WO2015023479A1 - Devices and systems anchored in the gastrointestinal tract - Google Patents

Abstract

A device for treating GERD, obesity, diabetes and allowing for controlled drug delivery in the GI tract is provided. The device includes a device body anchored through a tether to tissue in the oral cavity.

Description

DEVICES AND SYSTEMS ANCHORED IN THE GASTROINTESTINAL TRACT

CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of provisional patent application number 61/866,552 titled "Devices And Systems Anchored In The Gastrointestinal Tract", filed in the United States Patent and Trademark Office on 16 August 2013. The specification of the above referenced patent application is incorporated herein by reference in its entirety.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to devices that are anchored in the gastrointestinal tract. In particular, the present invention relates to devices and systems which can be used to treat gastrointestinal (GI) related disorders such as gastroesophageal reflux disorder (GERD), obesity, diabetes and to provide controlled drug delivery in the GI tract at any point along the GI tract.

Current methods of anchoring devices in the GI tract include stenting, which causes tissue damage or device migration, clipping which is temporary, percutaneous approaches which are invasive and prone to infection, or suturing which is prone to erosion and eventual elimination from the body.

Devices for treating GERD such as magnetic beads around the lower esophageal sphincter (LES) or electric stimulation are usually implanted invasively.

Operations for GERD such as fundoplication are irreversible and carry the risk of an invasive operation. The present invention describes a fully reversible, non-invasive device that provides long-term protection against GERD.

Separately, methods of delivering certain drugs such as peptides usually involve injections or IV administration since the stomach degrades such drugs.

Furthermore, controlled release of certain drugs is usually obtained with repeated dosing or implantable drug depots or pumps. The present invention overcomes these limitations and describes a way providing controlled drug delivery at any point along the GI tract, even beyond the stomach, without the need for injections, implantation, or repeated dosing.

The present inventor has devised a GERD treatment and drug delivery approach which overcome the limitations of prior art devices.

SUMMARY OF THE INVENTION According to one aspect of the present invention there is provided a device for reducing reflux comprising a device body and an anchor for anchoring the device body within or below the esophagus, wherein the device is configured for: (i) at least partially preventing reflux of stomach content into the esophagus; and (ii) enabling flow of esophageal content around the device body and into the stomach.

According to still further features in the described preferred embodiments the tether is an elastic tether.

According to still further features in the described preferred embodiments the tether stretches at least 0.3 meters when a force of 1 Newton is applied to it.

According to still further features in the described preferred embodiments the device is compressed and packaged in a water, acid or base soluble outer casing of a capsule shape and size in order to facilitate swallowing. The device body expands into its deployed state when the outer casing dissolves or is hydrolyzed in the GI tract.

According to still further features in the described preferred embodiments the tether is wound around the outer casing or capsule and unwinds when swallowing.

According to still further features in the described preferred embodiments the tether is wound or packaged inside the outer casing or capsule and emerges therefrom when swallowing.

According to still further features in the described preferred embodiments, at least one portion of the tether, connector, anchor, device body or the attachments between them is water, acid or base soluble and dissolves or hydrolyzes to detach and release device body into the GI tract after a set time period.

According to still further features in the described preferred embodiments the tether detaches from the device body with a force that is less than the force required to pull the deployed device body back out of the mouth (e.g. 50 grams of less).

According to still further features in the described preferred embodiments the device body comprises a hydrogel that can hydrate in the GI tract and eventually dissolve or degrade after a set period of time in the body.

According to still further features in the described preferred embodiments the device body releases an active agent used to treat a disease or condition. The present invention successfully addresses the shortcomings of the presently known configurations by providing a simple anchoring and tethering system which can be used to anchor and retain various devices inside the GI tract. The present invention further provides devices suitable for treatment of GERD, obesity, diabetes and controlled drug delivery in the GI tract.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In case of conflict, the patent

specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.

In the drawings:

FIG. 1 illustrates a GERD treatment device anchored to a tooth and connected via a tether running through the esophagus to a device body positioned under the lower esophageal sphincter (LES).

FIGs. 2 a-b illustrate a GERD treatment device close to (Fig. 2a) and mounted on top of (Fig. 2b) a tooth-mounted button anchor connected via a tether to a conical device body.

FIG. 3 illustrates an alternative embodiment of the tooth anchor.

FIG. 4 illustrates an alternative embodiment of the tooth anchor that includes a fluid port for the transfer of gas or liquid through a hollow tether.

FIGs. 5 a-1 illustrate alternative embodiments of a device body shaped with the wide portion concave down (Figs. 5a-d), flat (Figs. 5e-h) and concave up (Figs. 5i-l).

FIG. 6 illustrates an alternative embodiment of the connector region of a tether that makes it attachable between two teeth.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of devices and methods which can be used to treat acid reflux, obesity, diabetes and/or to provide controlled drug delivery to tissues in the GI tract in a subject such as a human.

The principles and operation of the present invention may be better understood with reference to the drawings and accompanying descriptions.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details set forth in the following description or exemplified by the Example. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

GERD is a condition in which the esophagus becomes irritated or inflamed because of acid or other fluids such as bile or water backing up from the stomach into the esophagus (reflux).

Although it has been shown that abnormal functioning of the lower esophageal sphincter (LES) which is at the junction of the esophagus and stomach leads to GERD, the underlying cause for GERD is not always apparent. Up to 25% of patients with

GERD do not respond to proton pump inhibitor (PPI) drugs that are very effective at lowering stomach acid production, indicating that it is not always acid reflux that causes GERD.

In addition to a malfunctioning LES, other factors such as obesity, slow emptying of stomach content, weak muscular contractions in the esophagus, exercise, pregnancy, smoking, certain hormones, many foods, and some medications can aggravate this disorder.

Approaches for treating GERD include lifestyle changes, medication and endoscopic procedures. Proton pump inhibitors (PPIs) represent the mainstay of therapy for patients with non-erosive reflux disease (NERD), and while modern technologic advances in endoscopic procedures have improved the efficacy of endoluminal GERD therapy, currently practiced approaches are still limited in as far as long term efficacy.

