Injection of therapeutic preparations into the wall of the gastrointestinal tract

Abstract

The device includes an inflatable balloon, a reservoir disposed within the inflatable balloon, a needle compartment attached to the balloon and the reservoir, an injection needle disposed within the needle compartment, and an inflation mechanism. The reservoir contains a therapeutic compound. The inflation mechanism is configured to inflate the balloon, such that upon inflation, the injection needle enters the reservoir. The method includes making the automatic injector available to the subject by instructing the subject to ingest the automatic injector. The automatic injector is configured to inject the therapeutic compound into a wall of the gastrointestinal tract of the subject in response to ingestion of the automatic injector. The automatic injector includes an injection needle disposed in a needle compartment attached to the reservoir. The injection needle is initially separate from the reservoir and configured to enter the reservoir to deliver the fluid therapeutic compound through the needle and into the wall.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to each of (i) U.S. Provisional Patent Application No. 62 / 978,222, entitled GASTROINTESTINAL LIQUID AUTOINJECTION, filed February 18, 2020, and U.S. Provisional Patent Application No. 63 / 020,811, entitled LIQUID INJECTION OF A THERAPEUTIC AGENT INTO A WALL OF THE GASTROINTESTINAL TRACT, filed May 6, 2020. The foregoing priority applications are hereby incorporated by reference in their respective entireties for all purposes. [Background technology]

[0002] FIELD OF THE DISCLOSURE Embodiments of the present disclosure relate to the injection of one or more therapeutic formulations into the walls of the gastrointestinal tract. More particularly, embodiments of the present disclosure relate to a swallowable, autonomous delivery device for injecting fluids from a location within the gastrointestinal tract.

[0003] Recent years have seen progress in the development of therapeutic agents for the treatment of a variety of diseases and conditions, many of which require parenteral injection, including many proteins, antibodies, and peptides.

[0004] Parenteral infusion has many disadvantages, including pain of infusion, risk of infection at the infusion site, the need to use aseptic technique during infusion, and the need and associated risks of placing and maintaining an intravenous line in the subject for extended periods of time. Other delivery approaches, such as implantable pumps, have been employed, but these require the semi-permanent implantation of a device, which has many limitations.

[0005] The inability to orally administer many therapeutic agents can occur for a variety of reasons, including poor oral tolerance with complications such as gastric irritation and bleeding, inadequate absorption of the therapeutic agent, or breakdown or degradation of the therapeutic agent compound in the stomach or intestine prior to absorption.

[0006] The delivery of solid doses using ingestible delivery devices has had some success by injecting the solid dose into the wall of the gastrointestinal tract. However, these devices may be limited to delivering a few milligrams of therapeutic agent. Some therapies require significantly higher doses, so the number or frequency of administration events required may make the use of these devices unattractive for convenience, cost, or other reasons.

[0007] Thus, there is a need for additional, alternative, and improved methods, devices, and articles for the oral delivery of therapeutic agents. Summary of the Invention

[0008] Embodiments of the present disclosure include devices, systems, and methods for automatic injection devices (which may be referred to herein as automatic injectors), for manufacturing automatic injectors, and for providing automatic injection of a therapeutic formulation in a fluid form delivered from within the gastrointestinal tract by the automatic injector. In various embodiments, the automatic injector is provided within an oral delivery device. In various embodiments, the automatic injector is provided with a dose of a therapeutic agent sufficient for most therapeutic regimens. For example, the automatic injector can hold up to about 0.5 cubic centimeters (cc) of a therapeutic formulation, which may include up to 200 milligrams (mg) or more of one or more therapeutic agents.

[0009] The automatic injector includes an injection needle. In one embodiment, the needle is sterile. In one embodiment, the injection needle disintegrates after use.

[0010] The power injector incorporates a balloon that is inflated with a gas, which also provides pressure against a reservoir to expel fluid through an injection needle, after which the balloon can be deflated and passed through the gastrointestinal tract until it is expelled from the anus.

[0011] The power injector is housed in an outer shell, such as a capsule, that degrades in whole or in part at or above or below a design threshold, such as degrading at a pH level above 5.5. Breach of the outer shell due to its degradation initiates the injection process, which is accomplished by forcing fluid from the power injector through an injection needle and into the wall of the gastrointestinal tract (e.g., the wall of the lumen of the gastrointestinal tract).

[0012] Further details of these and other embodiments and aspects are more fully described below with reference to the accompanying drawings. [Brief description of the drawings]

[0013] [Figure 1] 1 illustrates an automatic injector device according to one or more embodiments. [Figures 2A-2D] 1 illustrates an additional embodiment of an automatic injector device. [Figure 3A] 2 illustrates an embodiment of the automatic injector device of FIG. [Figure 3B] 2 illustrates the embodiment of the power injector device of FIG. 1 after at least a portion of a collar of a needle compartment of the power injector has disassembled. [Figure 3C] 2 illustrates the embodiment of the automatic injector device of FIG. 1 after the collapsible tube of the needle compartment has been collapsed. [Figure 3D] 2 illustrates the embodiment of the autoinjector device of FIG. 1 during injection of a therapeutic formulation into the gastrointestinal tract. [Figure 4] 1 illustrates an embodiment of a degradable injection needle. [Diagram 5] Illustrated are embodiments of methods of manufacturing an autoinjector device for delivering a therapeutic formulation in fluid form. [Figure 6] Illustrated are embodiments of methods of manufacturing an autoinjector device for delivering a therapeutic formulation in fluid form. [Figure 7] Illustrated are embodiments of methods of manufacturing an autoinjector device for delivering a therapeutic formulation in fluid form. [Figure 8]Illustrated are embodiments of methods of manufacturing an autoinjector device for delivering a therapeutic formulation in fluid form. [Figure 9] Illustrated are embodiments of methods of manufacturing an autoinjector device for delivering a therapeutic formulation in fluid form. [Figure 10] Illustrated are embodiments of methods of manufacturing an autoinjector device for delivering a therapeutic formulation in fluid form. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Embodiments of the present disclosure provide swallowable devices, including autoinjector devices, for delivering therapeutic formulations in fluid form into or through the wall of the gastrointestinal (GI) tract, such as the wall of the stomach, or the wall of the small intestine or other lumen of the digestive tract (the wall of the GI tract may be referred to herein as the "GIW"). In one embodiment, the drug is delivered through the mucosal layer of the GI tract (e.g., through the mucosa into the submucosa, muscle, or serosa). In one embodiment, the drug is delivered through the GIW into the peritoneum or peritoneal cavity.

[0015] The devices, systems, and methods of the present disclosure are suitable for delivering therapeutic formulations to the GIW even when digestive material is present at the delivery site.

[0016] 1 illustrates an autoinjector device ("autoinjector 10") according to one or more embodiments. Autoinjector 10 includes an expandable member in the form of an inflatable balloon 12, a deflation valve 28, a pouch 32, a conduit 34, a first reactant 38 contained within pouch 32, a second reactant 35, a release valve 36, a reservoir 40, a fill port 46 coupled to reservoir 40 via tubing 44, a fluid solution 48 contained in reservoir 40, a needle compartment 50, and an injection needle 100. Autoinjector 10 is an automated injection device capable of delivering one or more therapeutic formulations in fluid form upon inflation of balloon 12.

[0017] 1 does not show an outer shell, such as, in some embodiments, a coating or capsule, a coating on a capsule, or a capsule on a coating. The outer shell initially surrounds the power injector 10.

