Patent Description:
<CIT> describes a treatment system including an ingestible capsule for delivering a drug using a gas pressurizing module. <CIT> describes an ultrasonic diagnostic capsule with an ultrasonic vibrator. <CIT> describes a capsule for discharging drugs using a discharging compression spring to push out the drug.

In accordance with an embodiment of the present invention, please refer to the appended claims.

The foregoing discussion will be understood more readily from the following detailed description of the invention, when taken in conjunction with the accompanying <FIG>), in which:.

<FIG> does not form part of the claimed invention. Furthermore, the methods of use and delivery of medicament described below do not form part of the claimed invention and are left for illustrative purposes.

The principles of the inventive devices for delivery of an ingestible medicament into the body of a user, and specifically to devices for such delivery of an ingestible medicament which include a vibrating capsule, may be better understood with reference to the drawings and the accompanying description.

For the purposes of this application, the term "user" relates to a human.

For the purposes of this application, the term "vibrating ingestible capsule" relates to an ingestible capsule adapted to at least intermittently vibrate, for a cumulative duration of at least one minute, in accordance with a vibration protocol of the capsule.

For the purposes of this application, the term "vibrating agitation mechanism" refers to any type of mechanism that vibrates or causes elements in its vicinity to vibrate, including a motor drive agitator such as a motor drive eccentric weight or a motor drive pendulum.

For the purposes of this application, the term "intermittently activated vibrating agitation mechanism" refers to a vibration agitation mechanism that vibrates or causes elements in its vicinity to vibrate and is operative at certain times, and does not vibrate or cause elements in its vicinity to vibrate at other times, the activation times being selected by a control element or other control unit controlling the vibration agitation mechanism.

For the purposes of this application, the term "control element", and the equivalent term "controller" refer to a component for controlling operation of mechanical and/or electrical components of the capsule, which includes a processing unit functionally associated with a non-tangible computer readable storage medium. The storage medium stores instructions, which, when executed by the processing unit, cause the processing unit to carry out actions which control the operation of the mechanical and/or electrical components of the capsule. For example, the instructions may include instructions to activate operation of a vibrating agitation mechanism at a specific time, frequency, cycle, and/or for a specific duration. The control element may be functionally associated with, or may include, a transceiver for receiving input, which input may be used to trigger execution of specific instructions stored in the storage medium.

For the purposes of this application, the term "biasing mechanism" refers to any structure, or device, adapted to apply pressure to a second element, even when the position of the second element changes relative to an anchoring point of the structure or device. Biasing mechanisms include springs, such as compression springs and extension springs, as well as spring loaded leaves, plungers, and the like.

For the purposes of this application, the term "vibration protocol" relates to a protocol specifying vibration parameters of an intermittently activated vibrating agitation mechanism of a vibrating ingestible capsule. Typically, the vibration protocol relates to an activation delay for initiating vibration (e.g., a duration between "initial" activation of the capsule and the first activation of the vibration agitation mechanism), a vibration rate (number of vibration cycles per hour), a vibration duration and a repose duration for each vibration cycle, a vibration frequency, an amount of force exerted by the vibrations, and the like.

For the purposes of this application, the term "treatment procedure" relates to parameters of a treatment utilizing vibrating ingestible capsules, which are typically defined by a treating physician or medical practitioner. For example, the treatment procedure may include the number of capsules to be taken within a specific time duration (e.g., <NUM> capsules per week, <NUM> capsules per day), the frequency at which capsules should be taken, the time of day at which capsules should be taken, whether the capsule should be taken with or without food, and the like.

For the purpose of this application, the term "treatment protocol" relates to all aspects of treatment of a user with a vibrating ingestible capsule, and includes the treatment procedure as well as the vibration protocol to be used for treating the user.

For the purpose of this application, the term "activation input" relates to an input received by a control element or control element of a vibrating ingestible capsule, which causes the control element or control element of the capsule to activate itself, so as to be able to process inputs and/or to control additional components of the capsule. The activation input may be received from an element forming part of the capsule, such as a sensor sensing specific conditions in which the capsule should be activated, or from a remote source, such as a remote control element, for example by way of a signal transmitted to the capsule, magnetic field applied to the capsule, specific motion applied to the capsule, or any other type of input provided to the capsule from a remote source.

For the purpose of this application, a vibrating ingestible capsule is said to be in an "inoperative state" when the capsule is in a storage condition, intended to preserve the life of a battery thereof. In the inoperative state, components of the capsule which are intended to receive or to provide an activation input, such as specific sensors, transceivers, and/or timing mechanisms may be active at least to a minimal degree. However, in the inoperative state, no vibration takes place, and a control element controlling vibration of the capsule is inactive.

For the purpose of this application, a vibrating ingestible capsule is said to be in an "operative state" when the control element of the capsule is processing inputs and data, and can cause a vibrating agitation mechanism of the capsule to vibrate or cause elements in its vicinity to vibrate.

For the purpose of this application, an "ingestible medicament" is at least partially absorbable to the bloodstream from within the stomach, small intestine, and large intestine, and more typically, within the stomach or small intestine.

For the purpose of this application, the term "partially absorbable" is meant to include the possibility that the environment within the gastrointestinal tract (including acids, enzymes, etc. thereof) may chemically modify the ingested medicament in order to achieve the characteristic "partially absorbable".

For the purposes of this application the term "flowable ingestible medicament" relates to any dosage form of an ingestible medicament which can flow through a conduit, such as a liquid ingestible medicament, a suspension of an ingestible medicament, a gaseous ingestible medicament, a solution of an ingestible medicament, a dissolved ingestible medicament, a melted ingestible medicament, and the like.

For the purposes of this application, the disclosure of a commercial name of a material or drug is meant to be a disclosure of the corresponding generic material or drug, and of the active ingredient(s) within the commercial material or drug and/or within the corresponding generic material or drug.

For the purpose of this application, an estimated absorption time may be determined as follows:.

The location within the GI tract at which the particular ingestible medicament is absorbed to the bloodstream may often be public knowledge. This location may be provided by, or known to, the manufacturer and/or distributor of the particular ingestible medicament. Alternatively or additionally, the location may be known to relevant medical practitioners, including doctors and pharmacists, and more particularly, to a medical practitioner of the user.

For the purpose of this application, an actual absorption time may be determined from clinical data, in vivo or in vitro, according to accepted clinical procedures known to those of skill in the art. Since actual absorption is achieved over a period of time, the "actual absorption time" or "actual absorption time period" may be defined by the time period at which between <NUM>% and <NUM>% of the absorption occurs. In the absence of such data, the "actual absorption time" or "actual absorption time period" may be defined by determining the "peak" actual absorption time, and building a time period of up to <NUM> hour on each side of the peak time.

For the purpose of this application, a recovery time of a resilient conduit relates to the duration from a time from release of a force pinching the resilient conduit such that no fluid can flow therethrough, till the conduit is not blocking the flow. This may occur when the conduit is partially recovered, i.e. the force has been removed such that there is a hollow in the conduit but the conduit has not returned to its initial diameter, or when the conduit is fully recovered and has returned to its initial, nominal diameter.

