HK1248094B - Intragastric device - Google Patents

Description

Intragastric devices

This application is a divisional application of the Chinese invention patent application entitled “Intragastric Device” and having application number “201380076597.1”, which is an application for the PCT application with international application number “PCT/US2013/032663” to enter the Chinese national phase.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application No. 13/011,842, filed January 21, 2011, the contents of which are hereby incorporated by reference in their entirety and are hereby made a part of this specification.

Technical Field

Devices and methods for treating obesity are provided. More particularly, intragastric devices and methods for manufacturing, deploying, inflating, monitoring, and retrieving such devices are provided.

Background Art

Obesity is a major health problem in developed countries. Obesity increases the risk of many serious health problems, including high blood pressure and diabetes. In the United States, complications of being overweight or obese are estimated to affect nearly one-third of American adults, costing the economy over $80 billion annually in medical expenses and, including indirect costs such as lost wages, exceeding $120 billion annually. Except in rare pathological conditions, weight gain is directly linked to overeating.

Noninvasive methods for weight loss include increasing metabolic activity to burn calories and/or reducing caloric intake by either modifying behavior or using pharmacological interventions to reduce the desire to eat. Other methods include surgery to reduce stomach volume, banding to restrict stomach size, and intragastric devices that reduce the desire to eat by taking up space in the stomach.

Gastric volume-occupying devices provide a feeling of fullness after consuming only a small amount of food. Consequently, caloric intake is reduced, while the patient experiences a satisfying feeling of fullness. Currently available volume-occupying devices have several drawbacks. For example, some devices require complex gastric surgery to insert.

U.S. Patent No. 4,133,315 discloses a device for reducing obesity, comprising an inflatable elastic bag and tube combination. The contents of this patent are incorporated herein by reference in their entirety. The bag can be inserted into the patient's stomach by swallowing. An attached tube is distally connected to the end of the bag and remains in the patient's mouth. A second tube extends through the nasal cavity and into the patient's mouth. The ends of the tubes located in the patient's mouth are connected to form a continuous tube through the patient's nose to the bag for fluid communication. Alternatively, the bag can be implanted during gastric surgery. Before the patient eats, the bag is inflated to the desired level through the tube, thereby reducing appetite. After the patient eats, the bag is deflated. Throughout the treatment process, the tube extends beyond the patient's nose or abdominal cavity.

US Patent Nos. 5,234,454 and 6,454,785, the contents of which are incorporated herein by reference in their entirety, disclose gastric volume-occupying devices for weight management that must be surgically implanted.

U.S. Patent Nos. 4,416,267, 4,485,805, 4,607,618, 4,694,827, 4,723,547, 4,739,758, and 4,899,747, and European Patent No. 246,999, relate to endoscopically insertable gastric volume-occupying devices for weight management, the contents of which are incorporated herein by reference in their entirety. Of these, U.S. Patent Nos. 4,416,267, 4,694,827, 4,739,758, and 4,899,747, the contents of which are incorporated herein by reference in their entirety, relate to balloons having a contoured surface that is contoured in a manner to achieve a desired distal end. In U.S. Patent Nos. 4,416,267 and 4,694,827, the balloons are toroidal in shape with a trumpet-shaped central opening to facilitate the passage of solids and liquids through the gastric cavity, the contents of which are incorporated herein by reference in their entirety. U.S. Patent No. 4,694,827, the disclosure of which is incorporated herein by reference in its entirety, has multiple smooth, convex protrusions. The protrusions reduce the amount of surface area contacting the stomach wall, thereby reducing the harmful effects of excessive contact with the gastric mucosa. The protrusions also define passages between the balloon and the stomach wall through which solids and liquids may pass. U.S. Patent No. 4,739,758, the disclosure of which is incorporated herein by reference in its entirety, has a blister around its periphery to prevent it from seating against the cardia or pylorus.

U.S. Patent Nos. 4,899,747 and 4,694,827 disclose a deflated balloon and a releasably connected tube by pushing it down a gastric tube, the contents of which are incorporated herein by reference in their entirety. U.S. Patent No. 4,723,547 discloses a particularly suitable insertion catheter for positioning its balloon, the contents of which are incorporated herein by reference in their entirety. In U.S. Patent No. 4,739,758, a stuffing tube effects insertion of the balloon, the contents of which are incorporated herein by reference in their entirety. In U.S. Patent No. 4,485,805, the balloon is inserted into a finger cuff that is connected by a wire to the end of a conventional gastric tube that is inserted down into the patient's pharynx, the contents of which are incorporated herein by reference in their entirety. The balloon of European Patent No. 246,999 is inserted using a gastroscope with integral forceps.

In U.S. Patents Nos. 4,416,267, 4,485,805, 4,694,827, 4,739,758, and 4,899,747, and European Patent No. 246,999, the balloons are inflated with fluid from a tube extending downward from the patient's mouth. The contents of each of these patents are incorporated herein by reference in their entirety. In these patents, the balloons are also equipped with a self-sealing orifice (U.S. Patent No. 4,694,827, the contents of which are incorporated herein by reference in their entirety), an injection site (U.S. Patent Nos. 4,416,267 and 4,899,747, the contents of which are incorporated herein by reference in their entirety), a self-sealing filling valve (U.S. Patent No. 4,485,805, the contents of which are incorporated herein by reference in their entirety), a self-closing valve (European Patent No. 246,999, the contents of which are incorporated herein by reference in their entirety), or a duckbill valve (U.S. Patent No. 4,739,758, the contents of which are incorporated herein by reference in their entirety). US Patent No. 4,723,547, the contents of which are incorporated herein by reference in their entirety, uses an elongated thick plug, and the balloon is filled by a needle inserted through the plug connected to an air source.

U.S. Patent No. 4,607,618, the contents of which are incorporated herein by reference in their entirety, describes a collapsible device formed from semi-rigid skeletal components connected to form a collapsible hollow structure. The device is not inflatable. It is inserted endoscopically into the stomach using a specially adapted probe with an ejection rod to release the collapsed device. Once released, the device returns to its larger, relaxed size and shape.

U.S. Patent No. 5,129,915 relates to an intragastric balloon designed to be swallowed and automatically inflates in response to temperature, the contents of which are incorporated herein by reference in their entirety. Three ways in which the intragastric balloon might inflate in response to temperature changes are discussed. A composition comprising a solid acid and a non-toxic carbonate or bicarbonate is separated from water by coating with a coating of chocolate, cocoa paste, or cocoa butter that melts at body temperature. Alternatively, a composition comprising a solid acid and a non-toxic carbonate or bicarbonate is coated with a non-toxic plant or animal fat that melts at body temperature and placed in water, producing the same result. Finally, the solid acid and non-toxic carbonate or bicarbonate are separated from the water by a barrier bag of a synthetic material of low strength sufficient to rupture immediately before the balloon is swallowed. Rupture of the barrier bag allows the acid, carbonate or bicarbonate, and water to mix, and the balloon to expand immediately. A disadvantage of thermally triggered inflation is that it does not provide the degree of control and reproducibility of inflation time that is desirable and necessary for a safe self-inflating intragastric balloon.

Summary of the Invention

It would be desirable to have a free-floating gastric volume-occupying device that could be inserted into the stomach and swallowed by the patient and peristaltically transported to the stomach in the same manner as food, or positioned by a catheter.

Volume-occupying devices, as well as methods for manufacturing, deploying, inflating, tracking, and retrieving these devices, are provided. The devices and methods of preferred embodiments can be used to treat overweight and obese individuals. Methods employing the devices of preferred embodiments can be swallowed by the patient, with or without an attached catheter. Once in the patient's stomach, the device is inflated with a preselected gas or gas mixture at a preselected volume. After a predetermined period of time, the device can be removed using endoscopic tools or reduced in size or deflated to pass through the remainder of the patient's digestive tract.

Inflation may be achieved through the use of a removable catheter that initially remains in fluid contact with the device after it has been swallowed by the patient.

The volume-occupying subcomponent of the device can be injection molded, blow molded, or rotationally molded from a flexible, gas-impermeable, biocompatible material such as polyurethane, nylon, or polyethylene terephthalate. When reduced permeability is desired, materials that can be used to control the gas permeability/impermeability of the volume-occupying subcomponent include, but are not limited to, silicon oxide (SiOx), gold or any precious metal, saran, conformal coatings, and the like. To enhance the gas-impermeability of the device wall, the volume-occupying subcomponent can also be coated with one or more gas-barrier compounds, or formed from a Mylar polyester film coating or kelvalite, silver, or aluminum as a metallized surface to provide a gas-impermeable barrier, if desired.

In other embodiments, the device is packaged in a delivery state so that it can be swallowed while causing minimal discomfort to the patient. In the delivery state, the device can be packaged in a capsule. Alternatively, the device can be coated with a material operable to constrain the device and facilitate swallowing. Various techniques can also be employed to facilitate swallowing of the device, such as wetting agents, temperature treatment, lubrication, and treatment with medications such as anesthetics.

In other embodiments, the device may employ a tracking or visualization component that enables a physician to determine position and/or orientation within a patient's body. The tracking subcomponent may include incorporating barium stripes or geometric shapes into the walls of the volume-occupying subcomponent. Tracking and visualization may also be accomplished by incorporating microchips, infrared LED tags, ultraviolet absorbing compounds, fluorescent or colored compounds, and metallized strips and patterns into the volume-occupying subcomponent or other subcomponents of the device. Such techniques may also be used to obtain certain device-specific information and specifications while the device remains within the patient's body.

In a first aspect, a system for inflating an intragastric balloon is provided, the system comprising: an inflation catheter, wherein the inflation catheter comprises a needle assembly, the needle assembly comprising a hollow needle, a bell-shaped needle sleeve, and a mechanism for detaching the inflation catheter after completion of in vivo balloon inflation; an intragastric balloon comprising a polymer wall, wherein the polymer wall comprises one or more layers, and a balloon valve system comprising a self-sealing septum in a retaining structure, wherein the septum is configured to be pierced by the needle, wherein the retaining structure comprises a concentric valve system having a smaller inner barrel for housing the septum and a larger barrel for housing material. a large outer barrel of a material providing a compressive force to a bell-shaped needle sleeve of the inflation catheter for inflation and detachment, wherein the material providing the compressive force is a material having a harder durometer than the septum, and wherein the smaller inner barrel includes a lip configured for an interference fit with the bell-shaped needle sleeve to provide a valve seal to the inflation catheter sufficient to maintain a seal during inflation of the balloon; a container outside the balloon; and an inflation source container, wherein the inflation source container is configured to be connected to the inflation catheter; wherein the inflation catheter connected to the intragastric balloon prior to inflation is sized and shaped to be swallowed by the patient when desired.

In an embodiment of the first aspect, the polymeric wall comprises a barrier material comprising one or more of nylon or polyethylene.

In an embodiment of the first aspect, the polymeric wall comprises a barrier material comprising nylon/polyethylene.

In an embodiment of the first aspect, the polymeric wall comprises a barrier material comprising nylon/polyvinylidene chloride/polyethylene.

In an embodiment of the first aspect, the outer container is selected from the group consisting of a push-fit capsule, a wrap, and a strip, wherein the outer container comprises a material selected from the group consisting of gelatin, cellulose, and collagen.

In an embodiment of the first aspect, the partition wall is tapered.

In an embodiment of the first aspect, the inflation source container is configured to be connected to the inflation catheter via a connector or an inflation valve.

In an embodiment of the first aspect, the inflation catheter is 1 to 6 French in diameter and approximately 50 cm to 60 cm in length.

In an embodiment of the first aspect, the inflation catheter is a dual lumen catheter comprising an inflation lumen and a separation lumen, wherein the inflation lumen is fluidly connected to an inflation source container, and wherein the separation lumen is configured for connection to a separation fluid source container, wherein the separation fluid contains a physiologically compatible fluid, and wherein the interference fit is insufficient to maintain a seal when hydraulic pressure is applied through the separation fluid such that hydraulic pressure is ejected from the balloon valve when hydraulic pressure is applied to the needle assembly.

In an embodiment of the first aspect, the inflation catheter comprises a single lumen and a structural member that provides increased tensile strength, and an inflation valve configured to connect the single lumen to an inflation source container and a separation fluid source container, wherein the separation fluid contains a physiologically compatible fluid, and wherein the interference fit is insufficient to maintain a seal when hydraulic pressure is applied through the separation fluid such that when hydraulic pressure is applied to the needle assembly, it is ejected from the balloon valve.

In an embodiment of the first aspect, the inner barrel is configured to control alignment of the needle assembly with the septum, provide a barrier to the needle piercing the polymer wall, and provide compression to reseal the septum after inflation and needle retraction.

In an embodiment of the first aspect, the plurality of intragastric balloons are connected to a single inflation catheter.

In an embodiment of the first aspect, the inflation catheter has a consistent stiffness.

In an embodiment of the first aspect, the inflation catheter has a variable stiffness.

In an embodiment of the first aspect, the inflation source comprises a syringe.

In an embodiment of the first aspect, the inflation source is configured to utilize information regarding inflation pressure as a function of time to provide feedback to a user, wherein the feedback is indicative of a condition selected from the group consisting of a failure due to mechanical obstruction, a failure due to esophageal restriction, a failure due to inflation catheter leakage or separation, and successful balloon inflation.

In a second aspect, a method for inflating an intragastric balloon is provided, the method comprising: providing an intragastric balloon in an outer container, the gastric balloon comprising a polymeric wall, wherein the polymeric wall comprises one or more layers, and a balloon valve system comprising a self-sealing septum in a retaining structure, wherein the retaining structure comprises a concentric valve system having a smaller inner barrel containing the septum and a larger outer barrel containing a material configured to provide a compressive force to a bell-shaped needle sleeve of an inflation catheter, wherein the material providing the compressive force is a material having a harder durometer than the septum, and wherein the smaller inner barrel comprises a lip configured for an interference fit with the bell-shaped needle sleeve; providing an inflation catheter comprising a needle assembly, the needle assembly The invention relates to a device comprising a hollow needle, a bell-shaped needle sleeve; piercing the septum with the needle of an inflation catheter, thereby creating an interference fit between the bell-shaped needle sleeve and a lip of a smaller inner barrel; allowing an intragastric balloon in an outer container to be connected by the interference fit to the inflation catheter to be swallowed by the patient when the patient desires the inflation fluid; degrading the outer container to allow inflation of the intragastric balloon; inflating the intragastric balloon in the patient's stomach via the inflation catheter, wherein the inflation catheter is connected to an inflation fluid source container; and detaching the intragastric balloon from the inflation catheter, wherein a detaching fluid, including a physiologically compatible fluid, is forced through the inflation catheter to apply fluid pressure to the needle assembly, causing the interference fit between the lip and the bell-shaped needle sleeve to be broken, the needle assembly to be ejected from the balloon valve, and the self-sealing septum to reseal.

In an embodiment of the second aspect, the inflation catheter is a dual lumen catheter comprising an inflation lumen and a detachment lumen, wherein the inflation lumen is configured for fluid connection to an inflation source container, and wherein the detachment lumen is configured for connection to a detachment fluid source container for balloon detachment.

In an embodiment of the second aspect, the inflation catheter is a single lumen catheter comprising a structural member that provides increased tensile strength and an inflation valve configured for connecting the single lumen catheter first to an inflation source container and then to a detachment fluid source container for balloon detachment.

In an embodiment of the second aspect, the method further comprises: monitoring the inflation pressure as a function of time, and detaching when a predetermined end pressure is achieved, wherein successful balloon inflation is indicated by achievement of the preselected end pressure, the preselected end pressure being based on a starting pressure in the inflation source and an inflated volume of the balloon.

In a third aspect, a method for deflating an intragastric balloon is provided, the method comprising: providing an intragastric balloon in an in vivo intragastric environment, the intragastric balloon comprising a polymeric wall and a valve system, the valve system comprising a self-sealing valve, a shell, an external sealing member, a rigid retention structure, and a deflation assembly; wherein the shell has one or more vent paths and a lip configured to hold the external sealing member in place, wherein the external sealing member is positioned to block the one or more vent paths when positioned, wherein the rigid retention structure provides support to the septum and the external sealing member, and wherein the deflation assembly is located in the shell and behind the retention structure; exposing the deflation assembly to a moist environment inside the balloon via the one or more vent paths, whereby the deflation assembly expands, pushes the retention structure and thereby pushes the external sealing member linearly through the lip of the shell to open the one or more vent paths, thereby providing fluid communication between the in vivo intragastric environment and the balloon lumen; and deflating the balloon through the one or more vent paths.

In an embodiment of the third aspect, the retraction component comprises a solute material encapsulated in a binder material, wherein the retraction component is further surrounded by a moisture limiting material having a predefined moisture evaporation transmission rate.

In an embodiment of the third aspect, the solute source comprises polyacrylamide.

In an embodiment of the third aspect, the rigid retaining structure and the housing have a press-fit lock for preventing the rigid retaining structure from being ejected from the housing after the maximum displacement of the retraction assembly.

In a fourth aspect, a method for deflating an intragastric balloon is provided, the method comprising: providing an intragastric balloon in an in vivo intragastric environment, the intragastric balloon comprising a polymer wall, a self-sealing valve system, and a deflation system, the deflation system comprising a shell, a sealing member, a piston, and a deflation assembly; wherein the shell has one or more vent paths and is fixed in the polymer wall, wherein the piston provides support for the sealing member and holds the sealing member in an appropriate position to block one or more vent paths in the shell when in the appropriate position, and wherein the deflation assembly is in the shell and behind the piston; exposing the deflation assembly to a moist environment inside the balloon via the one or more vent paths, whereby the deflation assembly expands, pushing the piston and thereby pushing the sealing member linearly through the shell to open the one or more vent paths to provide fluid communication between the in vivo intragastric environment and the balloon lumen; and deflating the balloon through the one or more vent paths.

In an embodiment of the fourth aspect, the intragastric balloon further comprises a moisture retention material positioned between the deflation component and the one or more vent paths, wherein the moisture retention material is configured to retain moisture and hold it toward a surface of the deflation component to maintain a constant moist environment.

BRIEF DESCRIPTION OF THE DRAWINGS

1A-D depict perspective ( FIG. 1A ), side ( FIG. 1B ), top ( FIG. 1C ), and cross-sectional views ( FIG. 1D ) of a head assembly of a self-sealing valve system comprising a self-sealing septum housed within a metallic concentric cylinder.

2A-D depict a perspective view ( FIG. 2A ), a side view ( FIG. 2B ), and a cross-sectional view ( FIG. 2C ) of a tube system with a ring, which includes a concentric metal retaining structure of a smaller cylinder into which a septum can be inserted or otherwise fitted, as in the self-sealing valve system of FIG. 1A-D .

3A-C depict perspective ( FIG. 3A ), side ( FIG. 3B ), and top ( FIG. 3C ) views of a ring stop—an additional ring disposed at the distal end of the inner barrel to provide additional compression to ensure the septum material is sufficiently dense to reseal itself—as in the self-sealing valve system of FIGs. 1A-D .

Figures 4A-D depict a perspective view (Figure 4A), a side view (Figure 4B), a cross-sectional view (Figure 4C), and a top view (Figure 4D) of a head unit that includes an outer cylinder of a concentric valve housing that includes a material of higher durometer than the inner cylinder, as in the self-sealing valve system of Figures 1A-D.

5A-C depict perspective ( FIG. 5A ), side ( FIG. 5B ), and top views ( FIG. 5C ) of an annular retainer—an additional retaining ring that further enhances the seal between the metal and silicone valves—as in the self-sealing valve system of FIGs. 1A-D .

FIG6 depicts a connector for a double lumen catheter.

Figure 7 depicts the inflation valve.

Figures 8A-B depict a universal balloon valve for connection to an inflation catheter and a balloon enclosed in an outer container. Figure 8A depicts the valve coupled to the inflation catheter, while Figure 8B depicts the valve further connected to the enclosed balloon.

9A-C depict side views ( FIG. 9B ), bottom views ( FIG. 9B ), and top views ( FIG. 9C ) of a double lumen catheter coupled to a gel cap enclosing a balloon.

10A-D depict a perspective view ( FIG. 10A ), a side view ( FIG. 10B ), a top view ( FIG. 10C ), and a cross-sectional view ( FIG. 10C ) of a bell-shaped needle sleeve.

Figures 11A-C depict various embodiments of single lumen catheters. Figure 11A depicts a single lumen catheter having a bell-shaped needle sleeve protecting the needle. Figure 11B illustrates a perspective, cross-sectional view of the single lumen catheter, showing details of the needle, bell-shaped needle sleeve, and pull wire. Figure 11C illustrates a perspective, cross-sectional view of the single lumen catheter, showing additional details of the needle and bell-shaped needle sleeve when installed in a head including the self-sealing valve system of Figures 1A-D.

12A-D depict perspective ( FIG. 12A ), side ( FIG. 12B ), top ( FIG. 12C ), and cross-sectional ( FIG. 12C ) views of a needle sleeve configured to accommodate a larger diameter tube.

FIG. 13 depicts a variable stiffness catheter for administering a gastric balloon.

14A-C depict an inflation fluid container system ( FIG. 14A ) including a connector ( FIG. 14B ) to a catheter and a pressure gauge ( FIG. 14C ).

