Controlled substance delivery in mammals

Abstract

A device includes a reservoir and a therapeutic substance located in the reservoir, where the device is an implantable therapeutic substance delivery device, and the device is configured to deliver the therapeutic substance to a recipient thereof by diffusion controlled release. In an exemplary embodiment, the device is also a cochlear implant.

Description

Cross Reference to Related Applications

[0001] This application claims priority to U.S. Provisional Application No. 63 / 524,327, filed June 30, 2023, entitled “SUBSTANCE DELIVERY CONTROLLED INSIDE MAMMALS,” by Daniel Smith, inventor, the entire contents of which are incorporated herein by reference in their entirety. BACKGROUND

[0002] Medical devices have provided a wide range of therapeutic benefits to recipients in recent decades. A medical device can include an internal or implantable component / device, an external or wearable component / device, or a combination thereof (e.g., a device having external components that communicate with implantable components). Medical devices, such as traditional hearing aids, partially or completely implantable hearing prostheses (e.g., bone conduction devices, mechanical stimulators, cochlear implants, etc.), pacemakers, defibrillators, functional electrical stimulation devices, and other medical devices, have been successful for many years in performing life-saving and / or lifestyle improvement functions and / or recipient monitoring.

[0003] The types of medical devices, and the range of functions performed by them, have increased over the years. For example, many medical devices, sometimes referred to as “implantable medical devices,” now often include one or more instruments, apparatus, sensors, processors, controllers, or other functional mechanical or electrical components implanted in a recipient, either permanently or temporarily. These functional devices are typically used to diagnose, prevent, monitor, treat, or manage a disease, disorder, or injury or its symptoms, or study, replace or modify an anatomy or a physiological process. Many of these functional devices utilize power and / or data received from external devices that are part of, or operate in conjunction with, the implantable components. SUMMARY

[0004] In an example embodiment, there is a device comprising: a reservoir; and a therapeutic substance located in the reservoir, wherein the device is an implantable therapeutic substance delivery device and the device is configured to deliver the therapeutic substance to its recipient by diffusion controlled release.

[0005] In an example embodiment, there is a device comprising: a reservoir; and a therapeutic substance located in the reservoir, wherein the device is an implantable therapeutic substance delivery device and the device is configured to deliver the therapeutic substance to its recipient by diffusion controlled release.

[0006] In an example embodiment, there is a method comprising: entering an interior of a human body; and treating a disease of the human body by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the act of controllably delivering the therapeutic substance is performed passively.

[0007] In an example embodiment, there is an apparatus comprising: a first at least partially bounded volume; a second at least partially bounded volume; and at least one apparatus outlet at the second bounded volume, wherein the apparatus is an implantable therapeutic substance delivery apparatus, and the apparatus is effective to deliver the therapeutic substance to its recipient solely due to a concentration gradient.

[0008] In an example embodiment, there is a method comprising: entering an interior of a human body; and treating a disease of the human by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the act of controllably delivering the therapeutic substance is performed effectively without a net movement of a solvent in which the therapeutic substance exists from a volume of the device containing the therapeutic substance to an ambient environment outside of the device.

[0009] In an example embodiment, there is an implantable therapeutic substance delivery apparatus comprising a reservoir and a delivery tube device, wherein the delivery tube device comprises a tubular apparatus comprising a first lumen and a second lumen distinct from the first lumen, the delivery tube device is a diffusive delivery tube device, the first lumen is in fluid communication with the reservoir, and the second lumen is in fluid communication with the first lumen, and the apparatus is configured such that the therapeutic substance located in the reservoir travels to the delivery tube device for delivery to a human in which the device is implanted. BRIEF DESCRIPTION OF DRAWINGS