For the purpose of this application, the term "Parkinsonism" is meant to include Parkinson's disease, or symptoms of neurodegeneration associated therewith.

For the purpose of this application, the term "Parkinsonism" is meant to include progressive supranuclear palsy, or symptoms of neurodegeneration associated therewith.

For the purpose of this application, the term "Parkinsonism" is meant to include corticobasal degeneration, or symptoms of neurodegeneration associated therewith.

For the purpose of this application, the term "Parkinsonism" is meant to include multiple system atrophy, or symptoms of neurodegeneration associated therewith.

For the purpose of this application, the term "Parkinsonism" is meant to include Parkinson-plus syndromes (also known as disorders of multiple system degeneration), or symptoms of neurodegeneration associated therewith.

For the purpose of this application, the term "Parkinsonism" is meant to include any neurodegenerative disease in which the subject exhibits at least one (and typically at least two or three) of the classical features of Parkinson's disease: tremor, postural instability, and akinesia or bradykesia.

For the purpose of this application, the term "Parkinsonism" is meant to include any neurodegenerative disease in which the subject positively responds to a dopaminergic treatment.

For the purpose of this application, the term "Parkinsonism" is meant to include any neurodegenerative disease in which the particular subject positively responds to an anticholinergic treatment.

For the purpose of this application, the term "Parkinsonism" is meant to include any neurodegenerative disease in which a dopaminergic treatment is clinically utilized to treat the sufferers or subjects.

For the purpose of this application, the term "Parkinsonism" is meant to include any neurodegenerative disease in which an anticholinergic treatment is clinically utilized to treat the sufferers or subjects.

For the purpose of this application, the term "Parkinson's disease" (PD) is meant as used by those of skill in the art of neurodegenerative diseases. It is believed that PD is due to the loss of brain cells that produce dopamine. Early signs and symptoms of Parkinson's disease include at least one of tremors (or trembling), slowness of movement, body rigidity and stiffness, and gait problems.

For the purpose of this application, the term "treatment of Parkinsonism" and the like refers to at least one of: (i) delaying onset of Parkinsonism (e.g., PD); (ii) mitigating the development of Parkinsonism (e.g., PD); and (iii) managing a condition of Parkinsonism (e.g., PD).

For the purpose of this application, the term "ailment of the GI tract" is meant to include chronic or acute constipation, or symptoms associated therewith.

For the purpose of this application, the term "ailment of the GI tract" is meant to include gastroparesis, or symptoms associated therewith.

For the purpose of this application, the term "ailment of the GI tract" is meant to include Crohn's disease, or symptoms associated therewith.

For the purpose of this application, the term "ailment of the GI tract" is meant to include chronic or acute diarrhea, or symptoms associated therewith.

For the purpose of this application, the term "ailment of the GI tract" is meant to include colitis, or symptoms associated therewith.

For the purpose of this application, the term "ailment of the GI tract" is meant to include dyspepsia or dysphagia, or symptoms associated therewith.

For the purpose of this application, the term "ailment of the GI tract" is meant to include Hirschsprung's disease, or symptoms associated therewith.

For the purpose of this application, the term "ailment of the GI tract" is meant to include irritable bowel syndrome, or symptoms associated therewith.

For the purpose of this application, the term "ailment of the GI tract" is meant to include any disease in which the subject positively responds to an osmotic gastrointestinal treatment.

For the purpose of this application, the term "ailment of the GI tract" is meant to include any disease in which the particular subject positively responds to a stool softening treatment.

For the purpose of this application, the term "ailment of the GI tract" is meant to include any disease in which the particular subject positively responds to a GI contraction inducing treatment.

For the purpose of this application, the term "ailment of the GI tract" is meant to include any disease in which the subject positively responds to a GI fluid absorption inducing treatment.

For the purpose of this application, the term "managing a condition of", with respect to an ailment of the GI tract, is meant to include, inter alia, improving absorption of a medicament, such as a medicament used in the treatment of the ailment of the GI tract (e.g., Linaclotide (Linzess®)), into the bloodstream. Such condition management may be manifested by at least one of (i) improved medicament efficacy due to the increased absorption; and (ii) reduced dosage of the medicament, due to the increased medicament absorption efficacy.

For the purpose of this application, the term "managing a condition of", with respect to Parkinsonism and the like, is meant to include, inter alia, improving absorption of a medicament, such as a medicament used in the treatment of Parkinsonism (e.g., levodopa), into the bloodstream. Such condition management may be manifested by at least one of (i) improved medicament efficacy due to the increased absorption; and (ii) reduced dosage of the medicament, due to the increased medicament absorption efficacy.

Referring now to the drawings, <FIG> is a schematic block diagram of a device <NUM> for delivering a flowable ingestible medicament <NUM> into the gastrointestinal tract of a user according to an embodiment of the present invention.

It is a particular feature of the present invention that delivery of the flowable ingestible medicament is triggered by, and occurs only during a time at which a vibrating ingestible capsule is a vibration mode of operation, as explained in detail hereinbelow. Stated differently, delivery of the flowable ingestible medicament only occurs when the vibrating ingestible capsule is actually vibrating, and is triggered by such vibration of the vibrating ingestible capsule.

As seen in <FIG>, device <NUM> includes vibrating ingestible capsule <NUM>. Capsule <NUM> includes a capsule housing or shell <NUM>, also termed a first housing portion, arranged along a longitudinal axis <NUM> and having disposed therein a vibrating agitation mechanism <NUM>. A control element <NUM> is adapted to control operation of vibrating agitation mechanism <NUM>, and at least one power source <NUM> provides power to vibrating agitation mechanism <NUM> and control element <NUM>.

The vibrating ingestible capsule <NUM> is functionally associated with a medicament delivery compartment <NUM>.

In some embodiments, the medicament delivery compartment <NUM> is distinct from the vibrating ingestible capsule <NUM>, and is attached thereto, as illustrated in <FIG> and as explained hereinbelow with respect to <FIG>. In such embodiments, the medicament delivery compartment includes a hollow medicament compartment housing <NUM>, also termed a second housing portion, defining a hollow <NUM>. The hollow compartment housing includes a portal <NUM> and is attached to housing <NUM> of capsule <NUM>.

Medicament compartment housing <NUM> may be fixedly attached to housing <NUM> of vibrating ingestible capsule <NUM>, or removable attached thereto. Medicament compartment housing <NUM> may be attached to housing <NUM> of vibrating ingestible capsule <NUM> using any suitable attachment method, such as by adhering, by soldering, by snap fit engagement or by threaded engagement.

In some embodiments, housing <NUM> of vibrating ingestible capsule <NUM> includes an attachment mechanism, and hollow medicament compartment housing <NUM> includes a corresponding attachment mechanism, for mutual attachment of vibrating ingestible capsule <NUM> to hollow medicament compartment housing <NUM>. An exemplary arrangement of such attachment mechanisms is illustrated, for example, in <FIG> described in detail hereinbelow.

In other embodiments, the medicament delivery compartment <NUM> may form part of the vibrating ingestible capsule <NUM>, as explained hereinbelow with respect to <FIG>. In such embodiments, the portal <NUM> is formed in housing <NUM>, and the hollow of the vibrating ingestible capsule includes all components otherwise included in hollow <NUM>, as explained hereinbelow.