FIG. 15 depicts a stainless steel inflation fluid container.

16A and 16B depict a disposable inflation fluid container with and without a cap (FIG. 16A and FIG. 16B, respectively).

FIG. 17 is a graph depicting pressure as a function of time (pressure decay), obtained by feedback from an inflation source container.

FIG. 18 depicts the expected decay curve for a pressure source using a spring mechanism or a balloon-within-a-balloon mechanism.

19A and 19B depict the inflation fluid dispenser isolated ( FIG. 19A ) or connected ( FIG. 19B ) to the inflation fluid container.

FIG. 20 depicts an inflation system for inflating a gastric balloon.

21A-B depict top views ( FIG. 21A ) and side views ( FIG. 21B ) illustrating balloon seam structures for making balloons that resist in vivo explosion.

Figures 22A-D depict various embodiments of an eroding core for balloon deflation. Figure 22A (perspective view) and Figure 22B (side view) depict an eroding core with a protective barrier between the core and the intragastric environment. In another embodiment, the seal is held in place against the housing by the eroding core (Figure 22C). After the core erodes (Figure 22D), the housing releases the seal.

FIG. 23 depicts a one-piece seal with a protective cover.

FIG24A depicts an inflation mechanism using an erodible core in a radial ring seal, with a compression ring used to remove the seal once support from the erodible core is removed. FIG24B depicts an inflation mechanism utilizing a seal with an erodible core and a push-out spring. FIG24C depicts a wet expansion material that pulls the septum out of position to trigger balloon deflation.

Figures 25A-B depict plugs in the balloon wall containing compressed balloons or balloons releasing gas. Figure 25A depicts a view of the balloon compressed, while Figure 25B depicts a view of the balloon expanded.

FIG. 26 depicts a top view of the outermost layer of a balloon that has been "scored" or "hatched" with an erodible material to create small channels that erode over time.

Figures 27A-E depict a composite wall of a balloon comprising several material layers (Figures 27A and 27B, showing details of Figure 27A). The composite wall is slowly penetrated by water injected into the balloon during manufacturing or inflation, causing the thin outer protective layer to rupture (Figure 27C). Water can penetrate through pores (Figure 27D), and the balloon may include a weakened area in the patch bond to control the rupture location (Figure 27E).

28A-B depict a top view (FIG. 28A) and a cross-section (FIG. 28B) of a pressure-sealing button adhesively bonded to a perforation in a balloon material for deflating.

Figures 29A-C depict a top view (Figure 29A), a perspective view (Figure 29B), and a perspective view with internal details (Figure 29C) of a connection port attached to the interior of a septum of a composite wall of a balloon, wherein the port comprises water-soluble and acid-soluble materials. Multiple ports and channels can be provided in a configuration utilizing an expansion material and a push-out assembly, as depicted in the system of Figure 29D (perspective view with internal details) and Figure 29E (cross-section).

Figures 30A-D depict ports that include both inflation and deflation mechanisms in the same location. Figure 30A depicts a cross-section of the mechanism with a seal blocking the vent. Figure 30B depicts a cross-section of the mechanism with a seal displaced to enable fluid communication through the vent. Figure 30C provides an iso image of the mechanism with a seal displaced to enable fluid communication through the vent. Figure 30D provides an iso image of the mechanism positioned for balloon inflation.

Figures 31A-D depict the deflation port. Figure 31A depicts a cross-section of a deflation mechanism with a seal blocking the vent. Figure 31B depicts a cross-section of a deflation mechanism with a seal displaced to enable fluid communication through the vent. Figure 31C provides an iso image of the mechanism with a seal blocking the vent. Figure 31D provides an iso image of the mechanism with a seal displaced to enable fluid communication through the vent.

Figure 32 depicts the placement of two balloons in a patient's stomach.

FIG. 33 depicts the Obalon gastric balloon assembly.

34 depicts an extension tube and stopcock with a three-way valve for use with the Obalon gastric balloon assembly of FIG. 33 .

35 depicts a Procedure Canister with a disposable nitrogen filling system for use with the Obalon gastric balloon assembly of FIG. 33 .

Figure 36 depicts the process tank valve in the "open" position.

37 depicts a luer lock plug configured to cover the gauge end of a process canister.

Figure 38 depicts the process tank valve in the "open" position and attached to the extension tube.

Figure 39 depicts a detail of an extension tube with a three-way valve with the stopcock in the "off" position.

Figure 40 depicts details of the disposable nitrogen filling system.

Figure 41 depicts the process canister with the lever in the "open" position prior to receipt of the disposable nitrogen fill system.

42 depicts the process canister of FIG. 35 with the stem in the “off” position after receiving the disposable nitrogen filling system.

43 depicts the procedure canister valve in the closed position and the Balloon Ejection Syringe and Obalon Gastric Balloon Assembly attached to the extension tube via the three-way valve.

FIG. 44 depicts catheter markers employed in conjunction with placement of the Obalon Gastric Balloon Assembly.

Figure 45 depicts the connection of the conduit to the process tank.

Figure 46 depicts a detail of an extension tube with a three-way valve with the stopcock in the "open" position.

47 depicts the procedure canister valve in the "open" position and the Balloon Ejection Syringe and Obalon Gastric Balloon Assembly attached to the extension tube via the three-way valve.

Figure 48 depicts a detail of an extension tube with a three-way valve with the stopcock in the "off" position.

DETAILED DESCRIPTION

The following description and examples describe preferred embodiments of the present invention in detail. Those skilled in the art will recognize that many variations and modifications of the present invention are encompassed within its scope. Therefore, the description of the preferred embodiments should not be considered to limit the scope of the present invention.

The term "degradable" as used herein is a broad term and should be given its ordinary and customary meaning to those skilled in the art (and is not limited to a specific or specialized meaning), and refers to processes by which the structural integrity of the capsule is compromised (e.g., by chemical, mechanical, or other means (e.g., light, radiation, heat, etc.) such that deflation occurs.

The degradation process may include erosion, dissolution, separation, digestion, decomposition, delamination, comminution, and other such processes.

As used herein, the term "swallow" is a broad term and should be given its ordinary and customary meaning to those skilled in the art (and not limited to a specific or specialized meaning). It refers to, without limitation, ingestion of the balloon by the patient, such that the outer capsule and its components are delivered to the stomach via normal peristaltic motion. While preferred embodiments of the system are swallowable, they are also configured for ingestion by methods other than swallowing. The swallowability of the system is at least partially determined by the size of the outer container for self-inflating systems and catheters, and the size of the outer container for manual inflation systems. For self-inflating systems, the outer capsule is sufficient to accommodate the inner container and its components, the amount of activating agent injected prior to administration, the balloon size, and the thickness of the balloon material. The system is preferably sized to be smaller than the average normal esophageal diameter.

Described herein is an oral ingestion device. In preferred embodiments, the device is capable of traversing the digestive tract. The device may be useful, for example, as an intragastric volume-occupying device. The device overcomes one or more of the aforementioned problems and disadvantages of existing intragastric volume-occupying devices.

In order to more clearly describe the subject matter of the preferred embodiments, different embodiments of the same subassembly will be described under the subheading of a single related heading. This structure is not intended to limit the manner in which the embodiments of the different subassemblies can be combined according to the present invention.

Swallowable intragastric balloon system

A swallowable, self-inflating, or inflatable balloon system, according to selected preferred embodiments, includes the following components: a self-sealing valve system for adding fluid to the balloon's lumen or internal container ("valve system"), the balloon in its deflated and compacted state ("balloon"), and an outer capsule, container, or coating encompassing the balloon ("outer container"). For self-inflating balloons, an inner capsule or other container ("inner container") located within the balloon's lumen includes one or more CO2-generating components. For inflatable balloons, an inflation fluid source, conduit, and tubing ("inflation assembly") are provided for inflating the balloon following ingestion or placement in the stomach. In self-inflating balloon configurations, the valve is preferably attached to the inner surface of the balloon via adhesive or other means (e.g., welding) and is equipped with an inoculation septum to prevent puncture of the balloon and inner container walls by a needle or other device used to inject the activating fluid into the balloon's lumen via the self-sealing valve. In inflatable balloon configurations, a valve is provided to releasably attach the tubing to the balloon. Preferably, the self-sealing valve system attached to the balloon (e.g., on its inner surface) in the inflatable configuration is "universal," or compatible with swallowable catheters or physician-assisted catheters. The valve system is used to allow inflation of the balloon using a microcatheter that includes a needle assembly and also provides a mechanism for detachment of the catheter after inflation is complete.

The outer container preferably comprises a balloon in a compacted state (e.g., folded and rolled), preferably having sufficient space to allow the activation liquid to be injected into the balloon from the inflatable balloon structure, wherein upon contact with the inflation agent included in the inner container, the liquid activation agent initiates the separation, erosion, degradation, and/or dissolution of the inner container and the generation of carbon dioxide, which subsequently causes the separation, erosion, degradation, and/or dissolution of the outer container due to the carbon dioxide gas pressure. In the inflatable balloon structure, the outer container only needs to be combined with the balloon in a compacted state.

Optional components of the swallowable intragastric balloon system of a preferred embodiment may include a silicone head with a radiopaque labyrinth, a trimmed 30D silicone septum, a nylon 6 inoculation spacer, a compacted balloon, an inner container (if self-inflating), and an outer container as the system is constructed in its unassembled form. The fully assembled outer container may include a vent hole aligned with the septum for puncturing to inject a liquid activation agent (if self-inflating) or a port for tubing connection (if inflatable). As discussed further below, particularly preferred components of the system have the properties described herein; however, in certain embodiments, systems may utilize components having other properties and/or values.

Devices according to preferred embodiments are intended for ingestion and deployment by the patient without resorting to invasive methods. It is therefore desirable that the devices of preferred embodiments be operable to adhere to a compact delivery state that can be swallowed by the patient with minimal discomfort. Once in the stomach, the device desirably assumes a larger deployed state. To achieve the transition from the delivery state to the deployed state, the device is inflated.

To treat obesity or assist individuals in achieving their weight loss goals, the various embodiments of the intragastric devices described herein are preferably delivered to a patient's stomach and maintained in an inflated state there for preferably at least 30 days. In some embodiments, the inflated intragastric device remains in the patient's stomach for a treatment duration of one to three months, and in some embodiments, the device remains in the patient's stomach for six months or more. Multiple intragastric devices may be delivered to the patient's stomach during the treatment duration. For example, in some embodiments, up to two, three, or more inflated intragastric devices (of the same size or two or more different sizes) may be present in the patient's stomach at a given time. At the conclusion of treatment, the devices may be endoscopically removed. In other embodiments, the devices may be deflated and passed through the lower gastrointestinal tract. To maintain an appropriate level of inflation and minimize patient discomfort and/or side effects, the patient may be prescribed one or more medications to be taken regularly while the intragastric device is in the patient's stomach. For example, in some embodiments, a proton pump inhibitor, an antiemetic, and/or an antispasmodic may be prescribed.

inner container

To initiate inflation in the self-inflating configuration, the inflation subassembly may require an external input, such as an activator. The activator is preferably injected using a syringe with a 25-32 gauge needle. The needle length is preferably approximately 0.2 inches (0.6 cm) to 1 inch (2.54 cm) to generate a flow rate that allows for delivery of the full volume of inflation agent within 30 seconds, but in a form/stream/flow that does not physically damage the internal container, thereby causing premature carbon dioxide generation and inflation. The activator is preferably purified water, or a solution containing up to 50% anhydrous citric acid at 20°C, or an equivalent at varying solution temperatures based on the solubility of anhydrous citric acid. Preferably, the system is configured such that, when the balloon is in a compacted configuration within the external container, there is approximately 0.3 ml to approximately 4.5 ml of occupiable empty space within the central lumen of the balloon, allowing a corresponding volume of activator to be injected into the empty space.

In one embodiment, prior to folding, the free-floating inner container containing the inflating agent for carbon dioxide generation is preferably aligned vertically with the self-sealing valve system so that the septum/inoculation spacer is positioned directly above the top of the capsule. The capsule comprises the inner container. The self-sealing valve system is adhesively attached to the interior of the capsule wall, and the inverted configuration of the capsule is provided by inverting the aperture, which is sealed with a patch. Approximately one-quarter of the top of the capsule wall is folded over the inner capsule, with the pleats where the capsule is wrinkled similar to those formed in the second step of making a paper airplane, and then folded to the left or right. Approximately one-third of the bottom of the capsule is then accordion-folded using no more than two folds and folded over the capsule. The left half is then folded over the right half of the capsule, or vice versa, so that the wings touch. The material is then rolled until it forms a tight roll. The device is then placed within the outer container.

In the self-inflating structure, the balloon is folded to form a pocket around the inner capsule to ensure that the liquid injected through the self-sealing valve system is contained in an area less than 10% of the total balloon surface area. There is no need to provide a pocket in the inflatable structure because there is no inner capsule. The balloon is folded so that the total number of folds is minimized, thereby minimizing damage to the external material or possible damage to the barrier properties. The total number of folds is preferably less than 10. When all possible folds of the balloon material are used, the number of folds required to assemble the balloon in the external container is minimized. Such efforts are also intended to prevent damage to the tubular material. The self-sealing valve is also preferably constructed to be offset from the center of the balloon to minimize the number of folds of the layers on each other.

In the self-inflating structure, the material forming the balloon wall is treated and folded to maximize reaction efficiency by localizing the initiator injected into the balloon so that it remains proximal to the reactants within the inner container. The balloon is folded so that once the reaction is initiated and the outer container is separated, the balloon expands in a manner that creates the maximum possible surface area, which prevents the balloon from easily passing through the pyloric sphincter. The ratio of the reactants in the inflating agent and the activating agent is selected so that the pH of any residual liquid inside the balloon lumen is acidic, having a pH of less than 6, so that any balloon leaks or ruptures that allow gastric acid to enter do not lead to the production of additional carbon dioxide and cause unintentional re-inflation.

In a self-inflating structure, the inflating agent is compressed, formed, or otherwise maintained in a shape that provides good surface area availability for the reactants used for CO2 generation while minimizing the space and/or volume required to accommodate the internal container. Preferably, the internal container has a length (longest dimension) of approximately 0.748 inches (1.9 cm) to 1.06 inches (2.7 cm) and a diameter or width of approximately 0.239 inches (0.6 cm) to approximately 0.376 inches (1 cm). The internal container volume is preferably approximately 0.41 ml to approximately 1.37 ml. The internal container is preferably in the form of a standard push-fit capsule, although tape may be used in its place. The container is preferably designed to contain the inflating agent; however, additional seals or other encapsulation may be used to control the timing of inflation. Gelatin is particularly preferred for use as the internal container; however, other materials, such as cellulose, may also be suitable. To minimize the internal volume of the system, it is generally preferred to include only a single internal container; however, in certain embodiments, two or more internal containers may be advantageously employed. The timing of self-inflation is selected based on normal esophageal transit time and gastric emptying time for larger food particles, so that the balloon does not inflate to a size that could block esophageal passage or prematurely pass the pyloric sphincter. The timing can also be controlled by compressing the balloon so that the activator is substantially localized within the balloon, creating an effective carbon dioxide self-inflation method. Inflation of the balloon is initiated by a liquid activator that triggers degradation of the inner container, allowing the inflation agent within the inner container to contact the liquid activator, thereby initiating a gas generation reaction.

Inflation combination

In certain preferred embodiments, the volume-occupying subcomponent is filled with fluid using tubing that is subsequently detached and pulled away from the volume-occupying subcomponent. One section of the volume-occupying subcomponent has a port connected to a sufficiently long tube that, when deployed, can cover the entire length of the esophagus from the mouth to the stomach. The tube is connected to the volume-occupying subcomponent using a self-sealable valve or septum that can be removed from the volume-occupying subcomponent and self-seals once the volume-occupying subcomponent is inflated. A physician or other healthcare professional secures one end of the tubing while the patient swallows the device. Once the device is in the stomach, the physician uses the tubing to transfer a fluid, such as air, nitrogen, other gas (ES), saline solution, purified water, or the like, into the volume-occupying subcomponent and thereby inflate it. After the volume-occupying subcomponent is fully inflated, the tube is released and can be pulled out of the patient's body.

The tube can be released in a variety of ways. For example, the tube can be detached by applying gentle force or pulling firmly on the tube. Alternatively, the tube can be detached by actuating a remote release, such as a magnetic or electronic release. Furthermore, the tube can be released from the volume-occupying subcomponent by an automatic ejection mechanism. Such an ejection mechanism can be actuated by the internal pressure of the inflated volume-occupying subcomponent. For example, the ejection mechanism can be sensitive to a specific pressure, and when exceeded, it will open to release any excess pressure and simultaneously release the tube. This embodiment provides the desired feature by combining the release of the tube with a safe volume to avoid accidental overinflation of the volume-occupying subcomponent in the patient's stomach.

This automatic release embodiment also provides the benefit that the device inflation process can be more closely monitored and controlled. Current technology allows for self-inflating intragastric volume-occupying subcomponents, which typically begin to inflate within four minutes after injection of an activating agent, such as citric acid. In this approach, the volume-occupying subcomponent may, in some cases, begin to inflate before residing in the stomach (e.g., in the esophagus), or in patients with gastric dumping syndrome or rapid gastric emptying, the volume-occupying subcomponent may reach the small intestine before inflation occurs. Therefore, in certain embodiments, it may be desirable to inflate the volume-occupying subcomponent on command once it is determined that the volume-occupying subcomponent is properly located.

In certain embodiments, it may also be advantageous to inflate the volume-occupying subcomponent gradually or in several steps over time. For example, if gas escapes the volume-occupying subcomponent before the desired inflation time, it may be advantageous for the device to re-inflate to maintain it in an expanded state.

outer container

The capsule is preferably provided in a deflated and folded state within a capsule or other retaining, containing, or coating structure ("outer container"). The outer container is preferably in the form of a standard push-fit capsule, wherein the push-fit is relied upon to contain the deflated/folded capsule; however, in certain embodiments, a gelatin package may be advantageously employed. Gel is particularly preferred for use as the outer container; however, other materials such as cellulose, collagen, etc. may also be used. Preferably, the outer container has a length (longest dimension) of from about 0.95 inches (2.4 cm) to 2.5 inches (6.3 cm) and a diameter or width of from about 0.35 inches (0.9 cm) to about 0.9 inches (2.4 cm). For self-inflatable versions, the inner container volume is preferably from about 1.2 ml to about 8.25 ml. In the self-inflating configuration, the outer container is preferably configured with one or more holes, slits, channels, or other outlets, preferably at each end, which serve as vents to prevent any gases generated by exposure of the inflating agent to condensation or other ambient moisture present during processing from causing premature separation or degradation of the inner container before 30 seconds after inoculation with the liquid activating agent, which could undesirably affect reaction efficiency. Such outlets can also accelerate the dissolution of the outer container to prepare the balloon for inflation in the inflatable configuration. The pressure buildup generated by balloon inflation (either via self-inflation or inflation of the catheter) accelerates the degradation process (e.g., separation, dissolution, or other opening) of the outer capsule. The outer capsule can be briefly soaked in water to soften the material, but without releasing the balloon prior to swallowing, minimizing the time between swallowing and balloon expansion. In the inflatable configuration, the outer container is provided with an aperture to accommodate the inflation catheter needle assembly, wherein the diameter of the catheter needle housing is mechanically compatible with the diameter of the outer container aperture, allowing the needle to be inserted into the self-sealing valve while retaining the contained balloon for easy insertion or swallowing of the balloon assembly. In a preferred embodiment, the outer container is a capsule. When the compacted capsule is inserted into the capsule, the distal half of the capsule can expand to prevent abrasion of the capsule material by the leading edge of the capsule. The capsule can also include two portions of the capsule held together by a gel band and comprising a folded capsule, which allows for rapid separation of the capsule so that inflation can occur more rapidly. The outer capsule degrades (e.g., separates, dissolves, or otherwise opens) upon ingestion of fluid (e.g., water), preferably in 5 minutes or less, more preferably in 2 minutes or less, to avoid causing discomfort to the patient while the capsule/catheter is in place.

In a preferred embodiment, the device is assembled into a standard-sized capsule. The capsule can be formed from a material with a known degradation rate so that the device will not be released from the capsule or otherwise deployed before entering the stomach. For example, the capsule material can include one or more polysaccharides and/or one or more polyols.

Alternatively, the device can be coated in its delivery state with a substance that restricts the device in the delivery state while also facilitating swallowing. Coating can be performed by dipping, sputtering, vapor deposition, or spraying methods, which can be performed under ambient or positive pressure. The capsule can also be encapsulated by wrapping tape around the capsule and then placing the encapsulated capsule in a capsule as desired.

In certain preferred embodiments, the encapsulated or coated device is lubricated or otherwise treated to facilitate swallowing. For example, the encapsulated or coated device may be moistened, heated, or cooled before swallowing by the patient. Alternatively, the encapsulated or coated device may be dipped in a viscous substance, which will help lubricate the device's passage through the esophagus. Examples of possible coatings include any substance with lubricious and/or hydrophilic properties, including glycerin, polyvinylpyrrolidone (PVP), petrolatum, aloe vera, silicone-based materials (such as Dow 360), and tetrafluoroethylene (TFE). The coating may also be applied by sputtering, vapor deposition, or spraying.