[0018] In one embodiment, the balloon 12 includes a flexible material selection such that the balloon 12 may be folded when the balloon 12 is not inflated. Prior to adding the outer shell, the balloon 12 may be folded and / or rolled to a suitable size (e.g., a size suitable for disposable use in a 00 size capsule). In one embodiment, the outer shell includes a capsule and the balloon 12 is folded and / or rolled before being placed within the capsule. In one embodiment, the outer shell includes a coating and the balloon 12 is folded and / or rolled before being coated.

[0019] The outer shell can protect the autoinjector 10 from the fluid environment until the outer shell degrades. In one embodiment, the outer shell has a shape and composition that degrades at a pH level above about 5.5, which is equivalent to a pH level typically found in the intestinal tract. In one embodiment, the outer shell has a shape and composition that degrades at a pH level below about 5.5, which is equivalent to a pH level typically found in the stomach. Degradation of the outer shell can occur in whole or in part, and can occur in stages. In one embodiment, the outer shell comprises a size 00 capsule, 000 capsule, or other size capsule that degrades in the gastrointestinal tract.

[0020] In one embodiment, the balloon 12 is structured with a material such that the balloon undergoes some stretch during and / or after inflation. In one embodiment, the balloon 12 is structured with a material such that the balloon undergoes minimal or little stretch during and after inflation. The material of the balloon 12 may include multiple layers, where one or more layers provide flexibility and one or more layers provide structure to minimize or prevent stretching of another or other layer. In one embodiment, the balloon 12 includes a material having a first layer of an elastic polymer (e.g., polyethylene), a second layer of nylon mesh, and a third layer of an elastic polymer (e.g., polyethylene), where the nylon mesh is disposed between the elastic polymer layers to minimize stretching of the balloon 12 during and after inflation. The elastic polymer layers may provide for heat staking the edges of the balloon 12 to seal the balloon 12.

[0021] The balloon 12 is inflated by gas produced by mixing a first reactant 38 with a second reactant 35. A pouch 32 containing the first reactant 38 is contained within an interior volume 45 of the balloon 12. The first reactant 38 is retained within the pouch 32 by a constriction, pressure plug, or other sealing device applied to a conduit 34 from a release valve 36. The balloon 12 contains a second reactant 35. In the illustration of FIG. 1, the second reactant 35 is disposed in the bulbous section 22 of the balloon 12 adjacent the conduit 34. In other embodiments, the second reactant 35 is additionally or alternatively located elsewhere within the balloon 12. The conduit 34 is in fluid communication with both the interior volume of the pouch 32 and the interior volume 45 of the balloon 12.

[0022] In one embodiment, the release valve 36 comprises a reactive valve whereby upon contact with a fluid environment (e.g., digestive matter) via the disintegration of the outer shell and subsequent breaching of the fluid in the environment through the surface of the outer shell, the release valve 36 weakens or disintegrates, thereby relieving pressure on the conduit 34. In one embodiment, the pouch 32 is a flexible balloon that is biased to compress as the conduit 34 opens upon release of pressure by the release valve 36, thereby discharging the first reactant 38 through the conduit 34 and into the interior volume 45 of the balloon 12. The first reactant 38 contacts and / or mixes with the second reactant 35 in the interior volume 45. In one embodiment, the two reactants are selected to react to produce a gas to pressurize the interior volume 45, thereby inflating the balloon 12. The first reactant 38 and the second reactant 35 may be selected from a number of different biocompatible materials. In one embodiment, the first reactant 38 includes citric acid and the second reactant 35 includes sodium bicarbonate or potassium bicarbonate, and the combination of the first reactant 38 and the second reactant 35 produces carbon dioxide, which serves to inflate the balloon 12.

[0023] The gas pressurizes the balloon 12, causing it to expand to an inflated state. The balloon 12 is shaped to have a circumference such that the pressure within the balloon 12 aligns the elongate portion 20 of the balloon 12 against tissue at the delivery site (e.g., the GIW).

[0024] The gas that pressurizes and inflates the balloon 12 also exerts pressure against the exterior of the reservoir 40, forcing the fluid within the reservoir 40 through the injection needle 100 and thus out of the power injector 10. As the balloon 12 inflates, pressure is exerted against a high percentage of the surface area of ​​the membrane 42 of the reservoir 40, causing the membrane 42 to be squeezed from many directions simultaneously. This squeezing forces the fluid solution 48 contained in the reservoir 40 into the injection needle 100 and subsequently injected through the injection needle 100 into tissue at the delivery site (e.g., the GIW), as will be described in detail with respect to Figures 3A-3D.

[0025] The term "fluid" as used in this disclosure refers to any solution that exhibits fluid properties or that can otherwise be forced out of the reservoir 40 through the infusion needle 100 by pressure on the exterior surface of the reservoir 40. The fluid may be in the form of, for example, a gas, liquid, colloidal suspension, gel, slurry, nanopowder, or powder. The fluid may include a therapeutic formulation, a hydrating formulation, or other formulation, or a combination of formulations. In one embodiment, the reservoir 40 is configured to contain up to about 0.5 cc of fluid.

[0026] The fluid solution 48 in the reservoir 40 can include a therapeutic formulation. As discussed below, the therapeutic formulation can include one or more therapeutic agents. In one embodiment, the fluid solution 48 includes about 10 mg to about 15 mg of a therapeutic agent. In one embodiment, the fluid solution 48 includes up to about 50 mg of a therapeutic agent (e.g., about 10-40 mg, about 20-30 mg, about 10-50 mg, less than 50 mg, more than 10 mg). In other embodiments, the fluid solution 48 includes up to about 100 mg, up to about 200 mg, or more of a therapeutic agent.

[0027] The fluid solution 48 is propelled from the automatic injector 10 through an injection needle 100. The injection needle 100 is positioned within a needle compartment 50. The needle compartment 50 includes two subassemblies, an upper chamber 60 and a lower chamber 80, which collectively define a cavity for accommodating the injection needle 100. In one embodiment, the cavity is oriented along the longitudinal axis (A n ) The upper chamber 60 and the lower chamber 80 can be one adjacent structure or separate structures, as illustrated in FIG. 1. The embodiment of the power injector 10 illustrated in FIG. 1 utilizes an upper chamber 60 disposed on the exterior surface of the balloon 12 with a lower chamber 80 positioned inside the balloon 12 and inside the membrane 42 of the reservoir 40 and at least partially submerged in the fluid solution 48.

[0028] After the fluid solution 48 has been expelled from the reservoir 40, it may be desirable to deflate the balloon 12 to facilitate movement of the balloon 12 through the gastrointestinal tract towards the rectum, thereby facilitating faster evacuation from the body than would be possible if the balloon 12 remained inflated. A deflation valve 28 is provided to cause deflation of the balloon 12 upon completion of the injection. In one embodiment, the deflation valve 28 includes a reaction valve including a mechanism of action, whereby fluid entering through a breached outer shell opens the deflation valve 28 and releases gas from within the balloon 12. In one embodiment, multiple deflation valves 28 may be included in the autoinjector 10 at various locations on the balloon 12. The deflation valve 28 may be in a form similar to the release valve 36, for example, such that the deflation valve 28 disintegrates to open a channel (not shown) for gas to exit the balloon 12. In another example, the deflation valve 28 may be a degradable cover placed over a hole in the balloon 12 such that gas can exit the balloon 12 through the hole when the cover disintegrates.

