Patent Grant
10905875
The present invention relates generally to medical devices, and specifically to apparatus and methods for increasing the throughput of fluid through a tissue or otherwise modifying the fluid balance in a tissue.
Many ailments originate from excess fluid in tissues, e.g., due to insufficient or damaged drainage of fluid from the tissue. As a result, this fluid causes elevated pressure in the tissue, which may result in discomfort and/or tissue damage. Examples of tissues prone to this problem are the brain, kidneys, lymph nodes, and eyes.
For hydrocephalus (i.e., the abnormal accumulation of cerebrospinal fluid in the ventricles of the brain), a common treatment approach is to use a shunt, which includes a drainage tube and a valve that controls the volume and rate of cerebrospinal fluid outflow from the brain to another part of the body (e.g., the abdomen).
Techniques are described for electroosmotically driving fluid between a first tissue of a subject and a second tissue of the subject. For some applications, the fluid is driven in response to detecting a pressure at at least one of the tissues, and/or a pressure difference between the tissues. For some applications, the pressure difference is detected by detecting a voltage, such as a streaming potential, between the tissues.
For some applications of the present invention, a system for increasing the throughput of fluid in the brain is provided. Typically, a first electrode is coupled to the superior sagittal sinus of the subject, and a second electrode is coupled to the cerebral cortex of the subject. According to one application of the present invention, a control unit, coupled to the electrodes, is configured to apply a voltage between the first and second electrodes, and to configure the voltage to electroosmotically drive fluid from the superior sagittal sinus to the cerebral cortex.
For some applications of the present invention, a system for increasing the throughput of fluid in the kidney is provided. Typically, a first electrode is coupled to the renal artery of the subject, and a second electrode is coupled to the ureter of the subject. According to one application of the present invention, the control unit is configured to apply a voltage between the first and second electrodes, and to configure the voltage to electroosmotically drive fluid from the renal artery to the ureter.
For some applications of the present invention, a system for increasing the throughput of fluid in a lymph node is provided. Typically, a first electrode is coupled to the artery entering the lymph node of the subject, and a second electrode is coupled to the medullary sinus of the lymph node. According to one application of the present invention, the control unit is configured to apply a voltage between the first and second electrodes, and to configure the voltage to electroosmotically drive fluid from the artery entering the lymph node to the medullary sinus.
For some applications of the present invention, a system for increasing the throughput of fluid in the eye is provided. Typically, a first electrode is coupled to a vitreous cavity of the eye of the subject, and a second electrode is coupled to a Schlemm's canal of the subject. According to one application of the present invention, the control unit is configured to apply a voltage between the first and second electrodes, and to configure the voltage to electroosmotically drive fluid from the vitreous cavity to the Schlemm's canal.
For some applications of the present invention, a system for driving fluid between a nucleus pulposus of an intervertebral disc and a site outside of the nucleus pulposus is provided. Typically, a first electrode is coupled to (e.g., inserted into) the nucleus pulposus of the subject, and a second electrode is coupled to the site outside of the nucleus pulposus (e.g., to an outer surface of an annulus fibrosus of the intervertebral disc). According to one application of the present invention, the control unit is configured to apply a voltage between the first and second electrodes, and to configure the voltage to electroosmotically drive fluid from the site outside of the nucleus pulposus, to the nucleus pulposus.
For some applications of the present invention, electroosmosis is performed using insulated electrodes. Typically, when the control unit applies a voltage between the electrodes, a capacitance-based current flows toward one of the electrodes, resulting in fluid electroosmotically moving from one site to another. For example, this technique may be practiced to drive fluid in any of the sites described hereinabove.
It is noted that, for some applications, electroosmosis techniques as provided herein can be performed anywhere in a body of the subject where ionic filtration occurs.
There is further provided, in accordance with an application of the present invention, apparatus for driving fluid between first and second anatomical sites of a subject, the apparatus including:
a first electrode, configured to be coupled to the first anatomical site of the subject;
a second electrode, configured to be coupled to the second anatomical site of the subject; and
a control unit, configured to:
In an application, the control unit is configured to provide a rest period during which the treatment voltage is not applied, and to apply, between the first and second electrodes, an opposite voltage that is opposite to the treatment voltage and that has a lower magnitude than the treatment voltage.
In an application, each electrode is insulated such that no portion of the electrode may be in electrical contact with any tissue of the subject, and the control unit is configured to drive a capacitative current between the first and second insulated electrodes by applying the treatment voltage between the electrodes.
In an application, the apparatus further includes a pressure sensor, and the apparatus is configured to detect the pressure difference by the pressure sensor being configured to detect the pressure difference.
In an application, the pressure sensor includes a mechanical pressure sensor, configured to detect the pressure difference at least in part by detecting mechanical pressure pressing on a component of the pressure sensor.
In an application, the pressure sensor includes at least a first mechanical pressure sensor, configured to detect the pressure at the first anatomical site, and a second mechanical pressure sensor, configured to detect the pressure at the second anatomical site.
In an application, the apparatus is configured to detect the pressure difference by detecting a voltage between the first and second electrodes, and the control unit is configured to apply the treatment in response to the detected pressure difference by being configured to apply the treatment voltage in response to the detected voltage.
In an application, the apparatus is configured to detect the detected voltage by being configured to detect a streaming voltage.
In an application, the apparatus is configured not to apply the treatment voltage while detecting the detected voltage.