A flexible and collapsible medicament reservoir <NUM>, which is adapted to have the flowable ingestible medicament <NUM> disposed therein, is disposed within hollow <NUM>, and pressure is constantly applied thereto by a reservoir biasing mechanism <NUM>, which may be anchored to medicament compartment housing <NUM>. A conduit <NUM>, which may be a flexible and/or resilient conduit, extends from medicament reservoir <NUM> to portal <NUM>, such that a fluid flowing through the conduit is delivered to an environment surrounding device <NUM>. Typically, conduit <NUM> seals portal <NUM>, to prevent fluid from the environment surrounding device <NUM> from entering the device.

A valve, which includes a weight <NUM> and a valve biasing mechanism <NUM>, typically a spring, adapted, in a closed operative orientation, to block flow through the conduit <NUM> by biasing weight <NUM> against the conduit thereby to pinch the conduit, and, in an open operative orientation, to remove weight <NUM> from applying pressure to conduit <NUM>, such that, following the recovery time of the conduit, fluid may flow through the conduit.

It is a particular feature of the present invention that valve biasing mechanism <NUM> is functionally associated with housing <NUM> or with vibrating agitation mechanism <NUM>. When vibrating agitation mechanism <NUM> is in an inoperative state, or is operative but not in a vibration mode of operation, valve biasing mechanism <NUM> biases weight <NUM> against conduit <NUM>, such that the valve is in the closed operative orientation and fluid cannot flow through the conduit. When vibrating agitation mechanism <NUM> is in a vibration mode of operation and exerts vibrations on housing <NUM>, at least some of the exerted vibrations are applied to valve biasing mechanism <NUM>, and cause the valve biasing mechanism to move periodically. Periodic motion of the valve biasing mechanism <NUM> results in corresponding periodic motion of weight <NUM> away from conduit <NUM>, thereby transitioning the valve from the closed operative orientation to an open operative orientation and allowing fluid to flow through conduit <NUM>.

Due to the flexibility and resiliency of conduit <NUM>, when the weight <NUM> is moved away from the conduit, conduit <NUM> at least partially recovers such that fluid can flow through the conduit. Because reservoir biasing mechanism <NUM> constantly applies pressure to reservoir <NUM>, upon recovery of conduit <NUM>, enables the flowable ingestible medicament flows through the conduit, and out of portal <NUM>, into an environment surrounding the device <NUM>. As such, delivery of the flowable ingestible medicament is triggered by, and controlled by, vibration of the vibrating agitation mechanism <NUM>.

The rate at which the flowable ingestible medicament is delivered into the environment surrounding device <NUM> is dependent on characteristics of the conduit <NUM>, such as the diameter of the conduit, the thickness of the conduit walls, and the recovery time of the conduit, as well as on characteristics of the valve, such as the frequency of transitioning between the open and closed operative orientations of the valve.

It will be appreciated that the frequency at which valve biasing mechanism <NUM> transitions the valve between the open and closed operative orientations, by causing weight <NUM> to move towards and away from conduit <NUM>, is dependent on the frequency of vibrations exerted by vibrating agitation mechanism <NUM> or by housing <NUM>, as well as on the characteristics of the valve, such as the mass of weight <NUM> and the spring constant of the biasing mechanism <NUM>.

In some embodiments, the mass of weight <NUM> and the length and spring constant of biasing mechanism <NUM> may be selected such that the valve functions as a gear reducer. In such embodiments, the frequency at which the valve transitions between the closed and open operative orientations (i.e. the frequency at which the valve biasing mechanism <NUM> draws weight <NUM> away from conduit <NUM> and then pushes the weight <NUM> back to apply pressure to conduit <NUM>) may be smaller than the frequency of vibrations exerted by vibrating agitation mechanism <NUM>.

In some embodiments, valve biasing mechanism <NUM> is anchored to housing <NUM>. In some embodiments, valve biasing mechanism <NUM> may be anchored to medicament compartment housing <NUM>, provided that the attachment between the medicament compartment housing <NUM> and housing <NUM> of vibrating ingestible capsule <NUM> does not dampen or reduce the frequency or intensity of vibrations applied to valve biasing mechanism <NUM>, and that the frequency and intensity of vibrations exerted on medicament compartment housing <NUM> is substantially equal to that of vibrations exerted on housing <NUM>.

Relating now to characteristics of the medicament delivery compartment <NUM>, in some embodiments, in which the medicament delivery compartment <NUM> is distinct from vibrating ingestible capsule <NUM>, hollow <NUM> of medicament compartment housing <NUM> has a volume in the range of <NUM><NUM> to <NUM><NUM>, <NUM><NUM> to <NUM><NUM>, or <NUM><NUM> to <NUM><NUM>. In other embodiments, in which housing <NUM> houses components of medicament delivery compartment <NUM>, the housing <NUM> has a volume in the range of1000mm<NUM> to <NUM><NUM>.

In some embodiments, medicament reservoir <NUM> has a maximal volume in the range of <NUM><NUM> to <NUM><NUM>, <NUM><NUM> to <NUM><NUM>, <NUM><NUM> to <NUM><NUM>, <NUM><NUM> to <NUM><NUM>, <NUM><NUM> to <NUM><NUM>, <NUM><NUM> to <NUM><NUM>, or <NUM><NUM> to <NUM><NUM>.

In some embodiments, medicament reservoir <NUM> has elastic or elastomeric properties, and may have a low value for Young's modulus, typically smaller than <NUM> GPa. In some embodiments, medicament reservoir <NUM> is formed of a material selected from the group consisting of: silicone rubber, natural rubber, Polyethylene, and PVC.

In some embodiments, reservoir biasing mechanism <NUM> includes a reservoir spring terminating in a pressure applying surface which engages an exterior surface of medicament reservoir <NUM>, as illustrated in <FIG>. In such embodiments, the reservoir spring may be anchored to medicament compartment housing <NUM>.

In some embodiments, reservoir biasing mechanism <NUM> has a spring constant K in the range of <NUM> N/m to <NUM> N/m.

In some embodiments, flexible and resilient conduit <NUM> is integrally formed with flexible and collapsible medicament reservoir <NUM>. In other embodiments, conduit <NUM> is formed of a different material than medicament reservoir <NUM>.

In order to ensure that when vibrating agitation mechanism <NUM> is in the vibration mode of operation, fluid can be delivered through conduit <NUM>, the recovery time of the conduit must be sufficiently short for the conduit to recover its nominal diameter, and facilitate passage of fluid therethrough, before the conduit is once again pinched by weight <NUM>.

As such, in some embodiments, when vibrating agitation mechanism has a frequency f, a recovery time of conduit <NUM> is at most equal to <NUM>/f. In other embodiments, when valve biasing mechanism <NUM> has a frequency fv of transitioning the valve between the open and closed operative orientations, a recovery time of conduit <NUM> is at most equal to <NUM>/fv.

In some embodiments, a recovery time of conduit <NUM> is at most <NUM> seconds.

In some embodiments, conduit <NUM> has a diameter in the range of <NUM>-<NUM>.