In other embodiments, the coating or capsule is impregnated or treated with one or more local anesthetics or analgesics to facilitate swallowing. Such anesthetics may include aminoamide-based anesthetics, such as articaine, lidocaine, and trimecaine, and aminoester-based anesthetics, such as benzocaine, procaine, and tetracaine. Analgesics may include analgesic sprays.

In certain embodiments, the capsule may be weighted at one end to properly orient it as it travels down the esophagus for administration, and/or when it is in the stomach. The weighting member may comprise a polymeric material or an inflation reagent.

The swallowable, self-inflating intragastric balloon is equipped with a mechanism to reliably control the timing of self-inflation, preventing premature inflation in the esophagus during swallowing and ensuring sufficient inflation in the stomach to avoid passage through the pyloric sphincter. Normal esophageal transit time for large food particles has been documented to be 4-8 seconds, while gastric emptying of large food particles through the pylorus does not occur for at least 15-20 minutes. The outer container is preferably configured to disintegrate, dissolve, degrade, erode, and/or otherwise allow the deflated/folded balloon to begin expanding no less than 60 seconds but no more than 15 minutes after inoculation with the liquid activator. The inner container is preferably configured chemically, mechanically, or a combination thereof to delay the initial carbon dioxide generation chemical reaction, such that sufficient carbon dioxide to begin inflating the balloon is not available until 30 seconds after inoculation with the liquid activator, but to allow sufficient carbon dioxide generation to fill at least 10% of the balloon's occupiable volume within 30 minutes, at least 60% of the balloon's occupiable volume within 12 hours, and at least 90% of the balloon's occupiable volume within 24 hours. This timing allows the active agent to be injected into the external container by a medical professional as the device is delivered to the patient and swallowed by the patient by normal peristaltic means. This timing also prohibits the potential passage of an uninflated balloon into the duodenum by the balloon that is inflating to a sufficient size, making gastric emptying of the balloon difficult to achieve, as objects over 7 mm in diameter cannot easily pass through.

Conveying components

In certain embodiments, it may be advantageous for the device administrator to use a delivery tool to deliver the device to the oral cavity or facilitate its passage through the esophagus in optimal orientation. The delivery tool allows the device administrator to inject the device 10 with one or more inflating agents while the device is being administered to the patient. In preferred embodiments, such injection can be accomplished using the same mechanical action used by the administrator to release the device from the delivery tool into the oral cavity or esophagus. For example, the delivery tool may include a piston, a reservoir containing a liquid, and an injection needle. The administrator sequentially or approximately simultaneously pushes the pistons, forcing the injection needle into the device and thereby injecting the liquid contained in the reservoir into the device. Subsequent application of force to the piston pushes the device out of the delivery tool and into the desired location within the patient. Furthermore, the delivery tool may include a subassembly that applies an anesthetic or lubricant to the patient's oral cavity or esophagus to facilitate swallowability of the device.

cyst

The volume-occupying subcomponent ("balloon") of the preferred embodiment is generally formed of a flexible material forming walls defining an exterior surface and an interior lumen. The various subcomponents described above may be incorporated into either the wall or the interior lumen of the volume-occupying subcomponent. As shown, the size and shape of the volume-occupying subcomponent may vary depending on the patient's internal dimensions and the desired outcome. The volume-occupying subcomponent may be designed to be semi-compliant, allowing the volume-occupying subcomponent to stretch or expand with increasing pressure and/or temperature. Alternatively, in some embodiments, a compliant wall that offers little resistance to volume increase may be desirable.

Spherical or elliptical volume-occupying subcomponents are preferred in certain embodiments. Alternatively, the volume-occupying subcomponent can be constructed in the shape of a doughnut with a hole in the center and weighted and shaped in such a way that it is oriented in the stomach to cover all or part of the pyloric sphincter, similar to a check valve. The hole in the center of the volume-occupying subcomponent can then serve as the primary passage for gastric contents into the small intestine, restricting the passage of food out of the stomach and inducing satiety by reducing gastric emptying. The volume-occupying subcomponent can be manufactured with doughnut holes of different sizes depending on the degree to which gastric emptying is desired to be reduced. Delivery, inflation, and deflation of the volume-occupying subcomponent can be accomplished by any of the methods described above.

In certain embodiments for the volume-occupying subcomponent, it is advantageous for the wall to be both strong and thin to minimize the volume compacted by the device as it travels in the patient's esophagus. In certain embodiments, the wall material of the volume-occupying subcomponent is manufactured using biaxial orientation, which can impart a high modulus value to the volume-occupying subcomponent.

In one embodiment, the volume-occupying subcomponent is composed of a polymeric material such as polyurethane, polyethylene terephthalate, polyethylene naphthalate, polyvinyl chloride (PVC), nylon 6, nylon 12, or polyether block amide (PEBA). The volume-occupying subcomponent can be coated with one or more layers of a material that modifies (increases, decreases, or changes over time) other barrier properties, such as a thermoplastic material.

Preferably, the other barrier material has low permeability to carbon dioxide or other fluids that can be used to inflate the volume-occupying subcomponent. The barrier layer should adhere well to the substrate. Preferred barrier coating materials include biocompatible poly(hydroxyamino ether), polynaphthalene, polyvinylidene chloride (PVDC), saran, ethylene vinyl alcohol copolymer, polyvinyl acetate, silicon oxide (SiOx), acrylonitrile copolymer, or copolymers of terephthalic acid, ethylene glycol, and at least one diol. Alternative barrier materials may include polyamine-polyepoxides. These materials are typically available as solvent- or water-based thermosetting compositions and are typically spray-coated onto the preform and then heat-cured to form the final barrier coating. Alternative barrier materials that can be applied as a coating to the volume-occupying subcomponent include metals such as silver or aluminum. Other materials that can be used to improve the hermeticity of the volume-occupying subcomponent include, but are not limited to, gold or any precious metal, saran-coated PET, conformal coatings, and the like, such as those listed in Tables 1a-b.

In certain preferred embodiments, the volume-occupying subcomponent is injection molded, blow molded, or rotationally molded. Either immediately following such molding, or after a period of curing, a gas barrier coating may be applied if not already applied within the composite wall.

In another embodiment, the intragastric volume-occupying subcomponent is formed using Mylar polyester film coated with silver, aluminum, or kelvalite as a metallized surface to improve the gas impermeability of the volume-occupying subcomponent.

In cases where the wall of the volume-occupying subcomponent is composed of multiple layers of material, it may be necessary to use specific substances or methods to connect, attach, or hold the multiple layers together. These substances may include solvent or ether-based adhesives. The multiple layers may also be thermally bonded together. Once the layers are attached together to form, for example, a sheet of volume-occupying subcomponent material, it may also be necessary to subject these materials to additional processing steps to allow them to be sealed together (e.g., by applying a certain degree of heat and pressure) to form the volume-occupying subcomponent. Thus, for example, a volume-occupying subcomponent may include a specific sealing material as an additional layer. For example, a volume-occupying subcomponent composed of a combination of PET and SiO layers, which imparts good mechanical and gas-impermeability properties to the volume-occupying subcomponent, may be sealed by including a sealable polyethylene layer therein.

According to another embodiment of the preferred embodiment, the functionality of the volume-occupying subcomponent and the deflation component are partially or fully combined. For example, the volume-occupying subcomponent can be formed from a material that degrades within the stomach over a desired period of time. Once the degradation process has created a breach in the wall of the volume-occupying subcomponent, the volume-occupying subcomponent deflates, begins to degrade, and passes through the remainder of the digestive tract.

Preferably, an automated process is employed that uses a fully constructed volume-occupying subcomponent, evacuates all air from the lumen, and folds or compresses the volume-occupying subcomponent to the desired delivery state. For example, evacuation of air from the volume-occupying subcomponent can be actuated by vacuum or mechanical pressure (e.g., rolling the volume-occupying subcomponent). In certain embodiments, it is desirable to minimize the number of folds created when the volume-occupying subcomponent is in the delivery state.

In another embodiment, the volume-occupying subcomponent can be expanded and contracted by one or more injection sites within the wall of the volume-occupying subcomponent. For example, two self-sealing injection sites can be incorporated into opposing sides of the volume-occupying subcomponent. The volume-occupying subcomponent can be located within a fixture that utilizes two small metering needles to evacuate air from the volume-occupying subcomponent.

In one embodiment, the self-sealing injection site can further be used to insert the chemical elements of the inflatable subcomponent into the interior of the volume-occupying subcomponent. After the chemical elements are injected into the volume-occupying subcomponent, the same needle can be used to perform the deflation of the volume-occupying subcomponent.

It may be desirable for the volume-occupying subcomponent to be filled into a delivery state, for example, under negative vacuum pressure or positive external pressure.

The wall materials of the volume-occupying subcomponent may also be designed so that, once they are initially punctured or torn, they can be torn away relatively easily from the point of the puncture or tear. Such a property may be advantageous, for example, if deflation of the volume-occupying subcomponent is initiated by a tear or puncture of the volume-occupying subcomponent wall, as such an initial tear or puncture may subsequently increase, accelerate, and/or maximize the extent of the deflation process.

The volume-occupying subcomponent may also be coated with a lubricating substance to facilitate its passage out of the body after deflation. Examples of possible coatings may be any substance with lubricious and/or hydrophilic properties and include glycerin, polyvinylpyrrolidone (PVP), petrolatum, aloe vera, silicone-based materials (such as Dow 360), and tetrafluoroethylene (TFE). Coating may be performed by dipping, sputtering, vapor deposition, or spraying methods, which may be performed under ambient or positive pressure.

The composite wall material of the capsule can have similar structures and compositions to those described in U.S. Patent Publication No. 2010-0100116-A1, the contents of which are hereby incorporated by reference in their entirety. The material can accommodate fluids preferably in the form of compressed or non-compressed gases, such as nitrogen, argon, oxygen, carbon dioxide, or mixtures thereof, or atmospheric air (oxygen, argon, carbon dioxide, neon, methane, helium, krypton, hydrogen, and xenon), which simulate gastric space concentrations. In certain embodiments, the capsule can retain fluid (gas) and maintain an acceptable volume for up to 6 months, preferably at least 1 to 3 months after inflation. Particularly preferred filling gases include non-polar macromolecular gases that can be compressed for delivery.

Before being placed in the outer container, the sac is deflated and folded. In the inverted configuration in the deflated state, the sac is flat with an inverted seam extending around the periphery of the sac. The self-sealing valve system is secured to the inner wall of the lumen near the center of the deflated sac, with the inner container positioned adjacent the self-sealing valve system. The sac wall is then folded. As part of the sac design, the self-sealing valve system is manufactured in a manner that allows it to be, and preferably is, placed "off-center" to minimize the number of folds on itself (e.g., double or triple folds upward) required to assemble the sac in the outer container. For example, the self-sealing valve system may advantageously be placed at ½ r ± ¼ r from the center of the sac, where r is the radius of the sac along a line extending from the center of the sac through the septum.

Tracing and visualizing subcomponents

It may also be beneficial to implement tracking and visualization capabilities into the device according to the present invention.Due to the non-invasive nature of the present device, a physician may wish to determine or confirm the position and orientation of the device prior to inflation or during treatment.

When the volume-occupying subcomponent is in a folded or collapsed state, a radiographic marker may be applied to the volume-occupying subcomponent such that the marker appears concentrated when viewed on a visualization device when the volume-occupying subcomponent is in a deflated state, and less concentrated when viewed on a visualization device when the volume-occupying subcomponent is inflated. Alternatively, markers may be applied or incorporated into the volume-occupying subcomponent at multiple locations to facilitate identification and location of various subcomponents of the device, such as valves, heads, or weights. The marker may be printed or applied to the surface of the volume-occupying subcomponent or between layers of material forming the volume-occupying subcomponent. Alternatively, a metal coating, as described below, may be used as a marker to identify and/or locate the volume-occupying subcomponent. Metal coatings for visualization of the volume-occupying subcomponent may include silver, gold, tantalum, or any other precious metal. Alternatively, the marker may be applied to a sleeve of elastomeric material covering all or part of the volume-occupying subcomponent.

In another embodiment, the volume-occupying subcomponent includes a subcomponent that mechanically changes when the volume-occupying subcomponent is inflated, and the mechanical change can be visualized using X-ray or other visualization equipment. For example, a mechanical portion of the volume-occupying subcomponent containing a visual marker can elongate when pressure increases within the volume-occupying subcomponent.

Alternatively, the markers may be formed using a metallized grid positioned between the layers of material comprising the volume-occupying subcomponent.The pattern formed by the embedded markers will appear when the volume-occupying subcomponent is in an inflated or deflated state.

It is envisioned that marker materials may be incorporated into the volume-occupying subcomponent to facilitate various visualization techniques such as MRI, CT, and ultrasound.

The volume-occupying subcomponent may also contain a dye or marker that is released upon deflation to indicate that the volume-occupying subcomponent lumen has been breached. Such a dye or marker may be, for example, present in the patient's urine as an indicator that the volume-occupying subcomponent has begun to deflate.

In yet further embodiments, electronically enabled microchips and other components may be used to locate and identify the device. Microchips similar to those used for pet identification can be used to convey specific information and its approximate location to the device. For example, a Wheatstone or other bridge circuit may be incorporated into the device and used, along with radio frequency "ping and listening" technology, as part of a system to determine the device's approximate location and measure and convey device-specific information. Such device-specific information may include the pressure of the internal volume-occupying subcomponent, which may indicate the degree of inflation of the volume-occupying subcomponent.

In still further embodiments, mechanical, chemical, visual, and other sensors may be included as part of the device to measure, record, and/or transmit information related to the device and/or the patient's internal environment. For example, the device may include a camera and other imaging and transmission components of the PillCam device. As additional examples, the device may include sensors that measure, record, and/or transmit information related to gastric pH, gastric pressure, hormone levels, organ health, and organ safety.

Valve system

In a preferred embodiment, a self-sealing valve system is attached to the balloon (e.g., on its inner surface) that is "universal" or "compatible" with swallowable catheters as well as physician-assisted catheters. The valve system is used to allow inflation of the balloon using a microcatheter that includes a needle assembly and also provides a mechanism for detachment of the catheter after inflation is complete.

1A-D depict views representing a design for a self-sealing valve system comprising a self-sealing septum housed within a metal concentric barrel. In the inflatable configuration, the self-sealing valve system is preferably adhered to the underside of the balloon material, such that only a portion of the valve protrudes slightly beyond the balloon surface to ensure a smooth surface. The valve system for the inflatable configuration can utilize the same self-sealing septum as that designed for the self-inflating configuration. The septum is preferably comprised of a material having a durometer of 20 Shore A to 60 Shore D. The septum is inserted or otherwise assembled into the smaller barrel of the concentric metal retaining structure ( FIG. 2A - the smaller barrel within the larger barrel controls the alignment of the catheter needle sleeve/needle combination with the septum, provides a hard barrier to prevent the catheter needle from puncturing the balloon material (needle stop mechanism), and provides compression to allow the valve/septum to reseal after inflation and subsequent needle withdrawal.

Concentric valve systems can also provide radiopacity during implantation and are preferably made of titanium, gold, stainless steel, MP35N (a non-magnetic, nickel-cobalt-chromium-molybdenum alloy), etc. Non-metallic polymeric materials can also be used, such as acrylic, epoxy, polycarbonate, nylon, polyethylene, polyetheretherketone, ABS, or PVC, or any thermoplastic elastomer or thermoplastic polyurethane that can be made visible under x-ray (e.g., embedded with barium).

The septum can be tapered to maximize the compressive force after inflation, allowing for self-sealing. The self-sealing septum allows air to be evacuated from the balloon for handling/compacting and insertion into an external container. It also permits puncture with an inflation syringe needle (self-inflating configuration) or an inflation catheter needle (inflatable configuration), and subsequent withdrawal of the inflation syringe needle or detachment of the inflation catheter and catheter needle, significantly limiting gas leakage outside the balloon during the inflation process and needle and catheter withdrawal/detachment. The septum is inserted into the valve using a mechanical fit to provide compression. An additional ring (Figures 3A-C) can be placed at the distal end of the inner barrel to provide additional compression, ensuring that the septum material is preloaded to reseal itself. The ring is preferably metallic but can also be a non-metallic polymeric material such as acrylic, epoxy, or thermoplastic elastomer or thermoplastic polyurethane. The ring material is preferably the same as the barrel material, titanium, but can also be gold, stainless steel, MP35N, etc.

In the inflatable configuration, the larger outer barrel of the concentric valve housing (Figures 4A-D) comprises a slightly harder durometer material (50 Shore A or higher) than the inner barrel, preferably silicone. The harder durometer material ensures a tight seal during inflation with the needle sleeve. The silicone ring surrounding the concentric valve is bonded to the balloon from the inner surface. The entire outer barrel is filled with silicone and provided with a small, circular lip of the same material, slightly larger than the inner barrel diameter, extending to the outer surface of the balloon. This lip is compatible with the bell-shaped needle sleeve and provides a seal that strengthens the valve-catheter connection to withstand applied inflation pressures and increases catheter ejection distance or catheter attachment force. This silicone lip preferably protrudes no more than 2 mm beyond the balloon surface to ensure it remains relatively smooth and does not cause mucosal abrasion or ulceration. It is designed to provide compressive force against the catheter needle sleeve during inflation and detachment. When connected to the inflation catheter needle sleeve, the coupling can preferably withstand pressures of 35 PSI during inflation. The seal is then broken using hydraulic pressure, preferably greater than 40 PSI but less than 200 PSI, to decouple the coupling. An additional retaining ring (Figures 5A-C), preferably made of the same material as the concentric valve, may be included in the valve system to further improve the seal between the metal and the valve silicone, provide additional mechanical support to ensure proper mechanical fit, and is intended to break the silicone material from hardening the (metal) valve system and causing an increase in tension.

The valve structure for the inflatable structure uses a mechanical fit mechanism to provide a self-sealing function for inflation of the catheter and subsequent detachment of the catheter; however, primers and/or adhesives provide additional support in the assembly construction. The structure can be modified by modifying the surface of the metal components to make them more sticky or slippery, such as to facilitate adhesion, to provide the desired mechanical/interference fit. The interference fit between the valve and the catheter can be modified to change the pressure requirements for inflation and/or detachment. The inflation add-on assembly can include overmolding the metal portion or concentric system with silicone, so that additional support rings to ensure the mechanical fit, tensile strength, and force required to maintain the assembly during catheter inflation and detachment can be omitted.

The total valve diameter in the inflated configuration is designed to fit a microcatheter system with a diameter not exceeding 8 French (2.7 mm, 0.105 inches). Additional valves may be added if desired; however, it is generally preferred to use a single valve in order to keep the deflated/collapsed balloon volume (and therefore the outer container size) as small as possible. The valve system is preferably connected to the balloon and engaged such that a shear force greater than 9 pounds (40 N) is required to dislodge the valve system.

In a self-inflating configuration, the valve system can be attached to the balloon (e.g., on its inner surface) without using openings, holes, or other conduits in the balloon wall. The valve system can utilize a septum with a durometer of 20 Shore A to 60 Shore D. The valve can be inserted or otherwise assembled into a retaining structure with a higher durometer, such as 40 Shore D to 70 Shore D or more. The retaining structure can be made of silicone, rubber, soft plastic, or any suitable non-metallic polymeric material, such as acrylic, epoxy, thermoplastic elastomer, or thermoplastic polyurethane. Preferably, a structure, such as a ring, which can be metallic or non-metallic but radiopaque (e.g., barium) and visible under X-ray, can be embedded into the retaining structure. Using two structures of different durometers, a mechanically mating mechanism with a softer (septum) having a larger diameter can be inserted into a fitted, higher durometer structure, generating a compressive force in the previously open orifice to enable carbon dioxide retention and reduce susceptibility to carbon dioxide leakage. The radiopaque metal ring also helps support the compressive force on the septum. The self-sealing septum allows air to be evacuated from the balloon for handling/compacting and insertion into the outer container, and also allows the inflation agent to be injected into the outer container for inflation initiation. Additional septums may be added if desired; however, it is generally preferred to use a single septum to minimize the volume of the deflated/collapsed balloon (and therefore the outer capsule) to be as small as possible. The valve system is preferably attached to the interior of the balloon so that a shear force greater than 9 pounds (40 Newtons) is required to remove the valve system. A silicone tip and radiopaque ring can be used for the self-sealing valve system, as can a wedge-shaped septum.