[0029] The deflation valve 28 is designed to resist rupture until the infusion of the fluid solution 48 from the reservoir 40 is complete. To ensure resistance to premature rupture of the deflation valve 28, an optional flap 24 may be placed over the deflation valve 28 while the balloon 12 is in a folded (uninflated) state. This provides a barrier to fluid ingress into the deflation valve 28, thus ensuring delay in disassembly and rupture of the deflation valve 28 at least until the balloon 12 is inflated. Inflation of the balloon 12 and corresponding infusion of the fluid solution 48 at the delivery site occurs immediately (e.g., a few seconds) after rupture of the outer shell, such that in one embodiment, delaying rupture of the deflation valve 28 by design and / or by covering the deflation valve 28 with a folded portion of the balloon 12 until the balloon 12 is inflated is sufficient to ensure that deflation occurs after infusion without the use of the flap 24.

[0030] In one embodiment, the flap 24 is taped, tacked, or otherwise adhered to the location 24a while the balloon 12 is folded. When the balloon 12 expands, the attachment of the flap 24 to the location 24a is released by the balloon 12 rolling around its circumference due to the expansion, and the flap 24 rotates along an axis (e.g., A) from the location 24a toward the location shown in FIG. bf ) which exposes deflation valve 28 to the fluid environment of the gastrointestinal tract, which in turn initiates the degradation of deflation valve 28. Once deflation valve 28 has degraded to the extent that gas begins to escape from interior volume 45 of balloon 12, balloon 12 rapidly (e.g., in a matter of seconds or less than a second) significantly deflates and therefore passes more easily through the gastrointestinal tract.

[0031] In FIG. 1, the sizing member 14 is positioned on the opposite side of the hinge portion 16 from the long portion 20 of the balloon 12. In one embodiment, the selected material of the balloon 12 is not significantly stretchable, so that inflation of the balloon 12 creates pressure in the interior volume 45 of the body of the balloon 12, including the long portion 20, and creates pressure in the sizing member 14. Thus, the body of the balloon 12 and the sizing member 14 become largely inflexible (e.g., fairly rigid) when inflated. The hinge portion 16 may remain flexible due to its narrow dimensions (e.g., width, depth, and / or diameter) even when the balloon 12 is otherwise fully inflated.

[0032] Depending on the circumference of the delivery site (e.g., the circumference of the lumen of the digestive tract), the hinge portion 16 may be bThe balloon 12 may remain partially folded (along the periphery of the catheter) or may be fully extended. In this manner, the balloon 12 may self-adjust to the particular dimensions of the delivery site (e.g., the internal dimensions of the gastrointestinal tract of a particular subject) and a single size of balloon 12 may be sufficient for all or many of the disparate subjects (e.g., different sized humans, different genders or ages of subjects, and / or different animal species). In one embodiment, an autoinjector according to the present disclosure is designed to be delivered folded into a 00 size capsule or a 000 size capsule, with the same design being used for dogs, pigs, monkeys, and humans.

[0033] By way of example, if the delivery site is within the gastrointestinal lumen, the outer periphery of the balloon 12 when inflated will press against the tissue surface within the lumen (e.g., the sizing member 14 and elongate portion 20 will press against the inner wall of the lumen) with sufficient force to keep the balloon 12 aligned to the delivery site for a period of time or until deflation. If there is no impediment to its expansion, the balloon 12 will adopt a fully inflated configuration. However, if the balloon 12 encounters resistance during expansion, e.g., because the inner circumference of the lumen is smaller than the maximum fully inflated dimension of the balloon 12, the hinge portion 16 may remain somewhat spread apart (e.g., taking up an arc or bent shape between the sizing member 14 and the body of the balloon 12). In this manner, the same size balloon 12 may be used for a wide range of lumen circumferences, since the balloon 12 will expand to a size sufficient to hold the balloon 12 in place for delivery of the fluid solution 48.

[0034] The sizing member 14 may contact a portion of the GI wall and press the opposite side of the balloon 12 (e.g., the long portion 20, or a portion adjacent to the long portion 20) against another portion of the GI wall. This helps to align and position the needle compartment 50 and the infusion needle 100 in a direction generally perpendicular to the GIW, from which the needle compartment 50 may be actuated to advance the infusion needle 100 into the GIW for delivery of the fluid solution 48.

[0035] The power injector of the present disclosure can take a variety of different physical forms, one of which is illustrated by way of example in Figure 1, and several other forms are illustrated by way of further example in Figures 2A-2D.

[0036] 2A-2D illustrate various embodiments of the power injector 10 of FIG. 1. In FIGS. 2A, 2B, 2C, and 2D, the embodiments of the power injector 10 are referenced as power injectors 10A, 10B, 10C, and 10D, respectively. The embodiments of the balloon 12 are referenced as balloons 12a, 12b, 12c, and 12d, respectively. The embodiments of the sizing member 14 are referenced as sizing members 14a, 14b, 14c, and 14d, respectively. The embodiments of the hinge portion 16 are referenced as hinge portions 16a, 16b, 16c, and 16d, respectively.

[0037] In the power injector 10A of FIG. 2A, the balloon 12a includes an expandable body (having a long portion 20) coupled to a sizing member 14a by a narrower hinge portion 16a. The sizing member 14a is generally smaller than the balloon body to minimize the interior volume of the balloon 12a. The sizing member 14a is large enough so that the sizing member 14a, in conjunction with the main balloon body, can provide alignment / leverage with the lumen wall (e.g., GIW) to hold the balloon 12a in place at the delivery site.

[0038] In the power injector 10B of Figure 2B, balloon 12b includes an expandable main balloon body (having a long portion 20) coupled to a sizing member 14b by a hinge portion 16b. Sizing member 14b is similar in size to the main balloon body.

[0039] In the power injector 10C of FIG. 2C, the balloon 12c includes an expandable main balloon body (having a long portion 20) coupled to a sizing member 14c by a hinge portion 16c having an opening 17 to minimize the interior volume of the balloon 12 while providing a surface area for alignment / leverage with the lumen wall (e.g., GIW).

[0040] In the power injector 10D of Figure 2D, the balloon 12d includes an expandable main balloon body (having a long portion 20) and a pair of sizing members 14d. The pair of sizing members 14d may provide positioning for uneven inner circumferences of the delivery site and / or may provide improved alignment / leverage with the lumen wall (e.g., GIW).

[0041] Figures 3A-3D illustrate enlarged cross-sectional views of a portion of the power injector 10 of Figure 1, generally indicated by the dotted box in Figure 1 marked "3A-3D." The enlarged views include needle compartment 50 and reservoir 40 having an interior volume 49 filled with fluid solution 48. The power injector 10 is illustrated in Figures 3A-3D during various stages of deployment.

[0042] 3A illustrates the needle compartment 50 disposed adjacent to the GIW after degradation of the outer shell or capsule and after inflation of the balloon 12. Inflation of the balloon 12 can occur quickly (e.g., within a few seconds) after the power injector 10 is exposed to a fluid environment, and inflation can be rapid (e.g., less than a second) after the release valve 36 is ruptured, releasing the first reactant 38 within the balloon 12.

