) of approximately 65 mm when fully inflated and unconstrained. Device B has a maximum circumference (in the yz plane) of approximately 68 mm when fully inflated and unconstrained. For clarity, Device A and Device B have similar shapes and similar widths (the width of Device A and the width of Device B are approximately equal to W1), but Device B is taller than Device A (e.g., the height of Device A is equal to H1 and the height of Device B is greater than H1). Device C has a maximum circumference (in the yz plane) of approximately 80 mm when fully inflated and unconstrained.

[0136] When expanded, the internal volume V1 of the expandable component 1305 of device A is approximately 8 cubic centimeters (cc), while the internal volume V2 of the expandable component 1355 of device C is approximately 4cc. The volume reduction of the expandable component 1355 is due in part to the fact that the NCS1360 and NCS1361 of device 1350 each and together have a smaller circumference (in the yz plane) than the NCS1310 of device 1300. Even if the total height H2 of the expandable component 1355 is greater than the total height H1 of the expandable component 1305 of device A, the volume reduction of the expandable component 1355 of device C is also achieved. The greater height of the expandable component 1355 allows deployment in a larger diameter lumen. Compared with the amount of reactants required to achieve the same internal pressure in the expandable component 1305, the smaller volume of the expandable component 1355 allows the amount of reactants required to be reduced.

[0137] In the test device, the delivery mechanism 1375 includes a piston that delivers the therapeutic formulation through the pressure of carbon dioxide against the piston, causing the piston to move rapidly and eject a solid composition of the formulation into the wall of the barrel.

[0138] In the trial device, radiopaque markers are included in the therapeutic agent and elsewhere in the trial device. Imaging is performed in each trial to track the position of the corresponding trial device, to track whether the corresponding expandable component is separated from the capsule, and to track whether the therapeutic agent is delivered into the luminal wall of the small intestine.

[0139] result. Device A delivered the therapeutic agent to 25% of the GI lumen wall in 12 subjects; Device B delivered the therapeutic agent to 50% of the GI lumen wall in 20 subjects; and Device C delivered the therapeutic agent to 80% of the GI lumen wall in 20 subjects. A delivery rate of 25%-50% (e.g., for Device A and Device B) is acceptable, but a delivery rate of 80% (Device C) or more is certainly preferred.

[0140] The trial results indicate that increasing the circumference of the expandable component (Device A compared to Device B) improves the delivery rate in a group of subjects. However, the trial results indicate that the delivery rate in a particular subject may be affected by the maximum circumference (in the yz plane) of the unhinged device, and therefore, for certain treatments, each person may be tested with multiple devices (each with a different maximum circumference) prior to or at the start of treatment to identify which device size is best for that person.

[0141] In contrast, the trial results indicate that a single size and design of an expandable component including a hinge (e.g., Device C) can be successfully used in a high percentage of subjects. It is noteworthy that the results achieved with Device C were achieved using an initial version of the hinge design; it is expected that improvements in the hinge design will result in higher delivery rates.

[0142] It is also noteworthy that multiple batches of self-sizing devices having a structure similar to device 1350 and an expandable component 1355 having a hinge 1365 (e.g., similar to device C), all having the same design and size as expandable component 1355, were tested in various animal experiments, including species including humans, pigs, and dogs, resulting in high delivery rates in each species, even though the intestinal lumen sizes of different species varied significantly; in contrast, for devices having a structure similar to device 1300 but an expandable component 1305 without a hinge, multiple sizes of expandable component 1305 were used in different animal species to accommodate the lumen size of each specific species to avoid discomfort caused by excessive stretching of the intestine.

[0143] For devices similar in structure to device C, it was demonstrated that the delivery rate was consistent regardless of whether the subject was fed or fasted for several hours prior to ingestion of the device.