Although numerous devices for treating GERD have been described in the patent literature (see, for example, U.S. Pat. Nos. 4,846,836; 5,314,473; 5,861,036 and 6,264,700), such devices are designed to replace rather than augment the function of the LES and as such are bulky and intrusive and thus may lead to migration, erosion, dysphagia as well as other morbidities. Furthermore, many endoscopic techniques are quite complicated procedures and expensive devices requiring significant training, lengthy anesthesia and operating room times, and the expertise of a surgeon in addition to the endoscopist for implementation. Furthermore these techniques are generally not reversible, which is a desired feature for patients.

The present inventor proposes that effective GERD treatment can be accomplished without altering the anatomy of the LES or surrounding regions of tissue and in fully reversible, non-invasive manner without the need for intervention by medical personnel.

Thus, while reducing the present invention to practice, the present inventor has devised a treatment approach that overcomes the limitations of prior art devices and methods by providing a device configured for:

(i) minimally impacting normal LES anatomy and function;

(ii) allowing smooth passage of esophageal content (e.g food and liquids) into the stomach without causing dysphagia;

(iii) easy positioning in the esophagus/stomach in a non-invasive manner; (iv) minimizing flow of stomach content to the esophagus (e.g. reflux) regardless of the patient body position (lying/standing), reflux composition and reflux quantity;

(v) allowing passage of gas from stomach to esophagus while not preventing vomiting; and

(vi) being fully reversible and deployable by the user, ideally with no medical intervention.

A device having features which follow the guidelines above can be constructed by positioning a device body that blocks reflux in the region of the LES and anchoring such a device body via a tether to a tooth, bone (such as mandible, maxilla or palatine) or other oral tissue. Alternatively, the device can be anchored to a tissue in the nasal cavity or the nostril region.

Studies have shown that at least in some cases, incomplete closure of the LES leads to the formation of an LES fluid nozzle (1-2 mm in diameter) which generates a fluid jet directed at the esophageal walls under reflux [McMahon et al. World J Gastroenterol 2007 March 7; 13(9): 1360-1364]. Other studies indicate a bigger opening of the LES during GERD or NERD.

Without being bound to a theory, the present inventor postulates that partially or fully blocking the flow of fluid up through the LES opening via a one way "flap- valve" or "cover valve" type device positioned at or near the LES would be enough to prevent reflux into the esophagus. Thus, the present device can be designed for completely (and intermittently) blocking the LES region or for blocking only the transient orifice formed in the LES. Preferably, the present device is designed such that partial or complete blockage of the LES occurs only during reflux episodes in the esophageal direction. This can be achieved by suspending the present device in or under the LES in a position which lies in the path of reflux, such that a reflux episode pushes the device body against the lower or lateral LES surfaces or into the transient opening in the LES, thereby blocking it and preventing reflux from passing into the esophagus. Such positioning provides a movable 'cover' that can be pushed downward and out of the way with passage of food, and pushed upward to cover the LES (and optionally partially lodge therein) with reflux of stomach contents. As is further described hereinbelow, such a cover is preferably shaped as a cone suspended from an axially elastic tether attached to the cone tip.

In a further embodiment, the device of the present invention can block the orifice formed by the LES by residing in the lumen and being capable of elastic deformation, deflection or collapse in the radial direction.

In a further embodiment, peristaltic waves or food passing down through the esophagus deform, deflect or collapse the cone and minimize its profile, thereby minimizing the forces trying to detach the device. Reflux due to higher inter- stomach pressure will expand the device body outwards and therefore increase the sealing pressure of the device against the LES surface, thereby blocking reflux.

In a further embodiment, the peristaltic waves and/or ingested food or liquid can temporarily push the device body into the stomach by extension of the elastic tether. This axial extension of the tether can occur in parallel to the deflection, deformation or radial collapse of the device body.

In a further embodiment, the device of the present invention can have a generally cylindrical hollow or solid device body that is suspended like a "boat bumper" in the lumen right above the LES and terminates right under it, with or without a rim or disc at its distal end. Such a cylindrical device body, anywhere from 1 to 10 mm in diameter acts as an internal bulking of the LES lumen by forming a mandrel around which the LES contracts to improve the seal against reflux, yet does not significantly interfere with the diameter of the lumen when the LES is open for the passage of a food bolus. Such device body can be of a prefixed size made from elastic material such as silicone or hollow and with a gas or fluid to allow the proper volume of internal bulking to alleviate GERD. Such a device can be swallowed when at least a portion of it is in a compressed, collapsed, dry or desiccated form. A gas or fluid is then pumped in via a hollow tether, or water is absorbed from the GI tract due to osmotic or other forces, and the device body expands in order to provide the proper bulking of the lumen.

Figure 1 illustrates a device 2 that is anchored by connector 4 to one or more of teeth 42. Device 2 further comprises tether 6 that is connected to device body 8 that rests in or just below lower esophageal sphincter (LES) 40 that separates esophagus 44 from stomach 46.

Figures 2a and 2b illustrate further details of device 2. Anchor 10 is attached to tooth 42 and connector 4 reversibly attaches to anchor 10. Tether 6 is connected to connector 4 in region 12 and to device body 8 in region 14. Device body 8 in this embodiment is an open cone with two distinct regions. Narrow region 16 resides in the LES itself as a lumen bulking element and wide region 18 rests just below the LES. Transition region 20 is a change of curvature or angles ranging from 20 - 160 degrees between narrow region 16 and wide region 18 where device body 8 has the maximum wall thickness. The wide region 18 can be from 1-3 cm in maximal diameter, together with the wall thickness at transition region 20, which can be from 0.5-3 mm, and acts as an anchoring element to prevent device body 8 from moving into the esophagus during transient relaxations of the LES. In addition to its function as an anchoring disc, the bottom surface of wide region 18 acts as a "splash guard" or "breakwater" to prevent reflux from contacting esophageal tissue.

The length of tether 6 can be preset or adjusted before, after or during attachment of tether 6 to tooth 42. For example, anchor 10 or connector 4 can have a clasp that allows adjustment of the length of tether 6. Such an adjustment could be a one-way ratchet mechanism that allows excess length of tether 6 to be pulled out of the mouth and clipped close to anchor 10 or connector 4.