[0010] Embodiments are described below with reference to the accompanying drawings, in which: Figure 1A is a perspective view of an example hearing prosthesis to which at least some of the teachings detailed herein can be applicable; Figures 1B-1D is a quasi-functional diagram of an example device to which some embodiments can be applicable; Figure 1E and 2A and 2B and 2C and IF present some schematic diagrams related to the underlying technology with which some embodiments are associated; Figure 3 and 4 shows other example medical devices to which at least some of the teachings herein are applicable; Figure 5 shows a top view of an example implantable portion of a cochlear implant in accordance with embodiments; Figure 6and 7 Figures 7A, 40, 41, and 42 show some details of a portion of an exemplary implantable portion of a cochlear implant according to an embodiment; Figure 8 A side view of the ear is shown for reference purposes; Figure 9 Some details of some portions of an exemplary implantable portion of a cochlear implant according to an embodiment are shown; Figure 10 It is a functional diagram; Figures 11-19 Some exemplary design data are shown; Figures 20-21 Figures 22-26, 27-31, 32-37, and 39A show some exemplary performance data; and Figures 38-39 An exemplary flowchart is shown. Detailed Implementation

[0011] For ease of description only, this document primarily refers to illustrative medical devices (i.e., hearing prostheses) to describe the techniques presented herein. The cochlear implant is introduced first. The techniques presented herein can also be used with a variety of other medical devices that can benefit from the teachings of this document while providing a wide range of therapeutic benefits to recipients, patients, or other users. For example, any technique described herein for one type of hearing prosthesis (e.g., a cochlear implant) corresponds to the use of this teaching with at least another hearing prosthesis (including bone conduction devices (percutaneous, active percutaneous, and / or passive percutaneous), middle ear auditory prostheses, direct acoustic stimulators), and also utilizes the disclosure of another embodiment of this teaching with other electro-analogous auditory prostheses (e.g., auditory brain stimulators). The techniques presented herein can be used with implantable / implantable microphones (whether or not used as part of a hearing prosthesis (e.g., body noise or other monitors, whether or not they are part of a hearing prosthesis)) and / or external microphones. The techniques presented herein can also be used with vestibular devices (e.g., vestibular implants), sensors, seizure devices (e.g., devices for monitoring and / or treating epileptic events where applicable), sleep apnea devices, retinal implants, electroporation, etc. Therefore, any disclosure herein is a disclosure for using such devices in conjunction with the teachings herein, provided that it is possible to implement them in the art.

[0012] It should also be noted that the embodiments also include applying the teachings herein to medical devices that are non-implantable medical devices, such as minimally invasive probes used by medical personnel.

[0013] For example, any technology associated with a component implanted in a recipient, as detailed herein, can be combined with information delivery technologies disclosed herein, such as those eliciting auditory perception, to convey information to the recipient. By way of example only and not limitation, a sleep apnea implant can be combined with a device that eliciting auditory perception to provide the recipient with information, such as status information. In this regard, the various sensors and output devices detailed herein can be combined with such non-sensory prostheses or any other non-sensory prostheses that include implantable components to enable a user interface, as described herein, capable of conveying information associated with the implant to the recipient.

[0014] While the teachings detailed herein will describe hearing prostheses to the greatest extent possible, it should be noted, as above, that any disclosure herein regarding hearing prostheses corresponds to a disclosure of another embodiment of any other prosthesis described herein using the associated teachings, whether it be a hearing prosthesis or a sensory prosthesis.

[0015] The techniques presented herein also refer to the background art description of another illustrative medical device, namely a retinal implant. As mentioned above, the techniques presented herein are also applicable to vestibular devices (e.g., vestibular implants), visual devices (i.e., bionic eyes), as well as sensors, pacemakers, drug delivery systems, defibrillators, functional electrical stimulation devices, catheters, seizure devices (e.g., devices for monitoring and / or treating epileptic events), sleep apnea devices, electroporation devices, and the like.

[0016] Unless otherwise stated, any reference to one of the above-described sensory prostheses corresponds to an alternative disclosure using one of the other above-described sensory prostheses, provided that it is possible to implement it in the art.