In the self-inflating configuration, an inoculation septum is preferably incorporated to guide a needle into the self-sealing valve for injection of the liquid activating agent into the balloon lumen and prevent the needle from puncturing the deflated/folded balloon wall, which could prevent pressure from being maintained within the balloon lumen. The inoculation septum also helps prevent the liquid activating agent from penetrating the inner container or the folded balloon material, thereby properly concentrating the activating agent and properly mixing the reactants for carbon dioxide generation according to the aforementioned criteria. The inoculation septum is typically tubular or cylindrical in shape. It is preferably attached to the inner container and/or the self-sealing valve system using adhesive or other securing means; however, in certain embodiments, the inoculation septum may be "free-floating" and held in place by a fold or fold of the balloon wall. The inoculation septum may comprise any suitable material that can be passed through upon separation, erosion, degradation, digestion, and/or dissolution of the outer container; however, preferred materials include non-metallic materials with a minimum Shore D hardness of 40 or greater, any metallic material, or a combination thereof. A cup-shaped needle stop (inoculation septum) may be employed in preferred embodiments.

cyst

In a preferred embodiment, the self-inflating balloon is completely sealed 360 degrees around the periphery. In the self-inflating configuration, with the activating agent injected via a needle syringe, there is preferably no external opening or orifice to the central lumen. In the inflatable configuration, a valve structure (whether protruding, recessed, or flush with the balloon surface) is provided for delivering the inflation fluid to the central lumen. The balloon may have a "non-inverted," "inverted," or "overlapping" configuration. In the "non-inverted" configuration, the seams or welds and seam allowances, if any, are located outside the inflated balloon. In the "overlapping" configuration, the layers overlap, optionally with one or more folds, and are secured to each other by welds, seams, adhesives, etc., resulting in a smooth outer surface. In the "inverted" configuration, the balloon has a smooth outer surface within the inflated balloon, including welds, seams, adhesive beads, etc. To create a balloon with an inverted structure, such as one with no external seam allowance (no wall material between the edge of the balloon and the weld, seam, or other feature connecting the sides together), the two balloon halves are joined together in some manner (e.g., using adhesive, heat, etc., depending on the balloon material used). One balloon half includes an opening to allow the balloon to be pulled through itself after the two halves are attached, and has a balloon seam on the inside. The opening is preferably circular, but can be any similar shape, and the diameter of the opening is preferably no more than 3.8 cm; however, larger diameters may be acceptable in certain embodiments. A patch of material is attached (adhesive, heat welded, etc., depending on the material used) to cover the original balloon half opening. The resulting inverted hole, which is then patched, is small enough so that the forces applied during inflation do not damage the material used to maintain fluid in the balloon. The preferred shape of the inflatable balloon in final assembly is an ellipse, preferably a sphere or oblate spheroid, with a nominal radius of 1 inch (2.5 cm) to 3 inches (7.6 cm), a nominal height of 0.25 inches (0.6 cm) to 3 inches (7.6 cm), a volume of 90 cubic centimeters to 350 cubic centimeters (at 37°C and nominal internal pressure and/or fully inflated), an internal nominal pressure (at 37°C) of 0 psi (0 Pa) to 15 psi (103421 Pa), and a weight of less than 15 grams. The self-inflating balloon is configured to self-inflate with CO2 and is configured to maintain greater than 75% of its original nominal volume for at least 25 days, preferably at least 90 days, while residing in the stomach. The inflatable balloon is configured to be inflated with an appropriate gas mixture to deliver a preselected volume profile over a preselected time period, including one or more of a volume increase period, a volume decrease period, or a steady-state volume period.

The preferred shape of the inflated balloon in final assembly is an ellipse, preferably a sphere or oblate spheroid, having a nominal radius of 1 inch (2.5 cm) to 3 inches (7.6 cm), a nominal height of 0.25 inches (0.6 cm) to 3 inches (7.6 cm), a volume of 90 cubic centimeters to 350 cubic centimeters (at 37°C and nominal internal pressure and/or fully inflated), an internal nominal pressure (at 37°C) of 0 psi (0 Pa) to 15 psi (103421 Pa), and a weight of less than 15 grams. In certain embodiments, where a stable volume over the life of the device is preferred, the balloon is configured to maintain a volume of at least 90% to 110% of its original nominal volume. In other embodiments, it may be desirable for the balloon to increase and/or decrease in volume (e.g., linearly, in a stepwise manner, or in another non-linear manner) over its life.

inner container

An inner container for a self-inflating balloon is contained within the balloon lumen and includes a carbon dioxide generator for self-inflation. The carbon dioxide generator comprises an inflating agent mixture contained within the container. Preferably, approximately 10% to approximately 80% of the total inflating agent used comprises powdered citric acid, with the remainder comprising powdered sodium bicarbonate. Sufficient inflating agent is provided so that, after the CO2 generation reaction is complete, the balloon is inflated to the aforementioned nominal inflation pressure. Preferably, a total of approximately 0.28 to 4 grams of the inflating agent mixture is used, depending on the size of the balloon to be inflated; preferably, up to 1.15 grams of sodium bicarbonate is used, with the remainder being powdered citric acid, to generate 300 cubic centimeters of CO2 at the nominal pressure.

Inflatable components

In certain embodiments, an intragastric balloon system that is manually inflated via a microcatheter may be employed. This system is preferably still "swallowable." The balloon for delivery is in a compacted state and attached to a flexible microcatheter, preferably no larger than 4 French (1.35 mm) in diameter. The catheter is designed so that a portion of the catheter can be bundled or wrapped around itself for delivery with the enclosed balloon, allowing the patient to swallow both the catheter and the balloon simultaneously for delivery to the stomach. The balloon may contain a self-sealing valve system for catheter attachment and balloon inflation once it reaches the gastric cavity. The proximal end of the catheter may remain just outside the patient's mouth, allowing connection to an inflation fluid container containing the preferred inflation fluid (gas or liquid). After inflation, the catheter can be detached from the balloon valve and retracted through the mouth. This approach allows the intragastric balloon to maintain its swallowability while allowing for inflation via the catheter from a fluid source or a combination of fluid sources. Alternatively, a more rigid, pushable system may be employed, with the balloon valve compatible with either a swallowable flexible catheter or a pushable rigid catheter assembly.

The inflation catheter described herein (which can be swallowed or pushed with the assistance of an administrator) is configured for oral delivery of the balloon device and requires no additional tools. The application procedure does not require conscious sedation or other similar sedation procedures for delivery or the need for endoscopic tools. However, other versions of the device may incorporate endoscopic tools for visualization, or may be adapted so that the balloon can also be used for nasal delivery.

During operation, the proximal end of the inflation catheter is connected to a valve or connector, preferably a connector or inflation valve, that allows for connection and disconnection to an inflation source (Figures 6 and 7, respectively). The connector can be made of polycarbonate, among other materials, and can be connected to single- or multi-lumen catheter tubing. The distal end of the inflation catheter is connected to a universal balloon valve that has been compressed and contained within a capsule or tape-constrained balloon (Figures 8A-B). The catheter tubing preferably has a diameter of 1 French (0.33 mm) to 6 French (2 mm). The catheter is preferably long enough to extend through the mouth (where it is connected to the inflation connector or valve) and down the esophagus to at least the middle of the stomach—approximately 50-60 cm. A measuring tool may be added to the tube or catheter to help identify the location of the tube end. Inflation timing can be initiated by a tube containing a pH sensor that determines the pH difference between the esophagus (pH 5-7) and the stomach (pH 1-4) based on the pH difference between the two anatomical sources, or it can be derived or verified from the expected pressure in the constrained space (i.e., the esophagus) relative to the less constrained space (i.e., the stomach). The tube can also be made of nickel-titanium alloy, which has adjustable transmission of body temperature to take into account the timing of swallowing. The tube can also be connected to a single catheter with a series of encapsulated or compacted balloons. Each can be inflated and released separately. The number of balloons released can be adjusted to the patient's needs and desired weight loss.

In a preferred embodiment, a catheter with a balloon at its distal end (inflated with air) is used to temporarily and firmly hold the balloon in place. A small, deflated balloon catheter can be passed through the head of the gastric balloon (e.g., a "balloon within a balloon") and then inflated with air during delivery to firmly hold the capsule and balloon in place and prevent the balloon from spontaneously detaching from the catheter. This balloon catheter can incorporate a dual channel, which also allows larger gastric balloons to be inflated (with gas or liquid). Once the gastric balloon has been satisfactorily inflated, the small balloon catheter can be deflated, the valve pulled out (making it self-sealing), and expelled from the body, leaving the inflated gastric balloon in the stomach.

In other embodiments, the catheter may be coated to improve swallowability, or infused or treated with a flavoring and/or one or more local anesthetics or analgesics to facilitate swallowing. Such anesthetics may include aminoamide-based anesthetics, such as articaine, lidocaine, and trimecaine, and aminoester-based anesthetics, such as benzocaine, procaine, and tetracaine. Analgesics may include analgesic sprays.

Double-lumen catheter

In a preferred embodiment, a swallowable double-lumen catheter is provided. The double-lumen catheter (Figures 9A-C) has two lumens with a fully assembled diameter no greater than 5 French (1.67 mm), preferably no greater than 4 French (1.35 mm). The inner lumen is preferably no greater than 3 French (1 mm) and serves as the inflation tube, while the outer lumen is preferably no greater than 5 French (1.67 mm) and serves as the disconnect tube. As described in detail below, the distal end of the catheter assembly is connected to the needle assembly and the proximal end is connected to the dual-port inflation connector. The catheter assembly is designed to be swallowable, flexible, kink-resistant, able to withstand body temperature, acid-resistant, and biocompatible as it traverses the digestive tract and enters the gastric cavity. The tubing material is preferably soft and flexible, with moderate tensile strength and significant hoop strength to handle applied pressure. The lumens are preferably circular, coaxial, and free-floating, providing flexibility. The double-lumen assembly also preferably does not require adhesives or glue. Alternative lumen configurations may include two D lumens or a combination of a D lumen and a round lumen and may be used in a stiffer configuration of the final catheter assembly. Preferred materials for tubing include heat-resistant polyethylene tubing such as PEBAX® or heat-resistant polyurethane tubing such as PELLETHANE™, polyetheretherketone, or nylon. Tubing may also be made from bioresorbable materials such as polylactic acid (PLA), poly-L-aspartic acid (PLAA), polylactic/glycolic acid (PLG), polycaprolactone (PCL), DL-lactide-co-ε-caprolactone (DL-PLCL), etc., where the tubing can be released after normal inflation, detachment, and swallowing.

At the distal end of the catheter assembly, an internal lumen or inflation tube is attached to a needle assembly that punctures the balloon's self-sealing valve, which is preferably located at one of the apexes of the balloon, housed within a capsule serving as an outer container. The external lumen is connected to a needle sleeve and provides a connection between the catheter assembly and the balloon, providing tensile strength to withstand initial inflation pressures preferably up to 10 psi and preferably no more than 35 psi. The needle sleeve is configured to mechanically couple to the balloon's valve assembly. The needle is preferably made of metal, preferably stainless steel, with a maximum size of 25 gauge (0.455 mm), preferably no smaller than 30 gauge (0.255 mm), for inflation timing purposes. The needle sleeve is preferably made of a soft material such as nylon, but can also be made of polycarbonate, polyethylene, polyetheretherketone, ABS, or PVC. The needle sleeve covers the entire length of the needle to protect the patient from needle damage, and the needle can only pierce the septum wall. The needle sleeve preferably runs flush with the needle or slightly extends beyond it. The needle is inserted into the balloon septum prior to swallowing and maintains a retention force of approximately 0.5 lbs when coupled to the silicone area of the balloon valve. The needle sleeve is preferably slightly bell-shaped (FIGS. 10A-D) or includes a rounded ridge or lip, so that when inserted into the silicone area of the valve, a lock and key mechanism is created to increase the tensile strength of the assembly and enhance the seal for inflation.

At the proximal end, the catheter assembly is connected to a Y-adapter assembly, preferably made of polycarbonate. The Y-adapter is "keyed" so that inflation gas and connection fluids are properly connected to the catheter assembly and travel down the correct lumen.

Prior to inflation, a liquid-disconnected initiator can be used to decouple the lumen. For example, before the balloon is inflated, the outer lumen is first flushed with 2 cubic centimeters of water, such as saline or deionized water. Thereafter, an inflation source container is attached to the connector leading to the lumen. The inflation source container is designed to operate under the ideal gas law and the pressure decay model. For a given compressed gas formulation, the device is designed to balance so that the initial pressure used to inflate the balloon is higher than the final pressure achieved by the balloon. The initial pressure and volume depend on the selected gas formulation, as well as the catheter length, the starting temperature (typically room temperature), and the ending temperature (typically body temperature).

After inflation, the balloon is detached from the catheter assembly using hydraulic pressure. A syringe filled with water, deionized water, or preferably saline is attached to the female end of the Y-assembly. The syringe contains 2 cubic centimeters of liquid and when the syringe plunger is pushed in, sufficient hydraulic pressure is applied to eject the needle from the balloon valve.

Single-lumen catheter

To further reduce the diameter of the inflation catheter and thus improve the swallowing comfort of the balloon and catheter, single-lumen catheters (Figures 11A-C) can be used with a diameter not exceeding 3 French (1.0 mm) (0.033 inches).

The needle/needle sleeve set is similar in design to the dual-lumen catheter described herein. However, with a single-lumen system, the distal end of the catheter lumen is connected only to the needle sleeve, and there is no secondary catheter inside. Instead, a single wire attached to the needle hub runs coaxially along the length of the catheter to aid in tensile strength and overall flexibility for detachment.

The needle sleeve is slightly bell-shaped (pictured) or includes a rounded undulation or lip, which creates a lock and key mechanism to increase the tensile strength of the assembly and enhance the seal for inflation as the silicone inserted into the valve advances, and since this is a single lumen assembly, the lip increases the force required to remove the needle from the valve so that irregularities do not occur during inflation.

The proximal end of the catheter is connected to an inflation valve (Figure 7), preferably a 3-way valve, or any valve that allows the use of an exclusion method for balloon inflation and detachment. The distal end of the catheter includes a needle sleeve made of nylon or the like. The needle is metal, preferably stainless steel.

As the tube traverses the digestive tract and enters the gastric cavity, the catheter assembly is designed to be swallowable, flexible, kink-resistant, able to withstand body temperature, acid-resistant, and biocompatible. The tubing material is preferably soft and flexible, resistant to flexion, bending, or kinking. For single-lumen systems, the catheter tube is preferably made of PEBAX® or PELLETHANE® (ether-based polyurethane elastomers), but can also include bioresorbable materials such as polylactic acid, PLAA, PLG, PCL, DL-PLCL, etc., where the tube can be normally released after inflation and detachment. The filamentous wire inside the catheter tube that attaches to the needle (Figure 11B) is preferably nylon monofilament, but Kevlar or Nitinol wire or other suitable materials can also be used.

To inflate the balloon, the distal end of the catheter is attached to the balloon at a location where the needle protrudes through the self-sealing valve (Figure 11C). The container is swallowed, with part of the inflation catheter remaining outside the mouth. The inflation source container is connected to the proximal end of the inflation valve, where the port for the inflation gas is selected by eliminating other ports. The inflation fluid (preferably compressed nitrogen or a gas mixture) travels down a single catheter lumen, whereupon the inflation gas chooses the path of least resistance, or more specifically, through the needle lumen and into the balloon. The balloon is preferably inflated in less than 3 minutes.

To separate and remove the needle from the balloon valve, 2 cubic centimeters or other suitable volume of water or other liquid is injected into the catheter at high pressure. Due to the high surface tension and viscosity of water, it closes the needle passage, and the pressure is transmitted to the outer needle sleeve, thereby breaking the fit between the needle sleeve and the balloon valve.

If it is desired to place a substance such as water or acid or any alternative liquid within the balloon, this can be accomplished by using a lower pressure liquid injection.

Micro Rigid Shaped Inflation Catheter

In certain embodiments, a rigid, shaped inflation catheter that can be placed orally or nasally can be used. This system can have a diameter of 1 French (0.33 mm) to 10 French (3.3 mm), preferably 8 French (2.7 mm). Larger diameters are generally preferred to improve pushability, with thicker walls also aiding pushability and kink resistance. The length of the tube can be approximately 50-60 cm. As discussed above, a measurement device can be added to the tubing to identify the location of the end of the tube, or a pH or pressure sensor on the catheter can be used to detect the position of the balloon.

This inflation/detachment system is similar to the dual-lumen system described above, but features a larger needle sleeve to accommodate larger diameter tubes (FIGS. 12A-D). Materials that can be used in the lumen include, for example, expanded polytetrafluoroethylene (EPTFE) for the outer lumen and polyetheretherketone (PEEK) for the inner lumen. To further enhance pushability, strain relief can be added to both the distal and proximal ends. Strain relief is particularly preferred at the distal end, for example, between 1 and 8 inches, preferably 6 inches, to ensure the catheter bypasses the larynx and subsequently enters the esophagus. Strain relief can also be provided at the proximal end, for example to ensure connector fit. A preferred material for strain relief is polyolefin. The inflation/detachment method is the same for dual-lumen configurations, where the outer lumen is connected to the needle sleeve and the inner lumen is connected to the needle. Reinforcement members are strategically placed along the length of the catheter shaft to provide the correct amount of flexibility and pushability for proper device placement in the patient. As part of the procedure, the patient can swallow water or other suitable liquid to dilate the esophageal tissue for smooth downward passage of the device. People may also take an anesthetic in the back of their throat to numb the area and reduce the gag reflex.

The tube can also be connected to a single catheter with a series of encapsulated or compacted balloons, allowing a total volume of up to 1000 cubic centimeters or more to be administered if desired. Each can be inflated and released separately. The number of balloons released is adjustable to the patient's needs and desired weight loss.

Additionally, a catheter can be used to apply a gastric balloon, similar to the balloon catheters used in what are known as "over the wire" angioplasty procedures or rapid exchange catheters (Figure 13). In the event that the patient attempts to swallow the catheter but fails, a rigid catheter—or a physician-assisted catheter—can be slipped over the flexible catheter, and the balloon can be pushed down in the same manner as the physician-assisted catheter. Different materials can be used to provide varying degrees of flexibility, or the stiffness of the material can be varied using different diameter supports across its length.

Inflatable fluid container

The inflation fluid container is used to control the volume of fluid placed within the balloon. The inflation fluid container can be in the form of a catheter, for example, a canister made of a polymeric material such as polyvinyl chloride (PVC), tin-plated steel, stainless steel, aluminum, aluminum alloy, copper, or other suitable materials. The container can also be in the form of a syringe. The material used is capable of containing the fluid, preferably in the form of a compressed gas, such as compressed or uncompressed nitrogen, argon, oxygen, carbon dioxide, or mixtures thereof, or compressed or uncompressed atmospheric air (oxygen, argon, carbon dioxide, neon, methane, helium, krypton, hydrogen, and xenon), at gastric concentrations. The balloon wall composite material and its corresponding diffusion gradient and gas permeability properties are used to select the fluid for intragastric balloon inflation. The inflation fluid container material is selected to ensure that no fluid diffuses or leaks before being connected to the connector or valve of the inflation catheter. The inflation fluid container system (Figures 14A-C) includes a connector (Figure 14B) to the catheter and a pressure gauge (Figure 14C). The inflation container can be made of any suitable material, such as stainless steel (Figure 15). It may also include a smart chip that notifies healthcare professionals whether the charge was successful, or if the capsule should be detached due to an error in the system.

In certain embodiments, such as those shown in Figures 16A and 16B , the inflation fluid container is implemented as a conduit or container (flexible, rigid, or shaped), a compressible bag, a conformable bladder-like tube, or the like. As with the other embodiments described above, the canister or container has walls formed from stainless steel, pure aluminum, an aluminum alloy, brass, or other suitable barrier material. The walls surround and define an internal reservoir or cavity. The canister may include an actuator that activates the delivery system to deliver gas, a valve cup configured to retain the valve assembly, a spring, a stem connecting the actuator and spring, and the spring, a stem washer that seals around the open valve stem, a tube or straw extending from the valve to the bottom of the canister to allow gas to flow out of the canister under pressure, and a housing that retains the spring and connects the tube or straw to the valve assembly. An aperture is typically provided in one of the walls, providing access to the internal reservoir. The canister includes a lid configured to seal the aperture to prevent fluid from escaping the internal reservoir during storage (Figure 16A). When the lid is removed, the straw becomes visible (Figure 16B). A portion of the straw extends outward from the canister, with the remainder of the straw extending through the aperture into the inner reservoir. The straw can be formed of polypropylene, polyethylene, nylon, or other suitable polymeric materials. Some embodiments of the canister are configured to release inflation fluid from the inner reservoir through the straw when a low-pressure gradient fluid path is opened toward the bladder.

In some embodiments, it is desirable to inflate the intragastric balloon using an inflation fluid container with a known internal pressure or volume of gas. For example, in some embodiments, it is desirable to use an inflation fluid container configured to have a volume of, for example, 50 cubic centimeters or less to 400 cubic centimeters or more, or from 100 cubic centimeters to 200 cubic centimeters or 300 cubic centimeters, or from 125 cubic centimeters to 175 cubic centimeters, or approximately 150 cubic centimeters. In other embodiments, other volumes of gas may be used. In some embodiments, the inflation fluid container is filled at the procedure site by connecting the inflation fluid container to a tank of compressed gas prior to the procedure and filling the inflation fluid container until the desired volume or pressure is reached. The pressure can be monitored using a pressure gauge. In other embodiments, the inflation fluid container is pre-filled with the desired volume of fluid. In such embodiments, the altitude of the location (and the resulting atmospheric pressure) should be taken into account to provide an inflation fluid container with the desired volume of gas. Inflation fluid containers can be designed with different sizes, colors, or other unique markings indicating each customized altitude range.

