WO2009063377A1 - Ingestible electronic capsule - Google Patents

Ingestible electronic capsule Download PDF

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Publication number
WO2009063377A1
WO2009063377A1 PCT/IB2008/054675 IB2008054675W WO2009063377A1 WO 2009063377 A1 WO2009063377 A1 WO 2009063377A1 IB 2008054675 W IB2008054675 W IB 2008054675W WO 2009063377 A1 WO2009063377 A1 WO 2009063377A1
Authority
WO
WIPO (PCT)
Prior art keywords
capsule
ring
fin
capsule according
medicament
Prior art date
Application number
PCT/IB2008/054675
Other languages
French (fr)
Inventor
Hans Zou
Original Assignee
Koninklijke Philips Electronics N.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US98748207P priority Critical
Priority to US60/987,482 priority
Application filed by Koninklijke Philips Electronics N.V. filed Critical Koninklijke Philips Electronics N.V.
Publication of WO2009063377A1 publication Critical patent/WO2009063377A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/07Endoradiosondes
    • A61B5/073Intestinal transmitters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00147Holding or positioning arrangements
    • A61B1/00156Holding or positioning arrangements using self propulsion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/48Other medical applications
    • A61B5/4836Diagnosis combined with treatment in closed-loop systems or methods
    • A61B5/4839Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/04Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
    • A61B1/041Capsule endoscopes for imaging

Abstract

An ingestible capsule (100) comprising at least one fin (123) pivotable about a pivot pin (126) between a folded position and an unfolded position, and control circuitry for controlling folding and unfolding of the fin (123). In a specific embodiment, the capsule (100) comprises a first ring (120) and a concentric second ring (121) which are concentrically rotatable relative to each other, wherein the pivot pin (126) connects the fin to the first ring and a slider pin (128) is pivotably connected to the fin (123) and slideably engaged in a lot (127) in the second ring (121).

Description

Ingestible electronic capsule

FIELD OF THE INVENTION

The present invention relates to an electronically controlled ingestible capsule, e.g., for release of a medicament or for diagnostic purposes.

BACKGROUND OF THE INVENTION

Electronically controlled ingestible capsules can be used to provide therapeutic or diagnostic treatment during traversal of the gastrointestinal alimentary tract. For example, an ingestible capsule having a camera acquires diagnostic images as it traverses the gastrointestinal tract. If used for therapeutic treatment, the capsule can be provided with an electronically controlled medicament delivery system. The capsule is moved by the peristaltic movement of the muscles along the gastrointestinal tract.

An electronically controlled capsule can be programmed or controlled to deliver or dispense a medicament according to a dispensing timing pattern while traversing through the gastrointestinal tract. The electronically controlled capsule can include control and timing circuitry for controlling the opening and closing of a valve or hatch according to the desired dispensing timing pattern for dispensing a medicament stored within a medicament reservoir of the capsule.

The dispensing timing pattern can be preset and it can be fixed not being susceptible to a person's physiological processes and conditions, mood, age, gender, ailments, earlier-administered medicaments, etc. The electronically controlled capsule allows a person to take all capsules substantially simultaneously, e.g. with breakfast, so that no more capsules are required for the day. Medication that does not fit into one electronically controlled capsule can be coordinated with other electronically controlled capsules for the full day's payload regimen. All of the medicaments required to be taken during a particular time period, for example, during a 24-hour period, can be provided within one or more electronically controlled capsules which can all be taken at the same time. The electronically controlled capsules can have different dispensing timing patterns, so that a full day's coverage can be obtained. Further, at a preset moment in time during the dispensing timing patterns, the electronically controlled capsules present in the body may be programmed to stop dispensing medicament in the expectation that a new set of capsules will be taken. This prevents accidental overdose by having only the most recently taken capsules dispensing medicament in the body.

A program controlled medicament delivery system using such capsules avoids the need for a caregiver to wake up or otherwise disturb a patient or resident for the sole purpose of administering a medicament or to track down a patient or resident who may be in a different part of the hospital or nursing home for the sole purpose of administering a medicament. It also reduces the overload required for inventorying, ordering, tracking and logging the medicaments. As used herein, the word "medicament" refers to medicines, placebos, non- medicinal substances, contrast agents, gases, fluids, liquids, radiological agents, imaging or medical markers, sensors for monitoring the person's vitals, etc..

