Prosthetic management of body physiology

Abstract

A device, such as an implantable medical device, includes an implantable device configured to cause trauma in an inner ear and / or middle ear recipient. In an exemplary embodiment, the implantable device is a cochlear implant. In an exemplary embodiment, the implantable device is configured to deliver a therapeutic substance to recipient body tissue.

Description

[0001] Cross - reference to related applications

[0002] This application claims priority to U.S. Provisional Application No. 62 / 645,455, filed Mar. 20, 2018, entitled "PROSTHESIS MANAGEMENT OF BODY PHYSIOLOGY", naming Daniel SMYTH of Mechelen, Belgium as the inventor, the entire content of which is incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION

[0003] Hearing loss, which can be caused by a variety of different reasons, is generally of two types: conductive and sensorineural. Sensorineural hearing loss is due to the absence or damage of the hair cells in the cochlea that convert sound signals into nerve impulses. A variety of hearing prostheses are available on the market to provide the ability to perceive sound to individuals suffering from sensorineural hearing loss. An example of a hearing prosthesis is a cochlear implant.

[0004] Conductive hearing loss occurs when the normal mechanical pathway for sound to reach the hair cells in the cochlea is blocked, for example due to damage to the ossicular chain or ear canal. Individuals with conductive hearing loss may retain some form of residual hearing because the hair cells in the cochlea may not be damaged.

[0005] Individuals with hearing loss typically receive acoustic hearing aids. Conventional hearing aids rely on the principle of air conduction to transmit acoustic signals to the cochlea. In particular, hearing aids typically use an arrangement placed in or on the outer ear of the recipient to amplify the sound received by the recipient's outer ear. This amplified sound reaches the cochlea, causing movement of the perilymph fluid and stimulation of the auditory nerve. Cases of conductive hearing loss are typically treated with bone conduction hearing aids. In contrast to conventional hearing aids, these devices use a mechanical actuator that is coupled to the skull to apply amplified sound.

[0006] In contrast to hearing aids that primarily rely on the principle of air conduction, certain types of hearing prostheses, commonly referred to as cochlear implants, convert the received sound into electrical stimulation. The electrical stimulation is applied to the cochlea, which results in the perception of the received sound.

[0007] Many devices, such as medical devices that interface with a recipient, have structural and / or functional features that are of practical value in tailoring such features for an individual recipient. The process of customizing or otherwise adapting a device that interfaces with a recipient or is otherwise used by a recipient to the specific needs or requirements or characteristics of the recipient is generally referred to as fitting. One type of medical device that has practical value in such individual recipients is the cochlear implant described above. That is, there are other types of medical devices that have practical value in fitting a recipient, such as other types of hearing prostheses. Summary of the Invention

[0008] According to an exemplary embodiment, there is an implantable device configured to cause trauma in an inner ear and / or middle ear recipient. In some embodiments, the trauma is reversible, while in other embodiments, it is irreversible.

[0009] According to another exemplary embodiment, there is a method comprising: monitoring a physical phenomenon inside a recipient's cochlea; and managing the recipient's blood-labyrinth barrier based on the monitored physical phenomenon.

[0010] According to another exemplary embodiment, there is a method that includes administering a therapeutic substance to a person and causing trauma and / or eliciting a foreign body response in or near the person's anatomy so as to adjust the concentration / amount of the therapeutic substance in the anatomy relative to a situation where there is no trauma and / or foreign body response.

[0011] According to another exemplary embodiment, there is provided a system that includes an implantable blood-labyrinth barrier management component configured to affect the blood-labyrinth barrier to control the amount of a substance in an anatomy to be more than the amount in the absence of the affect. Brief Description of the Drawings

[0012] Embodiments are described below with reference to the drawings, where:

[0013] Figure 1 is a perspective view of an exemplary hearing prosthesis to which at least some of the teachings detailed herein may be applied;

[0014] Figure 1B depicts a side view of a cochlear implant 100 outside a recipient;

[0015] Figure 2 depicts a side view of a cochlear implant electrode array in a coiled configuration;

[0016] Figure 3A depicts an exemplary cochlear implant electrode array according to an exemplary embodiment;

[0017] Figure 3B depicts an exemplary cochlear implant electrode array inserted into the cochlea;

[0018] Figures 4A - 4C depicts Figure 3A some exemplary features of a portion of the cochlear implant electrode array of;

[0019] Figure 5 depicts the cochlear implant electrode array in use Figure 3A exemplary embodiments of;

[0020] Figure 6 and Figure 7 present alternative exemplary embodiments of an implantable component configured to perform at least some of the method acts detailed herein;

[0021] Figure 8 and Figure 9 present alternative exemplary embodiments of an implantable component configured to perform at least some of the method acts detailed herein;

[0022] Figures 10 - 13 presents an exemplary algorithm for an exemplary method according to some exemplary embodiments;

[0023] Figure 14 presents an exemplary system according to exemplary embodiments; and

[0024] Figure 15 presents Figure 3A alternative exemplary embodiments of the exemplary embodiments of; Detailed Description

[0025] Figure 1is a perspective view of a cochlear implant, referred to as cochlear implant 100, implanted in a recipient, to which some embodiments and / or variants thereof detailed herein may be applied. Cochlear implant 100 is part of system 10, which in some embodiments may include external components, as will be described in detail below. Additionally, it should be noted that the teachings detailed herein may also be applied to other types of hearing prostheses, such as, by way of example and not limitation, bone conduction devices (transcutaneous, active transcutaneous, and / or passive transcutaneous), direct acoustic cochlear stimulators, middle ear implants, and conventional hearing aids, among others. In fact, it should be noted that the teachings detailed herein may also be applied to so-called multimodal devices. In an exemplary embodiment, these multimodal devices apply both electrical and acoustic stimulation to the recipient. In an exemplary embodiment, these multimodal devices evoke auditory perception via electroacoustic and bone conduction hearing. Thus, unless otherwise specified, or unless its disclosure is incompatible with a given device based on the current state of the art, any disclosure herein regarding one of these types of hearing prostheses corresponds to the disclosure regarding another of these types of hearing prostheses or to any medical device in this regard. Thus, in at least some embodiments, the teachings detailed herein may be applied to partially implantable and / or fully implantable medical devices that provide a wide range of therapeutic benefits to the recipient, patient, or other user, including hearing implants with implanted microphones, auditory brain stimulators, pacemakers, visual prostheses (e.g., bionic eyes), sensors, drug delivery systems, defibrillators, functional electrical stimulation devices, and the like.

[0026] In view of the foregoing, it should be understood that at least some embodiments and / or variants thereof detailed herein are directed to body-worn sensory augmentation medical devices (e.g., Figure 1 a hearing prosthesis that augments the sense of hearing, even in the absence of natural hearing ability, e.g., due to prior degradation of natural hearing ability or due to any lack of natural hearing ability (e.g., from birth)). It should be noted that at least some exemplary embodiments of some sensory augmentation medical devices are directed to devices such as conventional hearing aids that augment the sense of hearing while some natural hearing ability is retained, as well as visual prostheses (which may be applied to recipients with some natural visual ability as well as those without natural visual ability). Thus, the teachings detailed herein may be applied to any type of sensory augmentation medical device, and the teachings detailed herein enable their use in a practical manner. In this regard, the phrase "sensory augmentation medical device" refers to any device that provides a sense to a recipient, regardless of whether the applicable natural sense is only partially impaired, fully impaired, or even non-existent.

[0027] The recipient has an outer ear 101, a middle ear 105, and an inner ear 107. The components of the outer ear 101, middle ear 105, and inner ear 107 are described below, followed by a description of cochlear implant 100.

[0028] In a fully functional ear, the outer ear 101 includes the auricle 110 and the ear canal 102. The auricle 110 collects sound pressure or sound waves 103 and conducts them into and through the ear canal 102. Arranged across the distal end of the ear canal 102 is the tympanic membrane 104, which vibrates in response to the sound waves 103. This vibration is coupled to the oval window or fenestra ovalis 112 through three bones of the middle ear 105 (collectively referred to as the ossicles 106 and including the malleus 108, the incus 109, and the stapes 111). The bones 108, 109, and 111 of the middle ear 105 are used to filter and amplify the sound waves 103, causing the oval window 112 to sound or vibrate in response to the vibration of the tympanic membrane 104. This vibration creates a fluid motion wave of perilymph fluid inside the cochlea 140. This fluid motion in turn activates tiny hair cells (not shown) inside the cochlea 140. The activation of the hair cells causes appropriate nerve impulses to be generated and transmitted through the spiral ganglion cells (not shown) and the auditory nerve 114 to the brain (also not shown), where they are perceived as sound.

[0029] As shown, the cochlear implant 100 includes one or more components that are temporarily or permanently implanted in a recipient. The cochlear implant 100 is shown in Figure 1 to have an external device 142, which is part of a system 10 (along with the cochlear implant 100) that is configured to provide power to the cochlear implant, where the implanted cochlear implant includes a battery that can be charged via a percutaneous link.

[0030] In Figure 1 an illustrative arrangement, the external device 142 can include a power source (not shown) housed in a behind-the-ear (BTE) unit 126. The external device 142 also includes components of a percutaneous energy transfer link, referred to as an external energy transfer component. The percutaneous energy transfer link is used to transfer power and / or data to the cochlear implant 100. Various types of energy transfer, such as infrared (IR), electromagnetic, capacitive, and inductive transfer, can be used to transfer power and / or data from the external device 142 to the cochlear implant 100. In Figure 1 an illustrative embodiment, the external energy transfer component includes an external coil 130, which forms part of an inductive radio frequency (RF) communication link. The external coil 130 is typically a wire antenna coil composed of multiple turns of electrically insulated single-strand or multi-strand platinum or gold wire. The external device 142 also includes a magnet (not shown) placed within the turns of the external coil 130. It should be understood that Figure 1 the external device shown in

[0031] The cochlear implant 100 includes an internal energy transfer component 132 that can be placed in a recess of the temporal bone adjacent to the recipient's auricle 110. As detailed below, the internal energy transfer component 132 is part of a transcutaneous energy transfer link and receives power and / or data from an external device 142. In an illustrative embodiment, the energy transfer link includes an inductive RF link, and the internal energy transfer component 132 includes a primary internal coil 136. The internal coil 136 is generally a wire antenna coil including multiple turns of electrically insulated single-strand or multi-strand platinum or gold wire.

[0032] The cochlear implant 100 also includes a main implantable component 120 and an elongated electrode assembly 118. In some embodiments, the internal energy transfer component 132 and the main implantable component 120 are hermetically sealed within a biocompatible housing. In some embodiments, the main implantable component 120 includes an implantable microphone assembly (not shown) and a sound processing unit (not shown) to convert sound signals received by the implantable microphone in the internal energy transfer component 132 into data signals. That is, in some alternative embodiments, the implantable microphone assembly may be located in a separate implantable component (e.g., having its own housing assembly, etc.) that communicates signals with the main implantable component 120 (e.g., via leads between the separate implantable component and the main implantable component 120). In at least some embodiments, the teachings detailed herein and / or variations thereof can be used with any type of implantable microphone arrangement.

[0033] The main implantable component 120 also includes a stimulator unit (also not shown) that generates electrical stimulation signals based on the data signals. The electrical stimulation signals are delivered to the recipient via the elongated electrode assembly 118.

[0034] The elongated electrode assembly 118 has a proximal end connected to the main implantable component 120 and a distal end implanted in the cochlea 140. The electrode assembly 118 extends from the main implantable component 120 through the mastoid bone 119 to the cochlea 140. In some embodiments, the electrode assembly 118 may be at least implanted in the basal region 116 and sometimes further implanted. For example, the electrode assembly 118 may extend towards the apex 134 of the cochlea 140, which is referred to as the cochlear apex. In certain cases, the electrode assembly 118 may be inserted into the cochlea 140 via the cochleostomy 122. In other cases, a cochleostomy may be formed through the round window 121, the oval window 112, the promontory 123, or through the apical turn 147 of the cochlea 140.