In an application, the control unit includes voltage-detecting circuitry, configured to detect the voltage.
In an application, the first anatomical site includes a superior sagittal sinus of the subject, the second anatomical site includes a cerebral cortex of the subject, and the control unit is configured to electroosmotically drive the fluid by electroosmotically driving the fluid between the superior sagittal sinus and the cerebral cortex of the subject.
In an application, the control unit is configured to electroosmotically drive the fluid from the cerebral cortex to the superior sagittal sinus of the subject.
In an application, the control unit is configured to detect the pressure by being configured to detect a voltage between the first and second electrodes.
In an application, the first anatomical site includes a renal artery of the subject, the second anatomical site includes a ureter of the subject, and the control unit is configured to configure the treatment voltage to electroosmotically drive the fluid by electroosmotically driving the fluid between the renal artery and the ureter of the subject.
In an application, the control unit is configured to electroosmotically drive the fluid from the renal artery to the ureter of the subject.
In an application, the control unit is configured to detect the pressure by being configured to detect a voltage between the first and second electrodes.
In an application, the first anatomical site includes an artery entering a lymph node of the subject, the second anatomical site includes a medullary sinus of the lymph node of the subject, and the control unit is configured to electroosmotically drive the fluid by electroosmotically driving the fluid between the artery and the medullary sinus of the subject.
In an application, the control unit is configured to electroosmotically drive the fluid from the artery to the medullary sinus of the subject.
In an application, the control unit is configured to detect the pressure by being configured to detect a voltage between the first and second electrodes, and to apply the treatment voltage only when the detected voltage is greater than.
In an application, the first anatomical site includes a vitreous cavity of an eye of the subject, the second anatomical site includes a Schlemm's canal of the subject, and the control unit is configured to electroosmotically drive the fluid by electroosmotically driving the fluid between the vitreous cavity and the Schlemm's canal of the subject.
In an application, the control unit is configured to electroosmotically drive the fluid from the vitreous cavity to the Schlemm's canal of the subject.
In an application, the control unit is configured to detect the pressure by being configured to detect a voltage between the first and second electrodes.
In an application, the first anatomical site includes a site within a subarachnoid cavity of the subject, the second anatomical site includes a site outside of the subarachnoid cavity of the subject, and the control unit is configured to electroosmotically drive the fluid by electroosmotically driving the fluid between the site within the subarachnoid cavity and the site outside of the subarachnoid cavity of the subject.
In an application, the control unit is configured to electroosmotically drive the fluid from the site within the subarachnoid cavity to the site outside of the subarachnoid cavity of the subject.
In an application, the control unit is configured to detect the pressure by being configured to detect a voltage between the first and second electrodes.
There is further provided, in accordance with an application of the present invention, a method, including: detecting a pressure difference between a first anatomical site and a second anatomical site of a subject; and in response to the detected pressure difference, electroosmotically driving fluid between the first and second anatomical sites by applying a treatment voltage between the first and second anatomical sites.
In an application, the method further includes providing a rest period during which the treatment voltage is not applied, and applying, during the rest period, an opposite voltage between the first and second anatomical sites, the opposite voltage being opposite to the treatment voltage and having a lower magnitude than the treatment voltage.
In an application, the method further includes implanting a first electrode at the first anatomical site, and implanting a second electrode at the second anatomical site, and applying the treatment voltage between the first and second anatomical sites includes applying the treatment voltage between the first and second electrodes.
In an application:
implanting the first electrode includes implanting a first insulated electrode, such that no portion of the first insulated electrode is in electrical contact with any tissue of the subject,
implanting the second electrode includes implanting a second insulated electrode, such that no portion of the second insulated electrode is in electrical contact with any tissue of the subject, and
applying the treatment voltage includes driving a capacitative current between the first and second insulated electrodes.
In an application, detecting the pressure difference includes detecting the pressure difference using at least one mechanical pressure sensor.
In an application, detecting the pressure difference includes detecting a pressure at the first anatomical site using a first mechanical pressure sensor, and detecting a pressure at the second anatomical site using a second mechanical pressure sensor.
In an application, detecting the pressure difference includes detecting the pressure difference by detecting a voltage between the first and second electrodes, and applying the treatment voltage in response to the detected pressure difference includes applying the treatment voltage in response to the detected voltage.
In an application, detecting the detected voltage includes detecting a streaming voltage.
In an application, applying the treatment voltage includes not applying the treatment voltage while detecting the detected voltage.
In an application:
the first anatomical site includes a superior sagittal sinus of the subject,
the second anatomical site includes a cerebral cortex of the subject, and
electroosmotically driving the fluid between the first and second anatomical sites includes electroosmotically driving the fluid between the superior sagittal sinus and the cerebral cortex of the subject.
In an application, driving the fluid between the superior sagittal sinus and the cerebral cortex of the subject includes driving the fluid from the cerebral cortex to the superior sagittal sinus of the subject.
In an application, detecting the pressure difference includes detecting the pressure difference by detecting a voltage between the first and second electrodes.
In an application:
the first anatomical site includes a renal artery of the subject,
the second anatomical site includes a ureter of the subject, and
electroosmotically driving the fluid between the first and second anatomical sites includes electroosmotically driving the fluid between the renal artery and the ureter of the subject.
In an application, driving the fluid between the renal artery and the ureter of the subject includes driving the fluid from the renal artery to the ureter of the subject.
