Methods and apparatus for enhanced and controlled delivery of a biologically active agent into the central nervous system of a mammal
First Claim
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1. A method of delivering a biologically active agent to the central nervous system (CNS) of a mammal utilizing pathways that bypass blood-brain barrier comprising the steps of:
- (a) establishing a source of the agent at a zone adjacent a mammal body surface area, the zones being selected from the group consisting of olfactory region, ocular region, brain surface, spinal cord, and intrabrain, (b) establishing a radiant energy gradient from the source to CNS and maintaining the gradiant by energy supply to drive the agent directly from the source to and into the CNS region adjacent the source and within CNS essentially bypassing the mammal'"'"'s blood-brain barrier, the biological agent being selected of a species and size responsive to the radiant energy driving force and mobile within its selected pathway to and within CNS, but larger than sizes of agents that readily traverse blood-brain barrier.
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Accused Products
Abstract
Disclosed are invasive and non-invasive central nervous system (CNS) drug delivery methods and devices for use in these methods that essentially circumvent the blood-brain barrier. More specifically, the disclosed methods and devices utilize iontophoresis as delivery technique that allows for enhanced delivery of a biologically active agent into the CNS of a mammal as well as for (pre)-programmable and controlled transport.
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Citations
31 Claims
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1. A method of delivering a biologically active agent to the central nervous system (CNS) of a mammal utilizing pathways that bypass blood-brain barrier comprising the steps of:
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(a) establishing a source of the agent at a zone adjacent a mammal body surface area, the zones being selected from the group consisting of olfactory region, ocular region, brain surface, spinal cord, and intrabrain, (b) establishing a radiant energy gradient from the source to CNS and maintaining the gradiant by energy supply to drive the agent directly from the source to and into the CNS region adjacent the source and within CNS essentially bypassing the mammal'"'"'s blood-brain barrier, the biological agent being selected of a species and size responsive to the radiant energy driving force and mobile within its selected pathway to and within CNS, but larger than sizes of agents that readily traverse blood-brain barrier. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 13)
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11. Apparatus usable in a non-invasive method for enhanced and controlled delivery of a biologically active agent to the central nervous system of a mammal and particularly a human being utilizing the olfactory pathways, the apparatus including:
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(i) a first electrode insertable in the olfactory area of said mammal and said first electrode being a donor electrode that is constructed and arranged to be positioned in the olfactory area of a mammal, (ii) a second electrode, the second electrode being a receptor pad electrode constructed and arranged to be positioned on or in proximity to the head of a mammal in one or more locations and constructed and arranged for co-operation with an energy source to establish a radiant energy gradient across at least a portion of the mammal'"'"'s olfactory area central nervous system, and (iii) means for energizing said first and second electrodes with an energy source providing a potential gradient so that delivery of the biologically active agent is accomplished in a direction from said first electrode means directly into the central nervous system via the olfactory pathways and thereby essentially circumventing the blood-brain barrier of the mammal. - View Dependent Claims (12, 14, 15, 16, 17, 18, 19, 20)
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21. A non-invasive method for enhanced and controlled delivery of a biologically active agent to the central nervous system of a mammal and particularly a human being utilizing the olfactory pathways that circumvent the blood-brain barrier, which includes the steps of:
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administering a biologically active agent in the olfactory area of a mammal;
inserting a first electrode(s) containing an electrolyte in the anterior part of the nasal cavity;
applying a complementary electrode as a passive iontophoresis electrode on or in proximity to the head of the mammal in one or more locations and to establish a radiant energy gradient across at least a portion of the mammal'"'"'s central nervous system; and
providing a potential gradient between the first and complementary electrode so that delivery of the biologically active agent is facilitated in a direction from said first electrode means directly into the central nervous system via the olfactory pathways and thereby essentially bypassing the blood-brain barrier of the mammal. - View Dependent Claims (22)
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23. A non-invasive method for enhanced and controlled delivery of a biologically active agent to the central nervous system of a mammal and particularly a human being utilizing the ocular pathway that circumvent the blood-brain barrier, which includes the steps of:
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applying a first active iontophoresis electrode on an eyelid of said mammal;
applying a second passive iontophoresis electrode on or in proximity to the head of the mammal in one or more locations and constructed and arranged for co-operation with an energy source to establish a radiant energy gradient across at least a portion of the mammal'"'"'s central nervous system; and
providing a potential gradient so that delivery of the biologically active agent is accomplished in a direction from said first electrode means directly into the central nervous system via the ocular pathway and thereby essentially bypassing the blood-brain barrier of a mammal. - View Dependent Claims (24)
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25. Apparatus for enhanced and controlled delivery of a biologically active agent to the central nervous system of a mammal and particularly a human being utilizing the ocular pathway which includes:
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a first active iontophoresis electrode that is constructed and arranged to be positioned on an eyelid of said mammal;
a second passive iontophoresis electrode that is constructed and arranged to be poisitioned on or in proximity to the head of the mammal in one or more locations and constructed and arranged for co-operation with an energy source to establish a radiant energy gradient across at least a portion of the mammal'"'"'s central nervous system; and
means for providing a potential gradient so that delivery of the biologically active agent is accomplished in a direction from said first electrode means directly into the central nervous system via the ocular pathway and thereby essentially bypassing the blood-brain barrier of the mammal.