To maintain the "swallowability" of the balloon and ensure patient comfort during the procedure, the amount of time the catheter is placed in the mouth/esophagus is preferably minimized. Inflation timing can be selected to minimize placement time. Once swallowed, the external container catheter assembly can take approximately 3 to 120 seconds to reach the stomach. Once in the stomach, the inflation fluid container can be attached to a valve or port on the catheter system. Inflation timing can be controlled by selecting the catheter length, catheter tube diameter, starting temperature, and starting pressure. Using the ideal gas law and Boyle's law for nitrogen (P1V1 = P2V2), volume/pressure quantities can be derived, where the starting pressure takes into account the final target pressure at body temperature. An inflation time of less than 5 minutes, preferably 2-3 minutes, after swallowing is desired, prior to balloon detachment and catheter withdrawal. Inputs used to determine balloon inflation (preferably in less than 3 minutes) include the inflation container volume, inflation fluid type (preferably a compressed gas or compressed gas mixture), starting pressure, catheter length and diameter, and the desired balloon ending volume and pressure. Therefore, due to the difference in diameter, a smaller 1 French or 2 French diameter catheter system requires a lower starting pressure to achieve the same target balloon volume and pressure in the same time as a larger 4 or 5 French diameter catheter, assuming the same compressed gas formulation is used. In general, it is understood that starting with a lower pressure at the same fluid rate/volume increases inflation time.

The inflation source container can provide feedback to the end user based on a pressure decay system. There is a desired starting pressure and a desired ending pressure to indicate whether the balloon is properly inflated, without the need for endoscopic visualization (see FIG17 ). Each of the desired pressure outputs depicted in FIG17 can have its own tolerances to reduce the likelihood of false positives, and the inflation fluid container can provide feedback based on these tolerances to assess the status of balloon inflation and detachment. The inflation fluid container includes an additional low-volume bolus of pressure, which is released to confirm device position, followed by a second, larger bolus intended to inflate the balloon. Gas release can be accomplished in one, two, three, or more boluses, depending on the event being detected. This is based on the ideal gas law, with a desired ending pressure based on a fixed balloon volume. If the pressure remains high and does not decay as expected, it may indicate a system malfunction (e.g., the balloon container is not dissolving, the balloon is expanding in the esophagus due to, for example, a kink in the tube, or other malfunction in the catheter system). For example, for successful deflation using only nitrogen as the inflation fluid, the starting pressure to inflate the balloon to 250 cubic centimeters is 22-30 PSI, while for nylon-based materials it is 1-2.5 psi (0.120 kg/cm2). To indicate successful balloon inflation, a math chip can be added to the inflation source container that provides at least one of a visual, audible, or tactile notification, or otherwise sends a notification to a medical professional or administrator as to whether the inflation was successful or if there is an error in the system based on the pressure curve and a set of predetermined pressure tolerances and desired inflation timing.

Alternatively, the balloon can be filled based on the starting pressure using a spring mechanism, a balloon-in-balloon mechanism, or other pressure source. These mechanisms can potentially result in a more predictable/consistent pressure decay curve, and can also have accompanying predetermined tolerances as feedback back to the end user. FIG18 depicts the expected decay curves for these methods of pressure sources, and can also have accompanying predetermined tolerances as feedback back to the end user.

Inflation fluid dispenser

In some embodiments, a canister, such as the canister of Figures 16A and 16B, is coupled to an inflation fluid dispenser to deliver inflation fluid to an intragastric balloon or other inflatable intragastric device. Figures 19A and 19B illustrate one such inflation fluid dispenser. The inflation fluid dispenser includes a housing configured to be coupled to the canister. Some embodiments include a securing latch, a receiving space configured to receive the canister, threaded features, and/or gas features configured to securely couple the housing to a spray canister.

The housing may also include a spring positioned to contact the spray can's straw when the spray can is in its secure position within the housing. In such an embodiment, as the can is brought into a secure position, the spring applies a force to the conduit in the direction of the can, causing an initial amount of inflation fluid to be released from the can. In some embodiments, the release of the initial amount of inflation fluid is designed to reduce the inflation fluid within the spray can to a desired starting volume or pressure. In some embodiments, the material, size, and strength of the spring are selected so that the amount of force exerted by the spring, and the resulting initial amount of inflation fluid released, is predetermined. The material, size, and strength of the spring can be selected based on the altitude and average atmospheric pressure of the location where the inflation fluid dispenser will be used. In this way, the inflation fluid dispenser can be calibrated for use in a specific area or altitude range, while using cans of standard size and fill volume regardless of location.

The housing may also have an inner wall defining a passageway extending at least partially through the housing. In such embodiments, when the canister is securely coupled to the housing, the proximal inlet of the passageway is positioned around the canister straw. A spring, if present, may be disposed within the proximal inlet. The distal outlet of the passageway is positioned at the distal end of the inflation fluid dispenser and configured as a port to which a catheter or other flexible tubing may be connected. In various embodiments, a valve is disposed in the passageway between the proximal inlet and the distal outlet and is configured to transition between a closed position and an open position. In the closed position, the valve blocks fluid flow between the proximal inlet and the distal outlet. In the open position, fluid flow is unobstructed. Thus, in the open position, inflation fluid can flow from the internal reservoir of the spray canister, through the canister straw and the passageway of the inflation fluid dispenser, and out the distal outlet to a catheter, an intragastric device, and/or other component coupled to the port.

In some embodiments, the inflation fluid dispenser includes a lever disposed on an outer surface of the housing and mechanically coupled to the valve. A healthcare professional can move the lever between a first and a second position to switch the valve between an open and a closed position. In other embodiments, the inflation fluid dispenser can include a button, key, trigger, or switch disposed on an outer surface of the housing and electrically coupled to the valve. When manipulated by a healthcare professional, the button, key, trigger, or switch can send an electrical signal to the valve to open or close. In yet other embodiments, any suitable valve control mechanism configured for user manipulation can be present in the inflation fluid dispenser.

In certain embodiments, a pressure gauge is coupled to the housing and configured to detect a pressure gauge pressure within the passage between the valve and the distal outlet. In some such embodiments, the pressure gauge includes a digital display; in other embodiments, the pressure gauge has a card and mechanical scale indication.

In some embodiments, the inflation fluid dispenser and canister (or other inflation fluid container) form part of a larger inflation system used to deliver inflation fluid to an inflatable intragastric device. An example of an inflation system is provided in FIG20 . In some such embodiments, a flexible tube and a substantially enclosed intragastric device are coupled to the inflation fluid dispenser and inflation fluid container. The flexible tube may comprise a catheter, an elastomeric extension tube, or other flexible, elongated device having a lumen. In some embodiments, the flexible tube comprises both the extension tube and the catheter, connected by spokes of a stopper having a three-way valve. A syringe may be connected to the third spoke of the three-way valve. Each of these system components is described in detail above.

In one method for delivering an inflatable intragastric device to a patient's stomach, an inflation fluid dispenser is first coupled to an inflation fluid container. In some embodiments, this coupling is performed with the dispenser valve in the open position. The inflation fluid dispenser may include a pressure-compensating valve for air pressure that accounts for temperature, altitude, and starting pressure; based on the current altitude setting, the final starting number of moles of gas required to inflate the balloon to its target pressure (constant, but within a range of 1-5 psi) is adjusted. This compensation is performed during coupling, and based on differences (e.g., altitude) between the manufacturing setup and the current environment in which the device is used, an initial amount of inflation fluid may be discharged from the distal outlet of the channel as the inflation fluid container initially contacts and experiences force from a spring located in the proximal inlet of the channel. In some embodiments with a pressure gauge, the pressure of the inflation fluid container is monitored while the valve is open. In some embodiments, it is desirable to discharge inflation fluid from the inflation fluid container until the pressure within the container reaches 250 kPa, 300 kPa, or any value therebetween. In other embodiments, the desired pressure within the inflation fluid container is between 257 and 297 kPa, inclusive. Once the inflation fluid container is securely coupled to the dispenser and the desired pressure has been achieved, the valve can be closed.

In some embodiments, the extension tube, stopper, catheter, syringe, and at least partially encapsulated intragastric device are connected to one another, with the proximal end of the extension tube attached to the distal end of the dispenser. Using a three-way valve located on the stopper at a position that allows fluid connection between the extension tube and the catheter, fluid will flow between the channels in the dispenser (with the valve downstream of the dispenser), the extension tube, the catheter, and the encapsulated intragastric device until equilibrium is reached. The pressure gauge reading should generally reflect the pressure within the intragastric device.

In some methods of delivering an inflatable intragastric device to a patient's stomach, the patient swallows the substantially enclosed intragastric device to facilitate its delivery to the stomach. In various embodiments, a catheter remains connected to the intragastric device and extends from the stomach through the esophagus and at least into the patient's mouth. In some embodiments, swallowing and positioning of the intragastric device are monitored using radiographic imaging methods, such as fluoroscopy.

Once in the stomach, various embodiments involve the capsule of the intragastric device beginning to dissolve. In some embodiments, the capsule dissolves in less than ten minutes. In some embodiments, the capsule dissolves in 30 seconds to four minutes. In some embodiments, the measured pressure will drop below 10 kPa upon dissolution. In some embodiments, the measured pressure will drop below 7 kPa upon dissolution. In various embodiments, the process of filling the inflatable intragastric device can begin upon capsule dissolution. To fill the inflatable intragastric device with inflation fluid, the valve of the dispenser is switched to the open position. The inflation fluid will essentially flow from the relatively high-pressure internal reservoir of the inflation fluid container to the relatively low-pressure lumen of the inflatable intragastric device until equilibrium pressure is achieved in the system. In some embodiments, approximately 150 cubic centimeters of gas in an unconfined atmosphere is confined to 28 psi, or approximately 450 milliliters at atmospheric pressure. For example, nitrogen gas may be delivered to the intragastric device. In some embodiments, the intragastric device can achieve a final volume of approximately 250 cc within the stomach. In other embodiments, the intragastric device can achieve a final volume within the stomach of 50 to 400 cc, and preferably 90 to 300 cc, or any single value or range therebetween. Some embodiments of the intragastric device will achieve a final pressure of 5 kPa, 20 kPa, or any value therebetween. In preferred embodiments, the final pressure within the intragastric device is between 8.3 kPa and 17.2 kPa, and more preferably, the final pressure within the intragastric device is 13.8 kPa. Some embodiments of the intragastric device achieve the desired final pressure in less than five minutes. In some embodiments, the final pressure is achieved in approximately two minutes.

In certain embodiments of the method, once the system pressure stabilizes and reaches equilibrium, the catheter can be detached from the gastric device and removed from the patient. In some embodiments, a syringe is used to detach the catheter from the intragastric device. The three-way valve is moved to a position in which the syringe is fluidically connected to the catheter and the intragastric device. The stopper of the syringe is quickly pushed with sufficient force to dislodge the catheter from the intragastric device to expel fluid from the syringe into the lumen of the balloon (as described in detail above).

Composite wall

The material selected for the composite wall of the balloon can be optimized to prevent significant diffusion of the initial inflation gas, or to allow diffusion of gases in the gastric environment, for example, CO2, O2, argon, or nitrogen, through the balloon wall to partially or fully inflate the balloon once the balloon is positioned in the stomach. Fluid (liquid or gas) can also be added to the interior of the balloon using the inflation catheter described herein to change the diffusion direction of the composite wall of the balloon and achieve stasis based on the internal and external environments.

Intragastric balloons inflated with nitrogen, CO2, a single fluid (gas), or a mixture of gases utilize a composite wall that provides barrier properties (fluid retention), resistance to the pH and moisture environment of the stomach or central lumen of the balloon, and resistance to gastric peristalsis, in vivo abrasion of the balloon wall, and damage during balloon manufacturing and folding. Certain materials used in the balloon are capable of withstanding the hostile gastric environment designed to break down foreign matter (e.g., food particles). Some gastric environmental variables include: gastric fluid pH of 1.5-5; temperature of approximately 37°C; relative humidity of 90-100%; inlet of gastric space gastric contents; and constant external gastric motility pressure of 0-4 pst. These motility events have variable frequency and cycle time depending on the fed state of the stomach. The external pressure exerted by gastric motility can also cause abrasions on the balloon surface. The interior of the balloon lumen may contain moisture from the injected solution used in the balloon for automatic inflation and deflation timing, or from any moisture transported through the septal wall due to the external moisture environment. In addition to these environmental threats, the wall material meets biocompatibility requirements and is constructed so that the total thickness of the wall (barrier material) is thin enough to be compacted and placed inside a swallowable-sized container ("outer container") without significant damage or collapse. The outer container is small enough to transcend the esophagus (it has a diameter of approximately 2.5 cm). The wall or barrier material is also thermoformable and sealable for balloon construction and maintains a bond strength that can include internal gas up to 10 psi generated by the initial inflation pressure and pressure due to the ingress of gas molecules from the gastric cavity until stasis is achieved in the system's gaseous environment. Film properties evaluated to determine practicality for use in balloon composite walls include pH, water vapor transmission rate, gas barrier properties, mechanical strength/wear properties, temperature resistance, formability, flex cracking (Gelbo) resistance, surface energy (wettability) compliance, and thermal bonding potential.

Each layer in the composite wall can impart one or more desired properties to the bladder (e.g., fluid retention for handling, resistance to moisture, resistance to acidic environments, wettability, and structural strength). Tables 1a-1b provide a list of polymer resins and coatings that can be incorporated into the multilayer preform system ("composite wall"). These films can be bonded together via tie layers, or a combination thereof, coextruded, or adhered to achieve the desired combination of properties of the composite wall as described below. The materials identified as film coatings are provided in Tables 1a-b as coatings applied to a base polymer film, e.g., polyester, nylon, or other structural layer.

Table 1a

Film resin

Table 1b

Thin film coating

Fluid retention layer

In a preferred embodiment, the use of multiple layers of mixed polymer resins is employed to maintain the shape and volume of the inflated balloon by retaining the inflation fluid for the duration of the intended use. Certain barrier films, widely used in the food packaging and plastic bottling industries, can be advantageously used for this purpose in the composite wall of the balloon. Preferably, the barrier material has good adhesion to the carbon dioxide (or other liquids or fluids that may alternatively or additionally be used to inflate the volume-occupying subcomponent) that may be used to inflate the volume-occupying subcomponent. These barrier layers preferably have good adhesion to the substrate. Preferred barrier coating materials and films include polyethylene terephthalate (PET), linear low-density polyethylene (LLDPE), ethylene vinyl alcohol (EVOH), polyamides such as nylon (PA) and nylon-6 (PA-6), polyimide (PI), liquid crystal polymer (LCP), high-density polyethylene (HDPE), polypropylene (PP), biocompatible poly(hydroxyamino ether), polynaphthalene, polyvinylidene chloride (PVDC), saran, ethylene vinyl alcohol copolymer, polyvinyl acetate, silicon oxide (SiOx), silicon dioxide (SiO2), aluminum oxide (Al2O3), polyvinyl alcohol (PVOH), nanopolymers (e.g., nanoclays), polyimide thermoset films, EVALCA EVAL EF-XL, Hostaphan GN, Hostaphan RHBY, RHBMI, Techbarrier HX (SiOx-coated PET), Triad Silver (silver metallized PET), Oxyshield 2454, BICOR84 AOH, acrylonitrile copolymers, and copolymers of terephthalic acid and isophthalic acid with ethylene glycol and at least one diol. Alternative barrier materials may include polyamine-polyepoxides. These materials are typically provided as solvent-based or water-based thermosetting compositions and are typically spray-coated on the preform and then heat-cured to form the final barrier coating. Alternative barrier materials that can be applied as a coating to the volume-occupying subcomponent include metals such as silver or aluminum. Other materials that can be used to improve the hermeticity of the volume-occupying subcomponent include, but are not limited to, gold or any precious metal, saran-coated PET, and conformal coatings.

One method used in the packaging industry to delay diffusion of the inflation fluid is to thicken the material. Thickening the material is generally not preferred because the total composite wall thickness preferably does not exceed 0.004 inches (0.010 cm) to allow the balloon to be collapsed into the desired delivery container size for swallowing by the patient.

The multilayer polymeric film capable of withstanding the gastric environment during the useful life of the balloon comprises linear low density polyethylene (LLDPE) adhesively bonded to a nylon 12 film. Alternatively, additional films with barrier properties, such as PVDC, may be added to the composite wall.

Layers providing gas barrier properties are preferably located as interior layers in the composite wall, as they are less mechanically robust than resins considered "structural", such as nylon.

Layers of structure

Layers such as polyurethane, nylon, or polyethylene terephthalate (PET) can be added to the composite wall for structural purposes and are preferably placed as the outermost layer (closer to the gastric environment or closer to the central lumen of the balloon) if the pH resistance of these layers can withstand the acidic environment of the stomach or the central lumen of the balloon.

Composite wall manufacturing

The layers of the composite wall, including the gas barrier layer, do not need to be arranged in any particular order, but those layers that have higher resistance to acidity, temperature, mechanical abrasion, and excellent biocompatibility properties are preferably used as the layers that contact the gastric environment. Those layers that have higher resistance to, for example, acidity and temperature are preferably used as the layers that contact the central cavity of the balloon.

The individual layers of the wall may comprise a single layer or up to 10 or more different monolayers. However, films thicker than 0.001 inches (0.0254 centimeters) to 0.004 inches (0.010 centimeters) are desirable so that the resulting capsule can be compacted to fit into a swallowable capsule. The resulting composite wall preferably has good performance specifications relative to each of the categories listed in Tables 1a-b.

Coextruded films are advantageously used because some adhesives may include leachables that are undesirable from a biocompatibility perspective. Additionally, coextrusion allows for better mixing so that the materials retain their original properties when combined in this manner and are less susceptible to delamination when exposed to the peristaltic forces of the stomach.

Composite films with similar properties, such as two films with excellent gas barrier properties, can be advantageously used in composite walls when used in applications containing nitrogen, oxygen, carbon dioxide, or mixtures thereof as inflation gases, or when the product is placed in an external environment containing a gas mixture including carbon dioxide, such as the stomach. A major advantage of such composite films is that limitations on film thickness can be observed without sacrificing gas barrier properties. This configuration also helps reduce the effects of handling hazards (such as manufacturing and compaction) and damage due to exposure to in vivo conditions (e.g., gastric motility).

In a particularly preferred embodiment, the composite wall comprises multiple layers. The first layer is an outer protective layer configured for exposure to the gastric environment. This layer is resistant to mechanical forces, exposure to water (steam), abrasion, and high acidity levels. More specifically, nylon or nylon 12 is particularly preferred for the layer exposed to the gastric environment and is particularly resistant to mechanical forces.

In an alternative embodiment, polyurethane is radio frequency welded to saran to create a composite wall 6-7 mils thick. In another embodiment, a five-layer system is provided, comprising a layer of saran sandwiched between two polyurethane layers. Between the saran layer and each polyurethane layer is a tie layer. These layers can be welded together, coextruded, or bonded using an adhesive. These three layers are then coextruded onto each side of the nylon, and a final sealant layer (or polyethylene, etc.) is then added to one of the nylon layers for a total composite wall. Representative examples of commercially available or manufacturable material combinations are provided in Table 2. The orientation of each layer (deepest - in contact with the central balloon lumen, or outermost - in contact with the gastric environment) is also indicated if more than two layers are described to support the proposed composite wall.

Most of the film resins listed in Table 2 provide some degree of gas barrier properties. Therefore, many can be used alone as single-layer films to form balloon walls; however, they can also be used in combination with other film resins to meet the gas retention and mechanical specifications required for the life of the balloon based on the inflation gas and the external environment in which the balloon will be placed. These film resins can also be coated with the gas barrier coatings listed in Tables 1a-b. Additional film layers can also be added to form the overall composite wall. While such additional layers may not impart substantial barrier properties, they may provide structural and/or mechanical properties, serve as protection for other layers of the composite wall that are susceptible to water vapor, humidity, pH, etc., or provide other desirable properties. The film layers can be assembled using various adhesives through coextrusion, lamination, and/or the use of tie layers, and the resulting composite wall can meet the applicable requirements for intragastric balloons with the specified gas retention properties for at least 25 days, or up to 90 days or more. Table 2 provides a list of layers and layer combinations suitable for use in composite walls for intragastric balloons. In the composite description, the resin abbreviation, structure (single-layer, double-layer, triple-layer, etc.), and commercially available trade name combination are listed. The number of layers indicated does not include any adhesive or tie layers used to make the composite wall, so that a 6-layer composite wall can, for example, have two or three adhesive and/or tie layers to make up the total composite wall, and thus the total number of layers in the final form can be 8 or 9. The term "layer" as used herein is a broad term and should be given its ordinary and customary meaning to those of ordinary skill (rather than being limited to a specific or specialized meaning), and refers to, but is not limited to, a single thickness of homogeneous material (e.g., a coating such as SiOx, or a layer such as PET), as well as a support layer having a coating thereon (where a "coating" is, for example, a suitable material typically in combination with a substrate that provides structural support for the coating). For example, a PET-SiOx "layer" herein refers to a layer in which the Si-Ox is provided on a supporting PET layer.

Table 2.