[0017] Figure 1A This is a perspective view of the implantable portion of a cochlear implant 100 implanted in a recipient. The implantable portion of the cochlear implant 100 is part of a partially implantable cochlear implant system 10, which may include external components, which will be described in detail below.

[0018] 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 the implant 100.

[0019] In a fully functional ear, the outer ear 101 includes an auricle 110 and an ear canal 102. Sound pressure, or sound wave 103, is collected by the auricle 110 and enters through the canal 102. A tympanic membrane 104, which vibrates in response to the sound wave 103, is disposed distally across the ear canal 102. This vibration is coupled to an oval or elliptical window 112 via three bones of the middle ear 105, collectively referred to as ossicles 106, and including the malleus 108, incus 109, and stapes 111. The bones 108, 109, and 111 of the middle ear 105 filter and amplify the sound wave 103, thereby causing the elliptical window 112 to pivot or vibrate in response to the vibration of the tympanic membrane 104. This vibration generates fluid motion waves in the perilymph within the cochlea 140. This fluid motion then activates tiny hair cells (not shown) within the cochlea 140. Activation of hair cells enables the generation of appropriate nerve impulses, which are transmitted to the brain (also not shown) via spiral ganglion cells (not shown) and auditory nerve 114, where they are perceived as sound.

[0020] As shown, the implantable portion of the cochlear implant 100 includes one or more components that are temporarily or permanently implanted in the recipient's body. Figure 1A The image shows an implant 100 having an external device 142, which is part of a system 10 (together with the implantable portion of the cochlear implant 100) and is configured to provide power to the implant as described below.

[0021] exist Figure 1A In the illustrative arrangement, external device 142 may include a power source (not shown) disposed in the behind-the-ear (BTE) unit 126. External device 142 also includes components of a transcutaneous power delivery link, referred to as an external power delivery assembly. The transcutaneous power delivery link is used to deliver power and / or data to implant 100. Various types of power delivery (e.g., infrared (IR), electromagnetic, capacitive, and inductive delivery) can be used to deliver power and / or data from external device 142 to implant 100. In the illustrative embodiment of FIG1, the external power delivery assembly includes an external coil 130 that forms part of an inductive radio communication link. External coil 130 is typically a wire antenna coil made of multi-turn electrically insulated single or multi-strand platinum or gold wire. External device 142 also includes a magnet (not shown) positioned within the turns of the external coil 130. It should be understood that Figure 1A The external devices shown are merely illustrative, and other external devices may be used in conjunction with embodiments of the present invention.

[0022] The implantable portion of the cochlear implant 100 includes an internal power delivery assembly 132, which is positionable within a recess of the temporal bone adjacent to the recipient's auricle 110. As detailed below, the internal power delivery assembly 132 is a component of a percutaneous power delivery link and receives power and / or data from an external device 142. In an illustrative embodiment, the power delivery link includes an inductive RF link, and the internal power delivery assembly 132 includes a primary internal coil 136. The internal coil 136 is typically a wire antenna coil composed of multi-turn electrically insulated single or multi-strand platinum or gold wire.

[0023] The implantable portion of the cochlear implant 100 also includes a main implantable component 120 and an elongated stimulator component 118. In embodiments of the invention, the internal power delivery component 132 and the main implantable component 120 are hermetically sealed within a biocompatible shell. In embodiments of the invention, the main implantable component 120 includes a sound processing unit (not shown) to convert sound signals received by an implantable microphone in the internal power delivery component 132 into data signals. The main implantable component 120 also includes a stimulator unit (also not shown) that generates an electrical stimulation signal based on the data signal. The electrical stimulation signal is delivered to the recipient via the elongated stimulator component 118.