Connector 4 can attach to anchor 10 via magnetic coupling. For example, anchor 10 comprises a permanent magnet and connector 4 comprises within it a ferrous metal or another magnet. The magnetic coupling can be disconnected with a preset force, for example 1 newton or less.

Figures 5a-l illustrate three embodiments of device body 8. A device with a concave-down wide region 18 is illustrated in Fig. 5a in a transparent side view, in Fig 5b in a transparent top or equivalently transparent bottom view, in Fig 5c in a transparent perspective view and in Fig 5d in an opaque perspective view. A device with a flat (i.e. normal to the direction of tether 6 which attaches to apex 26) wide region 18 is illustrated in Fig. 5e in a transparent side view, in Fig 5f in a transparent top or equivalently transparent bottom view, in Fig 5g in a transparent perspective view and in Fig 5h in an opaque perspective view. A device with a concave-up wide region 18 is illustrated in Fig. 5i in a transparent side view, in Fig 5j in a transparent top or equivalently transparent bottom view, in Fig 5k in a transparent perspective view and in Fig 51 in an opaque perspective view.

When device body 8 as illustrated in Figs 5i-l is positioned in or below the LES and is pulled upwards by tether 6 at apex 26, wide region 18 may deflect/deform to assume the shape of wide region 18 illustrated in Figs. 5f-h (i.e. straight) or even invert as per wide region 18 as illustrated in Figs, a-e (concave down). The elastic deformation or inversion of wide region 18 applies additional sealing pressure against the stomach tissue, thereby increasing resistance to reflux.

The outer surface of device body 18, including region 14, should preferably be smooth and continuous with no discontinuities or protrusions greater than 1mm to prevent any ingested material from catching on and being retained by the outer surface of device body 8.

In a further embodiment, connector 4, region 12, tether 6, region 14, device body 8 or portions thereof, can be water soluble and/or acid and /or base labile and dissolve in a set time period. By way of example, connector 4 can be made of a polymer that dissolves after a preset time period (e.g. in a range selected from 7 - 90 days), thereby releasing device 2 to be swallowed and eliminated via defecation. A new device 2 is then attached to anchor 10 via connector 4 to provide an additional 7 - 90 days of protection against GERD.

Alternatively or additionally, region 14 can be water soluble and release device body 8 into the stomach after a set time period, thereby allowing the user to remove empty tether 6 and connector 4 from the body via the mouth, while device body 8 is released into the stomach and removed via defecation.

In a further embodiment, device body 8 is connected to tether 6 in region 14 in a link that can only tolerate a pre-defined force before detaching. Such a pre-defined force can be selected to be less than the force required to pull device body 8 up through the esophagus and out the mouth. Such a force, in the range of 1-50 grams, will detach device body 8 from tether 6 in the event that the user pulls on connecter 4 or tether 6 to remove device 2 from the mouth, thereby releasing device body 8 into the stomach. This prevents a gagging or retching sensation of device body 8 passing through the pharynx when removed via the mouth. Only empty tether 6 is removed via the mouth and no gagging or retching is experienced.

In a further embodiment, device body 8 is collapsed or compressed into a water soluble outer coating or package such as a gelatin or hypromellose capsule with a typical dimensions of up to 25 mm length and 7 mm diameter. Tether 6 can be packaged inside such a capsule, packaged as a separate compressed or wound unit, or wound around the inside or outside of the capsule. If tether 6 or portion thereof is would around the outside of the capsule or wound around itself separate from the capsule containing device body 8, a water soluble material can be used to keep tether 6 windings in place. The material restraining the tether windings should dissolve quickly after the capsule containing device body 8 is swallowed. In this manner, after connector 4 is attached to anchor 10 using 5-10 cm of free length of tether 6, the capsule containing device body 8 and wound tether 6 is swallowed. The wound portion of tether 6 unwinds before the capsule dissolves, thereby quickly placing the compressed device body 8 in the region of the LES where there is no foreign body sensation. At the same time, premature expansion of device body 8 in the mouth, pharynx or upper esophagus is avoided since there is a strong resistance to swallowing large objects and a strong foreign body sensation in these regions. Over time, the capsule dissolves in the region of the LES and device body 8 elastically unfolds to its expanded shape to provide protection against GERD.

In a further embodiment, tether 6 is wound around the capsule or compressed device body 8 as described above, however tether 6 is then restrained from unwinding due to a restraining feature, such as for example a clip, friction grip, groove, tab, or a loose knot. The force applied to the capsule due to natural peristalsis following passage of food or fluid during swallowing is sufficient to undue this restraining feature and tether 6 is quickly unwound immediately after the capsule is swallowed.

This two stage un-packaging, dissolving of a material holding tether 6 in a compressed or wound state or detachment of a restraining feature that performs the same function before the dissolution of the capsule compressing device body 8, allows for easy swallowing and rapid positioning of device body 8 in the LES at the full length of tether 6 while minimizing foreign body sensations during and after swallowing device body 8.

In a further embodiment, anchor 10 can be a pedestal, button or mushroom- shaped bracket made of a metal, ceramic or polymer that is attached to a tooth via gluing or light curing as illustrated in Figure 2a. Connector 4 can be made of a soft or elastic polymer comprising a hole or internal space that is then press fit over the pedestal portion of anchor 10. Pulling on connector 4 or tether 6 with sufficient force, e.g. up to 100 grams, separates connector 4 from anchor 10. Figure 2b illustrates connector 4 press fit onto anchor 10 when device 2 is in use.

In a further embodiment, anchor 10 is attached to the rear molar within the quarter circle defined by the posterior and buccal directions to avoid irritating sensitive lingual tissues.

In a further embodiment, to prevent irritation of the lingual (tongue) or buccal (cheek) tissues by anchor 10 when no device 2 is in use, a connector 4 without tether 6 can be attached to anchor 10 as a protective and removable cap.

In a further embodiment, anchor 10 comprises a female feature (e.g. a socket) that allows a male feature of connector 4 (e.g. a button) to latch inside anchor 10.