[0035] The electrode assembly 118 includes an array 146 of electrodes 148 longitudinally aligned and extending distally along its length. As noted, the stimulator unit generates stimulation signals applied by the electrodes 148 to the cochlea 140 to stimulate the auditory nerve 114.

[0036] Figure 1B is a side view of a cochlear implant 100 that does not have other components (e.g., external components) of the system 10. The cochlear implant 100 includes a receiver / stimulator 180 and an electrode assembly or lead 118. The electrode assembly 118 includes a helical region 182, a transition region 184, a proximal region 186, and an intracochlear region 188. The proximal region 186 and the intracochlear region 188 form an electrode array assembly 190. In an exemplary embodiment, after the intracochlear region 188 is implanted into the cochlea, the proximal region 186 is located in the middle ear cavity of the recipient. Thus, the proximal region 186 corresponds to the middle ear cavity sub-part of the electrode array assembly 190. The electrode array assembly 190, particularly the intracochlear region 188 of the electrode array assembly 190, supports a plurality of electrode contacts 148. Each of these electrode contacts 148 is connected to a corresponding conductive path, such as a wire, a PCB trace, etc. (not shown), which is connected to the receiver / stimulator 180 through the lead 118, and the corresponding stimulation electrical signals for each electrode contact 148 propagate therethrough.

[0037] Figure 2 is a side view of the electrode array assembly 190 in a coiled orientation, as it would be in situ in a patient's cochlea, where the electrode contacts 148 are located on the inner side of the bend. Figure 3A Depicts a side view of a device 390 corresponding to a cochlear implant electrode array assembly, which may include Figure 1B some or all of the features of the electrode array assembly 190. More specifically, in an exemplary embodiment, the electrode assembly 118 includes an electrode array assembly 390 instead of the electrode array assembly 190 (i.e., 190 is replaced by 390). Thus, according to an exemplary embodiment, there is a cochlear implant 100 as described above, which includes an electrode array assembly 390, wherein the electrodes of the electrode array assembly 390 communicate with the rest of the implantable components in the cochlear implant in a conventional manner (although leads, etc. may be re-wired with respect to the electrode array assembly 390 to accommodate the teachings detailed herein and / or its variations). Additional details of the assembly 390 will now be provided.

[0038] The electrode array assembly 390 includes a cochlear implant electrode array 310 and a device 320 configured to cause trauma in the cochlea. In an exemplary embodiment, the device elicits a foreign body response in the cochlea. In an exemplary embodiment, the trauma elicits a foreign body response in the cochlea, while in other exemplary embodiments, the trauma does not elicit a foreign body response. In an exemplary embodiment, it elicits in one and does not elicit in the other, and in other embodiments, it elicits both. In an exemplary embodiment, the trauma is reversible. In an exemplary embodiment, the trauma is irreversible or at least not completely reversible. In an exemplary embodiment, the trauma is at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more reversible. In an exemplary embodiment, the trauma is 100% reversible. In an exemplary embodiment, the foreign body response exceeds the foreign body response caused solely by the insertion / implantation process of inserting the cochlear electrode array. In an exemplary embodiment, the foreign body response is a deliberately exaggerated foreign body response that exceeds the foreign body response caused by the insertion / implantation of the electrode array. That is, the foreign body response is purposefully elicited to be more severe than otherwise. In an exemplary embodiment, the foreign body response is a process caused by something that is at least partially reversible, such as at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more reversible. In an exemplary embodiment, the foreign body response is a foreign body response caused by something that prevents trauma (atraumatic). In an exemplary embodiment, the foreign body response is a foreign body response caused by something that is non-traumatic. In an exemplary embodiment, the electrode array assembly 390 has some and / or all of the functionality of the electrode array assembly 190, where the electrode array assembly 190 corresponds to a state-of-the-art electrode array assembly and / or its variants and / or earlier model electrode array assemblies. By way of example only and not limitation, the electrode array assembly 390 includes any electrode array 310 having a plurality of electrodes 148. The electrode array assembly 390 is configured such that the electrodes 148 of the electrode array 310 are in and / or are placed into signal communication with the receiver stimulator 180. Thereafter, in alternative embodiments, unless otherwise indicated that the art is capable of achieving this, any disclosure of trauma corresponds to eliciting a foreign body response and vice versa. It should be clear that this does not mean that they are the same. Quite the contrary. The purpose of this statement is merely to provide an easy way to convey various concepts. It should also be noted that the two are not mutually exclusive. Trauma can cause a foreign body response.

[0039] In some embodiments, the device 320 is configured to expand to contact the wall of the cochlea. In Figure 3AIn an exemplary embodiment, device 320 is a pressure-based component. Along these lines, in an exemplary embodiment, device 320 is configured to expand when pressurized.

[0040] More specifically, device 320 includes an inflatable subassembly 330 that is in fluid communication with a catheter 340, which in turn is in fluid communication with a pressure generator subassembly 350 (e.g., a pump coupled to a reservoir of fluid). As can be seen, pressure generator subassembly 350 includes electrical lead ports 303 that electrically communicate the pressure generator subassembly with the receiver stimulator of the cochlear implant. That is, in an exemplary embodiment, component 350 can be Figure 3B depicts a conceptual representation of an electrode array assembly 390 inserted into the cochlea 140, which is configured to be prosthetically retained in the cochlea (i.e., it is configured to remain in the cochlea for a period of time associated with the use of a prosthetic device, as opposed to a temporary insertion such as might be the case with a needle, etc.). Figure 3B depicts a conceptual diagram that depicts the intracochlear region 188 of the electrode array assembly 390 in the cochlea 140 and the proximal region 186 of the electrode array assembly 390 that is located external to the cochlea 140, where the catheter 340 of device 320 extends from inside the cochlea 140 to outside the cochlea into the middle ear cavity, which is functionally represented by the dashed enclosure 105. It should be noted that Figure 3B and Figure 3A this figure in is only conceptual and is provided at least to present the concept of a cochlear implant electrode array with a device 320 that is only partially inserted into the cochlea. In an exemplary embodiment, the electrode array assembly is inserted into the scala tympani together with the inflatable subassembly (hereinafter referred to as an inflator). That is, in an alternative embodiment, at least the inflator is inserted into the scala vestibuli. Thus, in an exemplary embodiment, there is an electrode array assembly that is configured such that the electrode array can be inserted into the scala tympani while the inflator can be inserted into the scala vestibuli. In an exemplary embodiment, the entire electrode array assembly is configured to be insertable into the scala vestibuli.

[0041] Additional details of the components of component 390 will now be described.

[0042] Before describing some details of the array 390, it is briefly pointed out that this is presented in terms of a conceptual device. For example, it can be seen that the boost pump 330 is located at the base portion of the electrode array. More precisely, it can be seen that the boost pump 330 is located only at the base portion of the electrode array. In some embodiments, the boost pump 330 is located midway along the electrode array, such as after the first 11 electrodes (thus, in the exemplary embodiment, between two sets of 11 electrodes of a 22 - electrode array). In some embodiments, the boost pump can be located at the top of the electrode array. The boost pump can be located anywhere where it can have practical value. It should also be noted that although this embodiment depicts the boost pump as a discrete component located in only one position, in the exemplary embodiment, multiple boost pumps can be utilized and positioned along the electrode array. It should also be noted that although the embodiments described herein detail the pressure generator 350 located near the electrode array / part of the electrode array, in the exemplary embodiment, the pressure generator is remote from the electrode array, such as, by way of example and not limitation, located in the receiver stimulator. In fact, in this exemplary embodiment, a tube or catheter can extend from the electrode array along the electrode lead to the receiver stimulator (where the pump is located).

[0043] In the exemplary embodiment, the pump is an electric pump that is operated by an inductive field that is communicated transcutaneously to the receiver stimulator unit. In the exemplary embodiment, the pump can be a manually - operated pump. In fact, in the exemplary embodiment of an embodiment where the pump is located remotely from the electrode array assembly, the receiver stimulator can be configured with a flexible member that can be repeatedly depressed through the recipient's skin. For example, the recipient can press his or her finger against his or her skin over the flexible member in order to pump fluid to the boost pump.

[0044] In the exemplary embodiment, the boost pump 330 is made of a titanium cylinder 332 that has a closed end and an end 336 that is open via a port 338. The port 338 provides fluid communication between the inside and the outside of the cylinder. The boost pump 330 includes four membranes 334 that are arranged around the longitudinal surface of the cylinder. (The membranes are depicted as curved membranes, but in alternative embodiments, the membranes are flat or can be other shapes.) In the embodiment of the drawings, the membranes 334 cover through - holes 333 that extend through the longitudinal surface of the cylinder 332. The membranes 334 hermetically seal these holes. The membranes 334 are configured to deflect or otherwise move in accordance with pressure changes inside the titanium cylinder due to the pump in the pressure generator sub - assembly 350. This causes pressure fluctuations within the boost pump 330. In the exemplary embodiment, this is because an increase in pressure in the cylinder 332 causes one or more of the membranes 334 to deflect outwardly.

[0045] In the embodiments of the drawings, there are four separate membranes provided with the booster pump 330. As can be seen, these membranes are evenly spaced transversely around the longitudinal axis of the cylinder 332. Some embodiments may use fewer or more membranes. In an exemplary embodiment, one, two, three, four, five, six or more membranes may be utilized. In at least some embodiments, any number of membranes capable of implementing the teachings detailed herein and / or variations thereof may be utilized.

[0046] In Figures 4A to 4C the embodiments, the membrane 334 is depicted as an individual membrane. In some exemplary embodiments, these membranes may be welded or glued or curled etc. to the cylinder 332. In an exemplary embodiment, a membrane assembly is utilized, wherein the membrane is held within a frame that is attached to the cylinder 332. In at least some embodiments, any device, system or method that will enable the membrane to be attached to the cylinder 332 such that the teachings detailed herein can be practiced may be utilized. In fact, along these lines, in an exemplary embodiment, the cylinder 332 includes four through-holes. A single membrane sheet is wrapped around the cylinder 332. An adhesion process may be utilized to adhere the membrane to the cylinder 332. This process adheres the sheet to the portion of the cylinder where there are no holes. Thus, the sheet freely flexes over the holes of the cylinder 332 due to pressure changes. Thus, in the case of using only one sheet, four membranes are obtained from the manufacturing process.

[0047] Figure 5Depicts an exemplary scenario utilizing the array 390, where two of the membranes in the membrane 334 are extended / outwardly inflated. In fact, in at least some embodiments, all four membranes will be inflated. In some aspects, this figure is presented to convey the general concept of inflation. That is, in some embodiments, it should be noted that actually fewer than all of the membranes will be inflated - this can be achieved by utilizing certain types of materials that are different for some membranes than for others (and thus, more precisely, the amount of inflation can be different). A more rigid material can be used for one membrane relative to another membrane, and thus for a given pressure, the amount of deformation will be different. In the exemplary embodiment, the pressure generator 350 pumps an inert gas through the conduit 324 to increase the pressure inside the cylinder 332, causing the membrane 334 to expand outwardly. In the exemplary embodiment, the membrane 334 expands to contact the wall of the cochlea. In some embodiments, the fact that the membrane contacts the cochlear wall is sufficient to cause trauma and / or induce / initiate a foreign body response. In the exemplary embodiment, the membrane is repeatedly inflated and deflated in order to "tap" the wall of the cochlea, which will ultimately result in the initiation of trauma and / or the induction of a foreign body response. In the exemplary embodiment, the membrane can be undulating so as to rub against the cochlear wall back and forth. In this regard, in the exemplary embodiment, the membrane can be configured such that after a certain pressure is reached, one side of the membrane will expand more than the other side, and thus this expansion will rub against the wall of the membrane in at least one direction, as the other parts that are no longer expanding will be fixed relative to the wall.

[0048] In the exemplary embodiment, the membrane can have barbs or spikes or protuberances or abrasive surfaces thereon that, when expanded against the wall of the cochlea, will cause a similar irritation, resulting in trauma or a foreign body response.