[0043] The upper chamber 60 of the needle compartment 50 includes a collar 62 and a collapsible tube 64. The collar 62 and the collapsible tube 64 protect the injection needle 100 during manufacturing, storage, shipping, handling, and oral delivery of the autoinjector 10. The collar 62 also provides support and protection for the collapsible tube 64 during manufacturing, storage, shipping, handling, and oral delivery of the autoinjector 10. The collar 62 may be disposed (e.g., formed or disposed about) the collapsible tube 64, such as via casting, injection molding, deposition, or other process. The collar 62 is at least partially formed of a degradable material that begins to degrade when fluid contacts the collar 62 after breaching the outer shell surrounding the autoinjector 10. The autoinjector 10 is designed such that the structural integrity and strength of the collar 62 is rapidly and significantly degraded by degradation due to exposure to a fluid environment. In one embodiment, collar 62 is formed from or includes polyvinylpyrrolidone (eg, Polyplasdone™ polymer available from Ashland).

[0044] Collapsible tube 64 includes an upper flange 66 and a lower flange 68, each of which may be integrally formed with or attached to collapsible tube 64. Lower flange 68 provides a surface for collapsible tube 64 to be coupled with balloon 12, such as by adhesive, hot staking, or other attachment.

[0045] Top seal 52 is attached to collapsible tube 64 along the exterior surface of top flange 66. Top seal 52 and collapsible tube 64 together seal the upper extent 70 of cavity 88. In one embodiment, top seal 52 is a thin film of aluminum foil attached to collapsible tube 64 with a biocompatible adhesive or the like or by hot staking.

[0046] The collapsible tube 64, as supported by the collar 62, provides a structure to protect the infusion needle 100. The collapsible tube 64 is constructed to easily collapse under vertical pressure when not supported by the collar 62. For example, the material used to form the collapsible tube 64 may be thin and / or formed in a pattern (e.g., honeycomb, strips, lattice, or herringbone) so as to collapse under pressure.

[0047] The lower chamber 80 of the needle compartment 50 includes a tubular body 82 that extends into the balloon 12 and the reservoir 40. The tubular body 82 includes an upper flange 84 that is structured to bond to the membrane 42 at a boss 86 (e.g., by adhesive, hot staking, or other attachment). The lower chamber 80 includes an inner boss 92 that serves as a stop against the downward movement of the infusion needle 100 by a protrusion 110 on the outer surface of the infusion needle 100. The protrusion 110 extends partially or completely circumferentially around the infusion needle 100 and can be integrally formed with the infusion needle 100 or added to the infusion needle 100. The inner boss 92 extends partially or completely circumferentially around the inner circumference of the tubular body 82. The inner boss 92 and the protrusion 110 are designed such that the movement of the infusion needle 100 through the tubular body 82 of the lower chamber 80 stops when the protrusion 110 encounters the inner boss 92.

[0048] In one embodiment, the lower chamber 80 contains a gasket, O-ring or other elastomeric radial shaft seal 90 having an inner diameter smaller than or at least matching the outer diameter of the infusion needle 100 .

[0049] The bottom surface of the tubular body 82 is covered by a bottom seal 54 that is attached to the tubular body 82. In one embodiment, the bottom seal 54 is a thin film of aluminum foil that is attached to the tubular body 82, such as by adhesive, hot staking, or other attachment.

[0050] The cavity 88 is defined by the upper chamber 60 and the lower chamber 80. The collapsible tube 64, the tubular body 82, the upper seal 52, and the lower seal 54, together with the balloon 12 and the membrane 42, maintain the cavity 88 in a closed environment prior to infusion. Thus, if the needle compartment 50, the infusion needle 100, the reservoir 40, and the balloon 12 are assembled such that the cavity 88 and the infusion needle 100 are initially sterile, the infusion needle 100 can remain sterile within the cavity 88 until the infusion needle 100 is deployed.

[0051] In one embodiment, the cavity 88 is defined primarily by the substantially cylindrical inner surfaces of the collapsible tube 64 of the upper chamber 60 and the tubular body 82 of the lower chamber 80, such that the cavity 88 has a substantially circular perimeter in the cross-section of the needle compartment 50. In other embodiments, the perimeter of the cavity 88 in the cross-section of the needle compartment 50 has a shape other than circular.

[0052] In one embodiment, the tubular body 82 is formed of a polymer such as polyethylene (PE). In one embodiment, the collapsible tube 64 is formed of a polymer such as PE.

[0053] An embodiment of the infusion needle 100 is illustrated in Figures 3A-3D and is also shown alone in Figure 4. In this embodiment, the infusion needle 100 has a tubular shape with a central channel 106 extending between a distal end 104 and a proximal end 108. The distal end 104 terminates in a sharp tip 102 so as to provide a piercing action when ejected from the needle compartment 50. In one embodiment, the sharp tip 102 is formed of the material used in the remainder of the infusion needle 100. In one embodiment, the sharp tip 102 is an insert of a material different from the material of the remainder of the infusion needle 100. For example, the sharp tip 102 can be any hard material, such as metal. In one embodiment, the sharp tip 102 is formed of degradable magnesium. The remainder of the infusion needle 100 can be composed of a degradable material.

[0054] The proximal end 108 of the infusion needle 100 may be angled as shown by dotted line A. Additionally, the outer surface of the proximal end 108 of the infusion needle 100 may be beveled as shown by dotted line B. The angle and bevel can separately and in combination provide a cutting edge for piercing the lower seal 54. The distal end 104 of the infusion needle 100 may be angled as shown by dotted line C and may additionally or alternatively beveled. The angle and bevel can separately or in combination provide a cutting edge for piercing the upper seal 52. The angled distal end 104 and sharp tip 102 also aid in puncturing / penetrating tissue at the delivery site.

[0055] 3A illustrates the initial configuration of the autoinjector 10 prior to disintegration of the collar 62 of the needle compartment 50 due to exposure to fluids in the gastrointestinal tract. At this stage, the outer shell of the autoinjector 10 has disintegrated sufficiently to allow fluids to breach the outer shell and reach the release valve 36 to initiate inflation of the balloon 12. Thus, the top seal 52 is shown positioned adjacent the GIW in an orientation suitable for delivering the fluid solution 48 to the GIW. Although not shown, a portion of the outer shell may still remain at this stage, including between the top seal 52 and the GIW. The collar 62 of the upper chamber 60 continues to support the collapsible tube 64.

[0056] 3B-3D illustrate the progression of the power injector 10 during (FIG. 3B) and after (FIGS. 3C-3D) disassembly of the collar 62.

[0057] FIG. 3B shows the autoinjector 10 during the disintegration of the collar 62. At this stage, fluid from the gastrointestinal tract has reached the collar 62 and begun to disintegrate. The collar 62 may disintegrate into pieces or particles 62a as shown in FIG. 3B, or additionally or alternatively, may disintegrate by weakening such that the collar 62 no longer provides sufficient support to maintain the collapsible tube 64 in its initial form (e.g., cylindrical). In one embodiment, the collar 62 comprises a rapidly degrading material (e.g., poly(vinyl alcohol) (PVA), polyvinylpyrrolidone, etc.) that is susceptible to disintegration when exposed to fluids, particularly fluids present in the gastrointestinal tract.