In a further embodiment illustrated in Figure 3, anchor 10 comprises a plate with a hole, hook or slot 24 pointing up, down or to the front or back and connector 4 can fit into the hole, over the hook or in slot 24 of anchor 10. The hole, hook or slot 24 feature of anchor 10 can be covered in a soft polymer or have a smooth outer shape (e.g. dome shaped as in Figure 3) that does not irritate the lingual or buccal surfaces when connector 4 is not present. By way of example, connector 4 can be a loop of water soluble material that dissolves and leaves an empty slot 24 of anchor 10.

Connector 4 can be slid into the slot of anchor 10 using an applicator.

In a further embodiment, anchor 10 can comprise a rigid or elastic band that fits around tooth 42 and has a feature to receive connector 4.

In a further embodiment, anchor 10 can be a screw that is inserted into a bone with a head adapted for screwing in and out of the bone as well as for connection to connector 4.

In a further embodiment, anchor 10 can be an oral appliance that fits in the oral cavity and comprises a feature for attachment to connector 4.

In a further embodiment, connector 4 can be a T bar, disk, bar-bell or ball shape that fits between two teeth, two molars for example, in a manner similar to dental floss. In the bar bell shaped embodiment, a soft ball or other shape acts as the "bell" and rests against the outside surfaces of two teeth while the narrow "bar" region connecting the "bells" fits in between the teeth like dental floss. At least one and preferably two features of connector 4 in this embodiment are too large to fit between the teeth, and optionally the section of connector 4 between the teeth could be in tension by two features on each of the buccal and lingual surfaces of the teeth, thereby anchoring device 2 in place. At least a portion of connector 4 (or region 12) can be water soluble to dissolve after a set time period releasing tether 6 and device body 8 into the stomach. In this embodiment, no anchor 10 is necessary as the space between two teeth provides the functionality of anchor 10.

In a further embodiment illustrated in Figure 6, connector 4 comprises T-bar 34 and narrow inter-tooth region 30 that fits between two teeth like dental floss, and wider gum region 32 in the region of the tooth/gum line in order to not irritate and cut into the sensitive gums around the teeth, and then gets narrow again in the region that attaches to tether 6 (shown in a cut-off length). In this embodiment, T-bar 34 is preferably 0.5-2 mm in diameter and 2-8 mm in length. Inter-tooth region 30 is preferably 0.1 - 0.5 mm thick, 0.5 - 1 mm wide and 5 - 15 mm long. Gum region 32 is preferably 0.1 - 1 mm thick, 1 - 5 mm wide and 3 - 25 mm long. Alternatively, the entire length of tether 6 can be of the cross sectional shape of gum region 32 (e.g. oval or rectangular cross section with round corners). Tether 6 is preferably 0.2 - 2 mm in diameter. Alternative shapes for T-bar 34 include a ball, wedge or disk. Gum region 32 is wide to distribute the tension forces acting through tether 6 on connector 4, which would act to cut into the sensitive gum region around tooth 42 if gum region 32 was as narrow as tether 6, especially given that the gums protrude and deflect the path of tether 6 en-route to the esophagus, and hence receive a normal force when tether 6 is in tension. Inter-tooth region 30 needs to be thin in order to fit in between two teeth (like dental floss ribbon). Gum region 32 needs to rest flat around the gums in order to not protrude and irritate the tongue.

A method of introducing connector 4 between two teeth 42 is to twirl tether 6 around a finger on each hand and press tether 6 down into the groove between two teeth like dental floss with T-bar 34 oriented on the buccal side of the two teeth. Then tether 6 is pulled from the lingual side of the two teeth which pulls gum region 32 and inter-tooth region 30 through and into the groove between the two teeth until T-bar 34 seats on the buccal surface of the two teeth and acts to anchor connector 4. Any part of connector 4 can be water soluble and once dissolves will release tether 6 and device body 8 which will be eliminated through defecation.

In a further embodiment, Connector 4 can be a flexible or rigid T bar where tether 6 is connected to one arm of the T bar with a water soluble adhesive or band.

In a further embodiment, Connector 4 can be pre-assembled on a rigid applicator that allows the user to easily maneuver Connector 4 to the appropriate position between two teeth or to anchor 10.

In a further embodiment, device 2 or portions thereof are coated with a hydrogel to increase the biocompatibility and minimize the foreign body sensation of connector 4, tether 6 or device body 8.

In a further embodiment, device 2, or portions thereof, comprise a hydrogel that forms part of the structure and contributes to their mechanical integrity. The device can be deployed in the hydrated state, or alternatively in the desiccated state and hydrated in the GI tract. The hydrogel eventually dissolve or degrade after a set period of time in the body. By way of example, device body 8 can be an umbrella made of a hydrogel such as natural or crosslinked gelatin, acylamide, alginate or the like. After a set period of time, device body 8 melts, degrades, dissolves or is hydrolyzed and is eliminated naturally from the body.

In a further embodiment, device body 8 or portions thereof can be inflatable or can absorb fluid to increase in size and weight. By way of example, device body 8 can comprise an open or closed cell foam, or a hydrogel that swells when in a wet or humid environment (e.g. the GI tract).

In a further embodiment, the length of tether 6 is determined by having the patient swallow a sizing device with a longer-than-necessary and known initial length of tether 6. After device body 8 is present in the stomach, the proximal end of tether 6 is pulled by the doctor away from the mouth. There will be little or no resistance to the pulling of tether 6 while device body 8 is in the stomach and free to move. The pulling of tether 6 is continued until a predetermined force is achieved (e.g. 5-30 grams) indicating that device body 8 is seated up against the LES. At this point, tether 6 is marked or clamped adjacent to the location of anchor 10 in the mouth of the patient. The correct and final length of tether 6 is determined by measuring the length of tether 6 between the mark (or clamp) and device body 8. Tether 6 can be detached from device body 8 with a force that is small enough to prevent device body 8 from pulling pulled back out of the esophagus and causing gagging or retching (e.g. 50 grams or less).

Alternatively, tether 6 is cut at the location of anchor 10 and the length of the remaining stub of tether 6 outside the patient' s body is measured and subtracted from the know initial length of tether 6 to determine the appropriate length of tether 6 corresponding to the distance between anchor 10 and device body 8 when seated up against the LES. A similar technique can be utilized to position a device on the distal side of the pylorus in order to assure delivery of active agents beyond the stomach as described more fully below.