[0049] It should be noted that Figures 3A - 5The embodiments are merely exemplary. In some alternative embodiments, the electrode array may be configured with other types of devices that will cause trauma and / or induce / initiate a foreign body reaction. By way of example only and not limitation, an optical / light generating device may be utilized to cause trauma and / or induce / initiate a foreign body reaction. In this regard, an optical fiber or the like may be utilized to route light into the interior of the cochlea, which will cause / initiate trauma / a reaction. In an alternative embodiment, the electrode array may be a conventional cochlear implant electrode array, where the electrodes are utilized to cause / initiate trauma / a reaction. In an exemplary embodiment, the cochlear implant may be configured such that the electrode array may be utilized to generate a current at an amperage level higher than the current utilized to induce auditory perception in a normally operating cochlear implant, and / or an alternating current frequency higher and / or lower than the alternating current frequency utilized to induce auditory perception in a normally operating cochlear implant may be applied. In an exemplary embodiment, the cochlear implant may be configured such that the electrode array may be utilized to generate direct current at least for a limited period of time. Direct current is not a good type of current to apply to tissues in the human body. In this regard, direct current may be utilized to cause / initiate trauma / a reaction.

[0050] In at least some exemplary embodiments, any device, system, and / or method that will cause the initiation of trauma and / or induce a foreign body reaction or any other type of physical phenomenon in a human body practicing one or more of the teachings detailed herein may be utilized. Moreover, in some embodiments, any device capable of managing the blood-labyrinth barrier may be utilized, even if this does not cause trauma and / or a foreign body reaction. In some embodiments, any device that can cause inflammation or otherwise alter the blood-labyrinth barrier (e.g., by inflaming the blood-labyrinth barrier) may be used.

[0051] Figure 6is a perspective view of an exemplary internal component 344 of an implant that, when implanted, has a trauma-induced / foreign body response-triggering / eliciting component in the middle ear. The internal component 344 includes an internal receiver unit 632, a modified stimulator unit 620, and a stimulation arrangement 650. In an exemplary embodiment, the modified stimulator unit can be the stimulator unit of a middle ear implant that has been modified, for example, by reprogramming to actuate the stimulation arrangement 650 rather than actuating a middle ear actuator, etc. In some alternative embodiments, the stimulator unit can be a processor that has an output to a cable 328, where the processor receives an input via the receiver unit 632 and processes the input according to an algorithm therein (e.g., if a frequency is received at a certain amplitude, the processor places the signal in a certain way to control the stimulation arrangement 650 well. As shown, the receiver unit 632 includes an internal coil (not shown) and a magnet 320 fixed relative to the internal coil. In some embodiments, the internal receiver unit 632 and the modified stimulator unit 620 are hermetically sealed within a biocompatible housing. For ease of illustration, the housing has been omitted from Figure 6 for clarity.

[0052] The stimulator unit 620 is connected to the stimulation arrangement 650 via a cable 328. The stimulation arrangement 650 includes an actuator assembly 661, an actuator assembly mounting member 651, and an actuator assembly positioning arm 652. In an exemplary embodiment, the actuator assembly mounting member 651 is configured to be located in an artificial passage in the mastoid bone and fixed to the recipient's mastoid bone. As Figure 6 indicated by the curved arrow of, the actuator assembly mounting member 651 and the actuator assembly 661 are configured such that the actuator assembly positioning arm 652 can articulate relative to those components. Further, as Figure 6 indicated by the straight arrow in, the actuator assembly positioning arm 652 is configured to telescope to provide longitudinal adjustment between the actuator assembly 661 and the actuator assembly mounting member 651.

[0053] In operation, the actuator 661 applies a stimulus to the round window and / or oval window of the cochlea and / or another component of the cochlear outer wall in a manner that causes trauma and / or causes an induced / elicited foreign body response. In some embodiments, the body of the actuator assembly 661 remains fixed relative to the outer wall of the cochlea, and one or both of the output arms (two are shown, one for the round window and one for the oval window, but in some embodiments, there is only one output for the round window or the oval window) apply the stimulus to the respective round and oval windows. That is, in alternative embodiments, the actuator assembly mounting member, together with other components, can swing or otherwise cause the actuator 661 to impact the outer wall of the cochlea and / or the round window and / or the oval window, much like someone hitting a board with a hammer, etc. (or a manhole cover, with a hammer, etc.). In an exemplary embodiment, the actuator 661 is replaced by some other form of component that causes a stimulus, such as, for example, a blunt object or a pointed object, etc. In at least some exemplary embodiments, any component or configuration capable of causing trauma and / or eliciting a foreign body response can be utilized.

[0054] In an exemplary embodiment, the devices, systems, and / or methods detailed herein are configured to provide energy that generates a fluid motion wave of perilymph, thereby causing trauma / eliciting a foreign body response in or at or associated with the hair cells of the organ of Corti, and / or causing trauma or eliciting a foreign body response at the organ of Corti. In an exemplary embodiment, this is achieved by utilizing vibrations of a sufficient magnitude at certain frequencies or the lack thereof, which can cause the aforementioned trauma and / or foreign body response. In an exemplary embodiment, this can correspond to subsonic or supersonic frequencies provided over a sufficient period of time, which can cause trauma and / or elicit a foreign body response. In some cases, a sound can be heard, but the sound is only presented briefly.

[0055] Figure 7 An advanced concept diagram of a device that utilizes Figure 6 is depicted, where the actuator 361 is placed outside the cochlea 140. In this exemplary embodiment, the actuator 361 is configured to apply a compressive force and / or a tensile force to the round window 121 and / or apply a compressive force and / or a tensile force to the oval window 122. This can be done in a synchronous manner or in a separate manner. In some embodiments, the force corresponds to a knocking force rather than a more stable force (e.g., similar to using a hammer, etc.).

[0056] In view of the above, it can be seen that in an exemplary embodiment, there is a device that includes an implantable device configured to cause trauma to and / or elicit an inner ear foreign body response in the recipient's inner ear and / or middle ear. Regarding Figure 3A the embodiments, it can be seen that in some exemplary embodiments, the implantable device is a cochlear implant. Conversely, regardingFigure 6 As can be seen from the embodiments, in some embodiments, the implantable device is a component implanted in the middle ear.

[0057] In view of the foregoing, together with the following teachings, it will be seen that in exemplary embodiments, there is a device, system, and / or method that can cause inflammation and / or anti-inflammation of the BLB to control or otherwise manage the distribution of a compound or other substance in a human body structure (such as the cochlea, eye, kidney, etc.). In exemplary embodiments, there are devices, systems, and / or methods that are configured to achieve a degree of control over the BLB such that the BLB can be opened and / or closed, thereby affecting the permeability of the barrier to the substance in question. Such a device, system, and / or method can achieve systemic delivery of a drug or substance, achieve flushing of toxins from the structure in question, such as for ear protection. This can also control or otherwise manage the drug distribution and drug levels in the cochlea.

[0058] As noted above, in some embodiments, a mechanical stimulation / mechanical force output device can be utilized to induce a trauma / foreign body response. Also as noted above, in some embodiments, an electrical stimulation / electrical output device can be utilized to induce a trauma / foreign body response. Thus, in an exemplary embodiment, an implantable device is configured to extend into a recipient's cochlea and electrically stimulate tissue within the recipient to cause trauma and / or trigger a foreign body response. Further, consistent with the above embodiments, in some exemplary embodiments, the implantable device is a cochlear electrode array that is configured to extend into a recipient's cochlea and electrically stimulate the cochlear tissue in various ways to induce auditory perception (consistent with the typical operation of a cochlear implant) and to electrically stimulate tissue within the recipient to cause trauma and / or trigger a foreign body response (which is not consistent with the typical operation of a cochlear implant). It should be noted that although some embodiments utilize electrodes located within the cochlea to produce trauma and / or trigger a foreign body response, in some embodiments, only electrodes located outside the cochlea are utilized. By way of example and not limitation, in an exemplary embodiment, one or more electrodes can be placed against the outer wall of the cochlea in the middle ear, which can be utilized to trigger trauma and / or trigger a foreign body response. In an exemplary embodiment, the (multiple) electrodes can be ECE / hard ball / return. In an exemplary embodiment, the (multiple) electrodes can be placed against or otherwise adjacent to the round window, oval window, etc. The electrodes can be placed against or otherwise adjacent to the round window niche. Additionally, in some embodiments, the electrodes can be in communication with electrodes that are also within the cochlea in order to complete a circuit. Moreover, in some embodiments, the hard ball or return electrode / ECE can be utilized to complete a circuit through electrodes located in the middle ear and / or electrodes located in the cochlea. In at least some exemplary embodiments, any arrangement that can be utilized to establish electrical stimulation that causes trauma and / or triggers a foreign body response in the recipient's inner ear and / or middle ear can be utilized. Figure 3A An exemplary embodiment is shown where the implantable device is part of a cochlear implant that is configured to extend into a recipient's cochlea and electrically stimulate the cochlear tissue in a variety of ways to induce auditory perception as well as to electrically stimulate tissue within the recipient to cause trauma and / or trigger a foreign body response without inducing auditory perception. It should be noted that in some embodiments, even a normal electrode array without a boost pump 330 or other mechanical stimulation component can be utilized in at least some exemplary embodiments to cause trauma and / or trigger a foreign body response without inducing auditory perception. The key here is that causing trauma / triggering a foreign body response without the recipient "hearing" anything can have practical value. That is, in some embodiments, the trauma / foreign body response can lead to some associated auditory perception.

[0059] In some embodiments, the implantable device is configured to passively cause trauma and / or elicit a foreign body response. In some embodiments, the implantable device is configured to actively cause trauma and / or elicit a foreign body response.

[0060] Figure 8 Exemplary alternative embodiments are depicted, where the implantable device is a drug delivery device / substance delivery device in combination with a cochlear implant electrode array, but in other embodiments, the implantable device is only a drug delivery device. (Similarly, the mechanical stimulation device / detailed subsystem above can be utilized in such an implantable device itself (e.g., without an electrode array to induce auditory perception. The same holds for optical systems / light systems, etc. Any disclosure of any configuration herein can be used independently of or in combination with any other component disclosed herein.)

[0061] Figure 8 Component 230 is shown, which includes an elongate member 231, which corresponds to the electrode array (intracochlear portion), which has a distal end 233 that is first inserted into the cochlea when component 230 is inserted. As Figure 8 depicted, collar 240 is positioned (e.g., slidably or fixedly disposed) around lead 21 (which can be Figure 1 a lead). Collar 240 is for delivering one or more substances (drugs or bioactive substances or other substances) to a location just outside the cochlea (e.g., to the round or oval window, or to another location, such as to the cochlearostomy or any other useful location). In some embodiments, the substance delivered is a substance that elicits a foreign body response and / or causes trauma. In some embodiments, the substance delivered is a therapeutic substance. More on this is below.

[0062] Collar 240 has a stepped outer surface 241 defined by two cylindrical portions 242 and 243. In the depicted embodiment, collar 240 is symmetric about its longitudinal axis and has parallel proximal end 244 and distal end 245. The outlet of collar 240 is in distal end 245 of collar 240. In the depicted embodiment, collar 240 also has an inlet 250 in proximal end 244 of collar 240. The inlet and outlet are in communication with each other, such as in fluid communication. As Figure 8 depicted, the outlet 246 of collar 240 includes an annular opening in distal end 245 of the collar. The chamber 247 within the collar extends from the outlet 246 back into collar 240. Since the depicted outlet 246 is an annular opening, the chamber 247 is also annular and thus includes a cylindrical chamber having an outer surface and an inner surface and extending from the outlet 246 back into the collar. However, it should be understood that the outlet and chamber need not be annular to fall within the scope of this application.

[0063] The annular chamber 247 has a frustoconical region 248 where the outer and inner walls of the chamber 247 move away from the longitudinal axis of the collar 240, and has another cylindrical region 249 distal to the outlet. In this embodiment, the inlet 250 includes a pipeline extending from the proximal end 244 of the collar into the chamber 247. The inlet 250 is adjacent to the outer wall 241 of the collar 240.

[0064] The distal end 233 of the elongate member can be first inserted into the cochlear incision of the implantee during the placement of the implant. The chamber in the collar serves as a reservoir for the bioactive substance. The bioactive substance in the chamber diffuses from the chamber into the implantee through the semipermeable membrane 270 in the outlet 246. The membrane 270 allows the bioactive substance to leach out of the chamber to the desired site of action of the bioactive substance during and / or after implantation.