In some embodiments, conduit <NUM> has a length in the range of <NUM>-<NUM>.

In some embodiments, valve biasing mechanism <NUM> has a spring constant in the range of <NUM> N/m to <NUM> N/m.

In some embodiments, weight <NUM> has a mass in the range of <NUM> grams to <NUM> grams.

Relating specifically to capsule <NUM>, power source <NUM> may be any suitable power source, such as one or more alkaline or silver oxide batteries, primary batteries, rechargeable batteries, capacitors and/or supercapacitors.

Intermittently activated vibrating agitation mechanism <NUM> is adapted to have a vibration mode of operation (also termed the first mode of operation) and a rest mode of operation (also termed the second mode of operation). In the vibration mode of operation, intermittently activated vibrating agitation mechanism <NUM> is adapted to exert forces on capsule housing <NUM>, such that capsule housing <NUM> exerts vibrations on an environment surrounding capsule <NUM> and/or device <NUM>.

In some embodiments, the capsule <NUM> is in an inoperative state, until the receipt of an activation input, which causes control element <NUM> to transition the capsule from the inoperative state to an operative state.

In some embodiments, control element <NUM> is functionally associated with, or includes, a timer or timing mechanism <NUM>, such as a clock, universal clock, or stopwatch, powered by power source <NUM> and adapted to track at least one time characteristic, such as a duration that has passed since an activation input was received, or a duration that has passed since the user ingested capsule <NUM>.

In some embodiments, capsule <NUM> is devoid of any sensors for sensing an environment thereof. In some such embodiments, control element <NUM> is adapted, in response to receipt of an activation input, to wait a predetermined delay time, and following the predetermined delay time, to activate vibrating agitation mechanism <NUM> to operate in said first vibration mode of operation.

In other embodiments, such as the embodiment illustrated in <FIG>, capsule <NUM> further includes at least one sensor <NUM>, functionally associated with control element <NUM>. The at least one sensor <NUM> may be adapted to sense at least one parameter within capsule <NUM> or in an environment of capsule <NUM>, and may include a temperature sensor, an illumination sensor, a moisture sensor, a pressure sensor, an accelerometer, or any other suitable sensor. In some embodiments, the at least one sensor <NUM> is adapted to identify a specific condition in capsule <NUM> or in the vicinity thereof, and to provide an activation input to control element <NUM> in response to identification of the condition. For example, in some embodiments the condition is indicative of the user ingesting capsule <NUM>.

For example, in some embodiments sensor <NUM> may include an illumination sensor, adapted to identify transition of capsule <NUM> from an illuminated environment (e.g. outside the human body) to a dark environment (e.g. within the human body) and to provide an activation input in response to identification of such a transition.

As another example, in some embodiments sensor <NUM> may include a motion or acceleration sensor, such as an accelerometer, adapted to identify an activation motion carried out by a user on capsule <NUM> or on device <NUM> and to provide an activation input in response to identification of such a transition. An example of an accelerometer providing an activation input for a gastrointestinal capsule is provided in <CIT>.

As another example, in some embodiments sensor <NUM> may include a pressure sensor adapted identify pressure applied to the capsule <NUM> or to device <NUM>, which pressure is indicative of the capsule moving through a pharynx of the user, and to provide an activation input in response to identification of such pressure.

As a further example, in some embodiments sensor <NUM> may include a temperature sensor adapted to identify transition of capsule <NUM> or of device <NUM> from an area with ambient temperature (e.g. outside the human body) to an area with a human body temperature and to provide an activation input in response to identification of such a transition.

As a further example, in some embodiments sensor <NUM> may include a moisture sensor adapted to identify transition of capsule <NUM> or of device <NUM> from a dry area (e.g. outside the human body) to a moist area (e.g. within the human body) and to provide an activation input in response to identification of such a transition.

It will be appreciated by people of skill in the art that sensor <NUM> need not necessarily be disposed within capsule <NUM>, as illustrated in <FIG>, and may be disposed anywhere within device <NUM>, for example within hollow <NUM> of medicament compartment housing <NUM>, on an exterior of capsule <NUM>, or on the exterior of device <NUM>.

In some embodiments, device <NUM> may be functionally associated with a control unit <NUM>, which may be remote from device <NUM> and from capsule <NUM>, and which is adapted to provide one or more inputs to the capsule. In some such embodiments, capsule <NUM> further includes a remote input receiving mechanism <NUM>, functionally associated with control element <NUM>, and adapted to receive inputs from an input providing mechanism <NUM> of control unit <NUM>.

In some embodiments, control unit <NUM> may further include a timing mechanism <NUM>, adapted to track at least one time characteristic, such as a duration that has passed since a control instruction was provided to capsule <NUM>.

In some embodiments, control unit <NUM> may further include a user input receiver <NUM>, such as a keyboard, touch screen, or touch pad, adapted to receive input from a user, such as the user, a medical professional treating the user, or a caregiver of the user.

Control unit <NUM> may be any suitable type of control unit. In some embodiments, control unit may be a suitably configured smart phone or a tablet computer.

In some such embodiments, control unit <NUM> may provide inputs to capsule <NUM> by remotely transmitting the inputs from input providing mechanism <NUM> to remote input receiving mechanism <NUM>, for example using a short range wireless communication method, such as radio frequency (RF) communication or Bluetooth® communication. One example of such a mechanism for providing input to a capsule is described in <CIT>.

In some embodiments, control unit <NUM> is adapted to provide the activation input to control element <NUM> of capsule <NUM>. In some such embodiments, control unit <NUM> provides the activation input prior to the user ingesting device <NUM> including capsule <NUM>, whereas in other embodiments control unit <NUM> provides the activation input following ingestion of device <NUM> and capsule <NUM> by the user.

Relating to the characteristics of vibrating agitation mechanism <NUM>, the vibrating agitation mechanism may be any suitable mechanism that can be intermittently activated and can apply suitable forces onto capsule housing <NUM>.

In some embodiments, intermittently activated vibrating agitation mechanism <NUM> may include a radial agitation mechanism adapted to exert radial forces on capsule housing <NUM>, in a radial direction with respect to the longitudinal axis of housing <NUM>. For example, the radial agitation mechanism may include an unbalanced weight attached to a shaft of an electric motor powered by said battery, substantially as described in <CIT>.

In some embodiments, intermittently activated vibrating agitation mechanism <NUM> may include an axial agitation mechanism adapted to exert radial forces on the capsule housing <NUM>, in an axial direction with respect to a longitudinal axis of housing <NUM>. For example, the axial agitation mechanism may include an electric motor powered by the battery and an urging mechanism, associated with, and driven by, the electric motor, such that the urging mechanism adapted to exert said axial forces, substantially as described in <CIT>. In some embodiments, the urging mechanism adapted to exert the axial forces in opposite directions. In some embodiments, the urging mechanism is adapted to deliver at least a portion of the axial forces in a knocking mode.

In some embodiments, the forces exerted by intermittently activated vibrating agitation mechanism <NUM> on capsule housing <NUM> in the vibration mode of operation include radial forces in a radial direction with respect to the longitudinal axis of the housing and axial forces in an axial direction with respect to the longitudinal axis. In some embodiments, a single agitation mechanism exerts both the radial and the axial forces. In other embodiments, the axial forces are exerted by one agitation mechanism, and the radial forces are exerted by another, separate, agitation mechanism, where both agitation mechanisms form part of intermittently activated vibrating agitation mechanism <NUM>.