Example Film Composite Wall* abbreviation Trademark name polyethylene terephthalate PET Mylar Metallized oriented polyethylene terephthalate Metallized OPET Custom Polypropylene coated with polyvinyl alcohol PVOH coated OPP Bicor Metallized biaxially oriented nylon 6 Metallized OPA6 Custom Biaxially oriented nylon/ethylene vinyl alcohol/biaxially oriented nylon OPA/EVOH/OPA Honeywell Oxyshield Plus Nylon/ethylene vinyl alcohol/low-density polyethylene Nylon/EVOH/LDPE Custom Polyvinylidene chloride-coated polyethylene terephthalate PVDC/OPET Mylar polyvinylidene chloride-coated polypropylene PVCD/OPP Custom Polyvinylidene chloride coated biaxially oriented nylon 6 PVCD/OPA6 Honeywell Oxyshield High-density polyethylene/ethylene vinyl alcohol HDPE/EVOH Custom Polypropylene/ethylene vinyl alcohol laminate PP/EVOH Custom Polyethylene terephthalate/vinyl alcohol PET/EVOH Custom Metallized oriented polypropylene Metallized OPP Custom Polypropylene coated with sealable PVDC PVDC coated PP Custom polyvinylidene fluoride PVDF Custom polyvinyl chloride PVC Custom polyvinyl fluoride PVF Tedlar Polyvinyl chloride PCTFE ACLAR UltRx, SupRx, Rx Amino-epoxy coated nylon Epoxy-coated nylon Bairocade Polyvinyl chloride polyvinylidene chloride copolymer PVC-PVDC Custom Medium-density polyethylene MDPE Custom Nylon/Polypropylene Nylon/PP sheet Custom Nylon-High Density Polyethylene Nylon-HDPE sheet Custom Nylon 12/ethyl methacrylate/polyvinylidene chloride/ethyl methacrylate/nylon 12/linear low-density polyethylene+low-density polyethylene Coextruded Nylon 12-encapsulated PVDC-Nylon 12-LLDPE+LDPE Custom co-extruded blends Multilayer nylon 12/ linear low density polyethylene + low density polyethylene Co-extruded multi-layer nylon 12-LLDPE+LDPE Custom Co-Extrusion Mixing Acetylene plasma coated polyester PET/A Custom Vinylidene fluoride-coated polyethylene terephthalate PET/DA Custom Oriented polypropylene OPP Custom Casting acrylic CPP Custom High-density polyethylene HDPE Custom Cyclic olefin copolymers COC Custom Oriented Polyethylene OPS Custom Fluorinated ethylene propylene FEP Custom Vinylidene fluoride-coated low-density polyethylene LDPE/D Custom Vinylidene fluoride-coated polypropylene PP/D Custom Acetylene plasma coated polypropylene PP/A Custom Acetylene plasma coated low density polyethylene LDPE/A Custom Polyethylene terephthalate polyether glycol copolymer TPC-ET Hytrel Polyetheramide TPE PEBA Pebax Oxide-coated biaxially oriented nylon Oxide-coated PA Honeywell Oxyshield Ultra Nanoclay/Nylon MXD6/Nanoclay Imperm/ Aegis OXCE Polyethylene terephthalate/silicon dioxide PET/SiOx BestPET/ TechBarrier Polyethylene terephthalate/oxygen scavenger PET+02 scavenger MonoxBar Improved polyethylene terephthalate Improved PET DiamondClear Polyethylene terephthalate/nylon 6 PET/MXD6 HP867 Amorphous polyvinyl alcohol Amorphous PVOH Nichigo G-Polymer Nylon 6/ethyl vinyl alcohol/linear low-density polyethylene Nylon 6/EVOH/LLDPE Custom Ethyl vinyl alcohol/Polyethylene propylene/Ethyl vinyl alcohol EVOH/PP/EVOH Custom Ethyl Vinyl Alcohol/Nylon EVOH/Nylon Custom Polyethylene/Ethyl Vinyl Alcohol/Polyethylene PE/EVOH/PE Custom polyethylene terephthalate PE/EVOH/PET Custom Polyethylene terephthalate/Linear low density polyethylene/Ethyl vinyl alcohol/Linear low density polyethylene PET-SiOx/LLDPE/EVOH/LLDPE Custom Alumina coated polyethylene terephthalate/Polyethylene PET-Al2O3/LLDPE Custom Polyethylene/ethyl vinyl alcohol/linear low-density polyethylene PE/EVOH/LLDPE Custom Polyethylene terephthalate/Polyethylene/Biaxially oriented Ethylene Vinyl Alcohol PET/PE/OEVOH/PE Custom Polyethylene terephthalate/Polyethylene/Ethyl vinyl alcohol/Ethyl vinyl alcohol/Polyethylene PET/PE/EVOH/EVOH/EVOH/PE Custom Polyethylene terephthalate/Polyethylene/Nylon 6/Ethylene Vinyl Alcohol/Nylon 6/Polyethylene PET/PE/Nylon 6/EVOH/Nylon 6/PE Custom Silica-coated polyethylene terephthalate/polyethylene/ethyl vinyl alcohol/polyethylene PET-SiOx/ PE/EVOH/PE Custom Polyethylene/ethyl vinyl alcohol/polyvinyl chloride PE/EVOH/PVDC Custom Polyethylene terephthalate/Linear low density polyethylene/Ethyl vinyl alcohol/Linear low density polyethylene PET/LLDPE/EVOH/LLDPE Custom Kurrarister C coated polyethylene terephthalate/polyethylene/ethyl vinyl alcohol/polyethylene PET-Kurrarister-C/ PE/EVOH/PE Custom Polyethylene terephthalate/Polyethylene/Nylon 6/Ethylene Vinyl Alcohol/Nylon 6/Polyethylene PET/PE/Nylon 6/EVOH/Nylon 6/PE Custom Nylon 6/ethyl vinyl alcohol/linear polyvinyl chloride/low-density polyethylene Nylon 6/EVOH/PVDC/Nylon 6/LDPE Custom polyimide PI Custom Polyimide/Linear Low Density Polyethylene PI/LLDPE Custom Polyimide/polyvinyl chloride PI/PVdC Custom Polyimide/polyvinyl chloride/linear low-density polyethylene PI/PVdC/LLDPE Custom

In particularly preferred embodiments, the composite wall has a thickness of 0.005 inches or less (5.0 mils or less); however, thicker composite walls are acceptable in certain embodiments. It is generally preferred that the composite wall have a thickness of no more than 0.004 inches (4.0 mils).

Capsule manufacturing

To ensure good mechanical strength of the balloon, the balloon is preferably formed and sealed so that the edges of the sheets used to form the balloon overlap. This can be achieved by any suitable method. For example, the two sheets of material can be placed in a frame with magnetized edges to hold the sheets in place. Slack can be added to the film sheets to orient the material so that it retains its properties after the forming process. The frame can be placed over a mold representing the hemispherical balloon. Adding slack material before applying pressure reorients the material so that it is more evenly distributed around the hemispherical shape. The material is preferably thickest in the middle and thinner at the edges, which are welded to the second sheet, to easily produce a sphere or ellipsoid with a generally uniform wall thickness. For example, starting with 0.0295", the middle or subsequent apex of the film would have an ending film thickness of 0.0045", and the edges would have an ending film thickness of 0.0265", allowing for subsequent overlap during the welding process.

The valve can be adhered to the side (e.g. polyethylene, PE) of the hemisphere and protrude towards the opposite side (e.g. nylon). The first hemisphere typically has nylon as the outermost layer and the second hemisphere typically has polyethylene (sealing mesh) as the outermost layer. The edges of the two hemispheres are preferably aligned so that they overlap by at least 1 mm and not more than 5 mm. The alignment and overlap of the two hemispheres is to compensate for the thinning of the edges during the thermoforming process, which in turn inhibits seam rupture in vivo. Each half of the sphere is placed on a fixture and the excess resulting from the forming process is trimmed. On the multilayer film, a sealing layer, PE or similar layer is joined to the sealing layer of the second half of the film. To do this, the nylon exposed to the external environment is folded over along the edge on one half of the sphere (see Figures 21A-B) so that it can be joined to the polyethylene on the outermost layer of the hemisphere.

The two layers are then sealed using either a roller splicer or a belt heater. In a roller splicer, a pneumatic cylinder provides the compression, a heater provides the sealing heat, and a motor moves the splicer around a zone controlling the time required to ensure a proper seal. A belt heater has a heating element, an inflatable plug to provide the compression, and a timer. The belt is metal, preferably copper, and a reel-like fixture clamp provides the required compression. Using film layers with different melting temperatures helps ensure the integrity of the barrier layer of the final balloon structure. If two similar materials are being welded, an insulator can be used. In a preferred embodiment, the first sphere is provided with a nylon layer facing outward, while the second sphere has a PE layer facing outward.

Capsules resistant to spontaneous deflation

The largest percentage of intragastric balloon failures is due to spontaneous deflation. Spontaneous deflation can occur attributable to (1) puncture of the intragastric balloon due to gastric motility, (2) overinflation of the balloon due to increased internal pressure from the gastric environment of gas and water vapor, and (3) underinflation of the balloon, resulting in fatigue of excess material and subsequent balloon puncture. By managing these two variables and adjusting them to withstand the dynamic gastric environment, the balloon system can be tuned to ensure that it remains inflated throughout its service life. The occurrence of spontaneous deflation in this intragastric balloon can be minimized by selecting the initial inflation gas in combination with the selection of composite wall materials and structures. The selection of permeability characteristics relative to water vapor transmission rate and gas permeability of the composite wall allows the rate of gas diffusion into or out of the balloon to be controlled by utilizing the properties of the gastric space contents. This approach allows for a tunable method to prevent underinflation and overinflation.

Another phenomenon typically seen with gastric balloons and obesity is gastric adaptation. During gastric adaptation, the stomach grows to accommodate space-occupying devices or excess food intake. During gastric adaptation, the volume of the stomach, including the intragastric balloon, increases over time, causing the patient to become hungry. However, by controlling gas diffusion and water vapor transmission through the balloon wall over time, it is also possible to increase the balloon size over time to maintain weight loss by selecting the permeability properties of the initial inflation gas (ES) and water, as well as other in vivo gases. In addition to spontaneous deflation, by selecting the permeability properties of the composite wall in combination with the initial gas and utilizing the transmission of gas and water from the gastric environment within the balloon, the balloon can be designed to increase in size over its life in response to gastric adaptation.

Experiments were conducted using various starting inflation gases in combination with an external gaseous environment that mimicked the internal gas and water environment of the stomach. The stomach contains a mixture of water, acid (hydrochloric acid), gas, and semifluid digesta (a semifluid mass of partially digested food that passes through the stomach into the duodenum). Gastric gas is typically produced by swallowing air during feeding. The composition of air is nitrogen (N2) 78.084%; oxygen (O2) 20.9476%; argon (Ar) 0.934%; carbon dioxide (CO2) 0.0314%; neon (Ne) 0.001818%; methane (CH4) 0.0002%; helium (He) 0.000524%; krypton (Kr) 0.000114%; hydrogen (H2) 0.00005%; and xenon (Xe) 0.0000087%.

Five gases make up more than 99% of the gastrointestinal system: nitrogen (N2), oxygen (O2), carbon dioxide (CO2), hydrogen (H2), and methane, with nitrogen predominating. Gastric pCO2 is very similar to local (splanchnic) arterial and draining venous blood pCO2 values. Gases can also be produced by the neutralization of gastric acid. For example, when gastric acid reacts with bicarbonate in digestive fluids (for example, as found in some antacids), this chemical process produces carbon dioxide, which is normally absorbed into the bloodstream. Food digestion in the intestine, primarily by colonic bacteria, produces carbon dioxide, hydrogen (H2), and methane. Microorganisms appear to be the sole source of all hydrogen and methane produced in the intestine. These gases arise from fermentation and digestion of nutrients (polysaccharides from fruits and vegetables are not digested in the small intestine). Small amounts of several other gases may also be produced, including hydrogen sulfide, indole, and ammonia.

Controlled self-inflation of a gastric balloon in an in vivo environment can be achieved by having a semi-permeable or permeable composite wall within the balloon and by initially filling the balloon with a preselected single gas, such as nitrogen or oxygen. The balloon exploits the difference in gas and water concentrations between the internal balloon environment and the external environment in the in vivo (GI/stomach) environment to increase and/or decrease in volume and/or pressure over time. To achieve this controlled decrease in volume and/or pressure, a wall having a relatively high magnetic permeability for the single gas used to inflate the balloon compared to the gases present in the in vivo gastrointestinal environment can be employed. For example, if nitrogen is used as the inflation gas, the volume and/or pressure of the balloon will decrease over time in the in vivo environment as nitrogen diffuses out through the oxygen-permeable wall and into the in vivo environment. Similarly, if oxygen is used as the inflation gas, the volume and/or pressure of the balloon will decrease over time in the in vivo environment as oxygen diffuses out through the oxygen-permeable wall and into the in vivo environment. The difference in partial pressure of the single gas in the balloon (higher) relative to the gastric environment (lower) will drive this process until equilibrium or dynamic balance is reached. To achieve a controlled increase in volume and/or pressure, a wall having a relatively low magnetic permeability to the individual gas used to inflate the balloon compared to the gases present in the in vivo gastrointestinal environment can be employed. For example, if nitrogen is used as the inflation gas, the volume and/or pressure of the balloon will increase over time in the in vivo environment as CO2, etc., diffuses out through the CO2-permeable wall and into the body. The difference in partial pressure of the permeable gas in the balloon (lower) relative to the gastric environment (higher) will drive this process until a constant dynamic equilibrium is reached.

Additionally, maintaining and/or controlling the balloon inflation can also utilize the concentration differential between the internal balloon environment and the external stomach environment, wherein the balloon volume/pressure can be increased or decreased as needed to extend the useful life of the product. One reason for reducing the pressure can be by first inflating the balloon with large but highly diffusible/soluble gas molecules such as CO2, in addition to pre-stretching the balloon with a relatively inert gas such as nitrogen, wherein the soluble gas diffuses out of the balloon and gases not initially present in the balloon migrate in to fill the balloon.

The inflation gas can be selected to initially utilize the majority of the gas in the balloon, which consists of a largely inert gas or a gas with a low diffusivity through the selected composite wall. An inert gas combined with a less inert gas (ES) that is more soluble in the gastric environment can be combined to comprise the initial balloon inflation gas composition. The patient's diet and medications can also influence/control the balloon's inflation state—primarily by influencing the concentration of carbon dioxide generated in the gastric environment. Furthermore, gastric pH also influences CO2 concentrations. This particular approach can also allow for a greater degree of tuning of the device's lifespan based on composite wall materials, such as barrier/non-barrier layers, and whether diffused gas remains in the balloon longer with a barrier wall compared to a non-barrier wall. Specific forms of self-inflation can be used: self-inflating gastric balloons (e.g., initial inflation initiated by a gas-generating reaction in the balloon after swallowing) or inflatable gastric balloons (e.g., inflation using a catheter with or without endoscopic assistance, nasogastric delivery, or any other delivery method). This approach can be used with any gastric balloon, including swallowable balloons and balloons placed in the stomach, for example, via endoscopic methods. This method is particularly preferred for use in conjunction with intragastric devices; however, it is also applicable for use in, for example, pulmonary wedge catheters and urinary incontinence balloon devices. Advantages of this technology include the ability to compensate for gastric adaptation, allowing the balloon to adapt to the increasing volume of the stomach over time, thereby maintaining the patient's sense of fullness. It also allows for starting with a smaller amount of inflation gas composition for self-inflating balloons. It can prevent spontaneous deflation by exploiting the diffusion gradient between the gastric balloon system and the in vivo gastric environment.

In a particularly preferred embodiment, a coextruded mixture for the wall layer is used, along with nitrogen (with or without carbon dioxide) as the inflatant. A particularly preferred structure is nylon 12/ethyl methyl acrylate/polyvinylidene chloride/ethyl methyl acrylate/nylon 12/linear low-density polyethylene + low-density polyethylene (also known as a coextruded nylon 12-encapsulated PVDC-nylon 12-LLDPE + LDPE multilayer). Another particularly preferred structure is a coextruded multilayer nylon 12/linear low-density polyethylene + low-density polyethylene.

The choice of resin used for the composite wall structure (and the choice of coextrusion or adhesive) can be varied to control the compliance (ductility), puncture resistance, thickness, adhesion, seal bond strength, orientation, acid resistance, and permeability to gases and water vapor to achieve specific results.

Automatic inflation of the intragastric balloon system

Self-inflating (also known as auto-inflating) or inflatable (also known as manually inflatable) intragastric balloons are equipped with a mechanism to robustly control the timing of deflation. In a preferred embodiment, the balloon deflates automatically and passes through the stomach, through the lower gastrointestinal tract, and out of the body (non-spontaneously) at the end of its predetermined useful life, preferably between 30 and 90 days, but deflation can be timed up to 6 months. In the preferred embodiment described below, the timing of deflation can be controlled by the external gastric environment (e.g., temperature, humidity, solubility, and/or pH conditions) or by the environment within the inflation balloon lumen. Preferably, the initiation of the self-deflation process is controlled consistently by manipulating the internal balloon environment.

In other embodiments, a patch is applied to allow for the inverted seams described above and/or one or more additional patches or other structures attached to the balloon structure, made of an erodible, degradable, or dissolvable material (natural or synthetic) and integrated into the balloon wall. The patch is of sufficient size to ensure that the opening has sufficient surface area to induce rapid deflation and prevent the passage of gastric fluids into the balloon for re-inflation. The balloon patch comprises a material that can be applied to the balloon so as to maintain a substantially smooth surface, and preferably comprises a single layer or multiple layers of material. The patch is constructed of an erodible, disintegrable, degradable, or other such material, which is preferably tissue compatible and degrades into non-toxic products or a material that slowly hydrolyzes and/or dissolves over a period of time (e.g., poly(lactic-co-glycolic acid) (PLGA), poly(lactide/glycolide) (PLG), polyglycolic acid (PGA), polycaprolactone (PCL), polyesteramide (PEA), polyhydroxyalkanoate (PHBV), polybutylene succinate adipate (PBSA), aromatic copolyesters (PBAT), poly(lactide-co-glycolide) (PLCL), polyvinyl alcohol (PVOH), polylactic acid (PLA), poly-L-lactic acid PLAA, pullulan, polyethylene glycol (PEG), polyanhydrides, polyorthoesters, polyaryletherketone (PEEK), multi-block polyetheresters, poliglecaprone, polydioxanone, trimethylene carbonate, and other similar materials). These erodible, disintegrating, or degradable materials can be used alone or in combination with other materials, or can be cast/coextruded, laminated, and/or dip-coated in combination with non-erodible polymers (e.g., PET, etc.) and used in a balloon structure. Depending on what the patch is exposed to, degradation/erosion can occur by initiating and/or controlling the gastric environment (e.g., temperature, humidity, solubility, and/or pH conditions), or by controlling the lumen of the balloon (e.g., humidity and/or derived pH conditions). The thickness of the polymer, as well as the environment and exposure time that affect degradation, can also contribute to the timing of degradation. Degradation/erosion is timed so that it occurs once the intended balloon life has expired (e.g., inflation is maintained in the body for 25 to 90 days before degradation/erosion results in the formation of an opening that allows deflation). As an alternative to (or in combination with) a patch using a degradable material, the patch can include a similar fluid-retaining barrier membrane or the same membrane as the remaining wall of the balloon that is adhered or welded to the balloon using a weak adhesive, such that the patch delaminates from the applied area after a specified amount of time and has holes that allow the release of the inflation fluid for deflation. Alternatively, if rapid deflation is deemed necessary, the entire composite balloon wall can be made of an erodible material. The use of erodible materials or materials that mechanically fail after a pre-specified time is also similar to all of the embodiments described below for the deflation mechanism. The timing of degradation or erosion can be controlled using the external gastric environment (e.g., conditions of temperature, humidity, solubility, and/or pH) and/or the conditions within the balloon lumen (e.g., conditions of humidity and/or pH of the residual fluid in the balloon).

In other embodiments, a plug or multiple plugs (optionally in conjunction with another degradation retention structure) can be incorporated into the balloon structure and can include any erodible, disintegratable, or otherwise degradable synthetic or natural polymer similar to those described above (e.g., PLGA, PLAA, PEG, etc.). Plugs can be fabricated in a variety of shapes (e.g., cylindrical or radial, as depicted in Figures 22A-D) to achieve various surface-to-volume ratios, thereby providing a preselected, predictable bulk degradation pattern for the erodible polymer. The plug can include a release mechanism that can be chemically activated upon initiation of degradation/erosion, causing the septum or plug material to pop out of the balloon or descend into the balloon interior, thereby forming a channel for balloon fluid release and subsequent deflation. Mechanical additives that can be incorporated into the plug include degradable/erodible/disintegratable materials that hold the plug (e.g., of non-degradable or degradable material) in place, or compression springs housed within the retention structure or plug structure. More specifically, preferred embodiments for achieving deflation may include a housing, a radial seal, a solid erodible core, and a protective membrane attached to the outer surface of the erodible core (Figures 22A-B). The interior of the eroding core is exposed to the internal capsule fluid. The core generates a compressive force that holds the seal against the shell. As the core erodes, the compression between the shell and the radial seal decreases until a gap exists between the shell and the seal. Once a gap exists, gas can freely migrate from the capsule interior to the external environment (Figure 24A). The seal can fall out of the shell and into the capsule. The diameter, length, and material type can be adjusted to produce expansion at a desired time point. Example materials for each component used to implement this expansion mechanism include the following: Shell - A biocompatible structural material capable of withstanding sufficient radial force to form a hermetic seal. Materials may include polyethylene, polypropylene, polyurethane, ultra-high molecular weight polyethylene, titanium, stainless steel, cobalt-chromium alloy, PEEK, or nylon. Radial Seal - Constructed of a biocompatible elastomeric material capable of providing a liquid and gas barrier to acidic environments. Materials may include silicone, polyurethane, and latex. Eroding Core - Capable of decomposing at a predictable rate under given environmental conditions. Materials may include PLGA, PLA, or other polyanhydrides that can lose integrity over time, or any of the materials listed above that provide erodible characteristics.