[0024] The elongated stimulation component 118 has a proximal end connected to the main implantable component 120 and a distal end implanted in the cochlea 140. The stimulation component 118 extends from the main implantable component 120 through the mastoid bone 119 into the cochlea 140. In some embodiments, the stimulation component 118 may be implanted in at least the basal region 116, and sometimes deeper. For example, the stimulation component 118 may extend toward the apex of the cochlea 140, referred to as the cochlear apex 134. In some cases, the stimulation component 118 may be inserted into the cochlea 140 through a cochlear fenestration 122. In other cases, the cochlear fenestration may be formed through a round window 121, an oval window 112, a promontory 123, or through the apical gyrus 147 of the cochlea 140.

[0025] The stimulation assembly 118 includes an array 146 of longitudinally aligned and distally extending electrodes 148 disposed along its length. As noted, the stimulator unit generates a stimulation signal that is applied to the cochlea 140 by stimulation contacts 148 (which are electrodes in an exemplary embodiment), thereby stimulating the auditory nerve 114. In an exemplary embodiment, the stimulation contacts can be any type of component that stimulates the cochlea (e.g., a mechanical component that moves or vibrates and thus (e.g., by inducing fluid movement in the cochlea) to stimulate the cochlea, such as a piezoelectric device, electrodes that apply current to the cochlea, etc.). The embodiments detailed herein will generally be described with respect to the electrode assembly 118 using electrodes as elements 148. It should be noted that alternative embodiments may utilize other types of stimulation devices. In at least some embodiments, any device, system, or method that stimulates the cochlea via a means located in the cochlea can be utilized. In this regard, unless otherwise indicated, any implantable array that stimulates tissue, such as an array of retinal implants, a spinal cord array, or a pacemaker array, is covered within the teachings herein.

[0026] As noted, the implantable portion 100 includes a partially implantable prosthesis, in contrast to a fully implantable prosthesis capable of operating for at least a period of time without the external device 142. Therefore, the implantable portion of the cochlear implant 100 does not include a rechargeable power source for storing electricity received from the external device 142, in contrast to embodiments containing an implantable rechargeable power source (e.g., a rechargeable battery). During operation of the implant 100, power is transferred from the external component to the implantable component via a connection and distributed to various other implantable components as needed.

[0027] It should be noted that the teachings detailed herein and / or variations thereof may be used with fully implantable prostheses. That is, in alternative embodiments of cochlear implants or other hearing prostheses detailed herein, these prostheses are fully implantable, such as those containing an implantable microphone and sound processor and battery.

[0028] Figure 1BA schematic diagram of an exemplary conceptual sleep apnea system 1991 is provided. Here, this exemplary sleep apnea system utilizes a microphone 12 (conceptually represented) to capture a person's breathing or additional sounds emitted by the person during sleep. The microphone converts the captured sounds into electrical signals, which are provided via electrical leads 198 to a main unit 197, the main unit including a processor unit capable of evaluating the signal from leads 198, or, in another arrangement, unit 197 being configured to provide the signal to a remote processing location via the Internet or the like, where the signal is evaluated. After evaluating whether the sleep apnea system 1991 should take or can otherwise be effectively taken action, unit 197 is activated to implement sleep apnea countermeasures, which are performed by a hose 1902 sleep apnea mask 195. As an example only and not as a limitation, pressure changes can be used to treat sleep apnea based on indications of this event.

[0029] In exemplary embodiments, the advanced implantation methods and apparatus detailed herein can be used to treat sleep apnea in a therapeutically usable device. Specifically, electrodes of the implant disclosed below can replace electrode 194 (and are placed accordingly, of course), and the implant can have a configuration for treating sleep apnea. In this regard, in exemplary embodiments, the implantable component detailed herein can be located at a position for treating sleep apnea according to the teachings herein, with necessary modifications to implement the description, as necessary or otherwise practical.

