WO1992005822A1 - Medical capsule device actuated by rf signal - Google Patents

Medical capsule device actuated by rf signal Download PDF

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Publication number
WO1992005822A1
WO1992005822A1 PCT/US1991/007078 US9107078W WO9205822A1 WO 1992005822 A1 WO1992005822 A1 WO 1992005822A1 US 9107078 W US9107078 W US 9107078W WO 9205822 A1 WO9205822 A1 WO 9205822A1
Authority
WO
WIPO (PCT)
Prior art keywords
apertures
actuator
capsule body
sleeve member
capsule
Prior art date
Application number
PCT/US1991/007078
Other languages
French (fr)
Inventor
Robert A. Casper
Michael L. Mccartney
Warren J. Jochem
Alan F. Parr
Original Assignee
Glaxo Inc.
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
Application filed by Glaxo Inc. filed Critical Glaxo Inc.
Publication of WO1992005822A1 publication Critical patent/WO1992005822A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/07—Endoradiosondes
    • A61B5/073—Intestinal transmitters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B2010/0061—Alimentary tract secretions, e.g. biliary, gastric, intestinal, pancreatic secretions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0014—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof using shape memory or superelastic materials, e.g. nitinol
    • A61F2210/0023—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof using shape memory or superelastic materials, e.g. nitinol operated at different temperatures whilst inside or touching the human body, heated or cooled by external energy source or cold supply

Definitions

  • the present invention relates to an improved medical capsule device, and more particularly to an improved medical capsule device adapted for use to release and/or collect a substance at a defined location in the gastrointestinal tract.
  • nasogastric catheters are often used to deliver a drug to a target site within the gastrointestinal tract as a means of evaluating the absorption thereof. While this is a direct and highly accurate means of establishing the relationship between location and absorption, it does pose some uncertainties.
  • the procedure of insertion of the catheter can result in the release of catecholimines in the subject, and it could introduce responses which would interfere with the absorption or action of the drug.
  • the presence of the catheter in the gastrointestinal tract can cause local mechanical disturbances which further distort the responses to the drug.
  • One conventional solution to the problem of site- specific drug delivery is to place the drug in an untethered ingestible enclosure and to thereafter release the drug by remote control.
  • the location of the drug prior to release can be continuously monitored by radio- graphic methods such as X-ray or scintigraphy as well as by radio-frequency (RF) goniometry.
  • radio- graphic methods such as X-ray or scintigraphy as well as by radio-frequency (RF) goniometry.
  • U.S. Patent No. 4,425,117 to Hugeman et al. discloses a remote control drug release capsule which is actuated by application of a radio-frequency signal thereto.
  • the radio-frequency energy serves to heat a thin wire within the capsule which in turn burns through a thread so as to release a spring-actuated lance.
  • the lance is driven into a latex sphere contained within the capsule which is filled with a pharmaceutical drug and thereby releases the drug into the environment of the capsule.
  • this complex capsule device has been found to be very difficult to load with a drug since the latex sphere must be filled under slight pressure and then sealed.
  • the capsule device comprises a capsule body defining a chamber therein and a through-hole at the top thereof which is dimensioned so that it prevents medical fluid contained in the chamber from easily leaking.
  • a slidably movable piston is positioned within the body member so as to move axially in the chamber from a liquid-receiving position to a liquid-pushing position.
  • the piston is actuated by a shape memory alloy helical spring which will force the piston to the liquid-pushing position when heated by ultrasonic waves applied from a remote ultrasonic heating means.
  • This capsule has certain shortcomings in view of the ultrasonic actuation as well as the drug release from only a single aperture which could possibly render specific site application more difficult in the gastrointestinal tract. Also, the high concentration of drug at the singular release site could potentially be damaging to the intestinal mucosa.
  • the present invention is therefore intended to eliminate the shortcomings of these and other remote control drug delivery capsules and to provide a remote control drug delivery capsule device which is safe and reliable in use and possesses capabilities not heretofore known. Disclosure of the Invention
  • the medical capsule device comprises a capsule body having one or more apertures in the circumferential wall thereof.
  • a rotatably movable sleeve member is positioned within the capsule body which has one or more apertures in the circumferential wall thereof corresponding to the apertures in the capsule body, and the sleeve member is rotatably movable either from a closed position at which the apertures thereof are not in circumferential registration with the capsule body apertures to an open position at which the apertures thereof are in circumferential registration with the capsule body apertures or from the open position to the closed position.
  • An actuator means is positioned in the sleeve member for providing rotatable movement to the sleeve member from the closed position to the open position or vice versa wherein a drug may be released from the capsule or an external substance collected by the capsule.
  • the actuator means comprises (1) a circuit tuned to a magnetic field of high frequency comprising a coil and capacitor electrically connected to a heatable resistance member and (2) an actuator member which is operatively associated with the circuit and made of a shape memory alloy responsive to heat applied thereto by the resistance member so as to move from a non-heated first shape to a heated second shape.
  • An actuator stop means associated with the capsule body is provided for being engaged by th_ actuator member during movement from its non-heated first shape to its heated second shape so that the actuator member movement will thereby serve to rotatably move the sleeve member relative to the capsule body either from the closed position to the open position or from the open position to the closed position.
  • drugs e.g., anti-ulcer and chemotherapeutic drugs
  • Figure 1 is a perspective view of a medical capsule device according to the present invention.
  • Figure 2 is an exploded view of the capsule device
  • Figure 3 is a vertical cross-sectional view of the capsule device
  • Figure 4 is an enlarged view of the actuator mechanism for opening the apertures in the capsule device
  • Figures 5A and 5B are taken on the lines A-A and B-B of Figures 2 and 3 and show the capsule device in its closed position prior to actuation by application of a magnetic field;
  • Figures 6A and 6B are taken on the lines A-A and B-B of Figures 2 and 3 and show the capsule device in its open position subsequent to actuation by application of a magnetic field; and Figure 7 is a schematic diagram of the circuit of the capsule device for receiving radio-frequency (RF) signals when a magnetic field is applied thereto.
  • RF radio-frequency
  • Figures 1-3 show an embodiment of the present invention which is generally designated 10. Although applicant hereinafter describes in specific detail capsule device 10 capable of being actuated to move from a closed to an open or drug release mode, applicant contemplates that the instant invention also includes the embodiment of the capsule device capable of being actuated to move from an open to a closed or material collection mode.
  • Capsule device 10 includes a capsule body 12 and a sleeve member 14 which is slidably received and rotatably mounted within capsule body 12.
  • Capsule body 12 and sleeve member 14 each include a plurality of apertures, 12A and 14A, respectively, which are in circumferential registration when capsule device 10 is actuated and sleeve member 14 rotates therein to the capsule's open position.
  • An actuator mechanism 16 resides in the top portion of sleeve member 14 and is separated from the bottom portion of sleeve member 14 by a fluid impermeable wall or partition 14B.
  • a pair of retainer wires 20 are fixedly positioned within retainer wire groove 12B defined around the inner surface of the top of capsule body 12.
  • Retainer wires 20 serve as a fulcrum when actuator mechanism 16 is energized by heat derived from a magnetic field and thereby imparts rotatable movement to sleeve member 14 to which it is secured.
  • a cap 22 is provided to seal the top of the capsule when sleeve member 14 is positioned therein, and a fill plug 24 is provided in an aperture 12C in the bottom of capsule body 12 in order to facilitate introduction of a selected material and/or removal of a collected material.
  • capsule body 12, sleeve member 14, cap 22 and fill plug 24 may be formed from a PTFE compound (e.g., TEFLON) or acetal resin (e.g., DELRIN) although any other radio-frequency transparent materials could suitably be used.
  • a PTFE compound e.g., TEFLON
  • acetal resin e.g., DELRIN
  • Three copper wire coils 16A-16C are orthogonally wound around a common ferrite core C.
  • Ferrite core C serves to increase the effective cross- sectional area of coils 16A-16C and to thereby provide for the interception of more flux from the magnetic field transmitter (not shown) and minimize the dependence of received radio-frequency signal energy on the orientation of capsule device 10 within the gastrointestinal tract.
  • coils 16A-16C are tuned to the transmitter frequency with capacitors so as to apply the received radio-frequenci signal directly to resistive heaters 16D- 16F (for example. Bourns CR1206 brand 1000 ohm resistors) without the necessity of rectification and filtering of the signal.
  • Resistive heaters 16D-16F are mounted on circuit board 16G which is in turn secured to metallic heat plate 16H by a screw S passing through circuit board 16G and into a tapped hole 16H' in metallic heat plate 16H.
  • Resistive heaters 16D-16F are each electrically connected to a respective one of coils 16A-16C by corresponding capacitors 16K-16M mounted beneath circuit board 16G so that any magnetic flux received by one or more of respective coils 16A-16C will induce an RF current which will be converted to heat by resistive heaters 16D-16F and applied to heat plate 16H.
  • Thermally conductive grease (not shown) is used to improve thermal energy transfer between resistive heaters 16D-16F and metallic heat plate 16H.
  • Two shape memory metal fingers 161, 16J are each secured at one respective end thereof to heat plate l €H, and each extends across and parallel with heat plate 16H. Thermally conductive grease is also used to insure good thermal contact between metal fingers 161, 16J and heat plate 16H. Although many materials would be suitable for forming fingers 161, 16J, nickel titanium was used for the instant invention.
  • fingers 161, 16J from shape memory alloys since the material can be made to have a transition temperature in the range of normal mammalian body temperatures. This is advantageous since the shape or configuration transition occurs relatively abruptly with temperature, and it is generally necessary to elevate the temperature of fingers 161, 16J only a few degrees to effect rotatable movement of sleeve member 14 within capsule body 12. This is desirable for an ingestible device such as capsule device 10 since it is not necessary to raise the temperature of any part of device 10 significantly above that of the body temperature to cause actuation thereof, and thus the total energy delivered can be limited to a safe, nominal amount.
  • actuator mechanism 16 and sleeve member 14 essentially serve as a sleeve valve to release a drug or other substance from the reservoir space in capsule device 10 defined generally between the lower compartment of sleeve member 14 and capsule body 12.
  • Shape memory alloy fingers 161, 16J will tend to straighten when acted on by heat from resistive heaters 16D-16F and by applying force against retainer wires 20 (see Figures 5A-5B and 6A-6B) will thus serve to rotate sleeve member 14 within capsule body 12.
  • This movement opens the capsule by positioning apertures 14A of sleeve member 14 and apertures 12A of capsule body 12 in circumferential registration (or, in an alternative embodiment of the instant invention, closes the open capsule by moving apertures 14A and 12A out of circumferential registration) .
  • the sleeve valve takes advantage of the relatively large aperture area which may be achieved with only a small rotational relative displacement of sleeve member 14 within capsule body 12.
  • the instant invention may be made with only a single through-put aperture in capsule device 10, preferably a plurality of apertures are provided around the circumference of sleeve member 14 and capsule body 12 to (1) assure that the release time of a drug carried thereby is not dependent on the orientation of the capsule device in the gastrointestinal tract and (2) to decrease the possible negative effects of high drug concentration on the gastrointestinal mucosa.
  • capsule device 10 may most suitably be determined by scintigraphy.
  • the device may be followed in the gastrointestinal tract with a conventional scintigraphic imaging system. Radioactive material could also be placed on capsule device 10 in order to follow the capsule as well as the drug released thereby.
  • Other methodology to Determine the movement and location of capsule device 10 in the gastrointestinal tract would include X-ray, radar and sonar techniques which would be familiar to those skilled in the art.
  • the external transmitter for creating a high-frequency magnetic field to actuate capsule device 10 will be an electrostatically shielded coil which is energized by a radio-frequency power amplifier. Electrostatic shielding should be used to remove the large electrical field generated in the vicinity of the coil and thereby prevent electrical shock hazards and dielectric heating of tissues associated with the fields. The shielding results in a radio-frequency field which has only a magnetic component.
  • the external transmitter will be positioned in proximity to the body of a person or animal having ingested capsule device 10 and will generate a radio-frequency magnetic field at 6.78 MHz (a frequency set aside for industrial heating applications) which coils 16A-16C and capacitors 16K-16M have been tuned to receive.
  • Capsule device 10 may be used to evaluate the absorption of a drug from various sites of the gastrointestinal tract under non-invasive conditions. The information contained about regional drug absorption via the capsule device will aid in future development of complex site-specific drug dosage forms. Another application for capsule device 10 would be to sample the liquid environment of the gastrointestinal tract. This would permit the monitoring of drugs, enzymes, and bacteria as well as other intestinal compounds under non- invasive conditions. For this application, capsule device 10 would be administered orally as with the first described application but would be empty and the apertures open when administered so as to collect the desired gastrointestinal tract samples when actuated and the apertures closed by the high-frequency magnetic field created by the external transmitter located outside of but proximate to the body.
  • capsule device 10 would be to deliver highly toxic drugs to specific sites in the gastrointestinal tract in a clinical setting.
  • the capsule device could be used to deliver chemotherapeutic drugs to the colon of patients who have colon cancer as well as to deliver drugs that are effective at treating ulcerative colitis of the colon but which are irritating to the small intestine.
  • capsule device 10 would be administered and function in the same manner as under the first application.