In some embodiments, the intermittently activated vibrating agitation mechanism <NUM> may include a magnet mounted onto a rotor adapted to exert a magnetic field as well as radial forces on capsule housing <NUM>. For example, such a magnetic vibration agitation mechanism is described in <CIT>.

In some embodiments, housing <NUM> may include first and second members, and vibrating agitation mechanism <NUM> may include a mechanism adapted to effect a vibration by moving the first member of the housing in the opposite direction relative to the second member of the housing, substantially as described in <CIT>.

In some embodiments, housing <NUM> may include a vibration agitation mechanism <NUM> which makes use of a pendulum to cause vibration in the vicinity of the capsule, for example as described in <CIT>.

In some embodiments, or at some times, control element <NUM> is adapted to control vibration agitation mechanism <NUM>, and specifically to set at least one vibration parameter of vibration agitation mechanism <NUM>, so as to promote delivery of the flowable ingestible medicament into an environment surrounding device <NUM> and/or absorption of the ingestible medicament into the bloodstream of the user.

For example, delivery of the flowable ingestible medicament into an environment surrounding device <NUM> may be promoted by controlling one or more characteristics of the vibrating agitation mechanism <NUM> such that conduit <NUM> is open for relatively long durations, facilitating rapid delivery of the flowable medicament into the gastrointestinal tract.

As another example, absorption of the ingestible medicament may be promoted by the vibration promoting emulsification of the ingestible medicament. As yet another example, absorption of the ingestible medicament may be promoted by the vibration causing a hydrophobic phase of the ingestible medicament to form smaller bubbles, thereby increasing the surface area of the hydrophobic phase for absorption thereof. In another example, absorption of the ingestible medicament may be promoted by the vibration causing greater exposure of the ingestible medicament to the environment.

In some embodiments, or at some times, control element <NUM> may be adapted to control vibrating agitation mechanism <NUM> so that the capsule applies forces to an environment thereof, such that within the gastrointestinal tract, a mechanical stimulation of the wall of the gastrointestinal tract is effected.

In some such embodiments, the at least one vibration parameter includes at least one of a vibration frequency, a cumulative vibration duration, a number of vibration cycles per time unit, a duration of a vibration duration within a vibration cycle, a duration of a repose duration within a vibration cycle, a total duration of a single vibration cycle, and a net force exerted by said housing on said environment, as explained in further detail hereinbelow.

In some embodiments, control element <NUM> is adapted to control a timing or activation delay of the vibration mode of operation of the vibration agitation mechanism <NUM> such that the vibration mode of operation at least partially transpires within a region of the gastrointestinal tract in which the flowable ingestible medicament is absorbable by the body of the user, and at which it is desirable for the flowable ingestible medicament to be delivered into the gastrointestinal tract.

In some embodiments, control element <NUM> is adapted to control a timing or activation delay of the vibration mode of operation of the vibration agitation mechanism <NUM> such that the vibration mode of operation at least partially transpires within an estimated absorption time period of the flowable ingestible medicament <NUM> within the gastrointestinal tract of the user.

In some embodiments, control element <NUM> is adapted to control a timing or activation delay of the vibration mode of operation of the vibration agitation mechanism <NUM> such that the vibration mode of operation at least partially transpires within an actual absorption time period of the flowable ingestible medicament <NUM> within the gastrointestinal tract of the user.

In the vibrating mode of operation, intermittently activated vibrating agitation mechanism <NUM> is adapted to have a plurality of vibration cycles, where each cycle includes a vibration duration followed by a repose duration. Forces are exerted by the vibrating agitation mechanism <NUM> on capsule housing <NUM> only during the vibration duration, and as such, capsule housing <NUM> only exerts forces on an environment thereof during the vibration duration.

In some embodiments, the number of vibration cycles per hour is in the range of <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, or <NUM> to <NUM>.

In some embodiments, the repose duration is greater than the vibration duration.

In some embodiments, the vibration duration is in the range of <NUM> second to <NUM> seconds, <NUM> second to <NUM> seconds, <NUM> second to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, or <NUM> seconds to <NUM> seconds.

In some embodiments, the repose duration is in the range of <NUM> second to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, or <NUM> seconds to <NUM> seconds.

In some embodiments, the total duration of one vibration cycle is in the range of <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, or <NUM> seconds to <NUM> seconds.

In some embodiments, the cumulative duration of the vibrating mode of operation, or the cumulative duration during which vibration cycles are occurring, is in the range of <NUM> hour to <NUM> hours, <NUM> hours to <NUM> hours, <NUM> hours to <NUM> hours, <NUM> hours to <NUM> hours, <NUM> hours to <NUM> hours, or <NUM> hours to <NUM> hours. It will be appreciated that the cumulative duration of vibration cycles may be dependent on properties of power source <NUM>.

It will be appreciated by persons skilled in the art that the vibration mode of operation may be intermittent, or interrupted, such that vibrating agitation mechanism <NUM> is operative in the vibration mode for a first duration, for example <NUM> minutes, then does have any vibration cycles for a second duration, for example <NUM> hour, and then is operative in the vibration mode and has vibration cycles for a third duration, for example two hours. The cumulative duration relates to the sum of all durations during which vibrating agitation mechanism <NUM> was operative in the vibration mode and included vibration cycles, including the vibration duration and the repose duration of the vibration cycle.

In some embodiments, vibrating agitation mechanism <NUM> is configured to exert forces on the capsule housing <NUM>, such that a net force exerted by the capsule housing <NUM> on the environment thereof is preferably in the range of <NUM> grams force (gf) to 600gf, 50gf to 550gf, 100gf to 550gf, 100gf to 500gf, 150gf to 500gf, 200gf to 500gf, or 200gf to 450gf.

In some embodiments, vibrating agitation mechanism <NUM> is configured to exert said forces on capsule housing <NUM> to attain a capsule housing <NUM> vibrational frequency within a range of <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, or <NUM> to <NUM>.

It will be appreciated that the exact specifications of the capsule, such as the specific frequency and force ranges applicable to a specific capsule, are dependent on the specifications of the power source <NUM> and of the vibrating agitation mechanism <NUM>.

It will be further appreciated that a specific capsule may be controlled by the control element <NUM> such that different vibrational frequencies may be attained and/or different net forces may be exerted, by the capsule in different vibration cycles of the capsule. Due to the natural distinction between users, use of multiple different parameters in different vibration cycles of a single capsule would allow the capsule to successfully treat multiple users, even if the personal optimal treatment for those users is not the same, as there is a higher chance that in at least some of the vibration cycles the activation parameters of the capsule would reach, or be close to, the optimal parameters for each specific user.

Control element <NUM> is adapted to control the operation of intermittently activated vibrating agitation mechanism <NUM>. Such control may include control of any one or more of the force applied by the vibrating agitation mechanism <NUM>, the vibrational frequency reached, the times in which vibrating agitation mechanism <NUM> operates in the vibration mode of operation, the vibration duration of each vibration cycle, the repose duration of each vibration cycle, the vibration cycle duration, and cumulative vibration duration of the vibrating agitation mechanisms.