[0030] Figure 1C and 1D Another exemplary schematic diagram of a 1992 sleep apnea system is provided. Here, the sleep apnea system is related to... Figure 1B The difference with this sleep apnea system is that electrode 194 (which may be implanted in some embodiments) is used to provide stimulation to a human experiencing sleep apnea. Figure 1C The external unit is shown, and Figure 1D External unit 120 and implanted unit 110 are shown communicating signals via an inductor coil 707 of the external unit and a corresponding implanted inductor coil (not shown) of the implanted unit. The teachings herein are applicable based on said external unit and said implanted unit. Implanted unit 110 may be configured for implantation in the recipient's body at a location that allows it to modulate the nerves of the recipient 100 via electrode 194. In the treatment of sleep apnea, implanted unit 110 and / or its electrodes may be located on the genioglossus muscle of the patient. This location is suitable for modulating the hypoglossal nerve, whose branches extend within the genioglossus muscle.

[0031] The external unit 120 may be configured to be located outside the patient's body, in direct contact with or near the recipient's skin. The external unit 120 may be configured to be attached to the patient, for example, by adhering to the patient's skin, or by a band or other means configured to hold the external unit 120 in place. The skin attachment of the external unit 120 may occur near the location of the implant unit 110, such that, for example, the external unit 120 can signal communicate with the implant unit 110, as conceptually illustrated, this communication may be via an inductive link or an RF link or any link capable of treating sleep apnea using both the implant unit and the external unit. The external unit 120 may include a processor unit 198 configured to control stimuli performed by the implant unit 110. In this regard, the processor unit 198 may be via electrical leads (e.g., in an arrangement where the external unit 120 is a modular component) or via a wireless system (e.g., in… Figure 1D (Conceptual representation) communicates with microphone 12 via signal.

[0032] These sleep apnea treatment systems share the common feature of using a microphone to capture sound, and using the captured sound to perform one or more features of the sleep apnea system. In some embodiments, the teachings herein are used in conjunction with the sleep apnea device just described in detail.

[0033] Figure 3 Exemplary embodiments of generally neural prostheses, and specifically retinal prostheses and their use environments, are presented, with components that can be used, in whole or in part, with some of the teachings herein. In some embodiments of the retinal prosthesis, the retinal prosthesis sensor-stimulator 10801 is positioned close to the retina 11001. In an exemplary embodiment, photons entering the eye are absorbed by a microelectronic array of the sensor-stimulator 10801, which is hybridized with a glass element 11201 containing, for example, an embedded microwire array. The glass may have a curved surface conforming to the inner radius of the retina. The sensor-stimulator 108 may include a microelectronic imaging device, which may be made of thin silicone containing an integrated circuit system that converts incident photons into electronic charges.

[0034] Image processor 10201 communicates with sensor-stimulator 10801 via cable 10401, which extends through a surgical incision 00601 in the eye wall (although in other embodiments, image processor 10201 communicates wirelessly with sensor-stimulator 10801). Image processor 10201 processes inputs to sensor-stimulator 10801 and provides control signals back to sensor-stimulator 10801, thus enabling the device to provide processed outputs to the optic nerve. That is, in alternative embodiments, the processing is performed by components close to or integrated with sensor-stimulator 10801. The charge generated by the conversion of incident photons is converted into a proportional amount of electronic current, which is input to a nearby layer of retinal cells. The cells are excited, and the signal is sent to the optic nerve, thus triggering visual perception.

[0035] The retinal prosthesis may include an external device disposed in a behind-the-ear (BTE) unit or in a pair of glasses, or any other type of component that may have practical value. The retinal prosthesis may include an external light / image capturing device (e.g., located in / on a BTE device or a pair of glasses), and as noted above, in some embodiments, a sensor-stimulator 10801 captures light / images, which is implanted in the recipient.