To keep a steady concentration of medicament in a patients body and to minimize the number of medicament administrations, it is desirable to use a release capsule that can stay in the gastrointestinal tract for a longer period, e.g., for 10 hours or more. To this end, it has been proposed in WO 2006077529 to use a capsule comprising a balloon which is selectively inflatable and deflatable.

WO 2006077529 also discloses a treatment system which includes an ingestible capsule having a plurality of deflectable bristles biased to resume an original position. These are used to generate deflection signals for generating a topographical mapping of the alimentary tract traversed.

US 6719684 B2 discloses a micro capsule type robot for examining the internal organs of a human body with a stopping unit for stopping or delaying movement of the robot at a certain position. The stopping units can include electroactive polymers. Such stopping units can cause friction with surrounding tissue of the gastrointestinal tract.

The object of the invention is to provide an ingestible capsule allowing prolonged retention time on the site to be treated.

BRIEF DESCRIPTION OF THE INVENTION The object of the invention is achieved with ingestible capsule comprising: at least one fin pivotable about a pivot pin between a folded position and an unfolded position; control circuitry for controlling folding and unfolding of the fin. The unfolded fins enlarge the outer dimensions of the capsule in an effective and controllable way. Due to the enlarged dimensions, further movement of the capsule is stopped or delayed and the retention time of the capsule in the gastrointestinal tract is effectively prolonged. After retracting the fin back into the folded position, the dimensions are reduced again and the capsule can continue its travel through the gastrointestinal tract.

The capsule can for example comprise a first ring and a concentric second ring which are concentrically rotatable relative to each other, wherein the pivot pin connects the fin to the first ring and wherein a slider pin is pivotably connected to the fin and slideably engaged in a slot in the second ring. This allows a compact and simple construction. Rotation of the second ring forces the fin to move to the unfolded position. If the second ring is rotated in the other direction, the fin is retracted to the folded position. The rotation of the rings can for example be activated by means of a magnetic coil within the capsule.

In such a construction, the first ring can be a stationary outer ring and the second ring is a rotatable inner ring, or the other way around if so desired. If the capsule has a cylindrical shape or a rotation symmetric longitudinal or spherical shape, the outer diameter of the stationary ring may correspond to the outer diameter of the capsule, so that the ring is flush with the outer surface of the capsule. Similarly, the fin or fins may have an outer edge which is also flush with the outer surface of the capsule when the fin is in the folded position. The fins can, e.g., be made of a flexible bio-compatible plastic, such as for instance biocompatible materials used to fabricate implantable medical devices. These materials include Pellethane® 2363 polyether urethane series of materials available from Dow Chemical Company and Elasthane polyether urethane available from the Polymer Technology Group, Inc. Other materials include PurSil® and CarboSil® also available from the Polymer Technology Group, Inc.

Optionally the capsule is provided with a pliant membrane which envelopes at least one of the one or more fins. The pliant membrane minimizes friction with surrounding gastrointestinal tissue. Such membrane can for instance be made of a cloth or stretchable foil, stretchable under the action of the unfolded fin or fins. Suitable materials for such a membrane are for example high-pressure, non-elastic plastics, which are formed of materials such as flexible polyvinyl chloride (PVC), cross linked polyethylene (PE), polyester polyethylene terephthalate (PDT), polyamide, or polyurethane; or the low-pressure elastomeric variety, which are formed of materials such as latex or silicone. Optionally, the pliant membrane can be fixed to at least one of the one or more unfoldable fins, e.g., by a glue.

The pliant membrane can be permeable for medicament to be released by the capsule. Alternatively, the membrane can have an opening in line with a medicament dispensing opening or nozzle. In case the capsule is used for diagnostic purposes, the membrane may be provided with openings allowing a sensor in the capsule to interact with the environment to be examined.

Coatings may be provided on the membrane, such as lubricious coatings, hydrophilic or hydrophobic coatings, abrasion and puncture resistant coatings, tacky or high friction coatings, conductive coatings, anti-thrombogenic coatings, drug release coatings, reflective coatings and/or selective coatings.

The capsule according to the present invention can for example be an electronic pill comprising: a sensor sensitive to environmental conditions in the gastrointestinal tract of a patient; a medicine reservoir; a medicine dispenser.