Abstract

A medical capsule device (10) for releasing and/or collecting a substance at a defined location in the gastrointestinal tract. The device has a capsule body (12) defining one or more apertures in the circumferential wall thereof and a sleeve valve rotatably positioned therein having one or more corresponding apertures in the circumferential wall thereof. The sleeve valve comprises a coil and electrically connected heatable resistor which are operatively associated with an actuator member (16J, 16I) formed of a shape memory alloy responsive to heat and which will move from a non-heated first shape to a heated second shape. Actuator stop means (20) are provided in the capsule body for being engaged by the actuator member during movement from the non-heated first shape to the heated second shape so that the actuator member movement will serve to rotate the sleeve valve to either an open or closed position.

Description

Description
Medical CapsuleDe iceActuated by RF Signal
Technical Field
The present invention relates to an improved medical capsule device, and more particularly to an improved medical capsule device adapted for use to release and/or collect a substance at a defined location in the gastrointestinal tract.
Related Art
The delivery of drugs to specific sites within the gastrointestinal tract of humans as well as animals is a challenge in both clinical and research applications. During the research phase of pharmaceutical drug development, nasogastric catheters are often used to deliver a drug to a target site within the gastrointestinal tract as a means of evaluating the absorption thereof. While this is a direct and highly accurate means of establishing the relationship between location and absorption, it does pose some uncertainties. The procedure of insertion of the catheter can result in the release of catecholimines in the subject, and it could introduce responses which would interfere with the absorption or action of the drug. Moreover, the presence of the catheter in the gastrointestinal tract can cause local mechanical disturbances which further distort the responses to the drug.
One conventional solution to the problem of site- specific drug delivery is to place the drug in an untethered ingestible enclosure and to thereafter release the drug by remote control. The location of the drug prior to release can be continuously monitored by radio- graphic methods such as X-ray or scintigraphy as well as by radio-frequency (RF) goniometry.
Several conventional remote control drug release capsules are well known to those skilled in the art. For example, U.S. Patent No. 4,425,117 to Hugeman et al. discloses a remote control drug release capsule which is actuated by application of a radio-frequency signal thereto. The radio-frequency energy serves to heat a thin wire within the capsule which in turn burns through a thread so as to release a spring-actuated lance. The lance is driven into a latex sphere contained within the capsule which is filled with a pharmaceutical drug and thereby releases the drug into the environment of the capsule. However, this complex capsule device has been found to be very difficult to load with a drug since the latex sphere must be filled under slight pressure and then sealed. Another conventional, remote-control medical capsule device is disclosed in U.S. Patent No. 4,507,115 to Kambara et al. The capsule device comprises a capsule body defining a chamber therein and a through-hole at the top thereof which is dimensioned so that it prevents medical fluid contained in the chamber from easily leaking. A slidably movable piston is positioned within the body member so as to move axially in the chamber from a liquid-receiving position to a liquid-pushing position. The piston is actuated by a shape memory alloy helical spring which will force the piston to the liquid-pushing position when heated by ultrasonic waves applied from a remote ultrasonic heating means. This capsule has certain shortcomings in view of the ultrasonic actuation as well as the drug release from only a single aperture which could possibly render specific site application more difficult in the gastrointestinal tract. Also, the high concentration of drug at the singular release site could potentially be damaging to the intestinal mucosa.
The present invention is therefore intended to eliminate the shortcomings of these and other remote control drug delivery capsules and to provide a remote control drug delivery capsule device which is safe and reliable in use and possesses capabilities not heretofore known. Disclosure of the Invention
The medical capsule device according to the invention comprises a capsule body having one or more apertures in the circumferential wall thereof. A rotatably movable sleeve member is positioned within the capsule body which has one or more apertures in the circumferential wall thereof corresponding to the apertures in the capsule body, and the sleeve member is rotatably movable either from a closed position at which the apertures thereof are not in circumferential registration with the capsule body apertures to an open position at which the apertures thereof are in circumferential registration with the capsule body apertures or from the open position to the closed position.
An actuator means is positioned in the sleeve member for providing rotatable movement to the sleeve member from the closed position to the open position or vice versa wherein a drug may be released from the capsule or an external substance collected by the capsule. The actuator means comprises (1) a circuit tuned to a magnetic field of high frequency comprising a coil and capacitor electrically connected to a heatable resistance member and (2) an actuator member which is operatively associated with the circuit and made of a shape memory alloy responsive to heat applied thereto by the resistance member so as to move from a non-heated first shape to a heated second shape. An actuator stop means associated with the capsule body is provided for being engaged by th_ actuator member during movement from its non-heated first shape to its heated second shape so that the actuator member movement will thereby serve to rotatably move the sleeve member relative to the capsule body either from the closed position to the open position or from the open position to the closed position.
It is therefore the object of this invention to provide a remote control medical capsule device which will safely and reliably release and/or collect a substance at a predetermined location in the gastrointestinal tract of a human or animal.
It is another object of the present invention to provide a remote control medical capsule device which will safely and precisely deliver drugs (e.g., anti-ulcer and chemotherapeutic drugs) to specific predetermined sites in the gastrointestinal tract.
It is yet another object of the present invention to provide a remote control medical capsule device which is adapted to be easily actuated and to provide a large aperture area upon actuation thereof.
It is yet another object of the present invention to provide a remote control medical capsule device which is adapted to receive and be actuated by a radio-frequency signal regardless of the orientation of the device within the gastrointestinal tract.
Some of the objects of the invention having been stated, other objects will become evident as the description proceeds, when taken in connection with the accompanying drawings.
Brief Description of the Drawings
Figure 1 is a perspective view of a medical capsule device according to the present invention;
Figure 2 is an exploded view of the capsule device;
Figure 3 is a vertical cross-sectional view of the capsule device;
Figure 4 is an enlarged view of the actuator mechanism for opening the apertures in the capsule device;
Figures 5A and 5B are taken on the lines A-A and B-B of Figures 2 and 3 and show the capsule device in its closed position prior to actuation by application of a magnetic field;
Figures 6A and 6B are taken on the lines A-A and B-B of Figures 2 and 3 and show the capsule device in its open position subsequent to actuation by application of a magnetic field; and Figure 7 is a schematic diagram of the circuit of the capsule device for receiving radio-frequency (RF) signals when a magnetic field is applied thereto.
Best Mode for Carrying Out the Invention
Referring now more specifically to the drawings.
Figures 1-3 show an embodiment of the present invention which is generally designated 10. Although applicant hereinafter describes in specific detail capsule device 10 capable of being actuated to move from a closed to an open or drug release mode, applicant contemplates that the instant invention also includes the embodiment of the capsule device capable of being actuated to move from an open to a closed or material collection mode.