[0036] To keep the disclosure concise, any disclosure herein regarding microphones or sound capture devices corresponds to similar disclosures regarding optical / image capture devices, such as charge-coupled devices. By extension, any disclosure herein regarding stimulator units that generate electrical stimulation signals or otherwise energize tissue to evoke auditory perception corresponds to similar disclosures regarding stimulator devices for retinal prostheses. Any disclosure herein regarding sound processors or processing of captured sound, etc., corresponds to similar disclosures regarding optical processors / image processors having similar functionality to retinal prostheses and processing captured images in a similar manner. In fact, any disclosure herein regarding devices for hearing prostheses corresponds to disclosures regarding devices for retinal prostheses having similar functionality to retinal prostheses. Any disclosure herein regarding the assembly of hearing prostheses corresponds to disclosures regarding the assembly of retinal prostheses using similar actions. Any disclosure herein regarding methods of using or operating hearing prostheses or otherwise incorporating hearing prostheses to function corresponds herein to disclosures regarding the use or operation of retinal prostheses or otherwise incorporating retinal prostheses to function in a similar manner.

[0037] Figure 4An exemplary vestibular implant 400 according to an example is depicted. Some specific features of the contact points of various elements utilizing the cochlear implant described above in FIG1 are described. In this regard, some features of the cochlear implant are used in conjunction with those of the vestibular implant. For the sake of economy of text and graphics, the same numbers are used to refer to the various elements of the vestibular implant that generally correspond to the elements of the cochlear implant described above. It should still be noted that some features of the vestibular implant 400 will differ from those of the cochlear implant described above. By way of example only and not as a limitation, a microphone may not be present on the postauricular device 126. Alternatively, a sensor of practical value may be included in the vestibular implant in the BTE device 126. By way of example only and not as a limitation, a motion sensor may be located in the BTE device 126. There may also be no sound processor in the BTE device. Instead, other types of processors, such as those that process data obtained from the sensors, will be present in the BTE device 126. A power source such as a battery will also be included in the BTE device 126. Consistent with the BTE device of the cochlear implant in Figure 1, the transmitter / transceiver will be located within or otherwise communicate with the BTE device. Any one or more teachings herein may be related to... Figure 4 Use them together in the same arrangement.

[0038] The implantable component includes a receiver-stimulator in association with the cochlear implant described above. Here, the vestibular stimulator includes a main implantable component 120 and an elongated electrode assembly 14188 (wherein the elongated electrode assembly 14188 has some different features from the elongated electrode assembly 118 of the cochlear implant, some of which will be described later). In some embodiments, the internal energy delivery assembly 132 and the main implantable component 120 are hermetically sealed within a biocompatible housing. In some embodiments, the main implantable component 120 includes a processing unit (not shown) for converting data acquired by a sensor, which may be an onboard sensor implanted in the receiver.

[0039] The main implantable component 120 also includes a stimulator unit (not shown) that generates an electrical stimulation signal based on a data signal. The electrical stimulation signal is delivered to the recipient via an elongated electrode assembly 14188.

[0040] It should be briefly pointed out that, although Figure 4 The embodiments shown represent partially implantable vestibular implants, but embodiments may include fully implantable vestibular implants, such as those in which motion sensors are located in the implantable portion in a manner similar to that of a cochlear implant.

[0041] The elongated electrode assembly 14188 has a proximal end connected to the main implantable component 120 and extends through a hole in the mastoid 119 in a manner similar to the elongated electrode assembly 118 of a cochlear implant, and includes a distal end extending into the inner ear. In some embodiments, the distal portion of the electrode assembly 14188 includes a plurality of leads 410 that branch from the body of the electrode assembly 118 to an electrode 420. The electrode 420 may be positioned at the base of a semi-circular conduit, such as... Figure 4 As shown. In an exemplary embodiment, one or more of these electrodes are placed near the vestibular nerve branches that innervate the semicircular canal. In some embodiments, the electrodes are located outside the inner ear, while in other embodiments, the electrodes are inserted into the inner ear. Note that while this embodiment does not include an electrode array located in the cochlea, in other embodiments, one or more electrodes are located in the cochlea in a manner similar to a cochlear implant.