[0058] In FIG. 3C, as the balloon 12 continues to expand and presses the needle compartment 50 against tissue at the delivery site (e.g., GIW), the disassembled or partially disassembled collar 62 provides minimal resistance due to its disassembled state, reducing support for the collapsible tube 64. The collapsible tube 64 collapses due to vertical pressure applied to the needle compartment 50 between the balloon 12 and the tissue at the delivery site. When the collapsible tube 64 is collapsed, the infusion needle 100 is forced through the upper seal 52 and the lower seal 54 simultaneously or sequentially, with the distal end 105 of the infusion needle 100 breaching (puncturing) the upper seal 52 and the proximal end 108 of the infusion needle 100 breaching (e.g., puncturing) the lower seal 54. The infusion needle 100 is urged to advance into the tissue at the delivery site by being blocked by a stop function provided by the inner boss 92 of the lower chamber 80 in cooperation with the protrusion 110 of the infusion needle 100. When the proximal end 108 of the injection needle 100 approaches the lower seal 54, the radial shaft seal 90 comes into contact with the injection needle 100. The proximal end 108 breaks the lower seal 54 and enters the reservoir 40. The radial shaft seal 90 blocks the fluid solution 48 from exiting the reservoir 40 through the cavity 88 around the circumference of the injection needle 100.

[0059] In Fig. 3D, after the lower seal 54 is breached by the proximal end 108 of the infusion needle 100, pressure P exerted on the outer surface of the membrane 42 of the reservoir 40 by the build-up of pressure in the balloon 12 results in compression of the reservoir 40 and subsequent flow of the fluid solution 48 (containing one or more therapeutic formulations) from the reservoir 40 into the channel 106 of the infusion needle 100. If or when the upper seal 52 is breached by the distal end 104 of the infusion needle 100, the fluid solution 48 is delivered into the tissue at the delivery site. The radial shaft seal 90 remains in contact with the infusion needle 100 and blocks the fluid solution 48 from exiting the reservoir 40 through the cavity 88 around the circumference of the infusion needle 100.

[0060] In one embodiment, one or more of the injection needle 100, components of the upper chamber 60 and / or the lower chamber 80, or other components of the autoinjector 10 comprise a biodegradable material or a combination of biodegradable materials. Examples of biodegradable materials include biodegradable polymers, cellulose, sugars, and maltose. Examples of biodegradable polymers include polyethylene oxide (PEO), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), or combinations of PLA and PGA, such as poly(lactic-co-glycolic acid) (PLGA) or poly(glycolide-co-lactide) (PGLA).

[0061] One embodiment of a method for manufacturing the power injector 10 will now be described.

[0062] A bottom housing segment, such as lower chamber 80, is provided. A bottom seal, such as lower seal 54, is attached to the bottom housing segment.

[0063] The bottom housing segment (with the lower seal) is placed and secured to a reservoir (eg, reservoir 40) and the combination of the bottom housing segment and reservoir is placed and secured to an expandable member (eg, balloon 12).

[0064] A collapsible tube (e.g., collapsible tube 64) is attached to the expandable member and / or the bottom housing segment. In one embodiment, the collapsible tube is made of PE.

[0065] A collar (e.g., collar 62) is disposed around the collapsible tube. In one embodiment, the collar is made of PVA or polyvinylpyrrolidone.

[0066] A needle (eg, injection needle 100) is disposed within a cavity collectively formed by the bottom housing segment and the collapsible tube.

[0067] The collapsible tube has a seal secured thereto, such as top seal 52. A reservoir, such as reservoir 40, is filled with a therapeutic formulation through a port, such as through fill port 46 and tube 44 in FIG.

[0068] After filling the reservoir, the expandable member is completely sealed around its perimeter, such as by heat staking. The completed seal cuts a port (e.g., cuts the fill port 46 and the portion of the tube 44 that extends outside the expandable member, thus sealing the tube 44).

[0069] The reactants and associated assemblages (e.g., pouch 32 with first reactant 38, conduit 34, and second reactant 35) may be added to the expandable member at any stage of manufacture before the expandable member is completely sealed. Additionally, the expandable member may be partially sealed at any stage of manufacture, with sealing being completed after filling the reservoirs.

[0070] 5-10 illustrate an embodiment of a method of manufacturing a swallowable device for delivering drugs in fluid form.

[0071] 5, a bottom housing segment 505 is provided incorporating a radial shaft seal 506. Seal 510 is secured to bottom housing segment 505. In one embodiment, bottom housing segment 505 may be formed of PE, radial shaft seal 506 may be formed of an elastomer, and seal 510 may be formed of aluminum foil.

[0072] In FIG. 6, bottom housing segment 505 (having radial shaft seal 506 and seal 510) is placed and secured within reservoir 520, and the combination of bottom housing segment 505 and reservoir 520 is placed and secured within balloon 515.

[0073] In Figure 7, collapsible tube 525 is attached to balloon 515 and bottom housing segment 505. In one embodiment, collapsible tube 525 is made of PE.

[0074] In Figure 8, collar 530 is disposed around collapsible tube 525. In one embodiment, collar 530 is formed from PVA or polyvinylpyrrolidone.

[0075] In FIG. 9, the infusion needle 535 is disposed within a cavity defined by the bottom housing segment 505 and the collapsible tube 525 .

[0076] In FIG. 10, seal 540 is secured to collapsible tube 525 to complete the needle compartment including bottom housing segment 505 , collapsible tube 525 , collar 530 , seal 510 , and seal 540 .

[0077] Reservoir 520 is filled with a therapeutic formulation (e.g., including a drug or other therapeutic agent) through a port (e.g., similar to fill port 46 with tube 44 in FIG. 1). In one embodiment, reservoir 520 is exposed to a vacuum to remove any gas within reservoir 520 prior to filling reservoir 520.

[0078] After filling the reservoir 520, the assembly illustrated in FIG. 10 can be further assembled into an autoinjector (e.g., any of the autoinjectors 10, 10A, 10B, 10C, 10D of FIGS. 1, 2A, 2B, 2C, 2D, respectively, or other autoinjector designs). For example, the pouch 32 containing the first reactant 38, the conduit 34, the second reactant 35, the release valve 36, the flap 24, and the deflation valve 28 of FIG. 1 can be incorporated into the assembly illustrated in FIG. 10 (where the balloon 515 of FIG. 10 is the balloon 12 of FIG. 1). The balloon 515 can then be completely sealed around its perimeter, such as by heat staking. The completed seal blocks the port (e.g., the fill port 46) and seals the port tube (e.g., tube 44). In one embodiment, the port tube is sealed (e.g., by heat staking) after filling the reservoir 520. The balloon 515 is then completely sealed around its periphery.

[0079] Reactants and associated assemblies may be added to balloon 515 at any stage of the manufacturing methods described above. Additionally, balloon 515 may be partially sealed at any stage of the manufacturing methods described above, with the sealing being completed at a subsequent stage.

[0080] In one embodiment, at least a portion of the components illustrated in Figures 5-10 are assembled in an isolator and sterilized prior to being brought into the isolator or are sterilized in the isolator. In this manner, the infusion needle 535 can remain dry and sterile in the needle compartment including the bottom housing segment 505, the collapsible tube 525, the collar 530, the seal 510, and the seal 540 until the infusion needle 535 is deployed and breaks the seals 510 and 540. In one embodiment, after the assembly illustrated in Figure 10 is completed, the port tube is sealed in the isolator and the assembly is removed from the isolator (e.g., to a clean room) for completion of the device. In one embodiment, the assembly remains in the isolator for completion of the device.

[0081] In one embodiment, the needle compartment, including bottom housing segment 505, collapsible tube 525, collar 530, seal 510, and seal 540, is first assembled and then positioned to extend into reservoir 520 through an opening defined by the membrane of reservoir 520. Reservoir 520 is then filled.