Capsule device 10 includes a capsule body 12 and a sleeve member 14 which is slidably received and rotatably mounted within capsule body 12. Capsule body 12 and sleeve member 14 each include a plurality of apertures, 12A and 14A, respectively, which are in circumferential registration when capsule device 10 is actuated and sleeve member 14 rotates therein to the capsule's open position. An actuator mechanism 16 resides in the top portion of sleeve member 14 and is separated from the bottom portion of sleeve member 14 by a fluid impermeable wall or partition 14B. A pair of retainer wires 20 are fixedly positioned within retainer wire groove 12B defined around the inner surface of the top of capsule body 12. Retainer wires 20 serve as a fulcrum when actuator mechanism 16 is energized by heat derived from a magnetic field and thereby imparts rotatable movement to sleeve member 14 to which it is secured. A cap 22 is provided to seal the top of the capsule when sleeve member 14 is positioned therein, and a fill plug 24 is provided in an aperture 12C in the bottom of capsule body 12 in order to facilitate introduction of a selected material and/or removal of a collected material. It is presently contemplated that capsule body 12, sleeve member 14, cap 22 and fill plug 24 may be formed from a PTFE compound (e.g., TEFLON) or acetal resin (e.g., DELRIN) although any other radio-frequency transparent materials could suitably be used.
With specific reference now to Figures 4 and 7, actuator mechanism 16 will be described in more detail for a more complete appreciation of the instant invention. Three copper wire coils 16A-16C (see Figure 4) are orthogonally wound around a common ferrite core C. Ferrite core C serves to increase the effective cross- sectional area of coils 16A-16C and to thereby provide for the interception of more flux from the magnetic field transmitter (not shown) and minimize the dependence of received radio-frequency signal energy on the orientation of capsule device 10 within the gastrointestinal tract.
Most suitably, coils 16A-16C are tuned to the transmitter frequency with capacitors so as to apply the received radio-frequenci signal directly to resistive heaters 16D- 16F (for example. Bourns CR1206 brand 1000 ohm resistors) without the necessity of rectification and filtering of the signal. Resistive heaters 16D-16F are mounted on circuit board 16G which is in turn secured to metallic heat plate 16H by a screw S passing through circuit board 16G and into a tapped hole 16H' in metallic heat plate 16H. Resistive heaters 16D-16F are each electrically connected to a respective one of coils 16A-16C by corresponding capacitors 16K-16M mounted beneath circuit board 16G so that any magnetic flux received by one or more of respective coils 16A-16C will induce an RF current which will be converted to heat by resistive heaters 16D-16F and applied to heat plate 16H. Thermally conductive grease (not shown) is used to improve thermal energy transfer between resistive heaters 16D-16F and metallic heat plate 16H. Two shape memory metal fingers 161, 16J are each secured at one respective end thereof to heat plate l€H, and each extends across and parallel with heat plate 16H. Thermally conductive grease is also used to insure good thermal contact between metal fingers 161, 16J and heat plate 16H. Although many materials would be suitable for forming fingers 161, 16J, nickel titanium was used for the instant invention.
It is desirable to form fingers 161, 16J from shape memory alloys since the material can be made to have a transition temperature in the range of normal mammalian body temperatures. This is advantageous since the shape or configuration transition occurs relatively abruptly with temperature, and it is generally necessary to elevate the temperature of fingers 161, 16J only a few degrees to effect rotatable movement of sleeve member 14 within capsule body 12. This is desirable for an ingestible device such as capsule device 10 since it is not necessary to raise the temperature of any part of device 10 significantly above that of the body temperature to cause actuation thereof, and thus the total energy delivered can be limited to a safe, nominal amount.
As can now be appreciated, actuator mechanism 16 and sleeve member 14 essentially serve as a sleeve valve to release a drug or other substance from the reservoir space in capsule device 10 defined generally between the lower compartment of sleeve member 14 and capsule body 12. Shape memory alloy fingers 161, 16J will tend to straighten when acted on by heat from resistive heaters 16D-16F and by applying force against retainer wires 20 (see Figures 5A-5B and 6A-6B) will thus serve to rotate sleeve member 14 within capsule body 12. This movement opens the capsule by positioning apertures 14A of sleeve member 14 and apertures 12A of capsule body 12 in circumferential registration (or, in an alternative embodiment of the instant invention, closes the open capsule by moving apertures 14A and 12A out of circumferential registration) . The sleeve valve takes advantage of the relatively large aperture area which may be achieved with only a small rotational relative displacement of sleeve member 14 within capsule body 12. Though the instant invention may be made with only a single through-put aperture in capsule device 10, preferably a plurality of apertures are provided around the circumference of sleeve member 14 and capsule body 12 to (1) assure that the release time of a drug carried thereby is not dependent on the orientation of the capsule device in the gastrointestinal tract and (2) to decrease the possible negative effects of high drug concentration on the gastrointestinal mucosa.
Although other means are possible, location of capsule device 10 may most suitably be determined by scintigraphy. By introducing a small amount of radioactive material into the drug or other material carried by capsule device 10, the device may be followed in the gastrointestinal tract with a conventional scintigraphic imaging system. Radioactive material could also be placed on capsule device 10 in order to follow the capsule as well as the drug released thereby. Other methodology to Determine the movement and location of capsule device 10 in the gastrointestinal tract would include X-ray, radar and sonar techniques which would be familiar to those skilled in the art. While not shown in the drawings and not a per se element of the instant invention, it is contemplated that the external transmitter for creating a high-frequency magnetic field to actuate capsule device 10 will be an electrostatically shielded coil which is energized by a radio-frequency power amplifier. Electrostatic shielding should be used to remove the large electrical field generated in the vicinity of the coil and thereby prevent electrical shock hazards and dielectric heating of tissues associated with the fields. The shielding results in a radio-frequency field which has only a magnetic component. Most suitably, the external transmitter will be positioned in proximity to the body of a person or animal having ingested capsule device 10 and will generate a radio-frequency magnetic field at 6.78 MHz (a frequency set aside for industrial heating applications) which coils 16A-16C and capacitors 16K-16M have been tuned to receive.
Applications for the Capsule Device
Capsule device 10 may be used to evaluate the absorption of a drug from various sites of the gastrointestinal tract under non-invasive conditions. The information contained about regional drug absorption via the capsule device will aid in future development of complex site-specific drug dosage forms. Another application for capsule device 10 would be to sample the liquid environment of the gastrointestinal tract. This would permit the monitoring of drugs, enzymes, and bacteria as well as other intestinal compounds under non- invasive conditions. For this application, capsule device 10 would be administered orally as with the first described application but would be empty and the apertures open when administered so as to collect the desired gastrointestinal tract samples when actuated and the apertures closed by the high-frequency magnetic field created by the external transmitter located outside of but proximate to the body. Yet another application of capsule device 10 would be to deliver highly toxic drugs to specific sites in the gastrointestinal tract in a clinical setting. For example, the capsule device could be used to deliver chemotherapeutic drugs to the colon of patients who have colon cancer as well as to deliver drugs that are effective at treating ulcerative colitis of the colon but which are irritating to the small intestine. In this application, capsule device 10 would be administered and function in the same manner as under the first application.
It will be understood that various details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation—the invention being defined by the claims.