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26. An invasive method for enhanced and controlled delivery of a biologically active agent to the central nervous system of a mammal that circumvents the blood-brain barrier, which includes the steps of:
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positioning a first electrode or donor iontophoresis electrode that is constructed and arranged to be positioned on the brain surface or intrabrain of a mammal and applying a receptor iontophoresis electrode within the mammal'"'"'s head or on the exterior surface, providing an energy potential gradient so that delivery of the biologically active agent is accomplished in a direction from said first electrode means directly into the central nervous system thereby essentially bypassing the blood-brain barrier.
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27. Apparatus for enhanced and controlled delivery of a biologically active agent to the central nervous system of a mammal that bypasses the blood-brain barrier, which comprises:
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a first electrode or donor iontophoresis electrode that is constructed and arranged to be positioned on the brain surface or internally of the brain of the mammal and a further receptor iontophoresis electrode in or outside the mammal'"'"'s head, means for providing an energy potential gradient so that delivery of the biologically active agent is accomplished in a direction from said first electrode means directly into the central nervous system thereby essentially bypassing the blood-brain barrier.
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28. A method and device for enhanced and controlled delivery of a biologically active agent locally of the spinal cord or another portion of the central nervous system of a mammal that circumvents the blood-brain barrier, which includes the steps of:
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positioning a first donor iontophoresis electrode that is at or in close vicinity of the spinal cord of the mammal and applying a second receptor iontophoresis electrode in an internal complementary body location so that the two electrodes span the spinal cord;
providing a potential gradient between the electrodes so that delivery of the biologically active agent is accomplished in a direction from said first electrode means directly into the adjacent spinal tissue on another portion of the central nervous system thereby essentially bypassing the blood-brain barrier of the mammal; and
delivering said active substance into the spinal cord of said mammal.
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29. Apparatus for enhanced and controlled delivery of a biologically active agent to a local spinal cord region or another portion of the central nervous system of a mammal that circumvents the blood-brain barrier, comprising:
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a first electrode or donor iontophoresis electrode that is constructed and arranged to be positioned in close vicinity of the spinal cord of the mammal and a second receptor iontophoresis electrode that is constructed and arranged to be positioned in an internal complementary body location;
means for providing a potential gradient so that delivery of the biologically active agent is accomplished in a direction from said first electrode means directly into the adjacent spinal tissue or another portion of the central nervous system thereby essentially bypassing the blood-brain barrier of the mammal;
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30. A phonophoresis method of delivering a biologically active agent to the central nervous system (CNS) of a mammal utilizing pathways that bypass the blood-brain barrier with minimal surgical intervention comprising the steps of:
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(a) establishing a source of the agent at a zone adjacent a mammal body surface area, the zones being selected from the group consisting of olfactory region, ocular region, brain surface, spinal cord, (b) establishing a radiant energy gradient from the source to CNS and maintaining the gradiant phenopheretic by energy supply to drive the agent directly from the source to and into the adjacent CNS region and thereby essentially bypassing the mammal'"'"'s blood-brain barrier, the biological agent being selected of a species and size responsive to the radiant energy gradient and mobile within its selected pathway to and within CNS, but Larger than sizes of agents that readily traverse blood-brain barrier.
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31. Apparatus for enhanced and controlled delivery of a biologically active agent to the central nervous system of a mammal and particularly a human being utilizing the olfactory pathways that circumvent the blood-brain barrier, the apparatus including:
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a first electrode insertable in the olfactory area of said mammal, said first electrode being a donor electrode that is constructed and arranged to be positioned in the olfactory area of a mammal, a second electrode, constructed and arranged to be positioned on or in proximity to the head of a mammal in one or more locations and constructed and arranged for co-operation with an energy source to establish a radiant energy gradient across at least a portion of the mammal'"'"'s olfactory area central nervous system; and
means for energizing said first and second electrodes with an energy source providing a potential gradient so that delivery of the biologically active agent is accomplished in a direction from said first electrode means directly into the central nervous system via the olfactory pathways, essentially circumventing the blood-brain barrier of the mammal.
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Specification