The electronic pill can be controlled by an external control system, e.g. radiographical remote control, or the pill can comprise a processor programmed to release medicine from the reservoir via the medicine dispenser upon activation by the sensor.

The capsule according to the present invention can also be used for diagnostic purposes comprising a sensor for collecting desired information, e.g. a camera.

The capsule can also have one or more power sources, such as a battery, which provides power to control circuitry and/or other components of the capsule. An exemplary battery is a thin film lithium battery (e.g., available from Frontedge Technologies TM, located in Baldwin Park, California, US), having a small footprint and a suitable shelf life (e.g., 1% discharge/year). The battery may further be selected from other known batteries, such as photo lithium, silver oxide, lithium coin cells, zinc air cells, alkaline, etc.. Alternatively or additionally the capsule may use passive power. It is contemplated that the power source includes a device configured for scavenging power from another device, which may employ electrostatic, micro fuel cells, micro-heat, temperature gradient, etc..

There are significant numbers of drugs which can be absorbed by the body only in the proximal small intestine. It is therefore desirable to have those drugs available in the upper gastrointestinal tract for a long period. However, the natural transit time in the entire small intestine (from the stomach to colon) is more or less constant, only up to about 4 hours and varies a lot depending on food intake of a patient. It has been found that absorption in the proximal small intestine can substantially be improved by increasing the retention time of the capsule in the stomach. To this end, a capsule can be used comprising at least one expandable member which is expanded after entry into the stomach to a size preventing passage through the pylorus and which is re-contracted to a size allowing passage through the pylorus after release of an amount of one or more medicaments over a pre-determined period of time in accordance with a pre-set dispensing timing pattern. Such a capsule can, e.g., be an electronic pill comprising a processor which is programmed to unfold one or more unfoldable members responsive to a signal issued by the sensor after detecting a condition typical for the stomach environment. The processor can also be programmed to fold back the one or more unfoldable members after release of a pre-determined amount of medicine and/or after a preset time period. The capsule can contain particles of a medicament coated with a gastroresistant enteric coating. Such coatings are resistant to the acidic stomach environment but soluble in the less acidic intestinal environment of the intestine, enabling controlled release of the therapeutic substance in the intestine. The enteric coatings can for example be based on poly(meth)acrylates. Suitable examples of commercially available enteric coatings are for instance the Eudragit® coating materials of Degussa, and the Kollicoat® coating materials of BASF.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be elucidated with reference to the figures wherein: Figure IA shows a capsule according to the invention in longitudinal cross section; Figure IB shows the capsule of Figure IA with an unfolded fin;

Figure 1C shows the capsule in cross section along line A-A' in Figure IA; Figure ID shows the capsule with unfolded fin in cross section along line A-A' in Figure IA.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Figure IA shows an exemplary embodiment of an electronically controlled capsule according to the present invention, having two unfoldable fins. The same embodiment is shown with unfolded fins in Figure IB. Figures 1C and ID show the capsule in cross section. The electronically controlled capsule 100 is a self-contained electronically controlled medicine delivery system. The electronically controlled capsule 100 includes programmed electronics that control a release mechanism according to a dispensing pattern for dispensing a medicament. The capsule 100 is made from bio-compatible materials such that the capsule 100 is bio-compatible for at least the amount of time it requires to traverse the gastrointestinal tract. The bio -compatible materials are preferably stable in room temperature, such that the capsule has a long shelf life. The electronically controlled capsule 100 includes an outer shell or housing 102; a medicament reservoir 104 for storing a medicament; an electronically controlled release valve or hatch 106 for dispensing the medicaments stored in the medicament reservoir 104; control and timing circuitry 108 for opening and closing the valve 106; and a battery 109.

The control and timing circuitry 108 opens and closes the valve 106 throughout a dispensing time period in accordance with a preset dispensing timing pattern as further described below. The shell 102 can be manufactured from materials used to fabricate implantable devices. The amount that the valve 106 is opened at each moment in time (e.g., each second) of the dispensing time period is dependent upon the preset dispensing timing pattern which is programmed within timing circuitry 110 of the control and timing circuitry 108. The dispensing time period is defined as the time period from when the electronically controlled capsule 100 is placed in a person's mouth to the time all of the medicament stored within the medicament reservoir 104 has been dispensed, or the day (24-hour period) has expired. This 24-hour period may be shifted slightly to account for differences in absorption in the stomach versus the colon.