Claims

ClaimsWhat is claimed is:
1. A medical capsule device adapted for release and/or collection of a substance at a defined location in 5 the alimentary tract, said device comprising:
a capsule body defining one or more apertures in the circumferential wall thereof;
a rotatably movable sleeve member positioned within said capsule body and defining one or more
10 apertures in the circumferential wall thereof corresponding to said apertures in said capsule body, said sleeve member adapted to be rotatably movable either from a closed position at which said apertures thereof are not in registration
15 with said capsule body apertures to an open position at which said apertures thereof are in registration with said capsule body apertures or from said open position to said closed position;
actuator means positioned in said sleeve member for 20 rotatably moving said sleeve member and comprising (1) a circuit receptive to an alternating magnetic field and operatively associated with (2) an actuator member made of a shape memory alloy responsive to heat obtained 25 from said circuit so as to move from a non- heated first shape to a heated second shape; and actuator stop means associated with said capsule body for being engaged by said actuator member during movement from said non-heated first shape to said heated second shape so that said actuator member movement will thereby serve to rotatably move said sleeve member either from said closed position to said open position or from said open position to said closed position.
2. A medical capsule device according to claim 1 wherein said capsule body defines a plurality of spaced- apart apertures around the circumference thereof.
3. A medical capsule device according to claim 1 wherein said capsule body includes a removable plug at one end thereof to facilitate the insertion of a substance therein or the removal of a substance therefrom.
4. A medical capsule device according to claim 3 wherein said capsule body further includes a removable cap at the other end thereof to facilitate insertion and removal of said sleeve member therefrom.
5. A medical capsule device according to claim 1 wherein said sleeve member defines a first open compartment at one end for receiving said actuator means and a second open compartment at the other end for receiving a substance to be released and/or collected, said compartments being separated by a fluid impermeable wall therebetween and said one or more apertures being located in the circumferential wall of said second compartment.
6. A medical capsule device according to claim 5 wherein said one or more apertures in said sleeve member comprises a plurality of spaced-apart apertures around the circumference of said second open compartment thereof.
7. A medical capsule device according to claim 1 wherein said circuit comprises a ferrite core having three coils orthogonally wound thereon wherein each coil is electrically connected to a respective capacitor and a respective heatable resistor.
8. A medical capsule device according to claim 7 wherein a heat conductive plate is operatively connected to said heatable resistors and said actuator member comprises a pair of spaced-apart arcuate arms each being secured at one end to said heat conductive plate and being adapted to engage said actuator stop means with the other end thereof, said arms each extending parallel to said heat conductive plate with its stop means-engaging end terminating adjacent the perimeter of said heat conductive plate.
9. A medical capsule device according to claim 1 wherein said actuator stop means comprises a wire element adapted to fit within said capsule body and against a portion of the inner surface thereof, said wire element having one end thereof turned radially inwardly to be engaged by said actuator member.
10. A medical capsule device according to claims 8 and 9 wherein said actuator stop means comprises two of said wire elements in adjacent relationship within said groove wherein the inwardly turned end of one wire element is adjacent the non-inwardly turned end of the other wire element, said inwardly turned ends of said wire elements each being operatively engaged by a respective one of said pair of arcuate arms.
11. A medical capsule device adapted for release and/or collection of a substance at a defined location in the alimentary tract, said device comprising:
a capsule body defining a plurality of spaced-apart apertures in the circumferential wall thereof;
a rotatably movable sleeve member positioned within said capsule body and defining a plurality of spaced-apart apertures in the circumferential wall thereof corresponding to said apertures in said capsule body, said sleeve member adapted to be rotatably movable either from a closed position at which said apertures thereof are not in registration with said capsule body apertures to an open position at which said apertures thereof are in registration with said capsule body apertures or from said open position to said closed position;
actuator means positioned in said sleeve member for rotatably moving said sleeve member and comprising (1) a circuit receptive to a magnetic field of high frequency and having a ferrite core with a plurality of coils orthogonally wound thereon wherein each coil is electrically connected to a respective tuning capacitor and a respective heatable resistor and (2) an actuator member operatively associated with said circuit and made of a shape memory alloy responsive to heat applied thereto by said resistors so as to move from a non-heated first configuration to a heated second configuration; and
actuator stop means associated with the inner surface of said capsule body for being engaged by said actuator member during movement from said non-heated first configuration to said heated second configuration so that said actuator member movement will thereby serve to rotatably move said sleeve member either from said closed position to said open position or from said open position to said closed position.
12. A medical capsule device according to claim 11 wherein said capsule body includes a removable plug at one end thereof to facilitate the insertion of a substance therein or the removal of a substance therefrom.
13. A medical capsule device according to claim 12 wherein said capsule body further includes a removable cap at the other end thereof to facilitate insertion and removal of said sleeve member therefrom.
14. A medical capsule device according to claim 11 wherein said sleeve member defines a first open compartment at one end for receiving said actuator means and a second open compartment at the other end for receiving a substance to be released and/or collected, said compartments being separated by a fluid impermeable wall therebetween and said plurality of apertures being located in the circumferential wall of said second compartment.
15. A medical capsule device according to claim 11 wherein said coils are tuned to receive a 6.78 MHz radio- frequency signal.
16. A medical capsule device according to claim 15 wherein a heat conductive plate is operatively connected to said heatable resistors and said actuator member comprises a pair of spaced-apart arcuate arms each being secured at one end to said heat conductive plate and being adapted to engage said actuator stop means with the other end thereof, said arms each extending parallel to said heat conductive plate with its stop means-engaging
SUBSTITUTE SHEET end terminating adjacent the perimeter of said heat conductive plate.
17. A medical capsule device according to claim 11 wherein said actuator stop means comprises a wire element adapted to fit within said capsule body in a groove around the inner surface thereof, said wire element having one end thereof turned radially inwardly to be engaged by said actuator member.
18. A medical capsule device according to claims 16 and 17 wherein said actuator stop means comprises two of said wire elements in adjacent relationship within said groove wherein the inwardly turned end of one wire element is adjacent the non-inwardly turned end of the other wire element, said inwardly turned ends of said wire elements each being operatively engaged by a respective one of said pair of arcuate arms.
19. A medical capsule device according to claim 11 wherein said actuator member is formed of nickel titanium and said capsule body and sleeve member are formed of TEFLON.
PCT/US1991/007078 1990-10-02 1991-09-26 Medical capsule device actuated by rf signal WO1992005822A1 (en)