[0042] Returning to hearing prosthetic devices, especially cochlear implants, Figure 1E This is a side view of the internal components (implantable components) of the cochlear implant 100; other components of the system 10 (e.g., external components) are not shown. The implantable portion of the cochlear implant 100 includes a receiver / stimulator 180 (a combination of the main implantable component 120 and the internal energy delivery assembly 132) and a stimulation assembly or lead 118. The stimulation assembly 118 includes a helix 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 recipient's middle ear cavity. Therefore, the proximal region 186 corresponds to a middle ear cavity sub-segment 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, PCB trace, etc. (not shown), which is connected to the receiver / stimulator 180 via a lead 118. The corresponding stimulation electrical signal of each electrode contact 148 is propagated through the conductive path.

[0043] Figure 2A This is a side view of the coiled orientation of the electrode array assembly 190 when inserted into the recipient's cochlea, wherein the electrode contacts 148 are located inside the curve. Figure 2A Depicting the in situ cochlea 140 in the patient Figure 1B Electrode array.

[0044] Figure 2B A side view is depicted corresponding to a device 390 of a cochlear implant electrode array assembly, the device including... Figure 1BSome or all of the features of the electrode array assembly 190. More specifically, in an exemplary embodiment, the stimulation assembly 118 includes the electrode array assembly 390 instead of the electrode array assembly 190 (i.e., 190 is replaced by 390).

[0045] Electrode array assembly 390 includes the cochlear implant electrode array component comprising the aforementioned 190 components. Also note element 310, which is a quasi-handle-like device practically useful for inserting segment 188 into the cochlea. By way of example and not limitation, element 310 is a silicone body that extends laterally away from the longitudinal axis of electrode array assembly 390 and is less thick than the body of the assembly (the portion through which the electrical leads extending to the electrodes extend into the elongated lead assembly 302). The thickness, combined with the material structure, is sufficient to allow the handle to be held during implantation by force applied to the forceps, which can be transmitted to the electrode array assembly 390, enabling the insertion of segment 188 into the cochlea.

[0046] Figure 2C Further details of the external component assembly 242 corresponding to the external component 142 described above are presented. It should be noted that, in an improved form, this device can be used with other prostheses described herein (e.g., some such embodiments may not have earpiece 250).

[0047] External component 242 typically includes a voice converter 220 for detecting sound and generating an electrical audio signal, typically an analog audio signal. In this illustrative arrangement, the voice converter 220 is a microphone. In alternative arrangements, the voice converter 220 can be any now- or later-developed device capable of detecting sound and generating an electrical signal representing such sound. Exemplary alternative locations for the voice converter 220 will be detailed below. As will be detailed below, the voice converter can also be located in the earpiece, which can utilize the “decorative” features of the cerebellum to capture sound more naturally (described in detail below).

[0048] External component 242 also includes a signal processing unit, a power supply (not shown), and an external transmitter unit. The external transmitter unit 206 (sometimes referred to herein as the head component) includes an external coil 208 and a magnet (not shown) directly or indirectly attached to the external coil 208. The signal processing unit processes the output of microphone 220, which is positioned by the receiver's outer ear 201 in the depicted arrangement. The signal processing unit uses a signal processing device (sometimes referred to herein as a sound processing device) to generate coded signals, which can be a circuit system (typically a chip) configured to process received signals; since component 230 contains this circuit system, the entire component 230 is generally referred to as the sound processing unit or signal processing unit. These coded signals, which may be referred to herein as stimulus data signals, are provided to the external transmitter unit 206 via cable 247. Figure 1D In this exemplary arrangement, cable 247 includes a connector socket 221 that bayonet-fits into a socket 219 of signal processing unit 230 (an opening exists in a spine that receives the bayonet connector, including electrical contacts for positioning an external transmitter unit to communicate signalically with signal processor 230). It should also be noted that in an alternative arrangement, the external transmitter unit is hardwired to signal processor subassembly 230. That is, cable 247 communicates signalically with signal processor subassembly via hardwire. (Of course, the device can be disassembled, but this is different from...) Figure 1D (The arrangement shown utilizes a bayonet connector.) Conversely, in some embodiments, cable 247 is absent. Instead, a wireless transmitter and / or transceiver are housed in and / or attached to the housing of component 230 (e.g., the transmitter / transceiver may be attached to connector 219), and the head unit may include a receiver and / or transceiver and may communicate signalically with / associated with the transmitter / transceiver of component 230.