In an application, detecting the pressure difference includes detecting the pressure difference by detecting a voltage between the first and second electrodes.
In an application:
the first anatomical site includes an artery entering a lymph node of the subject,
the second anatomical site includes a medullary sinus of the lymph node of the subject, and
electroosmotically driving the fluid between the first and second anatomical sites includes electroosmotically driving the fluid between the artery entering a lymph node and the medullary sinus of the subject.
In an application, driving the fluid between the artery entering the lymph node and the medullary sinus of the subject includes driving the fluid from the medullary sinus to the artery entering the lymph node of the subject.
In an application, detecting the pressure difference includes detecting the pressure difference by detecting a voltage between the first and second electrodes.
In an application:
the first anatomical site includes a vitreous cavity of an eye of the subject,
the second anatomical site includes a Schlemm's canal of the eye of the subject, and
electroosmotically driving the fluid between the first and second anatomical sites includes electroosmotically driving the fluid between the vitreous cavity and the Schlemm's canal of the subject.
In an application, driving the fluid between the vitreous cavity and the Schlemm's canal of the subject includes driving the fluid from the vitreous cavity to the Schlemm's canal of the subject.
In an application, detecting the pressure difference includes detecting the pressure difference by detecting a voltage between the first and second electrodes.
In an application:
the first anatomical site includes a nucleus pulposus of an intervertebral disc of the subject,
the second anatomical site includes a site outside of the nucleus pulposus of the disc of the subject, and
electroosmotically driving the fluid between the first and second anatomical sites includes electroosmotically driving the fluid between the nucleus pulposus and the site outside of the nucleus pulposus of the subject.
In an application, driving the fluid between the nucleus pulposus and the site outside of the nucleus pulposus of the subject includes driving the fluid from the nucleus pulposus to the site outside of the nucleus pulposus of the subject.
In an application, driving the fluid between the nucleus pulposus and the site outside of the nucleus pulposus of the subject includes driving the fluid from the site outside of the nucleus pulposus to the nucleus pulposus of the subject.
In an application, detecting the pressure difference includes detecting the pressure difference by detecting a voltage between the first and second electrodes.
In an application:
the first anatomical site includes a site within a subarachnoid cavity of the subject,
the second anatomical site includes a site outside of the subarachnoid cavity of the subject, and
electroosmotically driving the fluid between the first and second anatomical sites includes electroosmotically driving the fluid between the site within the subarachnoid cavity of the subject and the site outside of the subarachnoid cavity of the subject.
In an application, driving the fluid between the site within the subarachnoid cavity and the site outside of the subarachnoid cavity of the subject includes driving the fluid from the site within the subarachnoid cavity to the site outside of the subarachnoid cavity of the subject.
In an application, detecting the pressure difference includes detecting the pressure difference by detecting a voltage between the first and second electrodes.
There is further provided, in accordance with an application of the present invention, a method, including:
electroosmotically driving fluid between a superior sagittal sinus of a subject and a cerebral cortex of the subject, by applying a treatment voltage between the superior sagittal sinus and the cerebral cortex of the subject.
In an application, the method further includes providing a rest period during which the treatment voltage is not applied, and applying, during the rest period, an opposite voltage between the superior sagittal sinus and the cerebral cortex, the opposite voltage being opposite to the treatment voltage and having a lower magnitude than the treatment voltage.
In an application, applying the treatment voltage includes applying a capacitative current.
In an application, driving the fluid between the superior sagittal sinus and the cerebral cortex of the subject includes driving the fluid from the cerebral cortex to the superior sagittal sinus of the subject.
In an application, the method further includes detecting a pressure difference between the superior sagittal sinus of the subject and the cerebral cortex of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected pressure difference.
In an application, detecting the pressure difference includes detecting a voltage between the superior sagittal sinus of the subject and the cerebral cortex of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected voltage.
In an application, detecting the detected voltage includes detecting a streaming potential.
In an application, the method further includes implanting a first electrode at the superior sagittal sinus of the subject, and a second electrode at the cerebral cortex of the subject, and detecting the voltage between the superior sagittal sinus of the subject and the cerebral cortex of the subject includes detecting a voltage between the first and second electrodes.
There is further provided, in accordance with an application of the present invention, a method, including:
electroosmotically driving fluid between a renal artery of a subject and a ureter of the subject, by applying a treatment voltage between the renal artery and the ureter of the subject.
In an application, the method further includes providing a rest period during which the treatment voltage is not applied, and applying, during the rest period, an opposite voltage between the renal artery and the ureter, the opposite voltage being opposite to the treatment voltage and having a lower magnitude than the treatment voltage.
In an application, applying the treatment voltage includes applying a capacitative current.
In an application, driving the fluid between the renal artery and the ureter of the subject includes driving the fluid from the renal artery to the ureter of the subject.
In an application, the method further includes detecting a pressure difference between the renal artery of the subject and the ureter of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected pressure difference.
In an application, detecting the pressure difference includes detecting a voltage between the renal artery of the subject and the ureter of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected voltage.
In an application, detecting the detected voltage includes detecting a streaming potential.
In an application, the method further includes implanting a first electrode at the renal artery of the subject, and a second electrode at the ureter of the subject, and detecting the voltage between the renal artery of the subject and the ureter of the subject includes detecting a voltage between the first and second electrodes.