In a further embodiment, device 2 includes device body 8 that comprises a reservoir of an active agent with a controlled release profile. Device 2 of this embodiment is particularly well suited for drugs requiring frequent dosing, significant adverse drug reactions due to fluctuations in plasma levels, low bioavailability, need for all night coverage, action site localized in the GI tract, or a pharmacological rationale to reduce exposure in the distal GI region By way of example, the reservoir of device body 8 can be formulated as a slowly dissolving formulation of an active pharmaceutical compound ("active agent") or embedded in a controlled release polymer or other matrix material.

Active agents can include agents such as carbidopa or levodopa (to treat Parkinson disease), zaleplon (to treat insomnia), baclofen (to treat spacicity), amino acids analogs (e.g., various drugs for CNS disorders), small peptide peptidomimetics (e.g., cardiovascular drugs, such as ACE inhibitors, ARB blockers), peptides, Beta- lactams and Cephalosporins (antibiotics), local gastrointestinal therapeutics (e.g., drugs for GI infections, obesity, IBD, GERD, anti-emetic), insulin (diabetes), Aciphex (rabeprazole sodium) for the treatment of symptomatic gastroesophageal reflux disease, afinitor (everolimus) for the treatment of advanced pancreatic neuroendocrine tumors, Alinia (nitazoxanide) for the treatment Diarrhea caused by Cryptosporidium and Giardia in children, Aloxi (palonosetron) for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, Amitiza (lubiprostone) for the treatment of chronic idiopathic constipation, Asacol (mesalamine) for the treatment of ulcerative colitis, Avastin (bevacizumab) for the treatment of metastatic carcinoma of the colon or rectum, Axid AR (nizatidine) for the treatment of ulcers, Canasa (mesalamine) for the treatment of active ulcerative proctitis, Cimetadine

Hydrochloride, Cimzia (certolizumab pegol) for the treatment of Crohn' s disease, Cipro (ciprofloxacin) for the treatment for complicated intra-abdominal infections, Colazal (balsalazide disodium) for the treatment of mild to moderately active ulcerative colitis, Dificid (fidaxomicin) for the treatment of Clostridium difficile- associated diarrhea, Duexis (ibuprofen and famotidine) for the relief of rheumatoid arthritis and osteoarthritis and prevention of gastric ulcers, Elelyso (taliglucerase alfa) for the treatment of Gaucher disease, Eloxatin (oxaliplatin/5-fluorouracil/leucovorin) for the treatment of colon or rectum carcinomas, Emend (aprepitant) for the treatment of nausea and vomiting associated with chemotherapy, Entereg (alvimopan) for the treatment of postoperative ileus, Entocort EC (budesonide) for the treatment of mild- to-moderate, active Crohn's disease, Erbitux (cetuximab) for the treatment of EGFR- expressing, metastatic colorectal cancer, GastroMARK as a contrast agent for magnetic resonance imaging of the gastrointestinal tract, Gleevec (imatinib mesylate) for the treatment of gastrointestinal stromal tumors (GISTs), Hepsera (adefovir dipivoxil) for the treatment of chronic hepatitis B in adults with evidence of active viral replication, Herceptin (trastuzumab) for the treatment of gastric cancer, Incivek (telaprevir) for the treatment of genotype 1 chronic hepatitis C, Linzess (linaclotide) for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation, Lotronex (alosetron HCL) for the treatment of Irritable Bowel Syndrome (IBS), Merrem I.V. (meropenem) for the treatment for intra-abdominal infections and bacterial meningitis, Metozolv ODT (metoclopramide hydrochloride) for the treatment of gastroesophageal reflux and diabetic gastroparesis, Nascobal Gel (Cyanocobalamin, USP) for the treatment for vitamin B-12 deficiency, Nexium (esomeprazole magnesium) for the eradication of Helicobacter pylori, the healing of erosive esophagitis, and the treatment of symptomatic GERD, Orfadin (nitisinone) for the treatment of hereditary tyrosinemia type I, Oxytrol (oxybutynin transdermal system) for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency, Pancreaze (pancrelipase) for the treatment of exocrine pancreatic insufficiency, Pegasys (peginterferon alfa-2a) for the treatment of chronic hepatitis C who have compensated liver disease, Pepcid Complete for use in the relief of heartburn associated with acid indigestion and sour stomach, Prevacid

(lansopraxole) for the treatment of heartburn associated with GERD, Prevpac for the treatment of H. pylori infection, Prevpac (lansoprazole, amoxicillin and

clarithromycin) for the treatment for duodenal ulcers, Prilosec (omeprazole) for the treatment for gastric ulcers, Prilosec (omeprazole)/Biaxin (clarithromycin)

Combination Therapy for the treatment for duodenal ulcers, Prochloroperazine or Compazine, Protonix (pantoprazole sodium) for the treatment of gastroesophageal and pathological hypersecretory conditions and for treatment of erosive esophagitis or gastroesophageal reflux disease, Rebetol (ribavirin) for the treatment of chronic hepatitis C, Rectiv (nitroglycerin) for the treatment of chronic anal fissure, Sancuso (granisetron) for the treatment of chemotherapy-induced nausea and vomiting, SecreFlo (secretin) to aid in the diagnosis of pancreatic dysfunction and gastrinoma, Stivarga (regorafenib) for the treatment of previously treated patients with metastatic colorectal cancer, Sutent (sunitinib malate) for the treatment of pancreatic

neuroendocrine tumors, Twinrix for the prevention of hepatitis A and B, Tygacil (tigecycline) for the treatment of complicated skin and skin structure and intraabdominal infections and bacterial pneumonia, Tysabri (natalizumab) for the maintenance treatment of moderate to severe Crohn' s disease or multiple sclerosis, Copaxone for the treatment of multiple sclerosis, Ultresa (pancrelipase) for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions, Urso for the treatment for primary biliary cirrhosis, Valsartan , Victrelis (boceprevir) for the treatment of chronic hepatitis C genotype 1 , Vimovo (naproxen + esomeprazole) for the treatment of arthritis in patients at risk for NSAID-associated ulcers, Viokace (pancrelipase) for the treatment of exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy, Visicol Tablet for cleansing of the bowel as a preparation for colonoscopy, Visipaque (iodixanol) as a diagnostic contrast agent, Xtandi (enzalutamide) for the treatment of metastatic castration-resistant prostate cancer, Zaltrap (ziv-aflibercept) for the treatment of metastatic colorectal cancer, Zantac (ranitidine) for the treatment for heartburn, Zelnorm (tegaserod maleate) for the treatment of irritable bowel syndrome, Zenpep (pancrelipase) for the treatment of pancreatic insufficiency due to cystic fibrosis or other conditions, Zuplenz (ondansetron) for the prevention of post-operative, chemotherapy and radiotherapy induced nausea and vomiting.