With a spring mechanism, once the material degrades, the spring is released and/or the plug/septum is pulled into or out of the capsule, thereby releasing the fluid once the orifice has been created by the spring mechanism releasing and the plug being pushed out or pulled in (Figure 24B).

The expansion and contraction mechanism utilizes a septum, a hygroscopic swelling material, and a moisture-eroding material. The eroding material slowly erodes upon contact with moisture, eventually exposing the hygroscopic swelling material. As the hygroscopic swelling material begins to absorb moisture, the swelling pulls the septum in the head out of position by pushing against the septum lip or the ring attached to the septum. This pulling of the septum out of position causes immediate deflation of the capsule (Figure 24C). To protect the swelling material from moisture until a desired time, the swelling material can be coated in a water-blocking material such as parylene or a slowly water-degrading material. Moisture exposure can be controlled via a small inlet port. The inlet port can be a small hole that extracts moisture in a controlled manner, or a wicking material. The desired deflation time is achieved through a combination of the eroding material, the barrier material, and the size of the inlet port.

In certain embodiments, the balloon may include one or more plugs within the balloon wall containing compressed or gas-releasing pellets ( FIG. 25A-B ). The pellets may be composed of any combination of components that release CO2 gas when activated (e.g., sodium bicarbonate and citric acid, potassium bicarbonate and citric acid, etc.). The pellets may be in the form of tablets or rods protected by an erodible, disintegrating, or degradable material, similar to the plugs and patches described above, that is preferably tissue-compatible and degrades or slowly hydrolyzes and/or dissolves into non-toxic products (e.g., poly(lactic-co-glycolic acid) (PLGA), polyvinyl alcohol (PVOH), polylactic acid (PLA), poly-L-lactic acid (PLA), pullulan, polyethylene glycol, polyanhydrides, polyorthoesters, polyaryletherketone (PEEK), polyblock polyetheresters, poliglecaprone, polydioxanone, trimethylene carbonate, and other similar materials). Degradation/erosion of the plug indicates a reaction between the two chemicals in the balloon, which subsequently leads to the formation of gas (e.g., CO2). When enough gas is trapped or built up, sufficient pressure is eventually generated to push out the softened polymer material and create larger channels within the balloon for the CO2 gas to escape. External pressure applied to the balloon by the stomach (e.g., squeezing) can trigger this process of creating larger channels. The size and properties of the polymer-containing plug (diameter, thickness, composition, molecular weight, etc.) drive the timing of degradation.

In other embodiments, plugs or patches of varying shapes and sizes, similar to those described above, can be used within the lumen of the balloon, having a multilayered structure including a semipermeable membrane that facilitates balloon expansion and contraction. The plugs or patches are constructed from degradable/erodible/dissolvable materials similar to those described above (e.g., poly(lactic-co-glycolic acid) (PLGA), polyvinyl alcohol (PVOH), polylactic acid (PLA), PLAA, pullulan, and other similar materials) and include a compartment surrounded by a semipermeable (impermeable to the osmotic agent) septum containing a concentrated solution of a solute or osmotic agent (e.g., glucose, sucrose, other sugars, salts, or combinations thereof). Once the plug or patch begins to degrade or erode, water molecules migrate downward through the water via osmosis, gradient from an area of greater water concentration to an area of lesser water concentration, across the semipermeable membrane, and into the hypertonic solution within the compartment. The compartment containing the osmotic agent swells and eventually ruptures, pushing out the septum and the degraded plug or patch, thereby allowing rapid gas loss through the newly created channel or area.

In certain embodiments, a capsule is constructed from a septum, a wet-erodible material within the inlet port, and a hygroscopic swelling material. The erodible material slowly erodes upon contact with moisture, eventually exposing the hygroscopic swelling material. As the hygroscopic swelling material begins to absorb moisture, the swelling pulls the septum in the head out of position by pushing against the lip of the septum or the ring attached to the septum. Pulling the septum out of position causes the capsule to immediately deflate. To protect the swelling material from moisture until the desired time point, the swelling material can be coated in a water-blocking material, such as parylene, or a slowly water-degrading material. Moisture exposure can be controlled by a small inlet port. The inlet port can be a small hole that extracts moisture in a controlled manner, or a wicking material. The desired deflation time is achieved through a combination of the erodible material, the barrier material, and the inlet port dimensions.

Another mechanism for self-deflation is to create a forced delamination scheme, which provides a larger surface area to ensure rapid deflation. For example, in a balloon with a three-layer wall, the outermost layer is substantially strong enough to contain the inflation fluid (e.g., polyethylene terephthalate (PET), etc.), the middle layer is composed of a fully erodible material (e.g., PVOH, etc.), and the middle layer is composed of a more fragile material (e.g., polyethylene (PE), etc.). The PET, or outermost layer, is "scored" or "hatched" with the erodible material to create small channels that erode over time ( FIG. 23 ). This creates channels that allow gastric fluid to penetrate the balloon layers and begin to degrade the fully erodible material. As the erodible layer degrades or dissolves, the material comprising the innermost layer also erodes, degrades, or dissolves, as it is not strong enough to withstand its own gastric dynamics/environment. The balloon then collapses on itself and ultimately passes through the lower gastrointestinal tract. Having an erodible layer sandwiched between strong and weak layers facilitates the timing of erosion by creating a longer path length than an erodible plug or patch subject to the gastric environment. The distance between the scores or openings can also be selected to provide the desired rate of expansion and contraction.

In another embodiment, to provide for sudden deflation of the balloon after a desired period of time has elapsed, the entire composite balloon wall, or a portion of the composite wall (a patch), comprises several layers of material that are slowly penetrated by water injected into the balloon during the manufacturing or inflation process (Figures 27A-E). This water penetrates these layers, eventually reaching the substantially inflated material, rupturing the thin outer protective layer and creating a large pore (Figure 27D) for gas escape and balloon deflation. The water-inflated material is protected from the liquid by a coating or sheath, such as parylene, which allows for controlled exposure to water. Once the water reaches the inflated material, the force it exerts on the protective outer layer causes it to rupture. The outer layer can be created by creating a weak joint area (Figure 27E), a partially scored area, or other methods that ensure the desired rupture location and facilitate the desired timing of automatic deflation. Any number of layers can be present between the moist environment and the moist, inflated core. Each material layer can have a different erosion rate (e.g., fast or slow) and can be selected based on the predetermined time at which deflation is desired to occur (e.g., over 30 days, 60 days, or more). By varying the number, thickness, and rate of each circumferential layer, the timing of expansion and contraction can be precisely controlled.

Alternatively, a pressure-sealed button adhesively bonded to a perforated hole in the balloon material is provided for deflation (Figures 28A and B). The adhesive bonding the button erodes over time as it interacts with moisture from gastric fluid or moisture already infused into the balloon. Once the adhesive is no longer able to bond and create an airtight seal between the adhesive and the button, the balloon will deflate rapidly. By controlling the hole size and moisture exposure of the adhesive, the erosion time can be accurately predicted.

Deflation can also be facilitated by creating a series of connecting ports within the septum or on another similar structure attached to the composite wall of the balloon. The ports can be constructed using a water- or acid-soluble, biocompatible, low-permeability material such as gelatin (Figures 29A-B). The pore diameter, number of pores, channel width, and channel length can all be adjusted to control dissolution parameters. Once the port and channel materials dissolve, a clear path is created for trapped gas within the balloon to escape, ultimately resulting in a deflated balloon. The water can be gastric fluid or internally controlled by including water within the balloon during assembly or inflation. Multiple port openings can be provided to ensure gas transport. In addition, several variables can be adjusted to control dissolution time: port opening size; number of openings; length of the internal channel; width of the internal channel; and rate of material dissolution. The port/channel layout can be designed to ensure that only a small amount of surface area is exposed to water at any given time, thereby controlling the erosion rate and ultimately deflation. In an alternative embodiment, depicted in Figures 29D-E, an inflatable material is used instead of a push-out member to initiate deflation.

A preferred embodiment of a manually inflatable balloon also features a self-deflation mechanism, with ports housing both the inflation and deflation mechanisms located in the same location (see Figure 30A). The device comprises a catheter needle sleeve, such as nylon or plastic, sealed to a silicone portion attached to the inflation tube during inflation. It further comprises a silicone head sealed to the needle sleeve, allowing for inflation and detachment from the catheter. The silicone head also seals to component #6 until it is pressed out to inflate component #7. The needle-inflatable balloon is made, for example, of stainless steel. Upon placement, the compression seal between component #6 and #2 vents internal gas. An insert, such as titanium, provides imaging visibility (Figure 30B) and rigid support for components #2 and #4, with an interference lock, slip-fit, and is press-fitted to component #6. A septum, such as silicone, seals to component #3 during inflation. A shell, such as PEEK or hard plastic, is bonded to the balloon exterior and provides a sealing surface for component #2. After inflation, component #7 includes a vent from the balloon interior to the exterior. The expansion device, in an adhesive material surrounded by a controlled water vapor transmission rate material (a polyurethane blend of varying thicknesses), uses the available moisture within the bladder to absorb and increase in volume. The press fit between parts #5 and #6 holds the parts securely in place until part #7 begins to expand from moisture absorption.

In a preferred embodiment, the present invention includes a self-sealing valve compatible with an inflation catheter comprising a needle and a needle sleeve. During inflation, the self-sealing valve seals to the needle sleeve. Distal to the self-sealing valve is an insert made of titanium, stainless steel, MP35N, or any other radiopaque, rigid material, which provides imaging visibility and mechanical support during inflation. Beneath the insert is a collapsible mechanism consisting of an expansion device. The expansion device comprises a solute material, such as polyacrylamide, encapsulated in an adhesive material surrounded by a moisture-limiting material with a defined water vapor transmission rate (MVTR). Examples of moisture-limiting materials include, but are not limited to, combinations of polyurethanes of various thicknesses. A hard plastic housing, such as PEEK, contains the self-sealing valve, the radiopaque insert, the inflation material, and the moisture-limiting material. The hard plastic housing includes vents that allow fluid to flow between the interior and exterior of the balloon if the external seal is not in place. The radiopaque insert is coupled to the hard plastic housing via a mechanical mechanism, such as a press-fit, that allows linear movement but prevents expulsion from the hard plastic housing. The second outer sealing valve creates an airtight seal against the hard plastic shell, blocking the shell vent, and moves linearly as the expansion device gains volume. Moisture deposited within the balloon is absorbed by the expansion device, as well as moisture contributed by the external gastric environment. Once moisture is delivered, the expansion material generates sufficient pressure to cause the outer sealing valve to be linearly moved past the lip of the shell. This opens a vent path, which allows the internal inflation fluid to quickly decompress and deflate the balloon. The deflated balloon is allowed to pass through the pylorus and the rest of the digestive tract. One or more inflation/deflation ports on the balloon surface can be used.

Figure 31 depicts an alternative embodiment in which the inflation and deflation ports are separate entities. The device includes a seal, such as nitrile rubber or a similar sealing material, to provide an airtight seal between components #1 and #3. It slides along the surface of sliding portion #3 until the airtight seal fails, allowing the internal air to escape. Once the seal is displaced, a vent allows gas to flow from the bladder. Also included are a titanium piston, a water retainer (cotton or sponge-like material that can retain water and hold it against the surface of component #4 to maintain a constant humidity environment), and an adhesive seal to the bladder membrane that provides a strict volume for components #1, 2, 4, and 5. This design also allows venting between the internal and external bladder environments, allowing water to enter component #4, which forces component #4 to expand in one direction. The expansion device, enclosed in an adhesive material surrounded by a controlled water vapor permeability material (a polyurethane blend of varying thicknesses), utilizes the available moisture within the bladder to absorb it. The device may include a hard outer shell made of hard plastic or metal, an inflation device consisting of a superabsorbent core surrounded by a water vapor transmission rate limiting membrane, and an airtight seal that can move linearly when the expansion device volume grows. Based on how much moisture it can obtain, the expansion device expands at a given rate. In order to control the expansion rate, a bulkhead such as polyurethane is used to control the desired water vapor transmission rate that can be used for the superabsorbent device. The water vapor transmission rate can be adjusted by material composition or material thickness. In order to maintain constant contact with the moisture of the water vapor limiting bulkhead, sponge materials such as cotton can be used as moisture reservoirs for the expansion device. Once the expansion material pushes the seal through the lip of the hard outer shell, fluid can be discharged from the bladder interior to the external environment, causing the bladder to expand and contract and pass through the remainder of the pylorus and digestive tract.

The balloon may have at least one deflation port, but may have more as needed, so that it may fully deflate with as much residual inflation fluid remaining without causing ileus (ie, partial deflation).

One mechanism for facilitating passage involves an erosion mechanism, which allows the balloon to disintegrate into a size with a higher probability of predictably traversing the lower gastrointestinal system. Preferably, the deflated balloon size is less than 5 cm long and 2 cm thick (similar to various foreign objects of similar size, which have been shown to predictably and easily traverse the pyloric sphincter). This can be achieved by providing the balloon with "erodible seams." A seam can be provided to split the balloon into (at least) two halves, or more seams can be provided so that multiple smaller balloon pieces are produced during the dissociation reaction ( FIG. 18 ). The number of seams used can be selected based on the original surface area of the balloon and the need to disintegrate the balloon into pieces of a size that predictably and more easily traverse the gastrointestinal tract. The seam erosion rate can be controlled by using materials that are affected by the pH, fluids, humidity, temperature, or combinations thereof of the external gastric environment. The seams can be a single layer or multiple layers comprised solely of erodible material. The timing of self-deflation can be further controlled by designing the seam layers, for example, such that the reaction and/or degradation of the seam material is dependent on the internal environment of the balloon rather than the external environment. By manipulating the reaction so that erosion or degradation is initiated by the internal environment (e.g., the balloon's internal pH, humidity, or other factors), the effects of human-to-human gastric variability (pH, etc.) that can affect erosion timing can be minimized. The internal balloon environment can be manipulated by, for example, adding excess water during injection to create a more humid internal environment or by adding variable amounts of components to manipulate pH.

Example

A disposable nitrogen filling system and a process tank device are provided as accessories for the Obalon gastric balloon (OGB). When in use, the cap is removed from the valve of the disposable nitrogen filling system. This disposable nitrogen filling system is inserted into the process tank, and the stem is closed to connect the valve to the disposable tank. The lack of a fluid pathway with a lower pressure gradient prevents fluid from being discharged. The process tank is attached to the accessory kit via a Luer connector. The 3-port 2-position valve on the accessory kit is confirmed to be closed before opening the 90° valve. The appropriate pressure is confirmed by a digital pressure gauge, and then the standard OGB system inflation process begins, and the fluid path is opened to the balloon in the body. After the process, the disposable nitrogen filling system is removed from the process tank and properly disposed of. The process is reused and can have a service life of, for example, at least 1 year.

The nitrogen filling system is appropriately sized to fit into the canister dispenser, for example, a non-valve canister with a maximum outer diameter of 45 ± 1 mm. The nitrogen filling system is appropriately sized to fit into the canister dispenser, for example, a non-valve canister with a maximum diameter of 115 ± 1 mm. The nitrogen filling system is pressure-resistant, for example, with a pressure resistance of 18 bar. The internal volume of the nitrogen filling system is sufficient to fill the bladder kit at the appropriate filling pressure, for example, a non-valve canister with a maximum volume of 161 ± 3 cm³. The nitrogen filling system is accurately pressurized, for example, with a sample direct pressure measurement within ± 1 psi or ± 7 kPa. The assembled nitrogen filling system is foam-tight, for example, pressurized disposable canisters can be visually tested for leaks using a water bath bubble test. The canister volume allows for sufficient gas at a pressure not high enough to rupture the canister, for example, a fully pressurized canister pressure does not exceed 75 psi. The process canister is capable of connecting to the bladder kit. The process canister includes a Luer connector for connection to a swallowing catheter. The process canister has a functioning valve for inflation. The nitrogen filling system has a 1/4-turn valve. The valve is designed for use with gases and has an operating pressure range of 1 to 75 psi, among others. The process tank accurately displays pressure. The process tank includes a digital pressure gauge with 0.01 psi resolution or 0.1 kPa resolution. The pressurized nitrogen filling system is bubble-tight, e.g., no bubbles were observed in a bubble leak test in a 130°F water bath for 1.5 minutes. The nitrogen filling system fills the balloon to the appropriate pressure, e.g., 2.0 +/- 5 PSI at sea level. This pressure is effectively maintained by the assembled nitrogen filling system without setting the balloon fill pressure outside of specification. The gas pressure will not drop by more than <5 psi over a 1-year period. The process tank is reliable for at least 1 year and has performed satisfactorily for at least 1,000 start-up cycles. The process tank is compatible with the nitrogen filling system. The process tank dynamic assembly can be cycled through the expected range of motion using the inserted disposable tank.

When the receiver is closed, the process tank opens the disposable tank valve. The process tank is capable of dispensing nitrogen fill system contents to support a total system process time target of 5-10 minutes. A fully pressurized nitrogen fill system can dispense in less than 30 seconds. The process tank's digital gauge provides advance notification of low battery conditions. The digital gauge includes a low-battery indicator. The process tank's digital gauge battery life should last the life of the unit. The digital gauge battery life is a minimum of 2,000 hours. Batteries are standard and field-replaceable as needed. The digital gauge retains its battery when not in use, for example, by automatically shutting off 60 minutes after the last key press. The process tank is sealed to the nitrogen fill system in a leak-proof manner. The nitrogen fill system used in the process tank leaks no more than 0.1 lb in 5 minutes. The process tank's digital pressure gauge is electromagnetically compatible. The digital pressure gauge on the process tank is easy to read, e.g., the gauge is at least 3" in diameter and has a digital display. The pressure gauge on the process tank is intuitive to operate, e.g., the gauge has open and close buttons that are clearly labeled. The actuator on the process tank used to inflate the bladder is intuitive, e.g., a colored valve stem with only open and closed positions is used for initial bladder filling from the process tank. The nitrogen filling system is easy to insert into the process tank, e.g., the process tank opening is large and clearly visible.

The nitrogen filling system includes a nitrogen mass suitable for achieving the desired final bladder pressure, for example, by weighing nitrogen filling system samples before and after filling to ensure 0.52 ± 0.01 grams of gas. The process tank's digital gauge has sufficient accuracy to ensure the final bladder pressure is achieved, for example, the process tank's digital gauge has an accuracy of 0.25% of full scale. The process tank has a digital gauge that maintains accuracy throughout the tank's service life, for example, after 1000 cycles of 0 psi to 30 psi or 0 kPa to 26 kPa, the process tank's digital gauge has an accuracy of 0.25% of full scale. The nitrogen filling system is preferably operated in a suitable ambient environment, such as a temperature of 18°C to 55°C and a relative humidity of 30% to 85%. This altitude classification system is for use at altitudes less than 2000 m (61 to 101 kPa).

The Obalon Gastric Balloon System (hereafter referred to as the "System" or OGB) is designed to aid weight loss by partially filling the stomach and inducing a feeling of fullness. The system consists of up to three intragastric balloons that are non-invasively placed in the stomach (via a catheter-capsule assembly) and remain in the stomach for up to three months (12 weeks). For administration, each balloon is contained within a medical-grade porcine gelatin capsule attached to a microcatheter. The balloon capsule delivers the balloon in the same manner as a pharmaceutical capsule delivers medication. The catheter is pre-attached to the radiopaque, resealable valve that holds the balloon in place. For device administration (placement), the catheter/capsule is swallowed by the patient. The catheter is then attached to a procedure canister containing a disposable nitrogen filling system for inflating the balloon. After the patient swallows the balloon capsule, a radiograph is performed to ensure that the balloon is located in the stomach after swallowing (visualized by radiopaque markers). Fluoroscopy is the preferred radiographic method because it provides real-time images of the balloon using low-level radiation. A fully inflated single balloon has an ellipsoidal volume of approximately 250 cc. When three balloons are placed, the total balloon volume is 750 cc. The procedure does not require sedation. After inflation, the catheter is manually ejected from the balloon valve and retrieved by the physician; the balloon is left floating freely in the patient's stomach for up to three months.