[0082] The embodiments can be used for the delivery of various formulations, including therapeutic formulations. The term "therapeutic formulation" refers herein to a formulation in which the formulation contains one or more components for therapeutic, diagnostic, or other biological purposes. Each therapeutic formulation can contain one or more components, and a device or system can contain one or more therapeutic formulations. A component of a therapeutic formulation can be, for example, a therapeutic agent, such as a pharmacologically active agent, a DNA or siRNA transcript, a cell, a cytotoxic agent, a vaccine or other preventative agent, a nutraceutical agent, a vasodilator, or a vasoconstrictor, or can be another type of component, such as a delivery enhancer, a retardant, an excipient, a diagnostic agent, or a substance for cosmetic enhancement.

[0083] The pharmacologically active agent can be, for example, an antibiotic, a nonsteroidal anti-inflammatory drug (NSAID), an angiogenesis inhibitor, a neuroprotective agent, a chemotherapeutic agent, a peptide, a protein, an immunoglobulin (e.g., a TNF-α antibody), an interleukin of the IL-17 family of interleukins, an anti-eosinophil antibody, other antibodies, a nanobody, a macromolecule, a small molecule, or a hormone, or a biologically active variant or derivative of any of the foregoing.

[0084] The cells may be, for example, stem cells, red blood cells, white blood cells, neurons, or other living cells. The cells may be generated by or from an organism, or may contain components of an organism. The cells may be allogeneic or autologous.

[0085] The vaccine can be, for example, against influenza, coronavirus, meningitis, human papillomavirus (HPV), or chickenpox. The vaccine can correspond to an attenuated virus.

[0086] The dietary supplement can be, for example, vitamin A, thiamine, niacin, riboflavin, vitamin B-6, vitamin B-12, other B vitamins, vitamin C (ascorbic acid), vitamin D, vitamin E, folic acid, phosphorus, iron, calcium, or magnesium.

[0087] The vasodilator can be, for example, l-arginine, sildenafil, a nitrate (eg, nitroglycerin), or epinephrine.

[0088] The vasoconstrictor can be, for example, a stimulant, an amphetamine, an antihistamine, epinephrine, or cocaine.

[0089] The delivery enhancer may be, for example, a penetration enhancer, an enzyme blocker, a peptide that penetrates mucous membranes, an antiviral drug such as a protease inhibitor, a disintegrant, a superdisintegrant, a pH modifier, a surfactant, a bile salt, a fatty acid, a chelating agent, or chitosan. The delivery enhancer may, for example, serve as a delivery vehicle for delivering a component of the therapeutic formulation or may serve to improve the absorption of a component of the therapeutic formulation into the body. The delivery enhancer may prime the intestinal epithelium (e.g., fluidize the outer layer of cells) to improve the absorption and / or bioavailability of one or more other components contained in the delivery device.

[0090] The retarding agent can be, for example, poly(lactic acid) (PLA), poly(glycolic acid) (PGA), polyethylene glycol (PEG), poly(ethylene oxide) (PEO), poly(l-lactic acid) (PLLA), poly(D-lactic acid) (PDLA), other polymers, or hydrogels. The retarding agent can be included with (e.g., mixed with or provide structure around) one or more other components in the therapeutic formulation to slow the release rate of the other components from the therapeutic formulation.

[0091] An excipient can be, for example, a binder, disintegrant, superdisintegrant, buffer, antioxidant, or preservative. An excipient can provide a vehicle for the components of a therapeutic formulation (e.g., to aid in manufacturing) or can provide for maintaining the integrity of the components of a therapeutic formulation (e.g., during manufacturing, storage, or after ingestion prior to distribution in the body).

[0092] The diagnostic agent can be, for example, a detection agent, a contrast agent, a radionuclide, a fluorescent material, a luminescent material, a radiopaque material, or a magnetic material.

[0093] Therapeutic formulations can include therapeutically effective amounts of various therapeutic agents for treating various diseases and conditions. Therapeutic agents include some macromolecular peptides and proteins that would otherwise require injection due to chemical degradation and / or inactivation in the stomach or intestines. Examples include antibodies (including various monoclonal antibodies such as, for example, TNF-alpha antibodies), growth hormones (e.g., IGF and other growth factors), parathyroid hormone, interferons, immunochemotherapeutic agents, antibiotics, antiviral agents, insulin and related compounds, glucagon-like peptides (e.g., GLP-1, exenatide), anti-seizure agents (e.g., furosemide), anti-migraine medications (e.g., sumatriptan), immunosuppressants (e.g., cyclosporine) and anti-parasitic agents (e.g., antimalarials).

[0094] The dosage of a particular therapeutic agent can be titrated to the subject's weight, age, or other parameters. The dosage to achieve a desired therapeutic effect delivered into or through the GIW via the autoinjector of the present disclosure may be less than that required for traditional oral delivery by absorption via the GIW. This is in part due to minimizing or preventing degradation of the therapeutic agent in biological or digestive materials by protecting the fluid in the autoinjector's reservoir until the moment of delivery of the fluid from the autoinjector to the GIW. In comparison, a therapeutic agent delivered by traditional oral delivery (e.g., a pill) may be significantly degraded by biological or digestive materials prior to absorption. Furthermore, the absorption rate of a therapeutic agent delivered by traditional oral delivery may be low. Thus, the bioavailability of a therapeutic agent delivered by traditional oral delivery may be low (e.g., absolute bioavailability less than 5%, or less than 1%) due to degradation and / or insufficient absorption. As used herein, absolute bioavailability means the bioavailability of an amount of a therapeutic agent delivered by a delivery mechanism under test (DMT) compared to the bioavailability of the same amount of a therapeutic agent delivered by intravenous injection (IV), and is calculated by dividing the area under the curve (AUC) of the bioavailability by the DMT vs. AUC of the IV bioavailability, and expressed as a percentage.

[0095] In one embodiment, the absolute bioavailability of a therapeutic agent delivered by an autoinjector of the present disclosure is at least 95%. In one embodiment, the absolute bioavailability of a therapeutic agent delivered by an autoinjector of the present disclosure is about 100%. In one embodiment, the absolute bioavailability of a therapeutic agent delivered by an autoinjector of the present disclosure is greater than 100%, because a therapeutic agent delivered by an autoinjector is retained in the body for a period of time (e.g., delivered into the intestinal wall or peritoneal cavity and enters the bloodstream and is eliminated from the body over time), whereas a therapeutic agent delivered by IV is eliminated from the body more quickly (i.e., delivered into the bloodstream and eliminated from the body). The longer the therapeutic agent spends in the body, the longer the therapeutic agent may have a therapeutic effect.

[0096] Depending on the therapeutic agent, the dose delivered by the autoinjector of the present disclosure can range from 5% to 100% of the dose delivered by conventional oral delivery means to achieve the desired therapeutic effect. In one embodiment, the ratio of the dose delivered by the autoinjector of the present disclosure to the dose delivered by conventional oral delivery is greater than 20:1. In one embodiment, the ratio of the dose delivered by the autoinjector of the present disclosure to the dose delivered by conventional oral delivery is greater than 90:1.

[0097] Dose reduction provides benefits to the subject. For example, potential toxicity and other side effects (e.g., stomach cramps, irritable bowel, bleeding, etc.) of a particular therapeutic agent alone or in combination with one or more other therapeutic agents delivered by the autoinjector of the present disclosure can be reduced because the delivered dose is reduced compared to conventional oral administration. This improves compliance because subjects may experience both reduced severity and reduced incidence of side effects. Additional benefits may include reduced likelihood that subjects will develop resistance to the therapeutic agent and, in the case of antibiotics, that subjects will develop resistant bacterial strains.