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US07/591,838 US5170801A (en) 1990-10-02 1990-10-02 Medical capsule device actuated by radio-frequency (rf) signal
US591,838 1990-10-02

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5316015A (en) * 1992-07-30 1994-05-31 Sinaiko Robert J Externally controlled intestinal content sampler
EP0662304A1 (en) * 1994-01-10 1995-07-12 The Research Foundation Of State University Of New York Sampling capsule and process
DE10302614A1 (en) * 2003-01-24 2004-11-18 Innovent E.V. Releasing device use for releasing therapeutic or diagnostically effective substances in digestive tract, has magnetic caps biased to closed state by spring such that caps are opened by application of magnetic force
US7500951B2 (en) 2004-01-16 2009-03-10 Olympus Corporation Lesion detecting system
US8147482B2 (en) 2006-06-20 2012-04-03 MEDIMETRICS Personalized Drug Delivery B.V. Electronic capsule for treating gastrointestinal disease
WO2023211394A1 (en) * 2022-04-29 2023-11-02 Mersi̇n Üni̇versi̇tesi̇ A local treatment kit in the form of an intra-organ capsule allowing local treatment in solid and hollow organ cancers

Families Citing this family (169)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5551953A (en) * 1994-10-31 1996-09-03 Alza Corporation Electrotransport system with remote telemetry link
US5778882A (en) * 1995-02-24 1998-07-14 Brigham And Women's Hospital Health monitoring system
US7070590B1 (en) 1996-07-02 2006-07-04 Massachusetts Institute Of Technology Microchip drug delivery devices
US5797898A (en) * 1996-07-02 1998-08-25 Massachusetts Institute Of Technology Microchip drug delivery devices
US6703197B1 (en) * 1996-11-27 2004-03-09 Martinex R&D, Inc. Human methionine synthase: cloning, and methods for evaluating risk of neural tube defects, cardiovascular disease, and cancer
US7114502B2 (en) * 1997-02-26 2006-10-03 Alfred E. Mann Foundation For Scientific Research Battery-powered patient implantable device
US6164284A (en) * 1997-02-26 2000-12-26 Schulman; Joseph H. System of implantable devices for monitoring and/or affecting body parameters
AU6667698A (en) * 1997-02-26 1998-09-18 Alfred E. Mann Foundation For Scientific Research Battery-powered patient implantable device
US6001090A (en) * 1998-02-09 1999-12-14 Lenhart; Douglas Thermal pharmaceutical delivery system
AUPP247798A0 (en) * 1998-03-18 1998-04-23 Rudduck, Dickory Fixing and release systems
US6149664A (en) * 1998-08-27 2000-11-21 Micrus Corporation Shape memory pusher introducer for vasoocclusive devices
US6500149B2 (en) 1998-08-31 2002-12-31 Deepak Gandhi Apparatus for deployment of micro-coil using a catheter
US6224610B1 (en) 1998-08-31 2001-05-01 Micrus Corporation Shape memory polymer intravascular delivery system with heat transfer medium
US6165140A (en) 1998-12-28 2000-12-26 Micrus Corporation Composite guidewire
US6887235B2 (en) 1999-03-24 2005-05-03 Micrus Corporation Variable stiffness heating catheter
US6352531B1 (en) 1999-03-24 2002-03-05 Micrus Corporation Variable stiffness optical fiber shaft
FR2794654B1 (en) * 1999-06-08 2001-10-19 Ct De Transfert Des Microtechn DEVICE FOR RELEASING SUBSTANCES IN A DIGESTIVE TUBE
US9006175B2 (en) 1999-06-29 2015-04-14 Mannkind Corporation Potentiation of glucose elimination
BR0017519B8 (en) * 1999-07-23 2021-06-22 Mannkind Corp medicine capsule for an inhaler, and process for manufacturing a capsule comprising a powdered medicine.
US7305986B1 (en) 1999-07-23 2007-12-11 Mannkind Corporation Unit dose capsules for use in a dry powder inhaler
US7464706B2 (en) * 1999-07-23 2008-12-16 Mannkind Corporation Unit dose cartridge and dry powder inhaler
WO2001012157A1 (en) 1999-08-18 2001-02-22 Microchips, Inc. Thermally-activated microchip chemical delivery devices
US6491666B1 (en) 1999-11-17 2002-12-10 Microchips, Inc. Microfabricated devices for the delivery of molecules into a carrier fluid
AU782639B2 (en) * 1999-12-10 2005-08-18 Massachusetts Institute Of Technology Microchip devices for delivery of molecules and methods of fabrication thereof
GB9930000D0 (en) * 1999-12-21 2000-02-09 Phaeton Research Ltd An ingestible device
US6454759B2 (en) * 2000-02-28 2002-09-24 The Regents Of The University Of California Microfabricated injectable drug delivery system
WO2001064344A2 (en) * 2000-03-02 2001-09-07 Microchips, Inc. Microfabricated devices for the storage and selective exposure of chemicals and devices
US6682521B2 (en) * 2000-03-23 2004-01-27 Dennis N. Petrakis Temperature activated systems
WO2001091902A2 (en) 2000-05-30 2001-12-06 Massachusetts Institute Of Technology Methods and devices for sealing microchip reservoir devices
AUPQ861300A0 (en) * 2000-07-06 2000-08-03 Telezygology Pty Limited Mulit-function tool
EP1339312B1 (en) * 2000-10-10 2006-01-04 Microchips, Inc. Microchip reservoir devices using wireless transmission of power and data
US6632175B1 (en) 2000-11-08 2003-10-14 Hewlett-Packard Development Company, L.P. Swallowable data recorder capsule medical device
US6929636B1 (en) 2000-11-08 2005-08-16 Hewlett-Packard Development Company, L.P. Internal drug dispenser capsule medical device
JP4657577B2 (en) 2001-01-09 2011-03-23 マイクロチップス・インコーポレーテッド Flexible microchip device for ocular and other applications
US7655001B2 (en) * 2001-03-23 2010-02-02 Petrakis Dennis N Temperature responsive systems
US7445616B2 (en) * 2001-03-23 2008-11-04 Petrakis Dennis N Temperature responsive systems
WO2002089767A1 (en) 2001-05-03 2002-11-14 Massachusetts Eye And Ear Infirmary Implantable drug delivery device and use thereof
JP4149376B2 (en) * 2001-05-17 2008-09-10 フェールグクレーマン・アクチボラゲット Sampling apparatus and method for obtaining a sample of a body material
US6973718B2 (en) * 2001-05-30 2005-12-13 Microchips, Inc. Methods for conformal coating and sealing microchip reservoir devices
ATE371778T1 (en) * 2001-06-07 2007-09-15 Telezygology Inc ADJUSTING DEVICE AND COMPONENT
US7160258B2 (en) * 2001-06-26 2007-01-09 Entrack, Inc. Capsule and method for treating or diagnosing the intestinal tract
EP1399135B1 (en) * 2001-06-28 2004-12-29 Microchips, Inc. Methods for hermetically sealing microchip reservoir devices
JP4744026B2 (en) * 2001-07-30 2011-08-10 オリンパス株式会社 Capsule endoscope and capsule endoscope system
US6663615B1 (en) 2001-09-04 2003-12-16 The Ohio State University Dual stage microvalve and method of use
JP4681231B2 (en) 2002-03-20 2011-05-11 マンカインド コーポレイション Inhaler
JP3869291B2 (en) * 2002-03-25 2007-01-17 オリンパス株式会社 Capsule medical device
US20040193229A1 (en) * 2002-05-17 2004-09-30 Medtronic, Inc. Gastric electrical stimulation for treatment of gastro-esophageal reflux disease
US7600301B2 (en) 2002-06-19 2009-10-13 Telezygology, Inc. Fixing and release systems and fastener networks
US7001329B2 (en) * 2002-07-23 2006-02-21 Pentax Corporation Capsule endoscope guidance system, capsule endoscope holder, and capsule endoscope
US6776165B2 (en) * 2002-09-12 2004-08-17 The Regents Of The University Of California Magnetic navigation system for diagnosis, biopsy and drug delivery vehicles
WO2004041068A2 (en) * 2002-10-31 2004-05-21 Regents Of The University Of Colorado Guided capsule for wireless endoscopy, biopsy, and drug delivery