The duration of balloon use can be managed with concurrent use of a proton pump inhibitor, such as 40 mg/day of pantoprazol or an equivalent dose. It is likely to be an effective treatment for confirmed pre-existing esophagitis and gastritis, which should improve tolerance to the device. Antiemetics and antispasmodics can be given immediately after balloon placement and as needed while the balloon is in the stomach.

Clinical trials have shown that it is preferable to initially place one balloon, followed by subsequent balloons over a 3-month period (Figure 32). The determination of whether a patient requires additional volume should be made based on the patient's weight loss progress and reported level of fullness. Additional balloons can be placed in the same manner as the first balloon; placement requires only radiography.

The balloon helps patients eat smaller portions of their main meals. Choosing less calorically dense foods in addition to the balloon will help promote weight loss. The balloon is designed to remain in the stomach for three months (12 weeks) from the time of the first balloon placement. All balloons are removed at the end of three months using standard endoscopic techniques. The device is removed by a trained medical professional proficient in gastroscopy.

The healthcare setting in which the device will be used has access to fluoroscopy or digital X-rays at the time of device administration to confirm bladder/capsule placement prior to inflation. Furthermore, the prescribing physician has immediate access to an endoscopy unit and personnel skilled in gastroscopy, should foreign body retrieval become an issue during administration. Gastroscopy equipment and trained foreign body removers are used for device removal.

The Obalon Gastric Balloon System (hereinafter referred to as the "System") is indicated for weight loss in overweight adults with a BMI greater than 27 who have previously failed a supervised weight management program. The Obalon Gastric Balloon System is intended for use in conjunction with a diet and behavior modification program. Based on the individual's weight loss progress and fullness level, up to three Obalon gastric balloons may be placed in the stomach over a 3-month (12-week) period. The maximum placement period for Obalon gastric balloons is 3 months (12 weeks), and all balloons must be removed at that time or earlier.

All components are supplied non-sterile. The system includes the following: a placebo capsule assembly, which includes a capsule of the same material, size, shape, and weight as the actual device, but does not include a balloon or catheter. This capsule is filled with food-grade sugar to simulate the weight of the device; an Obalon gastric balloon assembly, which includes a folded balloon contained in a swallowable Gelatin Capsule and attached to a disposable flexible catheter delivery system (Figure 33); an accessory kit, which includes two 3-cubic-centimeter syringes, extension tubing, and a tube stopper with a three-way stopcock (Figure 34), as well as a 60-cubic-centimeter syringe; a process canister, which is a reusable component used in conjunction with a disposable charging system with an attached digital pressure gauge (Figure 35); two AAA batteries; and a nitrogen filling system filled with 150 cubic centimeters of nitrogen. Other items that can be used in conjunction with the administration management and/or removal system include a small clean bowl, bottled water, a timer/clock, a digital X-ray or fluoroscope, a negative pressure suction source, a gastroscope, a gastroscopic injection needle compatible with the working channel of the gastroscope (the minimum length can be 6 mm and the minimum needle gauge can be 23), and a rat tooth band with an alligator claw grasper (the minimum opening width can be 15 mm) or other commercially available endoscopic retrieval tools such as a two-pronged grasper that are compatible with the working channel of the gastroscope.

Prepare the process canister for use by first ensuring the process canister is correct for the facility height or includes a pressure compensation valve to adjust the starting pressure to ensure proper balloon tip pressure. Failure to use the correct process canister may result in a deflated or overinflated balloon. The process canister valve is in the open position (Figure 36). The "Open" button is pressed to connect the process canister pressure gauge. The extension tube and the tube plug with three-way valve are removed from the accessory kit packaging. The Luer lock plug is removed from the end of the process canister pressure gauge (Figure 37). The Luer lock plug is saved and returned to the process canister after the process is complete to keep the process canister free of debris. The proximal end of the extension tube's Luer connector (from the accessory kit) is connected to the process canister with the valve open (Figure 38). The tube plug valve is in the closed position to stop further flow (Figure 39). The cap is removed from the disposable canister. If the cap is removed, the canister is configured not to fit into the canister dispenser. With the lever in the "Open" position, the disposable nitrogen filling system is inserted directly downward into the canister dispenser (Figure 41). The lever is set to the "closed" position to secure the disposable nitrogen filling system in place (Figure 42). The initial reading on the gauge is confirmed to be between 257 kPa and 297 kPa to ensure proper balloon inflation. The valve on the process canister is closed by turning the valve clockwise (to the right) (Figure 43). Before proceeding to the next step, the process canister valve is in the closed position to ensure proper positioning and condition of the balloon capsule before proceeding to the balloon filling step. The 3 cubic centimeter syringe is removed from its packaging and filled with 1.5 ml of room temperature water for use. A small clean bowl is filled halfway with water. The Obalon gastric balloon capsule and catheter delivery system are removed from their packaging.

Before patients swallow the functional device, they are advised to first swallow a placebo capsule. This process is designed to determine which patients will and will not be candidates for placement of the actual device. The placebo capsule should be easy to swallow. If the patient has no problems swallowing the placebo capsule, they are advised to proceed with the capsule therapy.

The Obalon balloon capsule is administered to the patient using the normal method of swallowing a tablet. No endoscope is required for placement. Fluoroscopy (or digital X-ray) is used during placement to verify that the balloon is seated in the stomach before the device is inflated. Any existing balloon is also imaged to confirm its integrity before swallowing another capsule. The total placement time for each balloon placement is less than 15 minutes.

If the patient has a strong gag reflex, a local anesthetic may be applied immediately before capsule administration. For balloon placement, it is preferred that the patient's lips be free of lipstick, lip gloss, or moisturizer that could interfere with the application process. The patient is ideally standing or sitting upright, and three large glasses of water are used to prepare for capsule administration. The patient may be instructed not to bite down on the catheter, close the catheter with their mouth, grasp the catheter with their hands, or hold the catheter. The capsule/catheter is moistened by immersing it in the bowl of water for no more than 10 seconds. After the capsule has been immersed in the water for 1 minute, the patient is handed the capsule/catheter and instructed to immediately place the capsule in their mouth and swallow it with another large glass of water. The proximal catheter port is held outside the patient's mouth. The time the capsule/catheter remains in the mouth is recorded. After swallowing, the patient is given additional water or juice (at least 100 ml). The patient remains in an upright sitting or standing position at all times. If the balloon does not clearly reach the stomach, the patient is instructed to continue drinking water or juice to facilitate peristaltic movement of the capsule/catheter. Once swallowed, the proximal end of the capsule/catheter assembly remains outside the patient's mouth until the balloon is inflated. The catheter may have markings that can be used as reference guides to help determine how far the catheter has advanced after swallowing, with or without radiographic verification, and with or without measurements provided by a digital table. When the 'bull's eye' marking is on the patient's teeth, this indicates that the balloon is approximately 45 cm down the esophagus, and fluoroscopy is used at this point to confirm that the balloon is in the stomach (Figure 44). The preferred method for correct balloon placement prior to inflation is to use radiographic imaging (fluoroscopy/digital X-ray). Catheter markings can be used as additional reference to ensure that radiographs are properly performed, or they can be used alone to verify the length of advancement into the stomach.

Connect the process canister with the extension tubing from the accessory kit to the balloon catheter by connecting the catheter to the male Luer port on the T-stop previously connected to the process canister's extension line (Figure 45). Use your fingers to snugly tighten the Luer fit. Before proceeding to the next step, the valve on the process canister is in the closed position to ensure proper positioning and stability of the balloon capsule before filling.

Approximately 1-2 minutes after swallowing, digital fluoroscopy or fluoroscopy is performed, with the patient standing or sitting upright, to determine the position of the radiopaque balloon marker in the stomach. At least 3-5 minutes after swallowing, a second verification of device position is performed using the process canister. This is accomplished by pressing the "ON" button to turn on the process canister digital gauge, turning on the gauge backlight, pressing the "ON" button again, and then opening the three-way valve on the tube stopper 90 degrees counterclockwise until it stops, allowing gas flow from the extension tube to the balloon (Figure 46). The pressure on the manometer is initially approximately 20 kPa and then increases to below 7 kPa as the capsule dissolves. This takes approximately 45 seconds but no longer than 4 minutes. If the pressure remains above 7 kPa, the capsule has not fully dissolved or the catheter is kinked. Having the patient drink more water may promote capsule dissolution. The pressure is monitored for up to 4 minutes. If the pressure has not dropped below 7.0 kPa after this time, the capsule has not dissolved or there is a kink in the catheter. The balloon filling procedure is initiated until the radiopaque balloon valve in the stomach is visualized and the procedure canister pressure gauge reads less than 7.0 kPa. During inflation, if there is an indication of inflation in the confined space (via pressure readings or patient symptoms), gas flow is shut off by closing the valve on the procedure canister, disconnecting the catheter from the procedure canister, and evacuating the balloon using a 60 cubic centimeter syringe. The balloon can then be removed endoscopically. If the pressure gauge reads less than 7.0 kPa, the balloon can be filled. The balloon is not disconnected from the catheter until balloon filling is complete. In the event of premature disconnection, the catheter is withdrawn and the balloon is then punctured and removed endoscopically.

A disposable nitrogen tank contains 150 cubic centimeters of nitrogen gas delivered to the balloon to fill a single balloon to 8.3-17.2 kPa and a volume of 250 cubic centimeters. When the pressure gauge remains stable after decreasing from the initial set inflation pressure, the balloon is filled to the desired volume of 250 cubic centimeters at a desired pressure of 13.8 kPa in approximately 2 minutes. To fill the balloon, the process tank valve is turned to the on/open position (Figure 47). Equilibrium (inflation time) is observed approximately 2 minutes after opening the valve. The final pressure reading on the process tank's digital pressure gauge is verified to be stable and reads 8.3-17.2 kPa. If the pressure is outside the specified range, endoscopic removal of the balloon is performed. The prefilled syringe is attached to a stopcock with a three-way valve. The stopcock with the three-way valve is rotated back 90 degrees to shut off the gas flow from the process tank (Figure 48). The three-way Stopcock valve is not turned until it is attached to the prefilled syringe, thus preventing a decrease in the final starting pressure in the balloon that would prevent the balloon from maintaining its volume over a 3-month period. The pressure gauge cannot be zeroed by holding the zero button while pressure is being transmitted, thus avoiding the need for subsequent endoscopic removal of the balloon.

The catheter is withdrawn by pushing the plunger of the filled 1.5-cc syringe in a quick, deliberate motion, thereby detaching it from the balloon valve in the stomach. If the catheter does not detach after the first attempt, a second 1.5-cc syringe filled with water can be used to attempt catheter removal again. On the second attempt, ensure that the catheter is straight (without kinks) and that the plunger is depressed in a quick, deliberate motion. Use force when advancing the syringe, and do not proceed slowly to avoid inadvertent ejection of the catheter. If the catheter remains attached to the balloon, a third 3-ml syringe can be injected halfway with water, and detachment attempted again. To facilitate detachment, the physician lifts their chin upward to help reduce any gag reflexes, then slowly withdraws the catheter from the patient's mouth. The catheter and needle within the needle sleeve are visualized (attached to the white protective hub of the capsule device) to ensure the needle is intact. If the needle is not within the needle sleeve, the balloon is removed. The catheter is detached from the tube stopper with the 3-way valve by unscrewing the Luer lock. The balloon's position can be reconfirmed using X-ray or fluoroscopy.

The disposable nitrogen filling system can be removed from the process tank and discarded. To remove, the process tank lever is moved to the "open" position and the nitrogen filling system is pushed up from the other side of the process tank, or the process tank is inverted and the disposable nitrogen filling system falls outward. The process tank is reused for the next balloon placement.

Patients may be advised to drink liquids for the first 24 hours and then transition to soft solids for the next 24 hours (for the first 48 hours after placement). Instruct patients not to drink alcohol, soda, or other "pops" or carbonated beverages. After 3 days, patients can return to solid foods and follow the dietary and behavioral modification plan provided by their physician.

Although balloon placement does not require an endoscope; it is desirable to have readily available a trained endoscopist when problems with balloon swallowing or undetected dysphagia are detected during the procedure. If the patient is unsuccessful on his/her first placement attempt, the following should be considered. If the device does not pass through the pharynx in the patient's mouth after 30 seconds of attempting to swallow, the capsule is removed from the mouth. A new moistened balloon capsule/catheter assembly is used. If the patient fails two attempts, this issue is discussed with the patient, and it is determined whether the patient is still a good candidate for treatment. If the swallowing failure is due to anxiety, standard methods can be used to reduce the patient's anxiety. Esophageal transit of the device can be facilitated by the use of clear carbonated beverages.

Patients are advised to report changes in satiety (i.e., increased hunger) and/or weight gain, as these may indicate that additional balloons for treatment may be warranted. If multiple balloons have been placed and the patient reports a change in fullness levels (i.e., decreased early satiety), this may be a sign of balloon deflation. Balloon deflation can be assessed using radiography (film X-ray, digital X-ray, or fluoroscopy) and gastroscopy as appropriate. Patients should consult their physician if adverse events occur more frequently than expected or become intolerable. Concomitant use of a proton pump inhibitor, such as 40 mg/day of pantoprazol or an equivalent dose, may be advisable for the duration of use and is likely to be an effective treatment for confirmed pre-existing esophagitis and gastritis that may improve tolerance of the device. Antiemetics and antispasmodics can be given immediately after balloon placement and as needed while the balloon is in the stomach.

After 12 weeks of use, the balloon is removed from the patient. The procedure is performed using an endoscope with a working length less than 1200 mm and an inner diameter compatible with the accessory tools recommended for puncturing and retrieving the balloon. Recommended tools include needle instruments, such as an injection needle in a 23G x 6mm Teflon sleeve or similar with a lumen for aspiration, rat tooth graspers with crocodile claws or two-jaw grasping forceps (minimum opening width of 15 mm), or two-pronged graspers with the same minimum opening. Other retrieval tools for balloon retrieval may be acceptable. The retrieval process is typically performed per the manufacturer's instructions for retrieval of foreign bodies. The endoscopic procedure performed is similar to that of an interventional or therapeutic procedure; however, it is recommended that the endoscopic approach be tailored to the unique product characteristics. For example, the balloon should be punctured only once so that the maximum amount of gas can be aspirated from it (via vacuum), and less gastric distension (less gas insufflation) allows for easier puncture of the balloon. A typical capsule may include porcine gelatin, water, methylparaben, propylparaben, and sodium lauryl sulfate as components. A typical balloon may be constructed from nylon and polyethylene (as wall materials), silicone (for the valve), and titanium (as the radiopaque component). The process tank is typically constructed from stainless steel, 6061 AL, brass, acetal, and silicone. The nitrogen fill system contains 150 cubic centimeters of nitrogen at 18 barr.

The patient should ideally fast for at least 24 hours, or as per the respective hospital protocol for the endoscopic procedure, to ensure the stomach is empty so the balloon(s) can be easily visualized. Anesthetizing the patient is recommended by every hospital and physician for endoscopic procedures. A gastroscope is inserted into the patient's stomach, and a clear view of the inflated balloon is obtained through the scope. A needle instrument is lowered into the working channel of the gastroscope. The balloon's valve is positioned, and the balloon is punctured only once with the needle (if possible, on the side opposite the valve to facilitate removal). A large syringe (60 ml) or suction cannula is used to apply suction and aspirate the balloon. The needle is removed from the working channel, and a grasper is inserted through the working channel. The balloon is grasped using the grasper on the side opposite the valve. With a firm grip on the balloon, the balloon is slowly withdrawn upward through the esophagus, and the balloon is removed through the mouth. The removal process is repeated for the remaining balloons, if any.

The present invention has been described with reference to specific embodiments. However, other embodiments than those described above are also possible within the scope of the present invention. Other method steps than those described above may be provided within the scope of the present invention. The different features and steps of the present invention may be combined in other combinations as described. The scope of the present invention is defined by the appended patent claims.

All references cited herein are hereby incorporated by reference in their entirety. To the extent that publications and patents or patent applications incorporated by reference contradict the disclosure in this specification, this specification is intended to supersede and/or take precedence over any such contradictory material.

To the extent publications and patents or patent applications incorporated herein by reference contradict the disclosure in this specification, the specification is intended to supersede and/or take precedence over any such contradictory material.

Unless otherwise defined, all terms (including technical and scientific terms) are given their ordinary and customary meanings to one of ordinary skill in the art and are not limited to specific or special meanings unless explicitly defined as such herein.

Phrases and terms used in this application and their variations, unless otherwise expressly stated, should be interpreted as open ended and not restrictive. As an example of the foregoing, the term "include" should be understood to mean "including but not limited to" and the like; as used herein, the term "include" is synonymous with "including," "containing," or "characterized by," and is inclusive or open ended and does not exclude additional unstated elements or method steps; the term "example" is used to provide illustrative examples of the items under discussion, rather than an exhaustive or limiting list; the adjectives "known," "normal," "standard," and terms of similar meaning should not be interpreted as referring to items available at a given time period or at a given time period, but should be read as including known normal or standard technology that may be available or known now or at any time in the future; and the use of terms such as "preferred," "preferred," "desirable," or "ideal," and words of similar meaning should not be interpreted as implying that certain features are critical, necessary, or even important structures or functions of the invention, but are not intended to emphasize alternative or additional features that may or may not be employed in a particular embodiment of the invention. Likewise, a group of items linked with "and" should not be understood as requiring that each of those items be present in the grouping, but rather should be read as "and/or" unless explicitly stated. Similarly, a group of items linked with "or" should not be understood as requiring mutual exclusivity between the groups, but rather should be read as "and/or" unless explicitly stated. Additionally, as used in this application, the articles "a" and "an" should be interpreted as referring to one or to more than one (i.e., to at least one) of the grammatical objects of the article. By way of example, "an element" means one element or more than one element.

The appearance in some instances of broad words and phrases such as "one or more," "at least," "but not limited to," or other similar phrases should not be construed to imply a narrower case or that such broad phrase may not be required.

All numerical values used in this specification expressing amounts of ingredients, reaction conditions, and the like should be interpreted as "about" in all instances. Therefore, unless otherwise indicated, the numerical parameters set forth herein are approximate values that may vary depending upon the desired properties sought to be obtained. At the very least, and without intending to limit the application of the doctrine of the scope of any claim equivalent to that in any application claiming priority to this application, each numerical parameter should be interpreted in light of significant digits and ordinary rounding techniques.

In addition, although the foregoing has been described in detail by way of illustration and example for the purposes of clarity and understanding, it is apparent to those skilled in the art that certain changes and modifications may be implemented. Therefore, the description and examples should not be interpreted as limiting the scope of the present invention to the specific embodiments and examples described herein, but rather include all modifications and alternatives that come with the true scope and spirit of the present invention.

Claims (10)

1. A system for inflating an inflatable gastric device, comprising: An expandable fluid container having expandable fluid container openings and a reservoir for holding expandable fluid; An inflatable fluid dispenser configured to provide a user with feedback on the inflatable intragastric device's inflation status based on a pressure decay system, wherein the inflatable fluid dispenser is robustly coupled to the inflatable fluid container and includes: The housing has an inner surface defining a channel having a proximal inlet coupled to an orifice of the expandable fluid container and a distal outlet located at the distal end of the expandable fluid distributor. A valve, disposed in the channel, and configured to switch between a closed state and an open state. A valve control device, coupled to the valve and configured for user operation, to switch the valve between the closed state and the open state. A pressure gauge configured to measure the pressure within the passage between the valve and the distal outlet, and A pressure compensation valve is configured to release a portion of the swelling fluid from the swelling fluid container through an exhaust port to achieve an initial pressure within the swelling fluid container, thereby achieving a predetermined end pressure for the gastric device located within the body. A swallowable, inflatable gastric device having an inner lumen and a proximal opening, wherein the inflatable gastric device is at least partially disposed within a soluble capsule configured for swallowing by a patient; and A catheter coupled to the inflatable gastric device, the catheter having a lumen located between and in fluid connection with the channel of the inflatable fluid dispenser and the proximal orifice of the inflatable gastric device, wherein the size and shape of the catheter are determined for placement in the patient's esophagus. 2. The system of claim 1, wherein the inner cavity of the inflatable gastric device is defined by the elliptical wall of the inflatable gastric device. 3. The system as described in claim 1 or 2, wherein the inflatable fluid dispenser is a reusable medical device product. 4. The system as claimed in claim 1 or 2, wherein the inflatable fluid container is disposable. 5. The system as described in claim 1 or 2, wherein the inflation fluid is pure nitrogen. 6. The system as claimed in claim 1 or 2, characterized in that a target initial volume is selected to achieve an internal volume of 90 cc to 300 cc within the inflatable gastric device upon inflation. 7. The system as claimed in claim 1 or 2, wherein the pressure compensation valve receives input regarding the current temperature, current altitude, current atmospheric pressure, or a combination thereof, and releases a portion of the inflating fluid based on the input. 8. The system as claimed in claim 1 or 2, wherein when in the stomach, the intragastric device comprises a final volume between 50 cc and 400 cc. 9. The system as claimed in claim 1 or 2, wherein the final pressure within the gastric device is between 8.3 kPa and 17.2 kPa. 10. The system as claimed in claim 1 or 2, wherein the feedback includes visual notification, auditory notification, or tactile notification.