There is further provided, in accordance with an application of the present invention, a method, including:
electroosmotically driving fluid between an artery entering a lymph node of a subject and a medullary sinus of the lymph node of the subject, by applying a treatment voltage between the artery and the medullary sinus of the subject.
In an application, the method further includes providing a rest period during which the treatment voltage is not applied, and applying, during the rest period, an opposite voltage between the artery and the medullary sinus, the opposite voltage being opposite to the treatment voltage and having a lower magnitude than the treatment voltage.
In an application, applying the treatment voltage includes applying a capacitative current.
In an application, driving the fluid between the artery entering the lymph node and the medullary sinus of the subject includes driving the fluid from the medullary sinus to the artery entering the lymph node of the subject.
In an application, the method further includes detecting a pressure difference between the artery of the subject and the medullary sinus of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected pressure difference.
In an application, detecting the pressure difference includes detecting a voltage between the artery of the subject and the medullary sinus of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected voltage.
In an application, detecting the detected voltage includes detecting a streaming potential.
In an application, the method further includes implanting a first electrode at the artery of the subject, and a second electrode at the medullary sinus of the subject, and detecting the voltage between the artery of the subject and the medullary sinus of the subject includes detecting a voltage between the first and second electrodes.
There is further provided, in accordance with an application of the present invention, a method, including:
electroosmotically driving fluid between a vitreous cavity of an eye of a subject and a Schlemm's canal of the eye of the subject, by applying a treatment voltage between the vitreous cavity and the Schlemm's canal of the subject.
In an application, the method further includes providing a rest period during which the treatment voltage is not applied, and applying, during the rest period, an opposite voltage between the vitreous cavity and the Schlemm's canal, the opposite voltage being opposite to the treatment voltage and having a lower magnitude than the treatment voltage.
In an application, applying the treatment voltage includes applying a capacitative current.
In an application, driving the fluid between the vitreous cavity and the Schlemm's canal of the subject includes driving the fluid from the vitreous cavity to the Schlemm's canal of the subject.
In an application, the method further includes detecting a pressure difference between the vitreous cavity of the subject and the Schlemm's canal of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected pressure difference.
In an application, detecting the pressure difference includes detecting a voltage between the vitreous cavity of the subject and the Schlemm's canal of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected voltage.
In an application, detecting the detected voltage includes detecting a streaming potential.
In an application, the method further includes implanting a first electrode at the vitreous cavity of the subject, and a second electrode at the Schlemm's canal of the subject, and detecting the voltage between the vitreous cavity of the subject and the Schlemm's canal of the subject includes detecting a voltage between the first and second electrodes.
There is further provided, in accordance with an application of the present invention, a method, including:
electroosmotically driving fluid between a site within a subarachnoid cavity of a subject and a site outside of the subarachnoid cavity of the subject, by applying a treatment voltage between the site within the subarachnoid cavity and the site outside of the subarachnoid cavity of the subject.
In an application, the method further includes providing a rest period during which the treatment voltage is not applied, and applying, during the rest period, an opposite voltage between the site within the subarachnoid cavity and the site outside of the subarachnoid cavity, the opposite voltage being opposite to the treatment voltage and having a lower magnitude than the treatment voltage.
In an application, electroosmotically driving the fluid by applying the treatment voltage includes electroosmotically driving fluid between a site within a subarachnoid cavity of a subject that is asymptomatic of Alzheimer's disease and a site outside of the subarachnoid cavity of the subject, by applying a treatment voltage between the site within the subarachnoid cavity and the site outside of the subarachnoid cavity of the subject that is asymptomatic of Alzheimer's disease.
In an application, applying the treatment voltage includes applying a capacitative current.
In an application, driving the fluid between the site within the subarachnoid cavity and the site outside of the subarachnoid cavity of the subject includes driving the fluid from the site within the subarachnoid cavity to the site outside of the subarachnoid cavity of the subject.
In an application, the method further includes detecting a pressure difference between the site within the subarachnoid cavity of the subject and the site outsider of the subarachnoid cavity of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected pressure difference.
In an application, detecting the pressure difference includes detecting a voltage between the site within the subarachnoid cavity of the subject and the site outside of the subarachnoid cavity of the subject, and applying the treatment voltage includes applying the treatment voltage in response to the detected voltage.
In an application, detecting the detected voltage includes detecting a streaming potential.
In an application, the method further includes implanting a first electrode at the site within the subarachnoid cavity of the subject, and a second electrode at the site outside of the subarachnoid cavity of the subject, and detecting the voltage between the site within the subarachnoid cavity of the subject and the site outside of the subarachnoid cavity of the subject includes detecting a voltage between the first and second electrodes.
The present invention will be more fully understood from the following detailed description of applications thereof, taken together with the drawings, in which:
Reference is made to
Typically, control unit 16 applies the treatment voltage as a direct current (DC). For some applications of the invention, the control unit is configured to apply the treatment voltage according to a pre-selected schedule, such as a duty cycle, such as for a few hours per day, such as when the subject is sleeping. For example, the control unit may be configured to be controlled and/or powered by an extracorporeal controller, such as a controller comprising a wireless transmitter, disposed in and/or in the vicinity of the subject's bed. For some applications, one or more rest periods during which the treatment voltage is not applied, are provided in the pre-selected schedule. It is hypothesized that for some applications, the rest period facilitates equilibration of charge in the body of the subject. For some such applications, during rest periods in which the treatment voltage is not being applied, an opposite voltage (i.e., a voltage having an opposite sign to the treatment voltage) having a different (e.g., lower) magnitude is applied.