US20040143221A1 (en) * 2002-12-27 2004-07-22 Shadduck John H. Biomedical implant for sustained agent release
CN100438937C (en) * 2002-12-30 2008-12-03 重庆大学 Mini medicine releasing device
US20040267240A1 (en) * 2003-01-29 2004-12-30 Yossi Gross Active drug delivery in the gastrointestinal tract
US20050058701A1 (en) * 2003-01-29 2005-03-17 Yossi Gross Active drug delivery in the gastrointestinal tract
KR20050098277A (en) * 2003-01-29 2005-10-11 이-필 파마 리미티드 Active drug delivery in the gastrointestinal tract
US20040158194A1 (en) * 2003-02-06 2004-08-12 Wolff Andy And Beiski Ben Z. Oral devices and methods for controlled drug release
DE10310825B3 (en) * 2003-03-07 2004-08-19 Fachhochschule Jena Unit releasing pharmaceutical substances under remote control, includes cavity with magnetic rotor turned by magnetic field to generate heat through friction
US7476224B2 (en) * 2003-03-17 2009-01-13 Petrakis Dennis N Temperature responsive systems
US7186247B2 (en) * 2003-04-04 2007-03-06 Medtronic, Inc. Apparatus and system for delivery of drug therapies
US7620454B2 (en) * 2003-05-19 2009-11-17 Medtronic, Inc. Gastro-electric stimulation for reducing the acidity of gastric secretions or reducing the amounts thereof
US7742818B2 (en) * 2003-05-19 2010-06-22 Medtronic, Inc. Gastro-electric stimulation for increasing the acidity of gastric secretions or increasing the amounts thereof
ITTO20030390A1 (en) * 2003-05-27 2004-11-28 Fiat Ricerche RADIOFREQUENCY CONTROLLED DEVICE FOR RELEASE /
WO2004111739A1 (en) * 2003-06-13 2004-12-23 Engstroem Nils G Liquid flow regulating device and dynamometer testing device
JP2005074031A (en) * 2003-09-01 2005-03-24 Pentax Corp Capsule endoscope
US20050181018A1 (en) * 2003-09-19 2005-08-18 Peyman Gholam A. Ocular drug delivery
JP4733918B2 (en) 2003-10-01 2011-07-27 オリンパス株式会社 Capsule dosing system
US8095197B2 (en) 2003-11-03 2012-01-10 Microchips, Inc. Medical device for sensing glucose
WO2005046485A1 (en) * 2003-11-12 2005-05-26 FäRGKLäMMAN AB Sampling device, method of producing a sampling device and use of a sampling device
US7450998B2 (en) 2003-11-21 2008-11-11 Alfred E. Mann Foundation For Scientific Research Method of placing an implantable device proximate to neural/muscular tissue
JP4594616B2 (en) * 2003-12-19 2010-12-08 オリンパス株式会社 Capsule medical system
JP2005245938A (en) * 2004-03-08 2005-09-15 Pentax Corp Clothing for diagnosis, system of clothing for diagnosis and endoscope system
US20050195785A1 (en) * 2004-03-08 2005-09-08 Pentax Corporation Image signal processing device
JP2005245937A (en) * 2004-03-08 2005-09-15 Pentax Corp Clothing with communication function and endoscope system
DE102004034355B4 (en) * 2004-07-13 2007-03-22 Fachhochschule Jena Capsule for releasing active substances located in it at defined locations in a body
WO2006015299A2 (en) 2004-07-30 2006-02-09 Microchips, Inc. Multi-reservoir device for transdermal drug delivery and sensing
BRPI0514263B8 (en) 2004-08-20 2021-05-25 Mannkind Corp method for the synthesis of n-protected bis-3,6-[4-aminobutyl]-2,5-diketopiperazine n-protected
KR101306384B1 (en) 2004-08-23 2013-09-09 맨카인드 코포레이션 Diketopiperazine salts, diketomorpholine salts or diketodioxane salts for drug delivery
US8518022B2 (en) 2004-08-27 2013-08-27 Medimetrics Personalized Drug Delivery, Inc. Electronically and remotely controlled pill and system for delivering at least one medicament
JP5107041B2 (en) 2004-09-01 2012-12-26 マイクロチップス・インコーポレーテッド Multi-cap reservoir device for controlled release or exposure of reservoir contents
WO2006056944A1 (en) * 2004-11-29 2006-06-01 Koninklijke Philips Electronics N.V. Electronically controlled pill
WO2006064502A2 (en) * 2004-12-14 2006-06-22 E-Pill Pharma, Ltd. Local delivery of drugs or substances using electronic permeability increase
WO2006077528A2 (en) * 2005-01-18 2006-07-27 Koninklijke Philips Electronics, N.V. Electronically controlled capsule
US20080076975A1 (en) * 2005-01-25 2008-03-27 Microchips, Inc. Method and implantable device with reservoir array for pre-clinical in vivo testing
JP2008540023A (en) * 2005-05-19 2008-11-20 イー−ピル ファーマ リミティド Ingestible device for nitric oxide production in tissues
US7382263B2 (en) * 2005-05-20 2008-06-03 Dow Global Technologies Inc. Oral drug compliance monitoring using radio frequency identification tags
US7444180B2 (en) * 2005-05-25 2008-10-28 Boston Scientific Neuromodulation Corporation Implantable microstimulator with dissecting tip and/or retrieving anchor and methods of manufacture and use
US20070106138A1 (en) * 2005-05-26 2007-05-10 Beiski Ben Z Intraoral apparatus for non-invasive blood and saliva monitoring & sensing
EP1928423B1 (en) 2005-09-14 2015-12-09 Mannkind Corporation Method of drug formulation based on increasing the affinity of active agents for crystalline microparticle surfaces
US20080167600A1 (en) * 2005-09-26 2008-07-10 Peyman Gholam A Device for delivery of an agent to the eye and other sites
US8273071B2 (en) 2006-01-18 2012-09-25 The Invention Science Fund I, Llc Remote controller for substance delivery system
US8992511B2 (en) 2005-11-09 2015-03-31 The Invention Science Fund I, Llc Acoustically controlled substance delivery device
US8936590B2 (en) 2005-11-09 2015-01-20 The Invention Science Fund I, Llc Acoustically controlled reaction device
US7817030B2 (en) 2005-11-09 2010-10-19 Invention Science Fund 1, Llc Remote controller for in situ reaction device
US7942867B2 (en) 2005-11-09 2011-05-17 The Invention Science Fund I, Llc Remotely controlled substance delivery device
US8083710B2 (en) 2006-03-09 2011-12-27 The Invention Science Fund I, Llc Acoustically controlled substance delivery device
US8998886B2 (en) 2005-12-13 2015-04-07 The Invention Science Fund I, Llc Remote control of osmotic pump device
WO2007098500A2 (en) 2006-02-22 2007-08-30 Mannkind Corporation A method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and an active agent
DE102006019419B4 (en) * 2006-04-26 2008-02-14 Siemens Ag Actuator, in particular an endo robot
WO2008012700A1 (en) * 2006-06-23 2008-01-31 Koninklijke Philips Electronics, N.V. Medicament delivery system
EP2101643B1 (en) * 2006-10-31 2013-04-24 Medimetrics Personalized Drug Delivery B.V. Design of swallowable multi-nozzle, dosing device for releasing medicines in the gastrointestinal tract
US20090149839A1 (en) * 2007-12-11 2009-06-11 Hyde Roderick A Treatment techniques using ingestible device
JP6230772B2 (en) * 2008-02-18 2017-11-15 シュトコ・ツェーン・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング Administration of drugs to patients
MX371521B (en) * 2008-03-27 2020-01-31 Mannkind Corp A dry powder inhalation system.
CA2982550C (en) 2008-06-13 2020-08-25 Mannkind Corporation A dry powder inhaler and system for drug delivery
US8485180B2 (en) 2008-06-13 2013-07-16 Mannkind Corporation Dry powder drug delivery system
CN102065942B (en) 2008-06-20 2013-12-11 曼金德公司 An interactive apparatus and method for real-time profiling of inhalation efforts
TWI494123B (en) 2008-08-11 2015-08-01 Mannkind Corp Use of ultrarapid acting insulin
US8314106B2 (en) 2008-12-29 2012-11-20 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