[0098] In addition to delivering a single therapeutic agent, embodiments can be used to deliver multiple therapeutic agents for the treatment of multiple conditions, or for multiple treatment prongs for a particular condition. In use, such embodiments allow a subject to forgo the need to take multiple medications for a particular condition or multiple conditions.

[0099] Due to differences in chemical makeup, molecular weight, or other parameters, therapeutic agents, when delivered by conventional techniques (e.g., pills), may be absorbed from the gastrointestinal tract through the intestinal wall, resulting in different pharmacokinetic distribution curves. The embodiments address this issue by injecting a mixture of desired therapeutic agents substantially simultaneously. This may thus improve the pharmacokinetics and therefore the efficacy of a selected mixture of therapeutic agents.

[0100] In various applications, the embodiments can be used to deliver formulations containing therapeutic agents to provide treatment for several conditions and diseases. Conditions and diseases that can be treated with the embodiments can include, but are not limited to, cancer, hormonal conditions (e.g., hypo / hyperthyroidism, growth hormone conditions), osteoporosis, high blood pressure, high cholesterol and high triglycerides, diabetes and other glucose regulation disorders, infections (focal or septic), epilepsy and other seizure disorders, osteoporosis, coronary arrhythmias (both atrial and ventricular), coronary ischemic anemia or other similar conditions. Still other conditions and diseases are also envisioned, such as various autoimmune disorders, including multiple sclerosis, Guillain-Barre syndrome, ankylosing spondylitis, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, lupus and other similar conditions. Therapeutic agents for the latter conditions can include IgG and rituximab, among others.

[0101] In many embodiments, the treatment of a particular disease or condition using the power injector of the present disclosure can completely replace other forms of treatment, while in other embodiments, the treatment of a particular disease or condition using the power injector of the present disclosure can augment or reduce other forms of treatment.

[0102] As apparent from the description and drawings of the present disclosure, embodiments include, but are not limited to, the following. an autoinjector including an inflatable balloon, a reservoir disposed within the inflatable balloon, a needle compartment attached to the balloon and the reservoir; an injection needle disposed within the needle compartment; and an inflation mechanism. The reservoir contains a fluid therapeutic formulation including a therapeutic agent. The inflation mechanism is configured to inflate the balloon, and upon inflation of the balloon, the injection needle is configured to enter the reservoir at a proximal end of the injection needle. A method of manufacturing an automatic injector includes providing a needle compartment and a reservoir, sealing one end of the needle compartment, disposing the needle compartment partially within the reservoir, disposing an injection needle in a cavity defined by the needle compartment, and adding a fluid therapeutic formulation including a therapeutic agent to the reservoir. The method includes making an autoinjector available to a subject by instructing the subject to ingest the autoinjector. The autoinjector is configured to inject a fluid therapeutic formulation including a therapeutic agent into a wall of the gastrointestinal tract of the subject in response to ingestion of the autoinjector. The autoinjector includes an infusion needle disposed in a needle compartment attached to a reservoir, the infusion needle being initially separated from the reservoir. The infusion needle is configured to enter the reservoir to deliver the fluid therapeutic formulation into the wall via the infusion needle. Any of the above autoinjectors or methods may have any one or combination of the following features: -Reservoir is configured to hold up to 0.5cc of liquid -Reservoir contains 0.5cc of fluid -The device is configured to contain up to 50 milligrams of a therapeutic agent - The therapeutic agent is one of two or more different therapeutic agents contained in a therapeutic formulation the expansion mechanism includes two reactants, the expansion mechanism being configured to keep the two reactants separated from each other until the device encounters a fluid environment; - the device is configured to deliver a therapeutic formulation through or through the wall of the gastrointestinal tract into the peritoneal cavity - The fluid treatment formulation is delivered through a port into a tube that is fluidly coupled to a reservoir The end of the needle compartment that is placed in the reservoir is sealed In response to the generation of gas within the automatic injector, a proximal end of the injection needle enters the reservoir and a distal end of the injection needle is exposed from the needle compartment to deliver the therapeutic formulation.

[0103] Although the present invention has been described and illustrated with reference to specific embodiments thereof, these descriptions and illustrations are not intended to limit the present invention. It can be clearly understood that various modifications can be made and equivalent elements can be substituted within the embodiments without departing from the true spirit and scope of the present disclosure as defined by the appended claims. Also, elements, properties, or acts from one embodiment can be easily recombined or substituted with one or more elements, properties, or acts from other embodiments to form numerous additional embodiments within the scope of the present invention. Furthermore, an element shown or described as being combined with other elements can exist as an independent element in various embodiments. Furthermore, for any positive description of an element, property, component, feature, act, step, etc., an embodiment of the present invention specifically contemplates the exclusion of that element, value, property, component, feature, act, step, etc. Illustrations are not necessarily drawn to scale. There may be a distinction between the artistic representations in the present disclosure and the actual devices. There may be other embodiments of the present disclosure that are not specifically illustrated. The specification and drawings should be considered illustrative rather than restrictive. Modifications may be made to adapt a particular situation, material, composition of matter, method, or process to the objective, spirit, and scope of the present disclosure. All such modifications are intended to be within the scope of the claims appended hereto. Although the methods disclosed herein have been described with reference to certain operations performed in a particular order, it will be understood that these operations can be combined, sub-divided, or rearranged to form equivalent methods without departing from the teachings of the present disclosure. Thus, unless specifically indicated herein, the order and grouping of operations is not limited in the present disclosure.

[0104] Various abbreviations may be used herein for standard units such as deciliter (dl), milliliter (ml), microliter (μl), international units (IU), centimeter (cm), millimeter (mm), nanometer (nm), inch (in), kilogram (kg), gram (gm), milligram (mg), microgram (μg), millimole (mM), degrees Celsius (°C), degrees Fahrenheit (°F), millitorr (mTorr), hours (hr), minutes (min), or seconds (s or sec).

[0105] As used in this disclosure, the terms "eg," "such as," "for example," "for example," "for another example," "example," "for example," and "such as" indicate a list of one or more non-limiting examples, and it is to be understood that other examples not listed are within the scope of the invention.

[0106] As used herein, the singular terms "a," "an," and "the" may include plural referents unless otherwise clear from the context. Reference to a singular object is not intended to mean "the only one," but rather "one or more," unless expressly stated.

[0107] The term "in an embodiment" or variations thereof (e.g., "in another embodiment" or "in one embodiment") is used herein to refer to use in one or more embodiments and does not in any way limit the scope of the invention to only the embodiment illustrated and / or described. Thus, elements illustrated and / or described herein with respect to an embodiment may be omitted or may be used in another embodiment (e.g., in another embodiment illustrated and described herein or in another embodiment not illustrated and / or described herein within the scope of the present disclosure).

[0108] The term "component" as used herein refers to one item of a set of one or more items that together constitute the device, formulation, or system under consideration. A component may be a solid, powder, gel, plasma, fluid, gas, or other form. For example, a device may include multiple solid components that are assembled together to structure the device and may further include a fluid component disposed within the device. As another example, a formulation may include two or more powder and / or fluid components that are mixed together to create the formulation.