For some applications of the invention, apparatus 10 is configured to detect a pressure at at least one of the electrodes (e.g., the pressure above atmospheric pressure, at the implantation site of the electrode), and to apply the treatment voltage in response to the detected pressure. For example, apparatus 10 may be configured to detect pressure at cerebral cortex 24, and to apply the treatment voltage if the detected pressure is greater than a threshold pressure.
For some applications of the present invention, apparatus 10 comprises a pressure sensor 18, configured to detect the pressure. For some applications of the invention, pressure sensor 18 comprises a mechanical transducer-based pressure sensor, as is known in the art. That is, for some applications, the pressure sensor is configured to detect the pressure by detecting the mechanical pressure pressing on a component of the pressure sensor. For some such applications, and as shown in
For some applications, apparatus 10 is configured to sense a pressure difference between the implantation sites of first electrode 12 and second electrode 14, and to apply the treatment voltage in response to the detected pressure difference. For example, and as shown in
Alternatively or additionally, apparatus 10 may sense the pressure difference by detecting a voltage, such as a streaming potential, between the electrodes, that is indicative of the pressure difference between the sites. For example, control unit 16 may comprise voltage-detecting circuitry 17, configured to detect the voltage between electrodes 12 and 14, and may be configured to apply the treatment voltage only if the detected voltage is greater than a threshold voltage. Typically, control unit 16 is configured to apply the voltage only when the detected voltage between first electrode 12 and second electrode 14 is greater than 2 mV (e.g., greater than 20 mV, but typically less than 500 mV, for example, less than 50 mV). For some such applications, apparatus 10 may be considered to comprise a pressure detector that comprises electrodes 12 and 14, and circuitry 17.
Typically, the detected voltage is detected while the treatment voltage is not applied. For example, control unit 16 may be configured to apply the treatment voltage and detect the detected voltage in a sequence, and/or to periodically stop applying the treatment voltage so as to detect the detected voltage.
For some applications of the invention, control unit 16 comprises a receiver 19 (e.g., an antenna), which receives power wirelessly from an extracorporeal device, e.g., a mattress-based transmitter, or a transmitter coupled to a belt, hat, eyeglasses, or clothing item of the subject. For some applications, receiver 19 of control unit 16 receives power wirelessly from an implanted transmitter coupled to a power source (e.g., a battery). Alternatively or additionally, the control unit receives power from a power source (e.g., a battery), which may be in a common housing with the control unit.
Reference is now made to
As described with reference to
Typically, the detected voltage is detected while the treatment voltage is not applied. For example, control unit 16 may be configured to apply the treatment voltage and detect the detected voltage in a sequence, and/or to periodically stop applying the treatment voltage so as to detect the detected voltage.
Reference is now made to
As described with reference to
Typically, the detected voltage is detected while the treatment voltage is not applied. For example, control unit may be configured to apply the treatment voltage and detect the detected voltage in a sequence, and/or to periodically stop applying the treatment voltage so as to detect the detected voltage.
Reference is now made to
As described with reference to
Typically, the detected voltage is detected while the treatment voltage is not applied. For example, control unit 16 may be configured to apply the treatment voltage and detect the detected voltage in a sequence, and/or to periodically stop applying the treatment voltage so as to detect the detected voltage.
Reference is made to
According to one application of the present invention, control unit 16 is configured to apply a voltage between first electrode 12 and second electrode 14, and to configure the voltage to electroosmotically drive fluid from the site outside nucleus pulposus 62, into the nucleus pulposus. It is hypothesized that this driving of the fluid is beneficial for subjects suffering from intervertebral disc fluid loss, by generally treating and/or preventing further degeneration in disc 60. Alternatively or additionally, control unit 16 may be configured to configure the voltage to electroosmotically drive fluid from the nucleus pulposus, to the site outside the nucleus pulposus.
As described with reference to
As described hereinabove, apparatus 10 may alternatively or additionally be configured to drive fluid out of the nucleus pulposus. For such applications, the apparatus may thereby be configured to detect the pressure at the nucleus pulposus (e.g., the pressure above atmospheric pressure), and/or to detect the pressure difference and/or the voltage between the nucleus pulposus and the site outside of the nucleus pulposus, and to apply the treatment voltage if the detected pressure, pressure difference, and/or voltage is greater than a threshold pressure, pressure difference, and/or voltage.
Typically, the detected voltage is detected while the treatment voltage is not applied. For example, control unit may be configured to apply the treatment voltage and detect the detected voltage in a sequence, and/or to periodically stop applying the treatment voltage so as to detect the detected voltage.
Reference is made to
According to one application of the present invention, control unit 16 is configured to apply a voltage between first electrode 12 and second electrode 14, and to configure the voltage to electroosmotically drive fluid out of subarachnoid cavity 80. It is further hypothesized by the inventor that the driving of the fluid is beneficial for subjects suffering from and/or at risk of Alzheimer's disease (e.g., that are asymptomatic of Alzheimer's disease), by facilitation of clearance of substances, such as amyloid-beta and metal ions (e.g., iron and copper ions), from the brain of the subject. For example, reduction of the concentration of amyloid beta monomers and/or oligomers from the brain may (1) inhibit the formation and/or growth of amyloid-beta plaques in the brain, and/or (2) reduce direct toxic effects of the oligomers on neurons of the brain. It is also hypothesized that, for some applications, this driving of the fluid may be used to treat a subject suffering from normal pressure hydrocephalus.