[0144] Prior to the concept of hinged structures for expandable components, concerns included how many device sizes should be provided and how to determine the appropriate device size for an individual. Clinical trial results indicate that the new concept of adding hinges to expandable components solves these and other problems. A single design of an articulated expandable component according to the present disclosure can deliver a formulation to a lumen within a selected circumferential range of the lumen inner wall at a high delivery rate. In an embodiment, the device is designed to be delivered in the small intestine of a person, and the selection range is about 10 mm to about 100 mm, or about 20 mm to about 80 mm. In an embodiment, a self-sizing device suitable for any different position of the GI tract (e.g., stomach, small intestine, large intestine, colon) of various animal species is designed to have a selection range of about 5 mm to about 500 mm. Other ranges can be selected, and different ranges can be selected for different types of lumens or other types of lumens in the body.

[0145] In an embodiment, the expandable component is designed to have at least one hinge visible from a first viewing angle and multiple hinges visible from a second viewing angle that are rotated from the first viewing angle, so that each of the three or more segments (NCS and / or hinge segments) of the expandable component contacts the lumen in which the expandable component is disposed. This structure can allow the compliance of multiple hinges to adapt the expandable component to a wider range of selected lumen circumferences.

[0146] Another benefit of the design concept using hinges is that the total surface area of ​​the expandable assembly can be reduced compared to expandable assemblies that do not use hinges, while still allowing a single self-sizing device design to be used in applications with a wide variety of lumens, a wide variety of animal species, and a wide variety of subjects within species. Thus, the amount of material may need to be reduced; this reduction in material, as well as the reduction in the number of reactants, may result in cost savings.

[0147] In an embodiment, the expandable component is constructed using one type of material throughout. In an embodiment, the expandable component is constructed using two or more different materials. In an embodiment, the compliance level of the expandable component can be adjusted based on the thickness of the material at certain areas of the expandable component. In an embodiment, the compliance level of the expandable component can be adjusted by adding layers of the same material or different materials in certain areas of the expandable component. Examples of materials that can be used to construct the expandable component include polyester, PET, HDPE, cross-linked polymers, silicone, polyurethane, or other elastomers or polymers.

[0148] In an embodiment, the formulation is in a solid composition. A delivery mechanism (e.g., delivery mechanism 1375) includes a propulsion device (e.g., a piston or rod) that is directly or otherwise operably connected to the solid composition to apply a force on the surface of the solid composition to propel it into the lumen wall. When the expandable component is expanded, the delivery mechanism can be in effective contact with the lumen wall or otherwise closely positioned near the lumen wall so that the solid composition is directly ejected into the lumen wall with minimal or no gap between the surface of the delivery mechanism and the lumen wall, which can improve the delivery rate of the self-sizing device.

[0149] In embodiments, the self-sizing device comprises a solid composition removably coupled to a piston such that after the solid composition is advanced to the lumen wall, the solid composition separates from the piston.

[0150] Specific materials can be selected to give the desired structure and material properties of solid composition (for example, for inserting the column strength of the luminal wall, or for controlling the disintegration of the solid composition and thus controlling the porosity and / or hydrophilicity of the therapeutic preparation release). In an 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 penetration performance of the tip. Once located in the luminal wall, the solid composition can be degraded by the interstitial fluid in the tissue, so that the therapeutic preparation is dissolved and absorbed into the blood flow. The properties of the solid composition can be selected, such as size, shape and chemical composition, to allow the medicine to dissolve and absorb in a few seconds, a few minutes or a few hours. Dissolution rate can be controlled by various excipients, such as disintegrants (for example, starch, sodium starch glycolate or cross-linked polymers such as carboxymethyl cellulose). The selection of disintegrants can be specifically adjusted for the environment in the luminal wall (for example, the average number of blood flow and peristaltic contraction).

[0151] The solid composition can be made entirely of a formulation, or a cavity containing a formulation can be defined. The self-sizing device can include and deliver one or more solid compositions, each of which can contain a formulation that is the same or different from another solid composition. Each solid component can have different properties; for example, two solid compositions can be designed to deliver their respective formulations simultaneously (e.g., two instances of one formulation, or an instance of each of two formulations), or can be designed to deliver their respective formulations at different times (e.g., to provide subsequent doses of the same formulation or to provide subsequent different formulations).

