NZ770867B2 - Using alternating electric fields to increase permeability of the blood brain barrier - Google Patents

Using alternating electric fields to increase permeability of the blood brain barrier Download PDF

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Publication number
NZ770867B2
NZ770867B2 NZ770867A NZ77086719A NZ770867B2 NZ 770867 B2 NZ770867 B2 NZ 770867B2 NZ 770867 A NZ770867 A NZ 770867A NZ 77086719 A NZ77086719 A NZ 77086719A NZ 770867 B2 NZ770867 B2 NZ 770867B2
Authority
NZ
New Zealand
Prior art keywords
frequency
state
electric field
alternating electric
control input
Prior art date
Application number
NZ770867A
Other versions
NZ770867A (en
Inventor
Catherine BRAMI
Malgorzata Burek
Carola Forster
Carsten Hagemann
Hadas Sara Hershkovich
Almuth F Kessler
Mario Lohr
Sela Tali Voloshin
Original Assignee
Novocure Gmbh
Filing date
Publication date
Application filed by Novocure Gmbh filed Critical Novocure Gmbh
Priority claimed from PCT/IB2019/057091 external-priority patent/WO2020039390A1/en
Publication of NZ770867A publication Critical patent/NZ770867A/en
Publication of NZ770867B2 publication Critical patent/NZ770867B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0085—Brain, e.g. brain implants; Spinal cord
    • 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M2037/0007—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
    • 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
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/0007—Special media to be introduced, removed or treated introduced into the body
    • 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/05—General characteristics of the apparatus combined with other kinds of therapy
    • A61M2205/054—General characteristics of the apparatus combined with other kinds of therapy with electrotherapy
    • 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
    • A61M2210/00—Anatomical parts of the body
    • A61M2210/06—Head
    • A61M2210/0693—Brain, cerebrum
    • 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
    • A61M2250/00—Specially adapted for animals
    • 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0092—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/325—Applying electric currents by contact electrodes alternating or intermittent currents for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/327—Applying electric currents by contact electrodes alternating or intermittent currents for enhancing the absorption properties of tissue, e.g. by electroporation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36002—Cancer treatment, e.g. tumour
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/36017—External stimulators, e.g. with patch electrodes with leads or electrodes penetrating the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/36025—External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/3603—Control systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/372—Arrangements in connection with the implantation of stimulators
    • A61N1/37211—Means for communicating with stimulators
    • A61N1/37217—Means for communicating with stimulators characterised by the communication link, e.g. acoustic or tactile
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N13/00—Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves

Abstract

Certain substances (e.g., large molecules) that ordinarily cannot traverse the blood brain barrier can be introduced into the brain by applying an alternating electric field to the brain for a period of time, wherein the frequency of the alternating electric field is selected so that application of the alternating electric field increases permeability of the blood brain barrier. In some embodiments, the frequency of the alternating electric field is less than 190 kHz (e.g., 100 kHz). Once the permeability of the blood brain barrier has been increased, the substance is able to cross the blood brain barrier.

Claims (16)

WHAT IS CLAIMED IS:
1. An apparatus for treating a tumor in a subject’s body and facilitating delivery of a substance across a blood brain barrier of the subject’s body, the apparatus comprising: an AC voltage generator configured to generate an alternating electric field at a first frequency between 50 and 190 kHz and a second frequency between 50 and 500 kHz, wherein the second frequency is different from the first frequency, the AC voltage generator having a control input, wherein the AC voltage generator is configured to output the alternating electric field at the first frequency when the control input is in a first state and to output at the second frequency when the control input is in a second state; and a controller programmed to (a) place the control input in the second state so that the AC voltage generator outputs the alternating electric field at the second frequency, (b) accept a request to switch to output the alternating electric field at the first frequency, (c) upon receipt of the request, place the control input in the first state so that the AC voltage generator outputs the alternating electric field at the first frequency for an interval of time, and (d) after the interval of time has elapsed, place the control input in the second state so that the AC voltage generator outputs the alternating electric field at the second frequency, wherein the interval of time is at least 24 hours.
2. The apparatus of claim 1, further comprising: a set of electrodes configured for affixation to the subject’s body; and wiring that connects an output of the AC voltage generator to the set of electrodes.
3. The apparatus of claim 1 or claim 2, wherein the first frequency is between 75 kHz and 125 kHz.
4. The apparatus of any one of the preceding claims wherein the second frequency is between 150 kHz and 250 kHz.
5. The apparatus of any one of the preceding claims wherein the interval of time is at least 48 hours.
6. The apparatus of any one of the preceding claims, wherein the interval of time is at least 72 hours.
7. The apparatus of any one of the preceding claims, wherein the controller is further programmed to, subsequent to the receipt of the request, switch the control input back and forth between the first state and the second state.
8. The apparatus of anyone of the preceding claims, wherein the AC voltage generator is configured to generate the electric field at at least one additional frequency between 50 and 500 kHz, and wherein the AC voltage generator is configured to output the alternating electric field at the at least one additional frequency when the control input is in at least one additional state, and wherein the controller is programmed to cycle the control input through the second state and the at least one additional state prior to receipt of the request, and to cycle the control input through the second state and the at least one additional state after the interval of time has elapsed.
9. The apparatus of any one of the preceding claims, further comprising a user interface, wherein the request is accepted via the user interface.
10. The apparatus of any one of the preceding claims, wherein the request is accepted via
11. The apparatus of any one of the preceding claims, wherein the alternating electric field has a field strength of at least 1 V/cm in at least a portion of the subject's brain.
12. The apparatus of any one of the preceding claims, wherein the interval of time comprises a single uninterrupted interval of time that is at least one week long.
13. The apparatus of any one of the preceding claims, wherein the substance has a molecular weight of at least 4 kDa.
14. The apparatus of any one of claims 1 to 13, wherein the substance has a molecular weight of at least 69 kDa.
15. The apparatus of any one of the preceding claims, wherein the substance comprises a drug for treating a disease, optionally the drug comprises a cancer treatment drug, an infectious disease treatment drug, a neurodegenerative disease treatment drug, an auto- immune disease treatment drug, an anti-epileptic drug, a hydrocephalus drug, a stroke intervention drug or a psychiatric drug.
16. The apparatus of any one of the preceding claims, wherein the substance is used for monitoring brain activity, optionally the substance is a brain dye, a reporter or a marker.
NZ770867A 2019-08-22 Using alternating electric fields to increase permeability of the blood brain barrier NZ770867B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862722100P 2018-08-23 2018-08-23
PCT/IB2019/057091 WO2020039390A1 (en) 2018-08-23 2019-08-22 Using alternating electric fields to increase permeability of the blood brain barrier

Publications (2)

Publication Number Publication Date
NZ770867A NZ770867A (en) 2023-11-24
NZ770867B2 true NZ770867B2 (en) 2024-02-27

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