During the dispensing time period, the control and timing circuitry 108 is programmed for closing the valve 106 and controlling the amount the valve 106 is opened for controlling the size of the valve opening. By controlling the size of the valve opening or frequency of valve opening, such as is enabled by micro fluidic systems of inkjet printers and the like, the electronically controlled capsule 100 can precisely control the quantity of medicament released during each moment in time (e.g., each second) of the dispensing time period.

The control and timing circuitry 108 includes timing circuitry 110 programmed with the preset dispensing timing pattern, a start timer mechanism 112, a release controller 114 and a pressure mechanism 116. The start timer mechanism 112 enables activation of the timing circuitry 110. The battery 109 powers the control and timing circuitry 108 in order for each of the electromechanical components to operate during the dispensing time period. Optionally, the start timer mechanism 112 is a micro-electromechanical (MEM) mechanism having a sensor 118 (not indicated) for sensing the presence of a liquid, such as water, saliva, etc. When the capsule 100 is taken or administered, the sensor 118 senses the presence of a liquid, and transmits an electrical signal to the timing circuitry 110. In an alternate embodiment the start timer mechanism is a button which is pushed to transmit the electrical signal to the timing circuitry 110. The button is pushed just before the capsule 100 is administered to a person or animal.

In another embodiment, this can be achieved by dissolving a thin, water soluble coating that separates two electrical contacts, enabling the switch to close the circuit. In still another embodiment, the switch is manually triggered by the patient or caregiver.

Upon receiving the electrical signal, the timing circuitry 110 begins to clock the dispensing time period and control the release controller 114 by transmitting a signal thereto. The timing circuitry 110 includes a microprocessor programmed with the preset dispensing timing pattern for relaying the signal to the release controller 114, such that the medicament is dispensed during the dispensing time period substantially according to the preset dispensing timing pattern.

The voltage level of the signal relays the size of the valve opening for controlling the quantity of the medicament dispensed at each moment of the dispensing time period substantially according to the preset dispensing timing pattern. In an alternative embodiment, the signal transmitted by the timing circuitry 110 to the release controller 114 only relays the opening and closing of the valve 106 and not the size of the valve opening.

The release controller 114 is can, e.g., be a micro-electromechanical mechanism capable of receiving the signal from the timing circuitry and generating a signal having a variable voltage level to the electronically controlled valve 106 for closing the valve 106 and controlling the size of the valve opening or degree of opening of the valve 106 (in accordance with the voltage level of the received signal). In the simplest case, the release controller 114 is a transistor or D/A circuit that provides voltages to the valve 106 causing it to open or close.

The electronically controlled valve 106 can, e.g., be a micro-electromechanical mechanism capable of being electrically controlled by a signal having a variable voltage levels. Each voltage level corresponds to a different size opening for the valve opening and one voltage level (or no voltage at all, i.e., no signal) corresponds to the valve 106 being closed. The valve 106 is similar in operation to valves used in ink-jet printers for dispensing ink in accordance with the amount that the valve is opened. The valve 106 is characterized as a microfluidic valve for controlling the movement of minute amount of liquids or gases in a miniaturized system.

In an alternative embodiment, the reservoir 104 is a micro-syringe, whereby pressure applied to a plunger of the syringe dispenses the medicament via a needle tip of the micro-syringe which is in fluid communication with an opening in the shell 102. In this embodiment, the opening replaces the valve 106. It is contemplated, however, that a check valve is placed at the needle tip of the micro-syringe to avoid leakage of the medicament during time periods within the dispensing time period where there should be no dispensing according to the preset dispensing timing pattern, and/or for controlling the quantity of medicament dispensed during the dispensing time period.

The pressure mechanism 116 is located outside the medicament reservoir 104 ensuring that the medicament is directed toward the valve 106. In the simplest case, the pressure mechanism 116 is a biodegradable spring as shown by Figure 1.