In some embodiments, control element <NUM> is adapted to receive information relating to the desired vibration protocol from control unit <NUM>, prior to ingestion of device <NUM> and capsule <NUM> or to activation of the capsule, or during the device's and capsule's traversal of the user's GI tract. For example, the information may be remotely transmitted from control unit <NUM> to control element <NUM>, for example using a short range wireless communication method. In some embodiments, the information is transmitted as a list of vibration parameters for effecting the vibration protocol. In some embodiments, the information is transmitted as executable code for effecting the first vibration protocol.

In some embodiments, the information includes a desired number of vibration cycles, a desired vibration duration in each vibration cycle, a desired repose duration in each vibration cycle, a desired cumulative vibration duration, and the like.

In some embodiments, the flowable ingestible medicament is absorbable or at least partially absorbable in the stomach of the user. In some embodiments, the flowable ingestible medicament is absorbable or at least partially absorbable in the small intestine of the user.

In some embodiments, the flowable ingestible medicament has a viscosity in the range of <NUM> Pa·s to <NUM> Pa·s.

In some embodiments, the flowable ingestible medicament is suitable for treatment of one or more symptom or disease, selected from the group consisting of: Parkinsonism; Parkinson's Disease; progressive supranuclear palsy; corticobasal degeneration; multiple system atrophy; Parkinson-plus syndromes (also known as disorders of multiple system degeneration); any neurodegenerative disease in which the subject exhibits at least one (and typically at least two or three) of the classical features of Parkinson's disease: tremor, postural instability, and akinesia or bradykesia; any neurodegenerative disease in which the subject positively responds to a dopaminergic treatment; any neurodegenerative disease in which the particular subject positively responds to an anticholinergic treatment; Constipation; Crohn's disease; Gastroparesis; irritable bowel syndrome (IBS); diarrhea or loose bowel movements; colitis; Hirschsprung's disease; Dyspepsia; and dysphagia.

In some embodiments, the flowable ingestible medicament comprises or includes an ingestible medicament selected from the group consisting of: levodopa; at least one dopaminergic agent; at least one catecholamine precursor; a dopamine precursor; at least one dopamine precursor agent; (L)-<NUM>,<NUM>-dihydroxyphenylalanine; N-methyl-N-(<NUM>-propynyl)-<NUM>-methyl-<NUM>-phenylethyl-<NUM>-amine; tyrosine hydroxylase; apomorphine; at least one anticholinergic agent; at least one agent selected to antagonize at least one cholinergic receptor; benzhexol; orphenadrine; at least one selective allosteric potentiator of metabotropic glutamate receptor <NUM> (mGluR4); N-phenyl-<NUM>-(hydroxylimino)cyclopropa[b]chromen-1a-carboxamide; at least one osmotic agent; magnesium citrate; magnesium hydroxide; polyethylene glycol; sodium phosphate; MiraLAX®; at least one contraction stimulating agent; bisacodyl; senna; Correctol; Ducodyl; Dulcolax; Senexon; Senokot; at least one stool softening agent; docusate sodium; Colace; Linaclotide; Lactulose; lubiprostone; plecanatide; prucaltride; loperamide; and bismuth subsalicylate.

Reference is now made to <FIG>, which is a planar sectional illustration of a device <NUM> for delivering a flowable ingestible medicament <NUM> into the gastrointestinal tract of a user according to another embodiment of the present invention, the device including a medicament reservoir <NUM> and a valve, to <FIG>, which is a partial perspective sectional illustration of device <NUM>, to <FIG> and <FIG>, which are partial planar sectional illustrations of device <NUM>, where medicament reservoir <NUM> is full, and the valve is in closed and open operative orientations, respectively, and to <FIG>, which is a partial planar sectional illustrations of device <NUM>, where medicament reservoir <NUM> is empty, and the valve is in a closed operative orientation.

As seen, device <NUM>, which is arranged along a longitudinal axis, includes a vibrating ingestible capsule <NUM> including a housing <NUM>, substantially as described hereinabove with respect to <FIG>. It will be appreciated that capsule <NUM> includes at least a vibrating agitation mechanism, a control element, and a power source, as described hereinabove with respect to <FIG>, even though these components are not explicitly shown in Figures 2A to 4B.

A medicament delivery compartment <NUM>, here illustrated as having the shape of a convex dome is formed by a medicament compartment housing <NUM> which defines a hollow <NUM>. A portal <NUM> is formed in medicament compartment housing <NUM>. Medicament reservoir <NUM> is disposed within hollow <NUM>, and is biased toward capsule <NUM> by a reservoir biasing mechanism. The reservoir biasing mechanism includes a spring 225a anchored at one end thereof to medicament compartment housing <NUM> and terminating, at an opposing end, in a biasing plate 225b which engages an exterior surface of medicament reservoir <NUM> and applies pressure thereto. The medicament reservoir <NUM> is flexible and collapsible, and may be formed of any suitable material such as silicone rubber, natural rubber, polyethylene, and PVC.

A conduit <NUM>, which may be a flexible and/or resilient conduit, extends from medicament reservoir <NUM> to portal <NUM>, and terminates with portal <NUM>, such that fluid can flow from medicament reservoir <NUM>, via conduit <NUM> and portal <NUM>, out of the device <NUM> and into an environment surrounding the device. In some embodiments, the end of conduit <NUM> disposed within portal <NUM> also seals the portal, so as to prevent material from the environment entering device <NUM>. In other embodiments, the end of conduit <NUM> may be surrounded by a seal sealing the portal.

A valve <NUM> disposed within hollow <NUM> includes a weight <NUM> attached to a compression spring <NUM>, which functions as a valve biasing mechanism. The spring <NUM> is anchored, at an end distal to weight <NUM>, to a rigid anchoring shelf <NUM> extending from medicament compartment housing <NUM> or from housing <NUM> of vibrating ingestible capsule <NUM>.

Biasing spring <NUM> and weight <NUM> are constructed such that, when vibrating ingestible capsule <NUM> is in an inoperative mode, or is in an operative mode but not vibrating, biasing spring <NUM> biases weight <NUM> against conduit <NUM>, thus pinching the conduit closed, as illustrated clearly in <FIG>. This is the closed operative orientation of valve <NUM>. When valve <NUM> is in the closed operative orientation, no fluid can flow through conduit <NUM>, and pressure applied by the reservoir biasing mechanism to medicament reservoir <NUM> is at an equilibrium with forces resisting such pressure by the content of the medicament reservoir and conduit.

However, when vibrating ingestible capsule <NUM> is in the vibrating mode of operation, vibration of the vibrating ingestible capsule <NUM> is applied also to biasing spring <NUM>, via anchoring shelf <NUM>. As discussed hereinabove, the vibrations of the capsule <NUM> are periodic, and cause the spring to periodically contract and extend. Contraction of the spring <NUM> results in weight <NUM> being withdrawn, or moved away, from conduit <NUM>, thus enabling the conduit <NUM> to recover its nominal diameter and fluid to flow through the conduit <NUM>, as illustrated in <FIG>. This is the open operative orientation of valve <NUM>. When valve <NUM> is in the open operative orientation, pressure applied by the reservoir biasing mechanism to medicament reservoir <NUM> causes medicament <NUM> to flow from reservoir <NUM>, via conduit <NUM> and portal <NUM>, into the environment surrounding device <NUM>.