PL2405963T3 (en) 2009-03-11 2014-04-30 Mannkind Corp Apparatus, system and method for measuring resistance of an inhaler
BRPI1006765A2 (en) 2009-04-07 2019-03-26 Koninl Philips Electronics Nv ingestible capsule for drug release
US8414559B2 (en) 2009-05-07 2013-04-09 Rainbow Medical Ltd. Gastroretentive duodenal pill
US20100286587A1 (en) * 2009-05-07 2010-11-11 Yossi Gross Sublingual electrical drug delivery
ES2943333T3 (en) 2009-06-12 2023-06-12 Mannkind Corp Diketopiperazine microparticles with defined surface areas
US10046109B2 (en) 2009-08-12 2018-08-14 Progenity, Inc. Drug delivery device with compressible drug reservoir
EP2496295A1 (en) 2009-11-03 2012-09-12 MannKind Corporation An apparatus and method for simulating inhalation efforts
US8771201B2 (en) * 2010-06-02 2014-07-08 Vital Herd, Inc. Health monitoring bolus
AU2011271097B2 (en) 2010-06-21 2014-11-27 Mannkind Corporation Dry powder drug delivery system and methods
USD666098S1 (en) 2010-11-01 2012-08-28 Colgate-Palmolive Company Cap for a container
USD666099S1 (en) 2010-11-01 2012-08-28 Colgate-Palmolive Company Cap for a container
USD666492S1 (en) 2010-11-01 2012-09-04 Colgate-Palmolive Company Cap for a container
USD666097S1 (en) 2010-11-01 2012-08-28 Colgate-Palmolive Company Cap for a container
USD666096S1 (en) 2010-11-01 2012-08-28 Colgate-Palmolive Company Cap for a container
USD666493S1 (en) 2010-11-01 2012-09-04 Colgate-Palmolive Company Cap for a container
CN103826988B (en) 2011-04-01 2016-03-09 曼金德公司 For the blister package of pharmaceutical kit
ES2776003T3 (en) * 2011-05-27 2020-07-28 Boehringer Ingelheim Int Inhaler and capsule for an inhaler
WO2012174472A1 (en) 2011-06-17 2012-12-20 Mannkind Corporation High capacity diketopiperazine microparticles
JP6018640B2 (en) 2011-10-24 2016-11-02 マンカインド コーポレイション Analgesic composition effective for alleviating pain, and dry powder and dry powder drug delivery system comprising the composition
US9802012B2 (en) 2012-07-12 2017-10-31 Mannkind Corporation Dry powder drug delivery system and methods
WO2014066856A1 (en) 2012-10-26 2014-05-01 Mannkind Corporation Inhalable influenza vaccine compositions and methods
US8915863B2 (en) * 2012-11-16 2014-12-23 L. Zane Shuck In vivo device and method for researching GI tract processes, microbes, and variables associated with illnesses and diseases
US9215997B2 (en) * 2012-11-16 2015-12-22 L. Zane Shuck In vivo technology system for human gut research, diagnostics and treatment
US8491495B1 (en) * 2012-11-16 2013-07-23 L. Zane Shuck Human intestinal tract research and diagnostic system to evaluate patients and advance medical science and bioengineering and to determine processes in the gut and causes of diseases
US8926526B2 (en) * 2012-11-30 2015-01-06 L. Zane Shuck Patient in vivo gut diagnostic and treatment tool
KR102391750B1 (en) 2013-03-15 2022-04-28 맨카인드 코포레이션 Microcrystalline diketopiperazine compositions and methods
CN105451716A (en) 2013-07-18 2016-03-30 曼金德公司 Heat-stable dry powder pharmaceutical compositions and methods
US20160159551A1 (en) * 2013-07-23 2016-06-09 Empire Technology Development Llc Packaging materials and methods for their preparation and use
US11446127B2 (en) 2013-08-05 2022-09-20 Mannkind Corporation Insufflation apparatus and methods
US10307464B2 (en) 2014-03-28 2019-06-04 Mannkind Corporation Use of ultrarapid acting insulin
US9114090B1 (en) 2014-05-30 2015-08-25 Yuri Busiashvili Capsule for sublingual and gastro-intestinal delivery of a liquid medication in a single volume limited dose
EP3197336B1 (en) 2014-09-25 2020-12-23 Progenity, Inc. Electromechanical pill device with localization capabilities
US10561806B2 (en) 2014-10-02 2020-02-18 Mannkind Corporation Mouthpiece cover for an inhaler
US9777715B2 (en) * 2015-01-14 2017-10-03 GM Global Technology Operations LLC Apparatus for cost effective wireless actuator using SMA and MRC
US9867932B2 (en) 2015-10-30 2018-01-16 International Business Machines Corporation Drug delivery device having a cavity sealed by a pressurized membrane
EP3405224B1 (en) 2016-01-21 2022-06-22 Stryker Corporation Sample cassette for collecting tissue samples from a fluid stream, the cassette including plural catch trays for retaining plural samples
JP2019526423A (en) 2016-09-09 2019-09-19 ミッチェル・ローレンス・ジョーンズＭｉｔｃｈｅｌｌ Ｌａｗｒｅｎｃｅ ＪＯＮＥＳ Electromechanically ingestible device for delivery of dispenseable substances
EP3512433B1 (en) * 2016-09-15 2023-06-07 Biora Therapeutics, Inc. Fluid sampling device
GB2554354B (en) 2016-09-21 2021-06-02 Vibrant Ltd Systems for adaptive treatment of disorders in the gastrointestinal tract
WO2018106931A1 (en) 2016-12-07 2018-06-14 Progenity Inc. Gastrointestinal tract detection methods, devices and systems
US20200315540A1 (en) * 2016-12-14 2020-10-08 Progenity, Inc. Treatment of a disease of the gastrointestinal tract with an il-1 inhibitor
CN106823113A (en) * 2017-01-24 2017-06-13 武汉市瑞达源科技有限公司 A kind of medical capsule device
US10905378B1 (en) 2017-01-30 2021-02-02 Vibrant Ltd Method for treating gastroparesis using a vibrating ingestible capsule
US10888277B1 (en) 2017-01-30 2021-01-12 Vibrant Ltd Method for treating diarrhea and reducing Bristol stool scores using a vibrating ingestible capsule
CA3055762A1 (en) 2017-03-31 2018-10-04 Progenity, Inc. Localization systems and methods for an ingestible device
US11439747B2 (en) * 2017-10-04 2022-09-13 Purdue Research Foundation Drug delivery device and method
US11504024B2 (en) 2018-03-30 2022-11-22 Vibrant Ltd. Gastrointestinal treatment system including a vibrating capsule, and method of use thereof
US11638678B1 (en) 2018-04-09 2023-05-02 Vibrant Ltd. Vibrating capsule system and treatment method
US10537720B2 (en) 2018-04-09 2020-01-21 Vibrant Ltd. Method of enhancing absorption of ingested medicaments for treatment of parkinsonism
US11510590B1 (en) 2018-05-07 2022-11-29 Vibrant Ltd. Methods and systems for treating gastrointestinal disorders
US10675248B2 (en) 2018-08-14 2020-06-09 Alma Therapeutics Ltd. Expandable pill
CN109009246B (en) * 2018-10-19 2023-11-28 安翰科技(武汉)股份有限公司 Sampling capsule and sampling capsule system
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US20210402161A1 (en) * 2018-11-02 2021-12-30 Bionaut Labs Ltd. Magnetomechanic triggering ofpayload release from miniaturized devices
EP3883635A1 (en) 2018-11-19 2021-09-29 Progenity, Inc. Methods and devices for treating a disease with biotherapeutics
JP7311917B2 (en) 2019-01-03 2023-07-20 ヴァイブラント リミテッド A device for delivering an ingestible agent into a user's gastrointestinal tract
GB201900780D0 (en) 2019-01-21 2019-03-06 Vibrant Ltd Device and method for delivering a flowable ingestible medicament into the gastrointestinal tract of a user
GB201901470D0 (en) 2019-02-04 2019-03-27 Vibrant Ltd Vibrating capsule for gastrointestinal treatment, and method of use thereof
US11707610B2 (en) 2019-12-13 2023-07-25 Biora Therapeutics, Inc. Ingestible device for delivery of therapeutic agent to the gastrointestinal tract
US20240000441A1 (en) * 2020-11-18 2024-01-04 Trustees Of Tufts College Spatially-Selective Sampling of Gut Microbiome