[0065] When the bioactive substance is carried in or includes a fluid, the semipermeable membrane 270 allows the fluid to leach out or diffuse therefrom.

[0066] The membrane 270 can be used as a valve or metering device that allows fluid to leave the chamber, but prevents or at least substantially prevents fluid from flowing back from outside the chamber into the chamber in the body.

[0067] Figure 8 The embodiments of... present exemplary embodiments where the trauma-induced / foreign body response triggering component is located outside the cochlea. Although Figure 8 The embodiments of... present a substance delivery device that causes trauma / triggers a foreign body response, but in alternative embodiments, the collar 240 can instead be a mechanical device etc. and / or an electrical stimulation device etc. In the exemplary embodiment, the expansion system detailed above can be located at the left surface of the collar to trigger mechanical stimulation on the outer wall of the cochlea and / or on the round window and / or oval window etc. of the cochlea.

[0068] Figure 9 Another exemplary embodiment of the electrode array 930 is presented, which includes the electrode 44 and also includes a catheter 933 through which the substance is ejected, indicated by the indicator / arrow "A". This exemplary embodiment presents a device that can enable the substance to be directly guided / supplied into the cochlea, which is contrary to Figure 8 the embodiments of..., where Figure 8 in the embodiments of..., the substance is provided at a location outside the cochlea and can diffuse into the interior of the cochlea through the wall and / or through the window. The corollary to this is that in the exemplary embodiment, the collar is configured with a needle etc. extending from outside the cochlea into the cochlea. In fact, Figure 9It can be conceptually represented as a needle that can be installed at the outlet of the collar 240 (minus electrodes, etc.) to inject substances or otherwise directly deliver them into the cochlea.

[0069] It should also be noted that in the exemplary embodiment, the electrode array can include components that move the electrode array within the cochlea. In the exemplary embodiment, magnetostrictive materials can be utilized to move the length of the electrode array like a whip or the like or to vibrate the electrode array, so as to cause trauma and / or trigger a foreign body reaction due to fluid movement within the cochlea caused by contact with the cochlear wall and / or perilymph that causes trauma to the cochlear wall.

[0070] It should be noted that since the boundary between the inner ear and the middle ear may not necessarily be clearly defined (when the wall of the cochlea ceases to be the middle ear and becomes the inner ear). Unless otherwise stated, any disclosure herein regarding inner ear trauma and / or foreign body reaction in the inner ear (cochlea) also corresponds to such disclosure at the boundary between the inner ear and the middle ear (e.g., the cochlear wall). The same is true for any reference to middle ear trauma and / or middle ear foreign body reaction.

[0071] As will be described in more detail below, there may be practical value in determining a condition regarding the presence within a recipient of an action that is guaranteed to cause trauma and / or elicit a foreign body response, relative to another condition where, absent that condition, the action would not be guaranteed. Thus, in an exemplary embodiment, there is an implantable device configured to detect a physical phenomenon within the cochlea. In this exemplary embodiment, the implantable device is configured to cause trauma and / or elicit a foreign body response when the physical phenomenon is detected. A corollary to this is that, in the exemplary embodiment, the implantable device is configured not to cause trauma and / or elicit a foreign body response when the physical phenomenon is not detected. In this regard, in the exemplary embodiment, instead of element 330 being a pressure pump, element 330 may be a detector or a receiver. In the exemplary embodiment, element 330 may include a diaphragm, etc., which may respond to a pressure change within the cochlea. Since diaphragm 330 is in fluid communication with element 350, in the exemplary embodiment, element 350 may be a pressure detector, etc., that can evaluate the pressure within the cochlea, since the pressure within the detector or receiver will change with the pressure change within the cochlea due to the elastic properties / flexibility of diaphragm 334. In fact, in the exemplary embodiment, an embodiment where element 334 is a membrane may be utilized, and pump 350 may be a combined pump / pressure detector. In the exemplary embodiment, when it is determined that the pressure within the inner ear has changed or otherwise been at a certain value for a particular period of time, this will indicate a phenomenon (e.g., disease, infection, etc.), since pressure detector 350 is in signal communication with the processor of the receiver simulator via lead output 303, and thus the processor programmed to evaluate the output signal can determine that the pressure has changed for a long enough period such that trauma should be caused and / or a foreign body response should be elicited.

[0072] In an exemplary embodiment, element 330 may be a temperature sensor, or, in an exemplary embodiment, the temperature sensor may be part of a component that is Figure 3A (delta). In the exemplary embodiment, the temperature sensor may detect the temperature within the cochlea. Monitoring this can determine whether there is a temperature increase within the cochlea, which can indicate an infection, etc., within the cochlea.

[0073] Figure 3A In an exemplary embodiment where element 330 is a pressure detector, rather than a trauma-causing / foreign body response-eliciting device, in some embodiments, electrode 148 may be utilized to cause trauma, etc. That is, in the exemplary embodiment, the trauma is not caused by the implantable device, but rather by another type of device. In this regard, in the exemplary embodiment, the implantable device is a device that only tests physical phenomena.

[0074] In at least some exemplary embodiments, the teachings detailed herein associated with causing trauma and / or triggering a foreign body response are directed to altering the blood-labyrinth barrier of a recipient. In an exemplary embodiment, there is an exemplary method 1000 such as represented by the algorithm presented in Figure 10 which includes method act 1010, which includes monitoring a physical phenomenon inside the cochlea of a recipient. In an exemplary embodiment, this monitoring act may be performed using the devices detailed above (such as pressure receivers, temperature receivers, etc.). More specifically, this may be performed by measuring the phenomenon with a probe outside the cochlea - the cochlea being the location of the phenomenon being addressed. In some embodiments, this is performed by measuring cochlear health from the round window niche or other additional cochlear locations as well as locations within the cochlea. Thus, in an exemplary embodiment, there is an implantable device configured to detect a physical phenomenon inside the cochlea by monitoring at the round window niche of a recipient and then opening the tight junctions of cells at the round window when the physical phenomenon is detected. In an exemplary embodiment, a method of using such a device may include implementing the device to achieve the functionality just described and then delivering a therapeutic substance at the opened junctions.

[0075] Any location from which the internal cochlear phenomenon can be monitored may be used, as well as other extra-cochlear locations. Additionally, it should be noted that claim 1010 also includes the use of latent variables. For example, it is outside the cochlea associated with the body and not inside the cochlea. In an exemplary embodiment, there may be a device that captures, or is in contact with the fluid inside the cochlea, or is otherwise directly exposed to the fluid inside the cochlea, and the fluid may be analyzed to determine whether there is a physical phenomenon inside the recipient's cochlea or whether it has changed. The physical phenomenon may be any phenomenon indicating a harmful occurrence inside the cochlea, such as an infection caused by the insertion of a cochlear implant, or a reaction to chemotherapy that causes damage to the inner ear tissue. In fact, the physical phenomenon may be the presence of a chemotherapy substance. In such an exemplary embodiment that may be platinum-based chemotherapy, it is liable to cause hearing loss in some cases.

[0076] Method 1000 also includes the action of method act 1020, which includes inducing a change in the blood-labyrinth barrier of a recipient based on the monitored physical phenomenon. In this regard, in an exemplary embodiment, the blood-labyrinth barrier can control or otherwise affect the amount of chemicals entering the inner ear or otherwise reaching the recipient's auditory system—when introduced externally to the auditory system. Referring to the chemotherapy example, in an exemplary embodiment, there is practical value in preventing or otherwise reducing the amount of chemotherapy chemicals reaching the auditory system in general, and specifically the inner ear and / or middle ear. Thus, by changing the blood-labyrinth barrier, the amount of chemicals reaching the auditory system can potentially be reduced relative to the case where no change occurs. Therefore, in an exemplary embodiment, the physical phenomenon is a phenomenon related to ototoxicity. In an exemplary embodiment, the induction of trauma and / or foreign body reaction can cause a change in the blood-labyrinth barrier. By way of example only and not limitation, causing trauma inside the inner ear can cause the blood-labyrinth barrier to become more "porous", such that the amount of chemicals used for chemotherapy accumulating in the inner ear or auditory system is reduced relative to the case where there is no change in the blood-labyrinth barrier. That is, in some embodiments, by making the barrier more porous, the outflow of chemicals will increase relative to otherwise. That is, in some alternative embodiments, there is practical value in maintaining the blood-labyrinth barrier such that the amount of chemicals reaching the inner ear is restricted in a manner that exceeds the initial control of accumulation. That is, rather than opening the barrier to flush the inner ear, the barrier is utilized to prevent accumulation. This can correspond to changing the blood-labyrinth barrier such that the porosity of the barrier is actually reduced relative to the case where there is no change.

[0077] In an exemplary embodiment, relative to a situation where there is no adjustment in the exemplary embodiment, the adjustment of the BLB can increase or decrease the rate of mass transfer from inside the structure to outside the structure. The rate increases by 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 225%, 250%, 275%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, 750%, 800%, 900%, 1000%, 1100%, 1200%, 1300%, 1400%, 1500%, 1600%, 1700%, 1800%, 1900%, 2000%, 2500%, 3000%, 3500%, 4000%, 4500%, 5000%, 5500%, 6000%, 7000%, 8000%, 9000% or 10000% or higher. In an exemplary embodiment, the rate decreases by 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

[0078] In view of the above, it can be understood that in an exemplary embodiment, the change in the blood-labyrinth barrier is an increase in its permeability, and relative to a situation where there is no increase, due to the increase in permeability, the amount and / or concentration of the substance in the cochlea decreases. More specifically, consistent with the case of chemotherapy, in an exemplary embodiment, the substance is a drug that is introduced into the recipient's body at a location remote from the cochlea and is a drug unrelated to the hearing disorder. By way of example only and not limitation, the substance can be a drug introduced into the recipient's arm or groin. In an exemplary embodiment, the substance can be a drug introduced into the recipient's mouth, such as by taking a pill or the like. In an exemplary embodiment, the substance can be a drug introduced through the recipient's nose, such as something inhaled (like that used in Dawn of the Planet of the Apes 2).

[0079] It should also be noted that the features of method 1000 can be applied in alternative embodiments that are not associated with the cochlea, but rather, for example, in embodiments associated with, for example, the kidney. In this regard, the method of claim 1000 can be modified to monitor physical phenomena inside the kidney in scenarios regarding managing or otherwise reducing the occurrence of aminoglycoside toxicity. In fact, in an exemplary embodiment, the teachings detailed herein can be utilized with regard to a bionic eye / retinal implant. In this regard, instead of an electrode array associated with a cochlear implant, the electrode array is associated with a retinal implant, and the associated devices detailed herein are associated therewith and modified for use in or around the recipient's eye.

[0080] It should be noted that although the above embodiments focus on substances that are drugs, in alternative embodiments, the substance can be another type of substance other than a drug.

[0081] Conversely, in an exemplary embodiment, the change in the blood-labyrinth barrier can be an increase in its permeability, and relative to the situation where there is no increase in permeability, due to the increase in permeability, the amount and / or concentration of the substance in the cochlea increases. By way of example only and not limitation, in an exemplary embodiment, such as in the case of providing an oral drug to a recipient, the oral drug is configured to control an infection in the cochlea associated with the implantation of a cochlear implant or otherwise treat the infection, in an exemplary embodiment, by increasing the permeability of the barrier, more of the drug can reach the recipient's cochlea / inner ear / auditory system, and thus, all other conditions being equal (e.g., the amount of the drug initially taken, the recipient's height, weight, body type, metabolism, etc.), it may be more effective relative to the situation where there is no barrier adjustment.

[0082] In an exemplary embodiment, the substance is a drug that is introduced into the recipient's body at a location remote from the cochlea and is a drug related to a hearing disorder / a drug related to the treatment of the recipient's hearing system. That is, for example, in the case of chemotherapy, in an exemplary embodiment, the drug is a drug unrelated to a hearing disorder. Further still, in an exemplary embodiment, such as with regard to the kidney, the drug can be a drug unrelated to a kidney disorder. In an exemplary embodiment where the teachings herein are directed to the eye, the drug can be a drug unrelated to an eye disorder. Of course, in the case where the teachings detailed herein apply to the above physical structures of the recipient, the drug or substance, etc. can be related to those structures.

