Method for transiently disrupting a region of the blood-brain barrier of a human
Inventors
Carpentier, Alexandre • Canney, Michael • Vignot, Alexandre
Assignees
Universite Pierre et Marie Curie • Assistance Publique Hopitaux de Paris APHP • Carthera SAS
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Publication Number
US-10981021-B2
Publication Date
2021-04-20
Expiration Date
Abstract
The present invention relates to a method for transiently disrupting a region of the blood-brain barrier (BBB) of a human using ultrasounds in the presence of an ultrasound contrast agent, and uses thereof. The method comprises the application of at least one ultrasound (US) beam with a pressure level higher than 1 MPa and a resonance frequency ranging from 0.5 to 1.5 MHz.
Core Innovation
The invention provides an in vivo method for transiently disrupting a region of a human blood-brain barrier (BBB) using ultrasound (US) and an ultrasound contrast agent. The method comprises administering a dose of the ultrasound contrast agent and applying onto the brain at least one US beam with a pressure level in a range of 1 to 1.1 MPa and a resonance frequency ranging from 0.5 to 1.5 MHz, using a mean pulse of duration between 10 msec and 50 msec.
A related aspect of the invention delivers a substance through a human BBB by injecting the human with a dose of an ultrasound contrast agent, applying the at least one US beam with the specified pressure and resonance frequency and mean pulse duration, and thereby disrupting the BBB. After BBB disruption, the method includes administering the substance to the human, so that the substance is delivered through the disrupted BBB.
Another aspect of the invention treats a brain disease in a human by applying ultrasound to the brain while an ultrasound contrast agent is present. The method comprises applying at least one US beam with a pressure level in a range of 1 to 1.1 MPa and a resonance frequency ranging from 0.5 to 1.5 MHz, with a mean pulse of duration between 10 msec and 50 msec, thereby disrupting a blood brain barrier (BBB) in the human.
Claims Coverage
The independent claims identified are clm-00001, clm-00010, and clm-00022. Across these independent claims, the inventive coverage centers on using an ultrasound contrast agent together with ultrasound application having a specific pressure range, resonance frequency range, and mean pulse duration, with additional features for administering a substance after BBB disruption and treating a brain disease.
Transiently disrupting a human BBB with ultrasound and an ultrasound contrast agent
An in vivo method for transiently disrupting a region of a human blood-brain barrier (BBB) using ultrasound (US) and an ultrasound contrast agent, comprising administering a dose of the ultrasound contrast agent to the human and applying onto the brain at least one ultrasound (US) beam with a pressure level in a range of 1 to 1.1 MPa and a resonance frequency ranging from 0.5 to 1.5 MHz, with a mean pulse of duration between 10 msec and 50 msec.
Delivering a substance through a human BBB by disrupting the BBB with ultrasound and an ultrasound contrast agent
An in vivo method of delivering a substance through a blood-brain barrier (BBB) of a human, comprising injecting the human with a dose of an ultrasound contrast agent, applying to the brain at least one ultrasound (US) beam with a pressure level in a range of 1 to 1.1 MPa and a resonance frequency ranging from 0.5 to 1.5 MHz, with a mean pulse of duration between 10 msec and 50 msec, thereby disrupting the BBB, and administering the substance to the human.
Treating a brain disease by disrupting the BBB with ultrasound and an ultrasound contrast agent present
An in vivo method for treating a brain disease in a human in which an ultrasound contrast agent is present, comprising applying to the brain at least one ultrasound (US) beam with a pressure level in a range of 1 to 1.1 MPa and a resonance frequency ranging from 0.5 to 1.5 MHz, with a mean pulse of duration between 10 msec and 50 msec, thereby disrupting a blood brain barrier (BBB) in the human.
The claim set provides three independent coverage themes: transient BBB disruption using ultrasound and an ultrasound contrast agent; BBB disruption enabling delivery of a substance; and BBB disruption used as the enabling step within treating a brain disease, each grounded in the same ultrasound pressure range, resonance frequency range, and mean pulse duration.
Stated Advantages
Transiently disrupts/openes the blood-brain barrier (BBB) in a human using ultrasound with an ultrasound contrast agent.
Enables delivery of a substance through a human BBB by disrupting the BBB.
Provides a method for treating a brain disease by disrupting a blood brain barrier (BBB) in the human.
Documented Applications
Clinical and technical implementation described for recurrent glioblastoma (GBM), including BBB disruption assessment using MRI-based assessment/grading and an example using an implantable ultrasound transducer.
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