In contrast to prior art gastro-retentive pills, the maximum mass, volume or surface area of device body 8 can be at the time of ingestion, with mass, volume and/or surface area decreasing when device body 8 is in the GI tract and the active agent is being released. Device body 8 does not need to unfold, absorb fluid, swell or increase in shape, surface area, or volume in the GI tract in order to be retained in the stomach or other portions of the GI lumen, as tether 6 provides the restraint to keep device body 8 in position.

In a further embodiment, device body 8 comprising an active substance is shaped as a cylinder and covered on all sides by a fluid impermeable coating except for one face or porous membrane. Active substance is dissolved from this exposed face or porous membrane at a known rate since the surface area of the exposed drug- eluting face or porous membrane does not change significantly. Eventually all of the active substance inside device body 8 is released leaving only an impermeable shell that is then dissolved over time or eliminated from the body by pulling it out of the mouth or through defecation.

In contrast again to the prior art gastro retentive pills that pass through the pylorus once they physically degrade, the time of retention in the GI tract of the device described in the present invention can be set not by the degradation of device body 8 by water, gastric acid, bile or other GI fluids, but rather by the degradation or dissolving of connector 4, and/or regions 12 or 14 of tether 6 in a time period independent of changes to device body 8. By way of example, dissolution of connector 4 in the oral cavity can release tether 6 and device body 8 to pass through the GI tract at a time independent of dissolution of device body 8, which may still be releasing an active agent. Furthermore, the patient or a health care professional can remove connector 4 from anchor 10 or from the space between the teeth, or simply cut tether 6, at a chosen time to allow device body 8 to pass through the GI tract, thereby allowing direct control of the termination of the dosing of the active agent.

The exact location of device body 8 and the resulting release of drug delivery in the GI tract can be set by varying the length of tether 6. For example, device body 8 will be advanced by natural peristaltic forces to the extent permitted by the length of tether 6. So for example, a tether length of approximately 10 - 40 cm will place device body 8 in the esophagus. A tether length of approximately 35 - 45 cm will place device body 8 in the area of the LES. A tether length of approximately 40 - 50 cm will place device body 8 in the stomach. A tether length of approximately 50 - 60 cm will place device body 8 in the duodenum. A tether length between 0.5 - 7 meters will place device body 8 in the small intestines. A tether length of approximately 7 - 9 meters will place device body 8 in the large intestines. The exact location of device body 8 can be detected using X-rays, CT, MRI or ultrasound with device body 8 containing the appropriate contrast agent for each of these imaging modalities.

Anchor 10 or connector 4 can reversibly connect to tether 6 in a manner that allows for length adjustment of tether 6 in real time to ensure proper placement of device body 8 in the GI tract. For example, device body 8 connected to excess length of tether 6 can be swallowed and allowed to overshoot the desired location in the GI tract due to natural peristaltic forces. Tether 6 can be pulled to bring device body 8 back to the proper position and connector 4 and/or anchor 10 can then lock tether 6 at this location with excess lengths of tether 6 cut and removed from the patient.

Connector 4 and/or region 12 and/or region 14 can be acid or base labile or water dissolvable to determine how long device body 8 is present in the tethered location to release the active substance, e.g. in the ranges of 1-24 hours, 1-7 days, 1-4 weeks or 1- 12 months.

In a further embodiment, device body 8 can be filled with active agent through a hollow tether 6 either once or multiple times. The drug release rate can be controlled by controlling the size of one or more pores, apertures or holes in device body 8.

In yet a further embodiment, device body 8 can comprise an "osmotic pump" such as an Alzet ® osmotic pump (Alzet, Cupertino CA) where the fluid or humidity in the GI tract causes displacement or a membrane or otherwise displaces the active agent from device body 8 in a controlled manner.

In yet a further embodiment, device body 8 can be a self-contained and self- powered infusion pump with a depot of an active agent, power source and programming means for controlling the release of active agent. The device can detach itself in an active manner from tether 6 at the end of a dosage schedule and be removed from the body via defecation or by pulling device body 8 back out through the mouth via tether 6. The dosing can follow complex dosing protocols, such as intermittent bolus dosing, variable dosing regimens, and/or chronic delivery for up to many months. This single-use internal infusion pump can swallowed after it has been prefilled with active substance, or filled (and refilled) using a hollow tether 6.

Electrical connections running along tether 6 can also be used to reprogram and/or recharge the pump of device body 8 from a connector in the oral or nasal cavity in the region of anchor 10.

In yet a further embodiment, device 2 can contain a sensor to measure any physiological or biochemical parameter of interest and feed that information to the dosage control unit of device body 8 to adjust dosing of an active agent in response to a physiological or biochemical parameter in a closed loop fashion. The dosage control unit can also be adjusted or controlled by other devices or sensors that provide information to it independently of any sensors on device 2.

By way of example, a glucose sensor can feed blood sugar information to device body 8 which is tethered in the GI tract and stores a supply of insulin in an internal reservoir. Insulin is then released from device body 8 via a hollow tether to the appropriate location in the GI tract as described below. The reservoir in device body 8 is refilled by the patient at regular intervals, for example on a daily basis.

Figure 4 illustrates anchor 10 which is affixed to tooth 42 and comprises a fluid port 22 which is in fluid communication with a hollow tether 6 leading to device body 8 (not pictured). Fluid port 22 can contain a one way valve or septum to prevent exit of fluid out of the proximal end of tether 6 even when such fluid is under pressure from an inflated elastic bladder or compressed spring in device body 8.

In a further embodiment, the distal end of tether 6 is not connected to device body 8 and all fluid or gas introduced into the proximal end of tether 6 exits into the GI tract immediately.