[0109] The term "design" or grammatical variations thereof (e.g., "design" or "designed") refers to properties that are intentionally built in based on, for example, estimates of tolerances (e.g., component tolerances and / or manufacturing tolerances) and environmental conditions expected to be encountered (e.g., temperature, humidity, external or internal ambient pressure, external or internal mechanical pressure, stress due to external or internal mechanical pressure, age of the product, or shelf life, or if introduced into the body, physiology, body chemistry, biological composition of body fluids or tissues, chemical composition of body fluids or tissues, pH, species, diet, health, sex, age, ancestry, disease, or tissue damage), with it being understood that different components, devices, formulations, or systems of the same design may have different actual values ​​for those properties because actual tolerances and environmental conditions before and / or after delivery may affect the properties. Design also includes pre- or post-manufacture variations or modifications.

[0110] The term "manufacture" or grammatical variations thereof (e.g., "manufacture" or "manufactured"), as used herein in connection with a component, device, formulation, or system, refers to making or assembling the component, device, formulation, or system. Manufacturing can be performed wholly or partially by manual and / or wholly or partially automated methods.

[0111] The term "structured" or grammatical variations thereof (e.g., "structure" or "structured"), as used herein, refers to a component, device, formulation, or system that is produced according to a concept or design, or variations or modifications thereto (whether such variations or modifications occur before, during, or after production), whether or not such concept or design is incorporated in a document.

[0112] The term "body" as used herein refers to an animal body.

[0113] The term "subject" as used herein refers to a body to which an embodiment of the present disclosure is delivered or intended to be delivered. For example, with respect to a human, the subject may be a patient receiving treatment from a medical professional.

[0114] The term "biological material" as used herein refers to blood, tissues, body fluids, enzymes, interstitial fluid, and other secretions of the body. The term "digestate" as used herein refers to the biological material along the gastrointestinal tract of an animal body, as well as other material that traverses the gastrointestinal tract (e.g., undigested or digested food, such as chyme).

[0115] The term "ingest" or grammatical variations thereof (e.g., "ingesting" or "ingested"), as used herein, refers to taking into the stomach, whether by swallowing or by other means of placement in the stomach (e.g., by placement in the stomach via an endoscope or by placement in the stomach via a port).

[0116] The term "degrade" or grammatical variations thereof (e.g., "degrading," "degraded," "degradable," and "degradation"), as used herein, refers to weakening, partial degradation, or complete degradation by dissolution, chemical degradation (including biodegradation), decomposition, chemical modification, mechanical degradation, or disintegration, including, but not limited to, dissolving, disintegrating, deforming, shrinking, or shrinking, in the expected environment, at least for the expected period of time. The term "non-degradable" refers to an expectation that degradation will be minimal or within a certain acceptable design percentage.

[0117] As used herein, the terms "substantially" and "about" are used to describe and convey small variations. For example, when used in conjunction with a numerical value, these terms can refer to a range of variation of ±10% or less of that numerical value, such as ±5% or less, ±4% or less, ±3% or less, ±2% or less, ±1% or less, ±0.5% or less, ±0.1% or less, or ±0.05% or less.

[0118] Additionally, amounts, ratios, and other numerical values ​​may be presented in a range format herein. As used herein, a range of numerical values ​​includes any numerical value within the range, or any subranges where the minimum and maximum numbers within the subrange are within the range. It should be understood that this range format is used for convenience and brevity, and includes numerical values ​​that are explicitly stated as the limits of the range, but should be flexibly understood to include all individual numerical values ​​or subranges encompassed within the range as if each numerical value and subrange were explicitly stated. Thus, for example, "<9" may refer to any numerical value less than 9, or a subrange of numerical values ​​where the minimum value of the subrange is equal to or greater than zero and the maximum value of the subrange is less than 9. Ratios may also be presented in a range format herein. For example, a ratio in the range of about 1 to about 200 should be understood to include the explicitly stated limits of about 1 and about 200, but also include individual ratios such as about 2, about 3, and about 4, and subranges such as about 10 to about 50, about 20 to about 100, etc.

[0119] The term "lumen," as used herein, refers to the interior space of a tubular structure. Examples of lumens in the body include arteries, veins, and tubular cavities within organs.

[0120] The term "lumen wall" refers to the wall of a lumen, where wall, in relation to a lumen within the body, includes all layers from the inner periphery of the lumen to the outer periphery, such as the mucosa, submucosa, muscularis, serosa, and the outer wall of the lumen, along with their constituent blood vessels and tissues.

[0121] The term "digestive tract" or "GI tract," as used herein, refers to the intake / excretion system of the body including, for example, the mouth, pharynx, esophagus, stomach, pylorus, small intestine, cecum, large intestine, colon, rectum, anus, and the valves or sphincters between them.

Claims

1. An automatic injector device for injection of a fluid therapeutic formulation into a wall of the gastrointestinal (GI) tract, comprising: an inflatable balloon; a reservoir disposed within the inflatable balloon, the reservoir containing a fluid treatment formulation including a therapeutic agent; a needle compartment attached to the balloon and the reservoir; an injection needle disposed within the needle compartment and protected by the needle compartment until exposure to fluids of the GI tract; an inflation mechanism configured to inflate the balloon upon contact with a fluid environment of the GI tract; The automatic injector device, wherein the injection needle is structured and configured such that, in response to pressure inside the inflated balloon, the proximal end of the injection needle enters the reservoir and simultaneously or sequentially the distal end of the injection needle enters GI wall tissue to deliver the fluid therapeutic formulation from the reservoir into the GI wall.

2. The device of claim 1 , wherein the reservoir is configured to hold up to 0.5 cubic centimeters of fluid.

3. The device of claim 1, wherein the reservoir contains 0.5 cubic centimeters of the fluid therapeutic formulation.

4. The device of claim 1 , wherein the device is configured to contain up to 50 milligrams of the therapeutic agent.

5. The device of claim 4, wherein the therapeutic agent is one of two or more different therapeutic agents contained in the fluid therapeutic formulation.

6. The device of claim 1, wherein the device contains 15 to 20 milligrams of the therapeutic agent.

7. 7. The device of any one of claims 1 to 6, wherein the expansion mechanism comprises two reactants, the expansion mechanism configured to keep the two reactants separated from each other until the device encounters the fluid environment of the GI tract.

8. The device of any one of claims 1 to 7, wherein the device is configured to deliver the fluid therapeutic formulation through a wall of the GI tract or through the wall of the GI tract into the abdominal cavity.

9. 1. A method of manufacturing an automatic injector, comprising the steps of: Providing a needle compartment and a reservoir; sealing one end of the needle compartment; disposing the needle compartment partially within the reservoir; placing an injection needle into a cavity defined by said needle compartment; adding to the reservoir a fluid therapeutic formulation comprising a therapeutic agent.

10. Adding to the reservoir comprises: (i) adding 0.4 to 0.5 cubic centimeters of the fluid therapeutic formulation to the reservoir; or (ii) adding 20 to 50 milligrams of said therapeutic agent to said reservoir; The method according to claim 9, wherein

11. The method of claim 9 or 10, wherein adding to the reservoir is accomplished by passing the fluid therapeutic formulation through a port and into a tube fluidly connected to the reservoir.

12. 12. The method of claim 11, wherein the fluid treatment formulation is a first treatment formulation, the therapeutic agent is a first therapeutic agent, and further comprising adding to the reservoir a second treatment formulation comprising a dose of a second therapeutic agent different from the first therapeutic agent.

13. The method of claim 9 , wherein sealing one end of the needle compartment comprises sealing an end of the needle compartment that is disposed within the reservoir.

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