[0152] Although the present disclosure has been described and illustrated with reference to its specific embodiments, these descriptions and illustrations do not limit the present disclosure. It can be clearly understood that various changes can be made and equivalent components can be replaced in the embodiments without departing from the true spirit and scope of the present disclosure defined by the attached claims. Components, characteristics or actions from one embodiment can be easily reorganized or replaced with one or more components, characteristics or actions from other embodiments to form many additional embodiments within the scope of the present invention. In addition, components shown or described as being combined with other components can exist as independent components in various embodiments. In addition, for any positive description of components, characteristics, ingredients, features, actions, steps, etc., the embodiments of the present invention specifically cover components, values, characteristics, ingredients, features, actions, steps, etc. that are not included. Illustrations may not necessarily be drawn to scale. Due to variables in aspects such as manufacturing processes, there may be differences between the artistic reproduction in the present disclosure and the actual equipment. The present disclosure may also have other embodiments that are not specifically described. The specification and drawings are considered to be illustrative rather than restrictive. Modifications can be made to adapt specific situations, materials, material compositions, methods or processes to the goals, spirit and scope of the present disclosure. All these modifications are intended to fall within the scope of the attached claims. Although the methods disclosed herein have been described with reference to specific operations performed in a specific order, it is understood that these operations can be combined, subdivided or reordered into equivalent methods without departing from the teachings of the present disclosure. Therefore, unless otherwise specifically stated herein, the order and grouping of operations do not limit the present disclosure.

Claims

1. A self-sizing device for delivering a therapeutic agent, the device comprising: a capsule sized and configured for oral ingestion; and An expandable component is disposed within a capsule, the expandable component comprising at least one non-compliant segment, the at least one non-compliant segment being configured to resist deformation in an expanded configuration, the expandable component further comprising at least one hinge, the at least one hinge being configured to allow deformation in an expanded configuration, the expandable component being configured to expand within a lumen independently of the circumference of the inner wall within a selected range and to bend about the hinge to accommodate the circumference of the inner wall of the lumen.

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

3. A device according to claim 1, wherein when in the capsule, the expandable component is in a folded and / or rolled arrangement and is configured to unfold and / or spread out when released from the capsule to expand to a maximum circumference in the absence of a restraining force and to less than the maximum circumference in the presence of a restraining force.

4. The device of claim 1, wherein the hinge has a width or circumference that is smaller than a corresponding width or circumference of the non-compliant section.

5. The device of claim 1, wherein the lumen is the lumen of the small intestine.

6. The device of claim 1, wherein the expandable component comprises at least two non-compliant sections.

7. The device of claim 1, wherein the expandable component comprises at least two hinges.

8. The device according to claim 1 further includes the therapeutic agent and a piston, wherein the self-sizing device is configured to cause the piston to apply a force to the therapeutic agent when the expandable component is expanded, and the force is designed to expel the expandable component from the device.

9. A system for delivering a formulation, the system comprising: a self-sizing device comprising an expandable component, the expandable component including at least one non-compliant section, the at least one non-compliant section being configured to resist deformation in an expanded configuration, the expandable component further comprising at least one hinge, the at least one hinge being configured to allow deformation in an expanded configuration, the expandable component being configured to flex about the hinge to conform to the inner circumference of a lumen within a selected range when expanded, independent of the inner circumference of the lumen; preparation; and A delivery mechanism, wherein the self-sizing device is configured such that upon expansion of the expandable component, the delivery mechanism applies a force to the formulation designed to expel the formulation from the self-sizing device.

10. The system of claim 9, further comprising a capsule in which the expandable component is disposed, wherein when in the capsule, the expandable component is in a folded and / or rolled arrangement and is configured to unfold and / or spread out when released from the capsule.

Images