In a further embodiment, insulin or other peptide drugs can be delivered to the small intestines and bypass the stomach altogether if tether 6 extends beyond the stomach into the small intestines. Tether 6 can have along its length a retentive feature such as a weight, balloon, cuff, ball, stent, protrusion, disk, cone, umbrella or other structure 0.2 to 5 cm, preferably 0.5 to 1.5 cm in maximal diameter that rests just beyond the pylorus and therefore remains in the proximal duodenum. A further 10 - 15 cm length of tether 6 can extend beyond this feature to position the distal opening of tether 6 in the region of the Ampulla of Vater, which is where insulin is naturally secreted, to fully simulate the natural effect of insulin secretions in diabetics. The distal end of tether 6 can also have a retentive feature as described above in addition to the retentive feature that is configured to rest behind the pylorus. Such retentive features keep tether 6 stretched to its maximal length in the GI tract due to peristaltic forces acting to advance such features through the GI tract, especially given that tether 6 itself may be too thin (i.e. 0.5 - 2 mm OD) to be acted on by such peristaltic forces. The active substance reservoir of device body 8 that can hold a volume of up to 10 ml fluid can also serve as such a retentive feature.

Additionally or alternatively, a retentive feature as described above can be at the distal edge of tether 6 or at multiple locations along tether 6. By way of example, the distal end of tether 6 can be clipped to an anchor that itself is retained in the common bile duct by a biliary stent. Thus, liver, gallbladder and/or pancreatic substances conveyed by tether 6 exit into the small intestines in the same region as the Ampulla of Vater, which is the natural point for such secretions. Many other substances produced by the liver, gallbladder or pancreas (such as enzymes, hormones, bile or glucagon) can be released in this manner.

A colorant, or a natural or artificial sweetener or flavorant can be added to the active substance to be injected through fluid port 22 to ensure that no active substance was inadvertently injected into the mouth. Proper injection through fluid port 22 would cause no colorant, flavorant or sweetener to be detected in the oral or nasal cavity.

The small size of tether 6, (e.g. less than 2mm OD) allows for it to avoid being pulled back into the stomach or causing any tissue irritation in the GI tract. The user simply connects a syringe with a blunt or sharp needle to fluid port 22 attached to anchor 10 and injects the active substance through tether 6 into the GI tract followed by a bolus of air or water to clean the inner lumen of tether 6. Tether 6 can have an inner and/or outer surface that is non- wetting, hydrophobic or super-hydrophobic so that liquid, bacteria, fungi, viruses or other organisms cannot take hold inside.

Clearing tether 6 with a gas such as air is sufficient to completely purge the inner lumen of all fluids. The syringe used to inject the active substance can have two separate compartments, one of which contains the active agent as a fluid and the other that contains a gas to purge tether 6, all in one plunger stroke. Alternatively, the gas and fluid can be combined into one chamber that injects the fluid first as long as the chamber is held vertical so the fluid is injected first and the gas second when the plunger is depressed. A flexible tube from the syringe leading to fluid port 22 can be part of the system to enable a horizontal docking to fluid port 22 and a vertical depression of the plunger containing the gas/fluid in the syringe.

In a further embodiment, device 2 comprises device body 8 that is a sensor that measures any physiological or biochemical parameter of interest such as temperature, pH, food or chyme flow, ultrasound, or visual images. In a further embodiment, device 2 comprises an actuator such as electrical stimulator or a drug pump. In a further embodiment, device 2 comprises a combination of at least one actuator and one sensor.

In a further embodiment, a sizing device can be used with markings along the length of tether 6 and an inflatable or expandable device body 8 in order to measure the distance from a known position in the GI tract, such as an LES or pylorus, to the site of anchor 10. The measuring device can be detachable from device body 8 with a force that is small enough to prevent device body 8 from being pulled back out of the esophagus and causing gagging or retching (e.g. 50 grams or less).

In a further embodiment, device body 8 can be an esophageal stent, esophageal sleeve (extending from the LES through the pylorus into the small intestines), duodenal sleeve (extending from the pylorus into the small intestines), or an inflatable gastric balloon. In such embodiments, tether 6 maintains device body 8 in position or prevents device body 8 from migrating deeper in the GI tract than is intended (e.g. an esophageal stent or a punctured or deflated gastric balloon is thereby prevented from migrating into and potentially blocking the small intestines).

In the embodiment where device body 8 is an esophageal or duodenal sleeve, tether 6 can be attached to such a sleeve through a set of two or more radial spokes that keep the opening of the sleeve centered about tether 6. In this manner, tension on tether 6 will keep the duodenal or duodenal sleeve pressed up against the bottom surface of the LES or back side of the pylorus (respectively) so that food or chyme will flow through the collapsible sleeve instead of through the bypassed portion of the GI tract. The leading edge of the esophageal or pyloric sleeves can be made of an elastic material such as nitinol or silicone so that it can be delivered in a collapsed state to the deployment position. When deployed, the open rim of the sleeve presses against the bottom of the LES or back side of the pylorus to provide resistance against migration in the oral direction. A separate tether 6 can be attached to one or more points along the rim of the sleeve to enable collapse of the open rim and withdrawal of the sleeve through the mouth. Additionally or alternatively, the distal ends of two or more tethers 6 can be attached to diametrically opposed sides of the proximal opening of the sleeve and the proximal ends of these tethers 6 can be anchored on the opposite sides of the oral and nasal cavity.

As used herein, the phrases "elastic properties" or "elastic compliance" are used interchangeably and refer to the ability of tether 6 or a portion thereof to reversibly increase in length (in the axial direction) under a pulling force. Tether 6 can have varying elasticity along its length. For example, tether 6 can be more elastic in the oral region and less elastic in the esophagus region.

Based on the Hooke's law represented by the equation F=K*X where Force is in Newtons and X is the extension in meters, the preferred K (spring constant) of the elastic tether is rather low, in the range of 0.1 - 3 Newton/meter, or preferably 0.3 - 2 Newton/meter. In other words, tether 6 should displace 0.1 to 3 meters, or preferably 0.3 - 2 meters for every Newton of force applied to it. This weak resistance to stretching allows a number of critical advantages:

1. It is possible to use a small number of tether lengths to fit a large range of esophageal lengths due to the easy stretching of tether 6.