[0083] The above embodiments have been directed to increasing the permeability of the blood-labyrinth barrier. In some embodiments, the method is directed to decreasing the permeability of the blood-labyrinth barrier. Thus, in an exemplary embodiment, method act 1020 results in a decrease in the permeability of the barrier. In such an exemplary embodiment, the amount and / or concentration of a substance in the cochlea increases due to the decrease in permeability, as compared to the case where there is no decrease in permeability. In an exemplary embodiment, in the scenario where the substance is a drug introduced into the body of the system at a location inside the cochlea, reducing the permeability of the BLB (or at least in some embodiments, preventing an increase in permeability or at least limiting the increase in permeability as compared to the case where no actions detailed herein are taken - unless otherwise stated, any disclosure herein regarding reducing the permeability of the BLB corresponds to the disclosure of the other two cases) has practical value in the scenario where the substance is a drug introduced into the body of the system at a location inside and / or adjacent to the cochlea. In an exemplary embodiment, there is a method act that is to stop active stimulation for hearing and / or increase active stimulation for hearing (including activating it) to affect the leakage associated with the BLB (e.g., in some cases, the stimulation can cause BLB leakage, and in other cases, the absence of stimulation can cause BLB leakage). Also, in some cases, closing the BLB / tightening the BLB can reduce the elimination of the drug and / or increase its half-life, thereby allowing it to further diffuse towards the apex. Conversely, in some embodiments, for example, if we only want to treat the base, controlling the BLB can be utilized to target a specific location, and the opposite of the foregoing embodiments can be applied, where the barrier is opened to limit the diffusion distance of the drug or other therapeutic substance at the apex of the cochlea.

[0084] By way of example and not limitation, embodiments such as Figure 9 or embodiments such as Figure 8 can deliver a therapeutic drug, such as an anti-rejection drug, via an electrode array, which delivers the therapeutic substance outside the cochlea, but the therapeutic substance diffuses through the cochlear wall into the cochlea interior and is thus delivered to a location adjacent to the cochlea. The therapeutic drug can be a drug that has practical value in preventing at least some drug leaching or otherwise diffusing or otherwise leaving the cochlea. That is, this can be a drug for which there is therapeutic value in maintaining the concentration and / or amount in the cochlea at a higher level than the case where the drug is allowed to escape from the cochlea. Thus, all other conditions being equal, a change in the blood-labyrinth barrier that reduces the BLB can limit the amount of therapeutic substance escaping from the cochlea, as compared to the case where there is no such change. That is, in an exemplary embodiment, simply preventing the BLB from becoming more permeable or even limiting the amount of increase in permeability can also have practical value, such as, for example, preserving residual hearing.

[0085] Figure 11Another exemplary method, method 1100, is provided, which includes method act 1110 that corresponds to method act 1010 detailed above. Method 1100 further includes method act 1120, which includes an act of managing the recipient's BLB based on the monitored physical phenomenon. In this regard, managing can include increasing permeability, restricting the decrease in permeability relative to the case where there is no management, or preventing the decrease in permeability. It should be noted that in at least some of the exemplary embodiments detailed herein, unless otherwise specified, any disclosure of increasing permeability herein corresponds to the disclosure of the other two. Similarly, managing can include decreasing permeability, restricting the increase in permeability relative to the case where there is no management, or preventing the increase in permeability. It should be noted that in at least some of the exemplary embodiments detailed herein, unless otherwise specified, any disclosure of decreasing permeability herein corresponds to the disclosure of the other two.

[0086] It should be noted that in at least some exemplary embodiments, the act of increasing the permeability of the BLB can be achieved by introducing a trauma and / or otherwise inducing a foreign body response or otherwise providing a stimulant to the tissue. In an exemplary embodiment, in some embodiments, the act of decreasing the permeability of the BLB can be achieved by removing the trauma or otherwise alleviating the trauma or otherwise removing the resulting foreign body response or otherwise alleviating the formed body response or otherwise removing the stimulant from the tissue. In an exemplary embodiment, this can be performed by alleviating the trauma at least in part by applying an active chemical, where the trauma is alleviated by applying any other treatment or other useful substance.

[0087] Any disclosure of managing that causes an increase in the amount and / or concentration of a substance also corresponds to the disclosure of preventing a decrease in the amount and / or concentration or restricting the decrease in the amount and / or concentration relative to the case where there is no management. Additionally, any disclosure of managing that causes a decrease in the amount and / or concentration of a substance also corresponds to the disclosure of preventing an increase in the amount and / or concentration where the increase in the amount and / or concentration is restricted relative to the case where there is no management.

[0088] It should be noted that the act of initiating a change or otherwise managing the recipient's BLB can be performed by injecting an inflammatory and / or anti-inflammatory compound into the scala tympani of the cochlea. In an exemplary embodiment, this can be performed using an exemplary embodiment of the device detailed above, such as Figure 9 the device. In an exemplary embodiment, this can be done manually using a needle and / or syringe assembly, etc. For example, this can be done during the surgery for implanting a cochlear implant or other hearing prosthesis.

[0089] Figure 12An exemplary algorithm for an exemplary method - method 1200 is presented, which includes method action 1210, and this method action 1210 includes the action of administering a therapeutic substance to a person. This can be done according to any of the teachings detailed herein, such as intravenously, orally, etc. This can be done using a combined drug delivery system and a prosthesis. This can be done using an implantable separate drug delivery system separate from the prosthesis. This can be done at or near the body structure being discussed or remotely.

[0090] Method 1200 also includes method action 1220, and this method action 1220 includes creating a trauma and / or triggering a foreign body response in or near a person's anatomy, thereby adjusting the concentration and / or amount of the therapeutic substance in the anatomy relative to the situation where there is no trauma and / or foreign body response.

[0091] In an embodiment, the adjustment is a decrease or increase in the amount and / or concentration of the therapeutic substance in the anatomy relative to the situation without trauma and / or foreign body response. In an exemplary embodiment, the increase results in an increase of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 7000, 8000, 9000 or 10000 or more. In an exemplary embodiment, the decrease results in a decrease of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100%.

[0092] In an exemplary embodiment, the anatomy can be the cochlea, kidney, eye, heart valve, etc.

[0093] In an exemplary embodiment, the anatomy can be the cochlea and the person is a recipient of a cochlear implant, and the cochlear implant includes an electrode array inserted into the cochlea. Consistent with the embodiment of FIG. 3 or Figure 8 the cochlear implant is a device that creates a trauma and / or triggers a foreign body response.

[0094] The teachings detailed herein can be combined with intelligent systems and the like to work with the recipient to enhance drug delivery regimens. By way of example and not limitation, an exemplary embodiment may require driving inflammation in the cochlea deliberately via electrical stimulation through existing electrodes or via other electrodes, or via other systems such as optrodes. Drugs can then be delivered systemically orally and / or via an intravenous injection system, and the drugs will be able to reach the cochlea better relative to the case where the aforementioned driving of inflammation is absent. Inflammation can be achieved by causing trauma and / or triggering a foreign body response. In an exemplary embodiment, a medical regimen can be carried out with the assistance of or in interaction with the recipient. By way of example and not limitation, a reminder such as a daily or weekly or monthly or hourly or multi-hour reminder can be provided to the recipient, such as an automatic reminder to take a pill at a certain moment. At some time a few minutes, hours, hours or even days later, the intelligent device can ask the recipient whether he or she has taken the pill, and if the answer is yes, initiate a trauma and / or foreign body response. In an exemplary embodiment, the recipient can instead enter the time at which he or she took the pill, and then the intelligent device will start a timed countdown, the end of which will result in an inflection that utilizes the implanted device to cause a foreign body response and / or trauma. In an exemplary embodiment, the intelligent device is a prosthesis. In an exemplary embodiment, the prosthesis can provide a question such as "Have you taken the pill?" that elicits an artificially induced auditory perception. After a "yes" indication (which may simply be the recipient saying "yes"), the prosthesis is configured to analyze the captured sound and can analyze it as a positive answer, or in an alternative embodiment, the input to the prosthesis will be via a smartphone or intelligent device, or even a dumb device or remote assistant, or via a button on the prosthesis (such as a button on a hearing aid, etc.).

[0095] In view of the above,[ Figure 13 there is presented an exemplary method, method 1300, that includes an algorithm according to an exemplary embodiment. Method 1300 includes method act 1310, which includes: automatically providing to the person, via a cochlear implant and / or its supporting device such as Figure 14 a smart phone as can be seen in, at least one of a reminder or an inquiry, to direct the person to perform an action of administering a therapeutic substance to the person (or which may be taking a pill).

[0096] Method 1300 further includes method act 1320, which includes: in response to the automatic provision, receiving feedback from the person that indicates that the person has administered the therapeutic substance to himself / herself and has thus performed the action of administering the therapeutic substance to the person (of method 1200).

[0097] Method 1300 further includes: based on the received feedback, using a cochlear implant to cause trauma and / or foreign body response, corresponding to method act 1220.

[0098] Figure 14 An exemplary system, system 2100, is presented which may be utilized in an exemplary embodiment of performing method 1300 or any other method detailed herein, where there is an input or a controller associated therewith. System 2100 includes a prosthesis 100 which is attached to a recipient 99 and signals with a smart phone 2400 via a wireless link 2300. It should be noted that in some exemplary embodiments, instead of a wireless link, a wired link may be utilized. In such exemplary embodiments, this may have practical value given the fact that foreign signals in the RF spectrum are unlikely to initiate one or more of the acts detailed herein. In other words, only something hard-wired to the smart phone 2400 can be utilized to control the prosthesis. In an exemplary embodiment, the prosthesis 10 is a cochlear implant. That is, in an exemplary embodiment, the prosthesis may be another one of the devices detailed herein, such as the dedicated drug delivery and / or dedicated trauma induction / foreign body response induction devices detailed herein and / or variants thereof. In an exemplary embodiment, the smart phone 2400 may provide an indicator of method 1300, such as by presenting it as a text message on its screen or by presenting it via an audio system. In an exemplary embodiment, the smart phone 2400 utilizes input from the recipient in accordance with the input associated with method 1300. Although Figure 14 the embodiments presented utilize a smart phone 2400, in alternative embodiments, the element 2400 need not be a smart device. The element 2400 may be a dumb device or a remote assistant for the prosthesis. Any device, system, and / or method capable of implementing one or more of the teachings detailed herein may be utilized in at least some exemplary embodiments.

[0099] It should be noted that in at least some exemplary embodiments, the act of causing trauma and / or foreign body response is performed by applying a stimulant to a structure of a person. In an exemplary embodiment, this may be a mechanical stimulant, such as Figure 3A an airbag / inflated membrane. In an exemplary embodiment, this may be a chemical stimulant. In an exemplary embodiment, the drug delivery devices detailed above and / or variants thereof may be utilized to deliver the stimulant. That is, in an exemplary embodiment, Figure 3A and Figure 7 the devices may be modified to provide a stimulant. By way of example only and not limitation, a chemical stimulant may be provided on the surface of the airbag such that when the airbag is inflated and thus contacts the cochlear wall, the chemical interacts with the cochlear wall to cause trauma. Figure 7The device can be utilized to exude chemical stimulants onto the round and / or oval walls of the cochlea, or otherwise onto the wall / barrier between the middle ear and the inner ear.