In use, when capsule <NUM> is in the vibrating mode of operation, valve <NUM> periodically transitions between the closed operative orientation and the open operative orientation, and vice versa. During such vibration times, and when the valve is in the open operative orientation, flowable ingestible medicament <NUM> is delivered from reservoir <NUM> to the environment surrounding device <NUM>. Because of the periodic opening and closing of valve <NUM>, such delivery occurs in bursts, or quanta, until the medicament reservoir is empty and all the flowable medicament has been delivered, as illustrated in <FIG>.

The volume of medicament delivered in each such burst, is dependent on the pressure applied by the reservoir biasing mechanism, the recovery time of conduit <NUM>, the diameter of the conduit, and the duration that valve <NUM> is in the open operative orientation. The duration that valve <NUM> is in the open operative orientation is based on the frequency of vibrations exerted by vibrating ingestible capsule <NUM>, as well as on the mass of weight <NUM>, the length and spring constant of biasing spring <NUM>, and the rigidity of anchoring shelf <NUM>. In some embodiments, the valve <NUM> functions as a gear reducer, such that the frequency at which the valve transitions between the open and closed configurations is lower than the frequency of vibration of the capsule <NUM>.

Medicament compartment housing <NUM> of medicament delivery compartment <NUM> is attached to housing <NUM> of vibrating ingestible capsule <NUM>. In the illustrated embodiment, housing <NUM> of vibrating ingestible capsule <NUM> includes a first attachment mechanism in the form of a circumferential slot <NUM> and a circumferential protrusion <NUM> disposed adjacent a longitudinal end <NUM> of capsule housing <NUM>. Medicament compartment housing <NUM> includes a second, corresponding attachment mechanism in the form of a circumferential slot <NUM> and a circumferential protrusion <NUM> disposed adjacent an end <NUM> of medicament compartment housing <NUM>. Circumferential slot <NUM> corresponds in dimensions to circumferential protrusion <NUM> of capsule <NUM>, and circumferential protrusion <NUM> corresponds in dimensions to circumferential slot <NUM> of capsule <NUM>.

In the illustrated embodiment, medicament compartment housing <NUM> is fixedly attached to vibrating ingestible capsule <NUM> by snap fit engagement of slot <NUM> with protrusion <NUM> and snap fit engagement of protrusion <NUM> with slot <NUM>. However, any type of attachment between medicament compartment housing <NUM> and vibrating ingestible capsule <NUM> is considered within the scope of the present invention, including threaded engagement, engagement by soldering, engagement by adhesive, and the like.

Reference is now made to <FIG>, which is a schematic diagram of a device <NUM> for delivering a flowable ingestible medicament <NUM> into the gastrointestinal tract of a user according to yet another embodiment of the present invention.

As seen, device <NUM>, which is arranged along a longitudinal axis, includes a vibrating ingestible capsule <NUM> including a housing <NUM>, formed of a first housing portion and a second housing portion which define a single hollow, and a vibrating agitation mechanism <NUM>, substantially as described hereinabove with respect to <FIG>. It will be appreciated that capsule <NUM> also includes a control element, and a power source, as described hereinabove with respect to <FIG>, even though these components are not explicitly shown in <FIG>.

Vibrating ingestible capsule <NUM> also functions as a medicament delivery compartment, such that a portal <NUM> is formed in the second housing portion of housing <NUM>. A medicament reservoir <NUM> is disposed within a hollow of capsule <NUM>, and is biased toward a shelf <NUM> extending radially inwardly from housing <NUM> by a reservoir biasing mechanism. The reservoir biasing mechanism includes a spring 325a anchored at one end thereof to a longitudinal end of housing <NUM> and terminating, at an opposing end, in a biasing plate 325b which engages an exterior surface of medicament reservoir <NUM> and applies pressure thereto. The medicament reservoir <NUM> is flexible and collapsible, and may be formed of any suitable material such as silicone rubber, natural rubber, polyethylene, and PVC.

Vibrating agitation mechanism <NUM> is attached to a biasing spring <NUM>, which is anchored to housing <NUM>. Vibrating agitation mechanism <NUM> and compression spring <NUM> form a valve, which functions in the manner described above with respect to valve <NUM> of <FIG>, which functions as a valve biasing mechanism. The spring <NUM> is anchored, at an end distal to weight <NUM>, to a rigid anchoring shelf <NUM> extending from medicament compartment housing <NUM> or from housing <NUM> of vibrating ingestible capsule <NUM>.

As such, in a closed operative orientation of the valve, biasing spring <NUM> biases vibrating agitation mechanism <NUM> against conduit <NUM>, thus pinching the conduit closed. In this closed operative orientation, no fluid can flow through conduit <NUM>, and pressure applied by the reservoir biasing mechanism to medicament reservoir <NUM> is at an equilibrium with forces resisting such pressure by the content of the medicament reservoir and conduit.

However, when vibrating agitation mechanism <NUM> is in the vibrating mode of operation, biasing spring <NUM> periodically contracts and extends, resulting in vibration agitation mechanism <NUM> being periodically withdrawn, or moved away, from conduit <NUM>, thus transitioning the valve to an open operative orientation, enabling conduit <NUM> to recover its nominal diameter and allowing fluid to flow through conduit <NUM>. When the valve is in the open operative orientation, pressure applied by the reservoir biasing mechanism to medicament reservoir <NUM> causes medicament <NUM> to flow from reservoir <NUM>, via conduit <NUM> and portal <NUM>, into the environment surrounding device <NUM>.

The delivery of the flowable medicament into the environment is as described hereinabove with respect to <FIG>.

Reference is now additionally made to <FIG>, which is a schematic flowchart of a method for delivering a flowable ingestible medicament into the gastrointestinal tract of user according to the present invention. The method may be based on the use of a device including a vibrating ingestible capsule and a flowable ingestible medicament, as described hereinabove with reference to <FIG>.

As seen at step <NUM>, a device, such as device <NUM>, <NUM>, or <NUM> described hereinabove, including a vibrating ingestible capsule and a medicament delivery compartment, is provided to a user.

In some embodiments, at step <NUM>, the vibrating ingestible capsule and the medicament delivery compartment are attached to each other. In some embodiments, step <NUM> may take place in a factory, prior to providing the device to the user at step <NUM>. In other embodiments, the device may be provided to the user as two separate pieces, namely the ingestible vibrating capsule and the medicament delivery compartment, and the user carries out step <NUM> following receipt of the device at step <NUM>. In some embodiments, in which the device is constructed as a unitary structure, for example as illustrated in <FIG>, step <NUM> may be obviated.

In some embodiments, the attaching at step <NUM> includes fixedly attaching the medicament delivery compartment to the vibrating ingestible capsule.

In some embodiments, the attaching at step <NUM> includes removably attaching the medicament delivery compartment to the vibrating ingestible capsule.