It is further hypothesized by the inventor that the driving of the fluid reduces the volume of fluid in at least parts of the brain, such as within ventricles of the brain, suppressing enlargement of the ventricles, e.g., caused by fluid pressure in the ventricles.
As described with reference to
Typically, the detected voltage is detected while the treatment voltage is not applied. For example, control unit may be configured to apply the treatment voltage and detect the detected voltage in a sequence, and/or to periodically stop applying the treatment voltage so as to detect the detected voltage.
Reference is now made to
Reference is again made to
Reference is again made to
Reference is again made to
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.
The present application is a continuation of U.S. patent application Ser. No. 13/872,794, filed Apr. 29, 2013, now U.S. Pat. No. 9,731,122. U.S. patent application Ser. No. 13/872,794, filed Apr. 29, 2013, is related to U.S. patent application Ser. No. 13/663,757 to Gross, filed Oct. 30, 2012, now U.S. Pat. No. 8,676,348, which is a continuation of U.S. patent application Ser. No. 12/373,306 to Gross, now U.S. Pat. No. 8,577,469, which is a US National Phase of PCT patent application PCT/IL07/00865 to Gross, filed Jul. 10, 2007, entitled “Iontophoretic and electroosmotic disc treatment”, which published as WO 2008/007369; which claims priority from U.S. provisional patent application 60/830,717 to Gross, filed Jul. 12, 2006, entitled “Iontophoretic and electroosmotic disc treatment”, all of which are incorporated herein by reference.
| Number | Name | Date | Kind |
|---|---|---|---|
| 4044774 | Corbin et al. | Aug 1977 | A |
| 4503863 | Katims | Mar 1985 | A |
| 5088977 | Sibalis | Feb 1992 | A |
| 5121754 | Mullett | Jun 1992 | A |
| 5433739 | Sluijter et al. | Jul 1995 | A |
| 5529574 | Frackelton | Jun 1996 | A |
| 5792100 | Shantha | Aug 1998 | A |
| 5911223 | Weaver et al. | Jun 1999 | A |
| 5938690 | Law et al. | Aug 1999 | A |
| 6041252 | Walker et al. | Mar 2000 | A |
| 6146380 | Racz et al. | Nov 2000 | A |
| 6161047 | King et al. | Dec 2000 | A |
| 6360750 | Gerber et al. | Mar 2002 | B1 |
| 6567702 | Nekhendzy et al. | May 2003 | B1 |
| 6591138 | Fischell et al. | Jul 2003 | B1 |
| 6602248 | Sharps et al. | Aug 2003 | B1 |
| 6620155 | Underwood et al. | Sep 2003 | B2 |
| 6941172 | Nachum | Sep 2005 | B2 |
| 6997941 | Sharkey et al. | Feb 2006 | B2 |
| 7013177 | Whitehurst et al. | Mar 2006 | B1 |
| 7120489 | Shalev et al. | Oct 2006 | B2 |
| 7217351 | Krumme | May 2007 | B2 |
| 7223227 | Pflueger | May 2007 | B2 |
| 7270659 | Ricart et al. | Sep 2007 | B2 |
| 7317947 | Wahlstrand et al. | Jan 2008 | B2 |
| 7398121 | Matsumura et al. | Jul 2008 | B2 |
| 7509171 | DiMauro | Mar 2009 | B2 |
| 7640062 | Shalev | Dec 2009 | B2 |
| 7831306 | Finch et al. | Nov 2010 | B2 |
| 7860569 | Solberg et al. | Dec 2010 | B2 |
| 8190248 | Besio et al. | May 2012 | B2 |
| 8457761 | Wariar | Jun 2013 | B2 |
| 8577469 | Gross | Nov 2013 | B2 |
| 8676348 | Gross | Mar 2014 | B2 |
| 9616221 | Gross | Apr 2017 | B2 |
| 9724513 | Lane et al. | Aug 2017 | B2 |
| 9731122 | Gross | Aug 2017 | B2 |
| 10398884 | Lad et al. | Sep 2019 | B2 |
| 20020151948 | King et al. | Oct 2002 | A1 |
| 20020183683 | Lerner | Dec 2002 | A1 |
| 20030130707 | Gan et al. | Jul 2003 | A1 |
| 20030158589 | Katsnelson | Aug 2003 | A1 |
| 20030216792 | Levin et al. | Nov 2003 | A1 |
| 20030225331 | Diederich et al. | Dec 2003 | A1 |
| 20040002746 | Ryan et al. | Jan 2004 | A1 |
| 20040019381 | Pflueger | Jan 2004 | A1 |
| 20040049180 | Sharps et al. | Mar 2004 | A1 |
| 20040116977 | Finch et al. | Jun 2004 | A1 |
| 20040210209 | Yeung et al. | Oct 2004 | A1 |
| 20050010205 | Hovda et al. | Jan 2005 | A1 |
| 20050021104 | DiLorenzo | Jan 2005 | A1 |
| 20050119650 | Sanders et al. | Jun 2005 | A1 |
| 20050137646 | Wallace et al. | Jun 2005 | A1 |
| 20050137647 | Wallace | Jun 2005 | A1 |
| 20050159790 | Shalev | Jul 2005 | A1 |
| 20050187589 | Wallace et al. | Aug 2005 | A1 |
| 20050203599 | Garabedian et al. | Sep 2005 | A1 |
| 20050203600 | Wallace et al. | Sep 2005 | A1 |
| 20050203602 | Wallace et al. | Sep 2005 | A1 |
| 20050222647 | Wahlstrand et al. | Oct 2005 | A1 |