[0100] In an exemplary embodiment, the stimulant can be an acoustic stimulant, such as an ultrasound device. In an exemplary embodiment, the stimulant can be a surface configured to cause irritation. Although the embodiments detailed above utilize moving components focused on an active trauma-inducing device, in an exemplary embodiment, the prosthesis detailed herein can be more of a passive arrangement. In this regard, in an exemplary embodiment, a surface or the like can be extended to contact the recipient's tissue, but after that, nothing happens with respect to the movement of the surface via an active action. Instead, the recipient's normal movement can be utilized to induce irritation, such as, for example, the irritation caused by a grain of sand in an oyster. For example, in an exemplary embodiment, Figure 3A the airbag can simply expand to contact the wall and remain expanded. When the recipient moves, or indeed, when the recipient is affected by sound, the movement wave of the fluid may move the airbag in a way that causes irritation. Instead of an airbag, a mechanical device can extend to contact the cell wall, such as, for example, a telescoping member that extends in an orthogonal direction or at an acute angle to the longitudinal direction of the array (locally) in order to place a service that will cause irritation to the cochlear wall. In an exemplary embodiment, this can be a spring-loaded device. In fact, in an exemplary embodiment, magnetostrictive materials can be utilized, which deform controllably under the action of an electric current or the like, thereby contacting the tissue in various ways and then retracting from the contact with the tissue. In some embodiments, a motor or the like can be utilized to move the structure actually with respect to the electrode array. By way of example only and not limitation, a series of linear structures can actually extend away from the longitudinal axis of the array, which can be supported when in a loop or the like. The motor can rotate the loop, but at a speed slow or fast enough to move the wire. When the wire scratches or otherwise moves along the cochlear wall, the wire may cause a little trauma or otherwise initiate a foreign body reaction. In fact, such an exemplary embodiment can have practical value in also positioning the cochlear implant electrode array in place. It should be noted that in at least some exemplary embodiments, spikes or the like are utilized to pierce at least a portion of the wall of a given structure. This will cause the initiation of trauma and / or a foreign body reaction. In fact, in an exemplary embodiment, a device similar to a splinter can be used, which induces a foreign body reaction when piercing the outer wall of the tissue.

[0101] Similarly, an optical electrode can be utilized. In some embodiments, heat can be utilized. In this regard, a heating device that applies thermal energy to the tissue structure can be utilized. In some embodiments, cold can be utilized. In this regard, a device that extracts thermal energy from the tissue structure can be utilized. In at least some other embodiments, any device, system, and / or method that can effect the introduction of a trauma and / or foreign body response or otherwise can cause irritation to manage the BLB can be utilized.

[0102] In an exemplary embodiment, the stimulant utilized can be a stimulant that inflames the blood-labyrinth barrier.

[0103] Consistent with the teachings detailed above, the stimulant can be applied to the structures of the middle ear portal and the cochlea. In an exemplary embodiment, the action of administering a therapeutic substance to a person is performed by administering the substance at a location remote from the structure. That is, in an exemplary embodiment, the action of administering the therapeutic substance to the person is performed by administering the substance at or near the location of the structure.

[0104] It should be noted that in many cases, the embodiments detailed above focus on utilizing a prosthesis that provides a trauma / initiates a foreign body response or otherwise causes irritation. In an exemplary embodiment, a manual device / non-prosthesis device can be utilized. For example, a hand-held needle that is utilized to initiate a trauma. In an exemplary embodiment, a range of analogs can be utilized to apply a chemical stimulant, also manually operated. In an exemplary embodiment, the stimulant can be delivered by a surgeon to the round window and / or oval window during surgery. Of course, this can also be accomplished by a prosthesis or alternatively after implantation. This can cause a mildly irritated BLB, thereby causing a mildly or even more than mildly opened BLB. After that, the therapeutic substance can be delivered in a manner that systematically operates the system. These can be provided orally, intravenously, or locally during surgery, or can be delivered via a device implanted in the recipient. This can result in a higher concentration and / or higher amount of the therapeutic substance at the local location. Relative to the situation where the teachings detailed herein are not present, this can be performed in a one-time delivery manner, which can be accomplished in a manner where the time of stimulating the BLB reaches a one-time dose, or can also be achieved in a more systematic manner to maintain an increased concentration and higher amount of the substance.

[0105] It should still be noted that at least some of the exemplary embodiments detailed above have focused on implantable devices. Thus, in an exemplary embodiment, there is a system that includes an implantable blood-labyrinth barrier management component that is configured to affect the blood-labyrinth barrier to control the amount of substance in the anatomical structure more than in the case where there is no effect. In the exemplary embodiments detailed above, such a system can be Figure 7systems, etc. In at least some exemplary embodiments, any arrangement that can affect the BLB can be utilized. The system need not be associated therewith an implantable sensory prosthesis. That is, in alternative embodiments, consistent with the teachings detailed above, the system can include an implantable sensory prosthesis. Such embodiments can correspond to, for example Figure 3A or Figure 8 or Figure 9 and so on. Consistent with these embodiments, in an exemplary embodiment, there is an implantable sensory prosthesis component that is part of the system, where the blood-labyrinth barrier management component is integrated with the sensory prosthesis component. Conversely, in some embodiments, the blood-labyrinth barrier management component can be utilized separately and can be a component separate from the sensory prosthesis. For example, Figure 7 embodiments of Figure 1 can be utilized together. RF inductance coils implanted in the receiver can be implanted adjacent to each other such that these components can be utilized separately. That is, using two separate external components, these components can be utilized simultaneously.

[0106] It should also be noted that although some of the embodiments detailed above have been directed to devices that combine the BLB management component with a sensory prosthesis, in some embodiments, the BLB management component can instead or also be part of an implantable drug delivery component, where the drug delivery component is configured to deliver a substance to an anatomical structure. In fact, in an exemplary embodiment, the implantable component is configured to measure or otherwise evaluate the concentration and / or amount of a drug or some other substance or other phenomena associated therewith at a local location and effectively open and / or close the BLB to achieve a desired concentration and / or amount of the substance, or otherwise alter or otherwise affect the amount and / or concentration of a therapeutic substance. In an exemplary embodiment, there can be method actions including loop delivery, such as a scheme including delivery / open / delivery / open / delivery / open / delivery / open, etc., to achieve a therapeutic purpose. In some cases, the loop can be performed in a manner that precisely modulates the concentration of an inner ear drug by increasing and / or decreasing the concentration as practical. In fact, in an exemplary embodiment, the loop can include delivery / open / delivery / open / close / delivery / open / open more / close / delivery / open, etc. In this regard, the actions of opening and / or closing can be repeatedly performed as practical to achieve a level of precision that exceeds that achieved by simply performing one or more methods once. In an exemplary embodiment, a cochlear implant can be utilized to potentially regulate a therapeutic substance within or near the cochlea in a closed-loop feedback. In an exemplary embodiment, a cochlear implant can be utilized to potentially regulate a harmful substance within or near the cochlea in a closed-loop feedback.

[0107] In this regard, in an exemplary embodiment, as inFigure 15 As can be seen in, a sensor 335 can be present, which is part of a sensory prosthesis (or part of a drug delivery system, or part of a trauma triggering and / or foreign body reaction inducing device, etc.), and is positioned such that when the prosthesis is implanted in a recipient, the sensor 335 can be located at a position where the concentration and / or amount of the substance in question can be or otherwise desired to be monitored or otherwise adjusted or managed. In this regard, in an exemplary embodiment, the sensor 335 is a chemical sensor and / or a mass sensor and / or a particulate sensor, which communicates with another component of the prosthesis either wired or wirelessly, and can be integrated with a controller or the like or otherwise communicate signals with a controller or the like, such as a processor programmed to execute one or more teachings detailed herein, which can be programmed to analyze signals from the sensor 335 and evaluate the amount and / or concentration of the substance in question. Based on this evaluation, the prosthesis can be controlled to manage the BLB in accordance with the teachings detailed herein, so as to adjust or maintain the BLB in such a way that the desired amount and / or concentration of the substance in question is achieved or otherwise maintained or otherwise push the amount and / or concentration of the substance in question towards the desired quantity.

[0108] As in some of the embodiments described in detail above, in an exemplary embodiment, the blood-labyrinth barrier management component can be configured to deliver an inflammatory substance to or near an anatomical structure.

[0109] In an exemplary embodiment, the blood-labyrinth barrier management component is configured to at least passively manage the blood-labyrinth barrier, while in other embodiments, the blood-labyrinth barrier management component is configured to at least actively manage the barrier. It should be noted that the two are not exclusive, and in some embodiments, the management component can manage the BLB both actively and passively.

[0110] In an exemplary embodiment, any disclosure herein regarding the foreign body reaction also corresponds to the disclosure of encapsulation after the foreign body reaction. In some embodiments, this can allow inflammation to be encouraged for a period of time and then allow normal healing.

[0111] In view of the above, it can be seen that in at least some exemplary embodiments, there is a device and system and method, the device and system implementing and the method causing or otherwise including managing the BLB using an inflammatory compound or inflammatory structure or inflammatory action. In an exemplary embodiment, the inflammatory compound is delivered to the middle ear and / or is located at the round window and / or oval window. In an exemplary embodiment, the methods detailed herein may include using an inflammatory compound delivered from a cochlear implant and / or from a drug pump and / or from a middle ear implant / direct acoustic cochlear stimulator. In some exemplary embodiments, an implant may be placed into a recipient, the implant having its primary purpose, and in at least some exemplary embodiments, its purpose is only as an implant that induces a foreign body reaction and / or triggers trauma and / or causes the above-mentioned irritation, which can manage the BLB - such as by opening the BLB and / or closing the BLB. The induction of a foreign body reaction, etc. can be done by active placement and / or by passive placement.

[0112] It should be clear that the inflammatory compound and / or irritating action and / or trauma-triggering action and / or foreign body-inducing action can be performed by using a prosthesis and / or can be performed in a manual manner. In fact, in an exemplary embodiment, a surgeon may implant debris, etc. in the cochlea or round wall, etc., which can induce a foreign body reaction. In some embodiments, electrical stimulation can be applied through the skin. In this regard, electrodes can be placed in the recipient's ear canal during an examination procedure.

[0113] Similarly, in at least some embodiments, any device, system, and / or method that enables the BLB to be managed can be utilized. For example, this may require using noise (audible noise), using ultrasound, using infrasound, and / or using pressure and / or using heat and / or cold. In some embodiments, any type of stimulus that enables the BLB to be managed can be utilized. In fact, in some embodiments, if a stimulus at a location remote from, for example, the cochlea can be utilized to manage the BLB, then this can be done.

[0114] It should be noted that in at least some exemplary embodiments, any one or more actions detailed herein that are not associated with inducing an auditory perception are performed in a manner that cannot be heard by the recipient. In this regard, in an exemplary embodiment, at least some of the actions herein are performed without inducing an auditory perception.

[0115] It should be clear that, in at least some exemplary embodiments, the function structure and / or the barrier between tissues of blood vessels and nerves and / or the organ under discussion can be managed, such as by controlling the inflammatory response. In at least some exemplary embodiments, the teachings detailed herein can be utilized to protect or otherwise reduce the likelihood that nerves that are very sensitive to chemotherapy or any other phenomenon may be damaged, or otherwise reduce the damage caused there due to the occurrence of a given phenomenon via the management of the BLB. In some embodiments, the teachings detailed herein are utilized to limit the entry of toxins and / or limit the entry of immune cells. In an exemplary embodiment, the teachings detailed herein are utilized to increase the entry of therapeutic substances such as steroids delivered intravenously. In an exemplary embodiment, the management of the BLB can be utilized to better treat comprehensively with therapeutic substances as compared to the situation where the teachings detailed herein are absent.

[0116] The teachings detailed herein can also be utilized in some exemplary embodiments where a drug is delivered during the implantation of a sensory prosthesis. In at least some scenarios, at least in the absence of the teachings detailed herein, the drug concentration decreases after the implantation time. The teachings detailed herein can be utilized to prevent this decrease or at least limit this decrease.

[0117] The various teachings above relate to the systemic delivery of substances. The various teachings above relate to the local delivery of substances (e.g., to the cochlea or to the cochlear wall or to the round or oval window, etc.). In at least some exemplary embodiments, the substance is a therapeutic substance such as a drug. In at least some exemplary embodiments, the delivered substance can be a steroid.