The pressure mechanism 116 can also be another type of spring, a piston, or any mechanism for performing the function of the pressure mechanism 116. That is, for performing the function of applying pressure to a piston-type member 130 when the valve 106 is open to push the piston -type member 130 towards the valve 106. As the piston-type member 130 moves towards the valve 106 pressure within the reservoir 104 causes the medicament to be dispensed. In an alternative embodiment, the medicament reservoir 104 is kept under pressure to assure a proper quantity of medicament is dispensed in accordance with the degree of openness of the valve 106, without the need for the pressure mechanism 116. The pressure can be monitored by a pressure sensor which relays the monitored pressure to the control and timing circuitry 108. If the pressure is outside a predetermined range, the circuitry 108 can then adjust the valve opening to increase or decrease the pressure. The pressure of the reservoir 104 can be different for each medicament and can depend on the medicament's viscosity.

It is contemplated that a look-up table or other data structure can be assessed by the circuitry 108 which correlates pressure, degree of valve opening, and other parameters, such as period of time in the dispensing time period, for determining, for example, the degree of valve opening by knowing the pressure, and vice versa. Based on the information obtained by assessing the look-up table, the circuitry 108 can then adjust the pressure, the valve opening, etc. These adjustments can be made in order to substantially track the preset dispensing timing pattern programmed within the capsule 100. Within its shell 102 capsule 100 further comprises a stationary ring 120 which is coaxial with the longitudinal axis of the capsule 100. Along its outer diameter the ring 120 is joint to the inner wall of the shell 102. Concentrically within the ring 120, a second ring 121 is disposed having an outer diameter corresponding to the inner diameter of the first ring 120. The inner ring 121 is coaxially rotatable within the stationary ring 120 under the action of an electric driving means 122 such as a magnet coil. The capsule 100 further comprises two fins 123 with the shape of a circle segment. The fin 123 has one end with two projections 124, 125, each provided with an opening. Through the opening in the projection 125 closest to the outer surface of the capsule 100, a pivot pin 126 joins the fin 123 with the stationary ring 120. The inner ring 121 is provided with a radial slot 127 provided with a slider pin 128 pivotably connected to the fin 123. Upon activation by driving means 122 the inner ring rotates relative to the stationary ring 120. This movement forces the slider pin 128 to slide to the other end of the slot 127. As a result, the fin 123 turns outwardly to an unfolded position, as shown in figure ID. The fin 123 is shaped as a C-shaped segment having an outer edge with a radius corresponding to the outer radius of the capsule 100. In the folded position, as shown in figure 1C, the fin 123 is sunk in the capsule 100 and the outer edge of the fin 123 is flush with the outer surface of the capsule 100. The fin can be made of a flexible material, e.g., the same or a similar material as listed above for the outer shell 102.

The described embodiment of the present invention is intended to be illustrative rather than restrictive, and is not intended to represent every embodiment of the present invention. Various modifications and variations can be made without departing from the spirit or scope of the disclosure as set forth in the following claims both literally and in equivalents recognized in law.

Claims

CLAIMS:
1. An ingestible capsule (100) comprising at least one fin (123) pivotable about a pivot pin (126) between a folded position and an unfolded position; control circuitry for controlling folding and unfolding of the fin (123).
2. Capsule according to claim 1 wherein the capsule (100) comprises a first ring (120) and a concentric second ring (121) which are concentrically rotatable relative to each other; and wherein the pivot pin (126) connects the fin to the first ring and a slider pin (128) is pivotably connected to the fin (123) and slideably engaged in a lot (127) in the second ring (121).
3. Capsule according to claim 2 wherein the first ring is a stationary outer ring (120) and the second ring is a rotatable inner ring (121).
4. Capsule according to claim 3 wherein the outer diameter of the stationary ring
(120) is flush with the outer surface of the capsule (1).
5. Capsule according to any one of the preceding claims wherein the fins (123) are made of a flexible bio -compatible plastic.
6. Capsule according to any one of the preceding claims wherein a pliant membrane envelopes the fins (123).
7. Capsule according to any one of the preceding claims wherein the capsule (1) comprises a processor programmed to unfold the at least one unfoldable members (123) responsive to a signal issued by a sensor after detecting a condition typical for the stomach environment.
8. Capsule according to claim 7 wherein the capsule (1) contains particles of a therapeutic compound coated with a gastroresistant enteric coating.
PCT/IB2008/054675 2007-11-13 2008-11-07 Ingestible electronic capsule WO2009063377A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US98748207P true 2007-11-13 2007-11-13
US60/987,482 2007-11-13

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