| 20050277996 | Podhajsky et al. | Dec 2005 | A1 |
| 20060030895 | Simon et al. | Feb 2006 | A1 |
| 20060106430 | Fowler et al. | May 2006 | A1 |
| 20060224223 | Podhajsky et al. | Oct 2006 | A1 |
| 20060293723 | Whitehurst et al. | Dec 2006 | A1 |
| 20070000784 | Paul et al. | Jan 2007 | A1 |
| 20070073402 | Vresilovic et al. | Mar 2007 | A1 |
| 20070162086 | DiLorenzo | Jul 2007 | A1 |
| 20070213700 | Davison et al. | Sep 2007 | A1 |
| 20070233202 | Wallace et al. | Oct 2007 | A1 |
| 20070255338 | Wahlstrand | Nov 2007 | A1 |
| 20080009927 | Vilims | Jan 2008 | A1 |
| 20080119907 | Stahmann | May 2008 | A1 |
| 20080260542 | Nishikawa et al. | Oct 2008 | A1 |
| 20090112278 | Wingeier et al. | Apr 2009 | A1 |
| 20090125080 | Montgomery | May 2009 | A1 |
| 20090126813 | Yanagisawa et al. | May 2009 | A1 |
| 20090131850 | Geiger | May 2009 | A1 |
| 20090312816 | Gross | Dec 2009 | A1 |
| 20100217369 | Gross | Aug 2010 | A1 |
| 20100324441 | Hargrove et al. | Dec 2010 | A1 |
| 20110046540 | Alterman et al. | Feb 2011 | A1 |
| 20110054518 | Carbunaru et al. | Mar 2011 | A1 |
| 20110160638 | Mauge | Jun 2011 | A1 |
| 20110160797 | Makous et al. | Jun 2011 | A1 |
| 20120053659 | Molnar et al. | Mar 2012 | A1 |
| 20120203307 | Schroeppel et al. | Aug 2012 | A1 |
| 20130066392 | Simon et al. | Mar 2013 | A1 |
| 20130102952 | Gross | Apr 2013 | A1 |
| 20130166006 | Williams | Jun 2013 | A1 |
| 20130289385 | Lozano et al. | Oct 2013 | A1 |
| 20140058189 | Stubbeman | Feb 2014 | A1 |
| 20140088672 | Bedenbaugh | Mar 2014 | A1 |
| 20140207224 | Simon | Jul 2014 | A1 |
| 20140257168 | Gill | Sep 2014 | A1 |
| 20140324128 | Gross | Oct 2014 | A1 |
| 20150011927 | Hua | Jan 2015 | A1 |
| 20150119898 | Desalles et al. | Apr 2015 | A1 |
| 20160331970 | Lozano | Nov 2016 | A1 |
| 20170007823 | Gross | Jan 2017 | A1 |
| 20170120053 | Fostick et al. | May 2017 | A1 |
| Number | Date | Country |
|---|---|---|
| 2004321242 | Nov 2004 | JP |
| 2007501067 | Jan 2007 | JP |
| 9405369 | Mar 1994 | WO |
| 0152931 | Jul 2001 | WO |
| 0185027 | Nov 2001 | WO |
| 2001085094 | Nov 2001 | WO |
| 2006090397 | Aug 2006 | WO |
| 2008007369 | Jan 2008 | WO |
| 2017072769 | May 2017 | WO |
| Entry |
|---|
| Sawyer, P N et al. “Measurement of streaming potentials of mammalian blood vessels, aorta and vena cava, in vivo.” Biophysical journal vol. 6,5 (1966): 641-51. doi:10.1016/S0006-3495(66)86683-3, https://www.ncbi.nim.nih.gov/pmc/articles/PMC1368020/, viewed on Jul. 22, 2019. |
| Sawyer, P N et al. “Measurement of streaming potentials of mammalian blood vessels, aorta and vena cava, in vivo.” Biophysical journal vol. 6,5 (1966): 641-51. doi:10.1016/S0006-3495(66)86683-3, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1368020/, viewed on Jul. 22, 2019. |
| An Office Action dated Apr. 25, 2018, which issued during the prosecution of U.S. Appl. No. 15/637,330. |
| An Office Action dated Mar. 25, 2019, which issued during the prosecution of U.S. Appl. No. 15/742,245. |
| International Search Report and Written Opinion dated May 23, 2019 from the International Searching Authority in application No. PCT/IL2019/050284. |
| Non-Final Office Action dated Nov. 29, 2019 issued in U.S. Appl. No. 15/969,411. |
| Communication dated Aug. 24, 2020 from Japanese Patent Office in JP Application No. 2018-521586. |
| Karran, E. et al, “The Amyloid cascade hypothesis for Alzheimer's Disease: an appraisal for the development of therapeutics,” Nature Reviews Drug Discovery, Sep. 2011, vol. 10; 698-712. |
| De La Torre, J.C., “Vascular Basis of Alzheimer's Pathogenesis,” Ann NY Acad. Sci. 977:196-215 (Nov. 2002). |
| Weller, Roy O. et al, “Perivascular Drainage of Amyloid-β Peptides from the Brain and Its Failure in Cerebral Amyloid Angiopathy and Alzheimer's Disease,” Brain Pathology 18 (Apr. 2008) 253-266. |
| Brief PubMed search for metal ions in Alzheimer. |
| An Office Action dated Sep. 27, 2016, which issued during the prosecution of U.S. Appl. No. 14/926,705. |
| An International Search Report and a Written Opinion both dated Aug. 7, 2008, which issued during the prosecution of Applicant's PCT/IL2007/000865. |
| An Office Action dated Mar. 29, 2013, which issued during the prosecution of U.S. Appl. No. 12/373,306. |