[0118] The teachings detailed herein can be utilized to manage the concentration and / or amount of a substance being delivered systemically and / or locally. The teachings herein can also be utilized to manage the concentration and / or amount of a substance being delivered systemically and locally. In this regard, in an exemplary embodiment, a substance can be delivered locally in a manner that is relatively closer in time to the systemic delivery of the substance. In an exemplary embodiment, there is a method that includes balancing or otherwise manipulating or controlling or influencing a substance gradient within a recipient's structure and a substance gradient external to the recipient's structure. In this regard, in an exemplary embodiment, a low substance concentration in a structure, in combination with the management of the BLB (such as by opening the BLB or otherwise increasing the permeability of the BLB), can cause a substance being applied systemically to be drawn into the structure. This may be because, in some exemplary embodiments, the concentration in the structure is low while the systemic and / or blood concentration is high. Conversely, in an exemplary embodiment, a high substance concentration in a structure and an open BLB can cause a substance being applied locally to be dissipated. For example, this may be because of the concentration gradient between the structure and the rest of the body. Thus, in view of the above examples, it can be seen that in at least some exemplary cases, systemic treatment is superior to local treatment, which may seem counterintuitive. It may be that in at least some exemplary scenarios, this counterintuitive result is due to the BLB being open. At least some exemplary embodiments include managing or otherwise controlling or otherwise balancing a substance being delivered systemically with a substance being delivered locally to achieve or otherwise manage a desired concentration and / or amount in a structure.

[0119] In view of the above, in an exemplary embodiment associated with the cochlea, there may be a scenario where, all other conditions being equal, systemic delivery of a steroid is superior to the results obtained with local steroid administration. In an exemplary embodiment, this may be because the perilymph fluid in the cochlea has no or very little drug concentration, but the blood-labyrinth barrier is open. This can result in a concentration gradient that can draw the steroid into the cochlea and thus into the perilymph fluid, increasing the concentration and / or amount therein relative to the situation in alternative local administrations. It should be noted that in at least some exemplary embodiments, these amounts are based on a period of days, weeks, or months over time. In an exemplary embodiment, the above differences or values or amounts are averaged over 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 7000, 8000, 9000, or 10000 hours or days. It should also be noted that the differences or values or amounts can be measured and / or averaged after a set period of time has elapsed. By way of example only and not limitation, in an exemplary embodiment, it is always the case that the concentration / amount of the drug administered locally is higher in the local area than in the case of systemic administration. However, this phenomenon will only exist for a period of time. Thus, in an exemplary embodiment, the balance that can be evaluated can begin after that period of superior performance. In this regard, it can be assumed that for the first two, three, four days or hours or weeks, the drug administered locally will be advantageous. After that period of advantage, management can begin. That is, in an alternative embodiment, the period of advantage can be considered and used as part of the treatment regimen. It should be noted that in some embodiments, the teachings detailed herein are not steroid-dependent. In some cases, some or most or all drugs will have side effects. This method / approach can allow for a reduced systemic concentration of the drug.

[0120] The above inference is that a drug administered locally can result in a high concentration of the drug in the perilymph, and if there is a relatively high gradient with respect to the amount of substance outside the cochlea when the BLB is open, the drug may quickly leak out of the cochlea. In this regard, it should be noted that the period until the drug leaks out of the cochlea can be the above-mentioned advantage.

[0121] In view of the above, exemplary embodiments can include customizing the systemic and local doses of a substance to achieve a desired amount and / or concentration, or otherwise driving the concentration and amount towards the desired amount and / or concentration. By way of example only and not limitation, for an exemplary drug, in some instances, it is practical to administer the drug not locally but rather entirely systemically. Further, for an exemplary drug, in some instances, it is practical to administer the drug only locally and not systemically. Further, by way of example, it is practical to administer the drug locally and systemically with various different doses for these two cases such that, in combination with an open and / or closed or partially closed BLB, the concentration inside and outside the structure (such as inside and outside the cochlea) can be managed such that the concentration and / or amount can be controlled. (Although the embodiments herein have been directed to the cochlea, it should be noted that the teachings detailed herein can also be applied to the hearing and balance organs—to the extent that they share common features applicable to the teachings detailed herein. It should also be noted that the teachings detailed herein can also be applied to the eye. Thus, any disclosure herein regarding a method of treating an organ or otherwise associated therewith and / or a device for treating an organ corresponds to a disclosure of treating any of the foregoing organs herein (including the eye), provided that the skilled person in the art is able to do so and can modify the specific teachings to achieve this.)

[0122] In an exemplary embodiment, the amount applied at the local location can range from zero to the highest possible amount or at least the highest amount whatever that may be, and additional amounts will be wasted or otherwise useless, while the amount applied systemically can range from the highest possible amount or at least the highest amount whatever that may be to zero, and additional amounts will be wasted or potentially dangerous. By balancing these two amounts, a practical treatment can be developed. The following table provides exemplary concept unit amounts. In an exemplary embodiment, in some embodiments, such as for a given BLB condition, an application combining a certain local amount with a certain systemic amount can produce practical results.

[0123]

[0124]

[0125] Unit - partial Unit - whole body 0 100 5 90 10 80 15 50 20 30 25 10 30 0

[0126] Unit - partial Unit - whole body 0 100 2.5 95 5 90 7.5 85 9 80 11 75 13 70

[0127] It should be noted that the above table is merely exemplary and is provided for conceptual purposes. Depending on the desired concentration and / or amount (related to the condition of the BLB), a given amount of the drug will be applied locally and systemically.

[0128] It should be noted that different doses can be applied for different BLB conditions. By way of example only and not limitation, in embodiments where the BLB is open and thus porous, it may be practical to provide a higher systemic dose than the local dose relative to what those particular doses might be, whereas in embodiments where the BLB is closed, it may be practical to provide a lower systemic dose than the local dose relative to what those particular doses would be. The key is that in the exemplary embodiments, by managing or otherwise exploiting the particular doses at the local and systemic sites, alone or in combination with the management or otherwise the assessment of the state of the BLB, the concentration and / or amount can be managed in a more practical way than would be the case without practicing these teachings.

[0129] An exemplary embodiment may include a method in which, when a drug is topically administered, the BLB is maintained or otherwise driven to a closed state, and then the BLB is opened after a period of time empirically or otherwise estimated or calculated during which the level of the therapeutic substance in the structure will decline, and then a large amount of the systemically administered drug is provided, and the gradient between the structure and the rest of the body is such that the drugs are drawn into the structure. In an exemplary embodiment, there is a method that forces the BLB to remain closed and / or open for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47 or 48 hours or days or weeks. In an exemplary embodiment, the closing and / or opening is achieved, for example, via the use of drugs and / or biotherapeutic substances and / or other stimulation regimens as detailed herein. It should be noted that the foregoing closing and / or opening may correspond to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1250, 1500, 1750, 2000, 2500, 3000, 3500, 4000, 4500 or 5000 more (in the case of opening) or less (of course limited to 100%) (in the case of closing) than the closing and / or opening relative to the situation without intervention. Any device, system, and / or method now or later developed that can fully or partially open and / or close the BLB such that this can have practical utility can be utilized in an exemplary embodiment.

[0130] In view of the foregoing, it can be seen that in an exemplary embodiment, there is a method that includes the following actions: administering a therapeutic substance to a human and managing the concentration and / or amount of the substance in the cochlea of the human by considering the blood-labyrinth barrier of the human. In an exemplary embodiment, the action of managing the concentration and / or amount is performed by altering the blood-labyrinth barrier. This can be done by opening and / or closing the barrier in any way detailed herein and / or any other way that can have practical utility.

[0131] In some embodiments, the therapeutic agent is administered both locally and systemically, and the management of the concentration and / or amount of the agent is performed by balancing the local and systemic amounts. In some embodiments, based on the state of the blood-labyrinth barrier (e.g., open, closed, etc.), the amount of the agent administered locally and / or the amount of the agent administered systemically is determined. Similarly, this can be done to adjust the concentration gradient of the agent / to obtain a concentration gradient of the agent between the inner and outer cochlea, thereby managing the amount and / or concentration. In some embodiments, the amount of the agent administered locally and the amount of the agent administered systemically are determined to maintain or obtain the concentration and / or amount of the agent in the cochlea (or at a particular location or within the scope of (a) region(s) of the cochlea, such as, for example, at a location corresponding to a particular frequency site in the cochlea), where the amount provided locally is less than the maximum amount that can be effectively administered (i.e., additional amounts would be wasted). In an exemplary embodiment, the amount administered locally is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 percent of the amount that can be effectively administered. In some embodiments, the amount of the agent provided systemically is less than the maximum amount that can be effectively administered (i.e., additional amounts would be wasted). In an exemplary embodiment, the amount administered locally is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 percent of the amount that can be effectively administered.

[0132] Regarding systemic administration, there may be a compromised BLB due to the injection of lipopolysaccharide (LPS). Exemplary embodiments include systemic administration that includes both an inflammatory component (such as LPS) and a treatment that are both targeted to the inner ear. Such exemplary embodiments also include controlling or otherwise mitigating the systemic damage resulting from performing such an operation. In an exemplary embodiment, the method may include the systemic delivery of safe molecules until they reach the ear or other targeted organ, and then the release of an inflammatory payload (LPS or others). Accordingly, the embodiments also include those molecules.

[0133] In an exemplary embodiment, there is an action of modifying the permeability of the round window and / or the oval window, such as a strike of a certain type like an electric shock, and then delivering a drug to that region. In an exemplary embodiment, an electric current is applied to the round window and / or the oval window. In an exemplary embodiment, mechanical stimulation is applied to the (a) window(s), such as using a needle or a scraping device. In an exemplary embodiment, a chemical compound is applied to the permeability of the window.

[0134] Consistent with the embodiments detailed above, in an exemplary embodiment, an electric current is utilized to implement at least some of the teachings detailed herein, such as implementing the trauma detailed above or otherwise inducing a foreign body response, using a cochlear implant electrode array to temporarily exceed the Shannon limit. This is for the safe charge density of platinum electrodes (and in the exemplary embodiment, the electrodes utilized to provide the current are platinum electrodes). In the exemplary embodiment, such a temporary exceeding of the Shannon limit can cause trauma and / or open the BLB.

[0135] It should be noted that the aforementioned Shannon limit can be associated with the electrode size and / or the charge injection level. Thus, in an exemplary embodiment, there is a method for evaluating the current required to exceed the Shannon limit and / or the voltage requirement for exceeding the Shannon limit by a certain percentage, which is achieved by considering the electrode size and / or the electrode composition and / or the exposed area of the electrode (e.g., the portion not covered by silicone or other types of materials) and controlling the conventional cochlear implant to exceed the Shannon limit by the aforementioned percentage. In an exemplary embodiment, for a given recipient, the standard excitation time and / or the average value (mean, median, or mode) of a given electrode used to induce auditory perception using a cochlear implant is greater than or less than or equal to 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1250, 1500, 1750, 2000, 2500, 3000, 3500, 4000, 4500 or 5000 or a higher percentage (or any value or range of values therebetween in increments of 0.01), the Shannon limit is exceeded by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1250, 1500, 1750, 2000, 2500, 3000, 3500, 4000, 4500 or 5000 or more (whatever is used to calculate the Shannon limit resulting in an increase) (e.g., the charge applied is 10 times the Shannon limit and the time of the charge applied is twice the standard pulse length, where the standard pulse is 400 microseconds).

[0136] It should be noted that in at least some embodiments, it is the increased charge that induces the response rather than the dissolved platinum, or at least the former is the main driving factor rather than the latter. In this regard, it should be noted that in some embodiments, the two are linked. The direct effect of a high current offset may damage cells (as well as some heat, protein denaturation, and / or the possible generation of bubbles). If achieved within a reasonable time period, platinum will also accumulate in the tissue, and according to the teachings detailed herein, platinum may also trigger trauma and / or open the BLB.