In some embodiments, the attaching at step <NUM> includes attaching the medicament delivery compartment to the vibrating ingestible capsule by one or more of snap fit engagement, threaded engagement, adhering, soldering, or any other suitable mechanism of attachment.

In some embodiments, the attaching at step <NUM> includes mutually attaching a first attachment mechanism on the vibrating ingestible capsule with a corresponding attachment mechanism on the medicament delivery compartment, for example as described with respect to <FIG>.

In some embodiments, the device is provided to the user having the flowable ingestible medicament disposed within the medicament reservoir and within the medicament delivery compartment.

In other embodiments, at step <NUM>, the flowable ingestible medicament is inserted into medicament delivery compartment. Step <NUM> may include filling of the medicament reservoir with the flowable ingestible medicament and/or inserting the medicament reservoir into the medicament delivery compartment or into the device.

In some embodiments, step <NUM> takes place prior to attaching the ingestible vibrating capsule with the medicament delivery compartment, either in a factory or by the user. The flowable ingestible medicament inserted at step <NUM> may be any suitable type of flowable ingestible medicament, as described in detail hereinabove.

Regardless of when the medicament reservoir is inserted into the device, the medicament reservoir is placed under pressure within the device, as explained hereinabove.

At step <NUM>, the device, including the vibrating ingestible capsule, the medicament delivery compartment, and the flowable ingestible medicament, is ingested by the user, and begins to travel through the gastrointestinal tract of the user.

At step <NUM>, which occurs following the user ingesting the device at step <NUM>, the vibrating ingestible capsule is controlled such that the vibration mode of operation (e.g., when the vibration mode is initiated, a duration of the vibration mode, etc.) at least partially transpire within an area of the gastrointestinal tract at which the flowable ingestible medicament should be delivered, or within an absorption time period of the flowable ingestible medicament within the gastrointestinal tract of the user.

The absorption time period may be an estimated absorption time period, as defined herein, and/or an actual absorption time period as defined herein.

In some embodiment, step <NUM> may include controlling a timing of the vibration mode of operation such that the vibration mode at least partially transpires when the capsule is in a region of the gastrointestinal tract in which the flowable ingestible medicament is typically absorbed into the bloodstream. The region of the gastrointestinal tract may include one or more of the stomach of the user, the duodenum of the user, the small intestine of the user, the large intestine of the user, or the colon of the user.

For example, when the flowable ingestible medicament is levadopa, which is typically absorbed into the bloodstream through the stomach walls and/or the small intestine walls, the vibration mode at least partially transpires within a time period in which the device traverses, or is expected to traverse, the stomach and small intestine.

In some embodiments, step <NUM> includes setting at least one vibration parameter of the vibrating ingestible capsule of the device so as to promote delivery of flowable ingestible medicament into the gastrointestinal tract of the user or absorption of the ingestible medicament into the bloodstream of the user. In some such embodiments, the at least one vibration parameter set at step <NUM> includes at least one of a vibration frequency, a cumulative vibration duration, a number of vibration cycles per time unit, a duration of a vibration duration within a vibration cycle, a duration of a repose duration within a vibration cycle, a total duration of a single vibration cycle, and a net force exerted by said housing on said environment.

In some embodiments, the controlling at step <NUM> includes controlling the vibration agitation mechanism such that the vibrating mode of operation includes a plurality of cycles, each of the cycles including a vibration duration followed by a repose duration, wherein the housing exerts the vibrations during the vibration duration.

In some embodiments, a duration of each of the plurality of cycles is in the range of <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, <NUM> seconds to <NUM> seconds, or <NUM> seconds to <NUM> seconds.

In some embodiments, the controlling at step <NUM> includes controlling the vibrating agitation mechanism such that a cumulative duration of the vibrating mode of operation is in the range of <NUM> hour to <NUM> hours, <NUM> hours to <NUM> hours, <NUM> hours to <NUM> hours, <NUM> hours to <NUM> hours, <NUM> hours to <NUM> hours, or <NUM> hours to <NUM> hours.

In some embodiments, the controlling at step <NUM> includes controlling the vibrating agitation mechanism to exert forces on the housing of the vibrating ingestible capsule, such that a net force exerted by the housing on the environment thereof is preferably in the range of <NUM> grams force (gf) to 600gf, 50gf to 550gf, 100gf to 550gf, 100gf to 500gf, 150gf to 500gf, 200gf to 500gf, or 200gf to 450gf.

In some embodiments, the controlling at step <NUM> includes controlling the vibrating agitation mechanism to exert the forces on the housing to attain a housing vibrational frequency within a range of <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, <NUM> to <NUM>, or <NUM> to <NUM>.

In some embodiments, and as described in further detail herein, the method may include a further step <NUM> of transitioning the capsule (from an inoperative state) to an operative state.

The capsule may be pre-programmed with a vibration protocol. This protocol may include, by way of example, a particular or pre-determined activation time following ingestion, in which the capsule is transitioned from an inoperative state to an operative state. In such embodiments, the step <NUM> may be omitted from the method.

Alternatively or additionally, the capsule may receive an activation input in an active fashion (e.g., from an external controller via RF) or in a passive fashion (e.g., a signal from a sensor to the on-board controller), as described in detail hereinabove. It will be appreciated that step <NUM>, in which the vibrating ingestible capsule is transitioned from the inoperative state to the operative state, may be performed prior to ingestion of the device by the user in step <NUM>, or following such ingestion, for example in the case of external control via RF.

Substantially as described hereinabove, step <NUM> may be carried out, and the vibrating ingestible capsule may be activated, prior to the user ingesting the capsule at step <NUM>, for example by a signal from the control unit or by the user carrying out an activation motion. In other embodiments, the activation input, and the transitioning of the capsule from being inoperative to being operative, occurs at the time of ingestion or immediately thereafter, for example by sensors sensing a change in the environment of the capsule due to its ingestion, as described at length hereinabove. In yet other embodiments, the transitioning of the capsule at step <NUM> may include the capsule receiving an activation input which is provided remotely when the capsule is already in the body of the user, for example by remote communication from control module <NUM>.

Claim 1:
A medicament delivery compartment (<NUM>) adapted to be attached to a vibrating ingestible capsule (<NUM>) having a first housing portion (<NUM>) and adapted to operate in a vibrating mode of operation, for delivery of a flowable ingestible medicament into the gastrointestinal tract of a user, the medicament delivery compartment including:
a second housing portion (<NUM>) adapted to be attached to said first housing portion of said vibrating ingestible capsule, and having a portal formed therein;
a flexible and collapsible medicament reservoir (<NUM>) dimensioned to contain the flowable ingestible medicament;
a reservoir biasing mechanism (<NUM>) adapted to apply pressure to said flexible and collapsible medicament reservoir;
a conduit (<NUM>) extending from said medicament reservoir to said portal, and sealing said portal; and
a valve including a weight (<NUM>) and a valve biasing mechanism (<NUM>) adapted, in a closed operative orientation, to bias said weight against said conduit so as to block flow through said conduit, and in an open operative orientation to remove the weight from said conduit so as to allow fluid to flow through said conduit.