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4507115A (en) * 1981-04-01 1985-03-26 Olympus Optical Co., Ltd. Medical capsule device
US4564363A (en) * 1983-07-13 1986-01-14 Smithkline Beckman Corporation Delayed action assembly

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3057344A (en) * 1957-05-21 1962-10-09 Abella Carlos Alberto Capsule for the study of the digestive tract and method of using the same
US3315660A (en) * 1963-08-08 1967-04-25 Carlos A Abella Capsule for insertion in the digestive track
US3485235A (en) * 1967-12-04 1969-12-23 Ronald Felson Capsule for the study and treatment of the digestive tract
US3659600A (en) * 1970-02-24 1972-05-02 Estin Hans H Magnetically operated capsule for administering drugs
US3923969A (en) * 1973-06-12 1975-12-02 Battelle Institut E V Carrier system for a drug with sustained release
US4239040A (en) * 1976-10-19 1980-12-16 Kabushiki Kaisha Daini Seikosha Capsule for medical use
DE2807132C2 (en) * 1978-02-20 1983-11-03 Battelle-Institut E.V., 6000 Frankfurt Implantable pharmaceutical depot
DE2928477C3 (en) * 1979-07-14 1982-04-15 Battelle-Institut E.V., 6000 Frankfurt Device for the release of substances at defined locations in the digestive tract
US4692147A (en) * 1980-04-02 1987-09-08 Medtronic, Inc. Drug administration device
CA1254091A (en) * 1984-09-28 1989-05-16 Vladimir Feingold Implantable medication infusion system
US4801459A (en) * 1986-08-05 1989-01-31 Liburdy Robert P Technique for drug and chemical delivery
US4915949A (en) * 1987-07-13 1990-04-10 Alza Corporation Dispenser with movable matrix comprising a plurality of tiny pills
DE3739580A1 (en) * 1987-11-23 1989-06-01 Battelle Institut E V METHOD AND DEVICE FOR CLEAVING A DISPERSE SYSTEM IN AN ELECTROCHEMICAL CELL

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4507115A (en) * 1981-04-01 1985-03-26 Olympus Optical Co., Ltd. Medical capsule device
US4564363A (en) * 1983-07-13 1986-01-14 Smithkline Beckman Corporation Delayed action assembly

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5316015A (en) * 1992-07-30 1994-05-31 Sinaiko Robert J Externally controlled intestinal content sampler
EP0662304A1 (en) * 1994-01-10 1995-07-12 The Research Foundation Of State University Of New York Sampling capsule and process
DE10302614A1 (en) * 2003-01-24 2004-11-18 Innovent E.V. Releasing device use for releasing therapeutic or diagnostically effective substances in digestive tract, has magnetic caps biased to closed state by spring such that caps are opened by application of magnetic force
DE10302614B4 (en) * 2003-01-24 2006-05-11 Innovent E.V. Apparatus and method for releasing or removing substances at or from inaccessible places
US7500951B2 (en) 2004-01-16 2009-03-10 Olympus Corporation Lesion detecting system
US8147482B2 (en) 2006-06-20 2012-04-03 MEDIMETRICS Personalized Drug Delivery B.V. Electronic capsule for treating gastrointestinal disease
WO2023211394A1 (en) * 2022-04-29 2023-11-02 Mersi̇n Üni̇versi̇tesi̇ A local treatment kit in the form of an intra-organ capsule allowing local treatment in solid and hollow organ cancers

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US5170801A (en) 1992-12-15
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