[0137] In view of the above, there are exemplary methods that include the following actions: altering the blood-labyrinth barrier by systemic delivery of an inflammatory substance such as LPS to manage the concentration and / or amount of a therapeutic substance in an organ. In an exemplary embodiment, the action of managing the concentration and / or amount (e.g., without the specified molecule detailed above) is performed by altering the blood-labyrinth barrier by systemic delivery of an inflammatory substance (e.g., LPS) that, when systemically delivered in an amount that would open the blood-labyrinth barrier in a first state, has a harmful effect on the recipient's tissue. In this embodiment, the inflammatory substance is systemically delivered in a second state that is different from the first state (in an amount that would be harmful if in the first state), where the second state is a state that is less harmful to the recipient's tissue relative to the first state (e.g., more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 60, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 97, 98 or 99% or equal to 100% harmless), and the method further includes: when the substance approaches the cochlea (or other target organ), transitioning the inflammatory substance from the second state to the first state, thereby managing the concentration and / or amount of the substance within the cochlea (or other target organ). In an exemplary embodiment, this can be accomplished via a timed-release system and / or via the application of a stimulus, such as for example the application of electrical energy and / or the application of another substance that temporarily alters the recipient's body chemistry (e.g., increases salinity), which triggers the transition from the second state to the first state, and / or via the application of a stimulus to the recipient's state, such as increasing and / or decreasing the recipient's blood pressure and / or inducing an increase or decrease in the recipient's temperature.

[0138] In an exemplary embodiment, the action of managing the concentration and / or amount is performed by applying an electrical stimulus from a cochlear implant electrode array located in the recipient's cochlea such that platinum of the electrodes constituting the electrode array diffuses / releases from the cochlea in an amount exceeding that which occurs during normal operation of the electrode array.

[0139] In an exemplary embodiment, the increase in platinum diffusion is 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, 1000%, 1250%, 1500%, 1750%, 2000%, 2500%, 3000%, 3500%, 4000%, 4500% or 5000% or more higher than normal.

[0140] It should also be noted that any disclosure of the devices and / or systems detailed herein also corresponds to a disclosure of providing the devices and / or systems in other ways. Any disclosure of method acts herein corresponds to a device and / or system configured to perform the method acts. Any disclosure of a device and / or system having functionality herein corresponds to a method of performing acts corresponding to the functionality. Any disclosure of a method of manufacturing a device and / or system corresponds to the resulting device and / or system, and vice versa. It should also be noted that unless otherwise stated, any element of any embodiment detailed herein can be combined with any other element of any embodiment detailed herein as long as it is possible in the art. It should also be noted that in at least some exemplary embodiments, any one or more elements of the embodiments detailed herein can be explicitly excluded in the exemplary embodiments. That is, in at least some exemplary embodiments, there are embodiments that clearly do not have one or more of the elements detailed herein. Although the various embodiments of the present invention have been described above, it should be understood that they are presented by way of example and not limitation. It will be apparent to those skilled in the relevant art that various changes can be made in form and detail without departing from the spirit and scope of the present invention.

Claims

1. A medical device, comprising: an implantable device configured to intentionally alter a recipient's blood-labyrinth barrier to manage the blood-labyrinth barrier, wherein the implantable device is configured to fully or partially open and / or close the blood-labyrinth barrier by causing trauma induced by mechanical or electrical stimulation in the inner ear and / or middle ear of the recipient.

2. The device according to claim 1, wherein: the implantable device is a cochlear implant.

3. The device according to claim 1, wherein: the implantable device is configured to extend into the cochlea of a recipient and electrically stimulate tissue inside the recipient to cause the trauma.

4. The device according to claim 1, wherein: the implantable device is a cochlear electrode array configured to extend into the cochlea of a recipient, configured to electrically stimulate the tissue of the cochlea in various ways to induce auditory perception, and configured to electrically stimulate tissue inside the recipient to cause the trauma.

5. The device according to claim 1, wherein: the implantable device is a cochlear implant configured to extend into the cochlea of a recipient, configured to electrically stimulate the tissue of the cochlea in various ways to induce auditory perception, and configured to electrically stimulate tissue inside the recipient to cause the trauma without inducing auditory perception.

6. The device according to claim 1, wherein: the implantable device is configured to passively cause the trauma.

7. The device according to claim 1, wherein: the implantable device is a drug delivery device.

8. The device according to claim 1, wherein: the implantable device is configured to detect a physical phenomenon inside the cochlea and cause the trauma after detecting the physical phenomenon.

9. The device according to claim 1, wherein: the implantable device is configured to detect the physical phenomenon inside the cochlea by monitoring at a location outside the cochlea, and then, after detecting the physical phenomenon, open the tight junctions of cells at the round window.

10. The device according to claim 1, wherein: the implantable device is configured to detect the physical phenomenon inside the cochlea by monitoring at the round window niche of the recipient, and then, after detecting the physical phenomenon, open the tight junctions of cells at the round window.

11. The device according to claim 1, wherein the device comprises: a component for monitoring a physical phenomenon inside the cochlea of the recipient; and a component for managing the blood-labyrinth barrier of the recipient based on the monitored physical phenomenon.

12. The device according to claim 11, wherein: the component for managing the blood-labyrinth barrier comprises a component for inducing a change in the blood-labyrinth barrier of the recipient based on the monitored physical phenomenon.

13. The device according to claim 11, wherein: the component for monitoring the physical phenomenon is configured to monitor a phenomenon related to ototoxicity.

14. The device according to claim 12, wherein: The component for inducing the alteration of the blood-labyrinth barrier is configured to: cause an increase in the permeability of the blood-labyrinth barrier; and reduce the amount and / or concentration of a substance in the cochlea due to the increase in permeability as compared to the case where there is no such increase in permeability.

15. The device according to claim 14, wherein: the substance is a drug introduced into the body of the recipient at a location remote from the cochlea and is a drug unrelated to a hearing disorder.

16. The device according to claim 12, wherein: the component for inducing the alteration of the blood-labyrinth barrier is configured to: cause an increase in the permeability of the blood-labyrinth barrier; and increase the amount and / or concentration of a substance in the cochlea due to the increase in permeability as compared to the case where there is no such increase in permeability.

17. The device according to claim 16, wherein: the substance is a drug introduced into the body of the recipient at a location remote from the cochlea and is a drug related to the treatment of the recipient's hearing system.

18. The device according to claim 11, wherein: the component for managing the blood-labyrinth barrier is configured to at least one of the following: limit an increase in the permeability of the blood-labyrinth barrier, induce a decrease in the permeability of the blood-labyrinth barrier, or prevent an increase in the permeability of the blood-labyrinth barrier as compared to the case where there is no such management of the blood-labyrinth barrier; and the amount and / or concentration of a substance in the cochlea is increased due to the management of the blood-labyrinth barrier as compared to the case where there is no decrease in permeability.

19. The device according to claim 18, wherein: the substance is a drug introduced into the body of the system at a location inside and / or near the cochlea.

20. The device according to claim 12, wherein: the component for inducing an alteration of the recipient's blood-labyrinth barrier is configured to introduce an inflammatory compound into the scala tympani of the cochlea.

21. The device according to claim 1, wherein the device comprises: a component for administering a therapeutic substance to a human; and a component for creating the trauma in or near the inner ear of the human so as to adjust the concentration and / or amount of the therapeutic substance in the inner ear as compared to the case where there is no such trauma.

22. The device according to claim 21, wherein: the adjustment is a decrease in the amount and / or concentration of the therapeutic substance in the inner ear as compared to the case where there is no such trauma.

23. The device according to claim 21, wherein: the adjustment is an increase in the amount and / or concentration of the therapeutic substance in the inner ear as compared to the case where there is no such trauma.

24. The device according to claim 21, wherein: the component for creating the trauma is configured to create the trauma in or near the cochlea.

25. The device according to claim 21, wherein: the component for creating the trauma is a cochlear implant, the cochlear implant comprising an electrode array inserted into the cochlea; and The cochlear implant is configured to cause the trauma.

26. The device according to claim 21, wherein: the component for causing the trauma is configured to apply a stimulant to the inner ear of the person.

27. The device according to claim 26, wherein: the stimulant is a mechanically-based stimulant.

28. The device according to claim 26, wherein: the stimulant is applied to the structures of the middle ear and / or the cochlea; and the component for administering the therapeutic substance to the person is configured to administer the substance at a location remote from the structures.

29. The device according to claim 21, wherein: the component for causing the trauma is a cochlear implant, the cochlear implant including an electrode array inserted into the cochlea; and the cochlear implant is configured to cause the trauma by exceeding the Shannon limit of the electrodes of the electrode array.

30. A medical system, comprising: an implantable blood-labyrinth barrier management component configured to intentionally affect the blood-labyrinth barrier to control the amount of substances in the inner ear of a recipient to be more than the amount in the absence of such effect, wherein the implantable blood-labyrinth barrier management component is configured to fully or partially open and / or close the blood-labyrinth barrier by causing a trauma induced by mechanical or electrical stimulation in the inner ear and / or middle ear of the recipient.

31. The system according to claim 30, further comprising: an implantable sensory prosthesis component, wherein the blood-labyrinth barrier management component is integrated with the sensory prosthesis component.

32. The system according to claim 30, wherein: the blood-labyrinth barrier management component is configured to deliver an inflammatory substance to or near the inner ear.

33. The system according to claim 30, wherein: the blood-labyrinth barrier management component is part of an implantable drug delivery component, wherein the drug delivery component is configured to deliver the substance to the inner ear.

34. The system according to claim 30, wherein: the blood-labyrinth barrier management component passively manages the blood-labyrinth barrier.

35. The system according to claim 30, wherein: the blood-labyrinth barrier management component actively manages the blood-labyrinth barrier.

36. The system according to claim 30, wherein: the blood-labyrinth barrier management component is configured to induce a foreign body reaction, followed by encapsulation to manage the blood-labyrinth barrier.

37. The system according to claim 30, wherein the system comprises: a component for administering a therapeutic substance to a person; wherein the implantable blood-labyrinth barrier management component is configured to manage the concentration and / or amount of the substance in the cochlea of the person by considering the person's blood-labyrinth barrier.

38. The system according to claim 37, wherein: the implantable blood-labyrinth barrier management component is configured to manage the action of the concentration and / or amount by changing the blood-labyrinth barrier.

39. The system according to claim 37, wherein: The component for administering a therapeutic substance is configured to administer the therapeutic substance locally and systemically; and The implantable blood-labyrinth barrier management component is configured to manage the concentration and / or amount of the substance by balancing the local amount and the systemic amount.

40. The system according to claim 37, wherein: The component for administering a therapeutic substance is configured to administer the substance locally and systemically; and The implantable blood-labyrinth barrier management component is configured to determine the amount of the substance administered locally and the amount of the substance administered systemically based on the state of the blood-labyrinth barrier.

41. The system according to claim 37, wherein: The component for administering a therapeutic substance is configured to administer the substance locally and systemically; and The implantable blood-labyrinth barrier management component is configured to determine the amount of the substance administered locally and the amount of the substance administered systemically to obtain a concentration gradient of the substance between the interior and the exterior of the cochlea, thereby managing the amount and / or concentration.

42. The system according to claim 37, wherein: The component for administering a therapeutic substance is configured to administer the substance locally and systemically; and The implantable blood-labyrinth barrier management component is configured to determine the amount of the substance administered locally and the amount of the substance administered systemically to maintain the concentration and / or amount of the substance in the cochlea, wherein the amount provided locally is less than the maximum amount that can be effectively administered.

43. The system according to claim 37, wherein: The implantable blood-labyrinth barrier management component is configured to intentionally alter the blood-labyrinth barrier of the recipient to manage the blood-labyrinth barrier.

44. The system according to claim 37, wherein: The implantable blood-labyrinth barrier management component is configured to manage the concentration and / or amount by applying electrical stimulation from a cochlear implant electrode array located in the cochlea of the recipient.

45. The system according to claim 37, wherein: The implantable blood-labyrinth barrier management component is configured to manage the concentration and / or amount by applying electrical stimulation from a cochlear implant electrode array located in the cochlea of the recipient such that the Shannon limit is intentionally exceeded.

46. The system according to claim 37, wherein: The implantable blood-labyrinth barrier management component is configured to manage the concentration and / or amount by causing the component for administering a therapeutic substance to systemically deliver an inflammatory substance to alter the blood-labyrinth barrier.

47. The system according to claim 37, wherein: The implantable blood-labyrinth barrier management component is configured to manage the concentration and / or amount by applying electrical stimulation from a cochlear implant electrode array located in the cochlea of the recipient such that the amount of platinum diffusing from the electrodes constituting the electrode array exceeds the amount that occurs during normal operation of the electrode array to induce auditory perception.

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