2. It allows for the passage of food to easily displace device body 8 into the stomach and not create resistance to swallowing, known as dysphagia. 3. It allows for the movement of device body 8 with a peristaltic wave, yet returns device body 8 to its intended position once the peristaltic wave passes.

Such an elastic increase in length can be at least 50%, preferably at least 100%, more preferably at least 200%. The elastic properties of tether 6 can be provided by the tether structure, cross sectional and axial geometries and/or tether material.

Materials such as silicone or thermoplastic elastomers could be used.

The devices described in this patent application can be provided as a kit with or without an applicator. The devices and kits can be pre-sized for various patient populations, from infants up to large morbidly obese individuals, or for individuals with only transient LES relaxation to major openings of the LES as occurs in Barrett's esophagus for example.

As used herein the term "about" refers to +/- 10 %.

Additional objects, advantages, and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples, which are not intended to be limiting. Additionally, each of the various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below finds experimental support in the following examples.

EXAMPLE 1

Deployment of a GERD treatment device

Reference is now made to the following example, which together with the above descriptions, illustrates the invention in a non-limiting fashion.

A GERD treatment device was constructed according to the embodiment illustrated in Figs 1 and 2 a-b and 5a-d.

The anchor for the device was an orthodontic button bonded on the buccal/posterior face of the rear right molar. The tether was connected to a connector in the form of washer 2.4 mm in OD, 0.5 mm ID and 1 mm thick made from silicone. The tether was made from silicone tube 0.64 mm in outer diameter and 0.32 mm inner diameter with a shore hardness of 50 A. The 38 cm long tether was attached to a conical device body made of shore 50A silicone and shaped as per the device body illustrated in Figs 5a-d with a maximum diameter of 22 mm and a tapering thickness from 2 mm at the center tapering to 0.5 mm thickness at the outer edge with a conical angle of 125 degrees from the vertical.

The device body was rolled into a cylinder and pushed into a size 0 V-CAP ® capsule (Capsugel, Morristown NJ) made from hydroxypropyl methylcellulose that dissolves within minutes in the GI tact. All but the last 7 cm of the silicone tether was wound around the outer surface of the V-CAP and held in place with a thin sheet of polyvinyl alcohol (PVA) that dissolves within seconds in the mouth.

The inner diameter of the elastic connector was expanded to fit over the anchor button. The capsule containing the compressed device body was placed in the mouth and swallowed with a glass of water. The tether fully unwound once the PVA film dissolved and the capsule was positioned at the LES of the subject. Within a couple of minutes, the capsule dissolved and the silicone device body deployed and prevented gastric reflux for the duration of the usage of the device. There was no discomfort from the use of the device or from eating and swallowing while the device was in place.

By way of clarification, the use of an inelastic tether (namely fishing line), proved to be very irritating to the tongue base and pharynx so was not utilized in the device described in the present example. An axially elastic and soft material (shore 70A or softer) was utilized and proved highly tolerable. The use of an elastic tether allows food and liquid to freely pass from the esophagus to the stomach. The elastic tether pulled the wide rim of the device body gently up against the bottom surface of the LES with a force of up to 50 grams while the narrow conical region of the device body was pulled into the LES lumen. During an acid reflux episode, the device body blocked the opening present between the stomach and esophagus and prevented the symptoms of GERD.

After 7 days, the connector was pulled off the tooth anchor button and swallowed. The entire device with the device body and tether was eventually evacuated via defecation.

EXAMPLE 2

Insulin Administration Device

Reference is now made to the following example, which together with the above descriptions, illustrates the invention in a non-limiting fashion.

An insulin administration device was constructed according to the embodiment illustrated in Figure 4. Glued to tooth 42 was an anchor 10 which comprised fluid port 22 which was in fluid communication with a hollow 55 cm long / 0.64 mm OD / 0.32 mm ID silicone tube which formed tether 6. Fluid port 22 contained a slit silicone septum to prevent contamination or blockage of tether 6. The distal 5 cm of tether 6 had retentive features of 5 mm diameter disks made of silicone from shore 10 spaces 4 cm apart to keep tether 6 in the small intestines, terminating in the region of the Papilla of Vater. Tether 6 along with the retentive features were compressed into a size 1 gelatin capsule and swallowed after being attached to tooth 42. After several hours when the distal portion of tether 6 had been transported using natural peristalsis into the small intestines, 1ml of insulin was injected into the split septum of fluid port 22 using a blunt 27 gauge needle. The insulin exited the distal end of tether 6 into the small intestines and bypassed the stomach altogether. Following the insulin injection, 1 ml of air was injected to purge any remaining insulin in tether 6. The insulin bolus was highly bioavailable since the insulin was delivered to the natural site of insulin secretion, namely the vicinity of the entrance of the pancreatic duct into the small intestines. It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.

Claims

I claim: 1. A device configured for residing in the gastrointestinal tract comprising a device body and a tether connected to an oral tissue.

2. The device of claim 1 , wherein said oral tissue is one or more teeth.

3. The device of claim 1, wherein said device body is compressed in a material that dissolves or hydrolyzes in water, acid or base.

4. The device of claim 1 , wherein said device body detaches from said tether with a force of 50 grams less.

5. The device of claim 1, wherein the attachment between one of said tether, said tooth or said device body detaches after a predetermined time in the body.

6. The device of claim 1 , wherein said tether is attached to said tooth via an anchor glued to said tooth.

7. The device of claim 1, wherein said device body releases an active agent.

8. The device of claim 1, wherein said tether stretches at least 0.3 meters when a force of 1 Newton is applied to it.

9. The device of claim 1 , wherein said device body is an open cone.

10. A method of retaining a device in the gastrointestinal tract comprising anchoring one end of a tether to one or more teeth, swallowing a device body attached to second end of said tether, wherein said device body is in a compressed

configuration in a water or acid soluble capsule.

11. The method of claim 10, wherein said device body detaches from said tether with a force of 50 grams or less.

12. The method of claim 10, wherein the attachment between said anchor, said tether and/or said device body detaches after a predetermined time in the body.