| An Office Action dated Oct. 31, 2011, which issued during the prosecution of U.S. Appl. No. 12/373,306. |
| An Office Action dated Oct. 1, 2012, which issued during the prosecution of U.S. Appl. No. 12/373,306. |
| Notice of Allowance dated Jul. 24, 2013, which issued during the prosecution of U.S. Appl. No. 12/373,306. |
| An Office Action dated Apr. 11, 2013, which issued during the prosecution of U.S. Appl. No. 13/663,757. |
| Notice of Allowance dated Oct. 28, 2013, which issued during the prosecution of U.S. Appl. No. 13/663,757. |
| Elixmann, I.M. et al., “In-vitro evaluation of a drainage catheter with integrated bioimpedance electrodes to determine ventricular size,” Biomed Tech 2013; 58 (Suppl. 1) Sep. 2013 (2 pages total). |
| An Office Action dated Aug. 31, 2015, which issued during the prosecution of U.S. Appl. No. 13/872,794. |
| An Applicant Initiated Interview Summary dated Dec. 14, 2015, which issued during the prosecution of U.S. Appl. No. 13/872,794. |
| An Office Action dated Feb. 3, 2016, which issued during the prosecution of U.S. Appl. No. 13/872,794. |
| Notice of Allowance dated Dec. 9, 2016, which issued during the prosecution of U.S. Appl. No. 14/794,739. |
| An Applicant Initiated Interview Summary dated Feb. 25, 2016, which issued during the prosecution of U.S. Appl. No. 13/872,794. |
| An Office Action dated Jun. 15, 2016, which issued during the prosecution of U.S. Appl. No. 13/872,794. |
| An International Search Report and a Written Opinion both dated Oct. 20, 2016, which issued during the prosecution of Applicant's PCT/IL2016/050728. |
| An Office Action dated Sep. 21, 2016, which issued during the prosecution of U.S. Appl. No. 14/794,739. |
| An International Search Report and a Written Opinion both dated Jan. 26, 2017, which issued during the prosecution of Applicant's PCT/IL2016/051161. |
| Notice of Allowance dated Jul. 14, 2017, which issued during the prosecution of U.S. Appl. No. 13/872,794. |
| An Office Action dated May 26, 2017, which issued during the prosecution of U.S. Appl. No. 15/453,290. |
| An International Preliminary Report on Patentability dated Apr. 7, 2009, which issued during the prosecution of Applicant's PCT/IL2007/000865. |
| Loutzenhiser, L. et al., “Membrane Potential measurements in renal afferent and efferent arterioles: actions of Angiotensin II”, American Journal of Physiology—Renal Physiol. Aug. 1, 1997 vol. 273 No. 2 F307-F314. |
| U.S. Appl. No. 60/830,717, filed Jul. 12, 2006. |
| Dao-Sheng, Liu et al., “Activation of Na+ and K+ Pumping Modes of (Na,K)-ATPase by an Oscillating Electric Field,” The Journal of Biological Chemistry, vol. 265. No. 13, May 5, 1990. (pp. 7260-7267). |
| Service, Robert F. “Electric fields deliver drugs into tumors.” http://news.sciencemaa.ora. Feb. 4, 2015. (5 Pages Total). |
| Vernengo J., “Injectable Bioadhesive Hydrogels for Nucleus Pulposus Replacement and Repair of the Damaged Intervertebral Disc: A Thesis,” Drexel University (Jan. 2007). |
| Urban, J. P. G. et al., “The nucleus of the intervertebral disc from development to degeneration,” American Zoologist 40(1): 53-61 (2000). |
| Cheung, K. M. C. et al., “Intervertebral disc regeneration by use of autologous mesenchymal stem cells, an experimental model in rabbits,” Abstract from the SRS 2004 Annual Meeting. |
| Freemont, T.J. et al., “Degeneration of intervertebral discs: current understanding of cellular and molecular events, and implications for novel therapies,” Expert Reviews in Molecular Biology, Mar. 29, 2001 (Cambridge University Press). |
| An Office Action dated Sep. 12, 2011, which issued during the prosecution of U.S. Appl. No. 12/373,306. |
| An Office Action dated Jul. 24, 2017, which issued during the prosecution of U.S. Appl. No. 14/982,187. |
| An International Search Report and a Written Opinion both dated Mar. 10, 2017, which issued during the prosecution of Applicant's PCT/IL2016/051363. |
| Office Action dated Jan. 22, 2020 issued in U.S. Appl. No. 15/771,551. |
| Communication dated Nov. 20, 2020 by the United States Patent and Trademark Office in U.S. Appl. No. 16/353,407. |
| Number | Date | Country | |
|---|---|---|---|
| 20170274207 A1 | Sep 2017 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 13872794 | Apr 2013 | US |
| Child | 15618325 | US |