[0049] Figure 1F Additional details are provided for an exemplary in-ear (ITE) component 250. In this illustration, the integral component containing the signal processing unit is constructed and arranged such that it can be fitted behind the outer ear 201 in a BTE (behind-the-ear) configuration, but can also be worn on different parts of the recipient's body or clothing.

[0050] In some arrangements, a signal processor (also known as a sound processor) can generate electrical stimulation alone, without producing any acoustic stimulation beyond what naturally enters the ear. However, in more advanced arrangements, two signal processors can be used. One signal processor is used in conjunction with a second speech processor, which is used to generate acoustic stimulation, to produce electrical stimulation.

[0051] like Figure 1FAs shown, the ITE component 250 is connected via cable 252 to the spine of the BTE (a general term used to describe the component to which the battery 270 is attached, which contains a signal (sound) processor and supports various components such as a microphone—described in detail below) (and thus connected to the sound processor / signal processor). The ITE component 250 includes a housing 256, which may be a molded part shaped for the recipient. Inside the ITE component 250, an acoustic transducer 220 is provided that can be located on the element 250, allowing sound to be delivered to the acoustic transducer of the external component in a more natural way by utilizing the natural wonder of the human ear. In the exemplary arrangement, the sound transducer 242 communicates signalally with the rest of the BTE unit via cable 252, such as Figure 1F The sub-cable extending from the transducer 242 to the cable 252 is schematically depicted. Lead 21324 extending from the transducer 220 to the cable 252 is shown in dashed lines. An air vent, extending from the left side of housing 256 to the right side of housing (at or near the tip on the right side), is not shown to balance the air pressure "behind" housing 256 and the surrounding atmosphere when housing 256 is in the ear canal.

[0052] in addition, Figure 2C A removable power supply component 270 (sometimes a battery spare, or a battery used in case of a short circuit) is shown attached directly to the base of the body / spine 230 of the BTE device. As can be seen, in some embodiments, the BTE device includes a control button 274. The BTE device may have an indicator light 276 on the ear hook to indicate the operating status of the signal processor. Examples of status indications include flashing when receiving incoming sound, flashing at a low rate when power is low, or flashing at a high rate when there are other problems.

[0053] In one arrangement, the outer coil 130 transmits electrical signals to the inner coil via an inductive communication link. The inner coil is typically a wire antenna coil consisting of at least one, two, three, or more turns of electrically insulated single or multiple strands of platinum or gold wire. The electrical insulation of the inner coil is provided by a flexible silicone molding (not shown). In use, the inner receiver unit can be positioned in a recess of the temporal bone adjacent to the receiver's outer ear 101.

[0054] In the case of the above as a primer (the above should be regarded as the basic technology on which we have built and is not part of the present invention, but the teachings below may use any one or more of these features in some embodiments, as long as it is feasible in the art), the embodiments involve cochlear implants and other implants using one or more of the teachings above, although modifications have been made in at least some cases for the purposes of the teachings herein.

[0055] Figure 5 This shows the corresponding details described above.Figure 1A The implantable portion 500 of the cochlear implant is part 100. In this regard, the features detailed above regarding the cochlear implant are included in this embodiment. Element 181 corresponds to an RF antenna that receives transcutaneous magneto-inductive signals from external components. Antenna 181 communicates with electronics located in housing 185. Housing 185 is a hermetically sealed titanium housing containing components of the cochlear implant configured to receive signals from antenna 181 and, based on these signals, output signals to electrodes of electrode assembly 590, which may correspond to electrode assembly 190 detailed above. Overall, the electronics in housing 185 and antenna 181 together establish receiver-stimulator assembly 580, which may correspond to receiver-stimulator assembly 180 detailed above. Antenna 181 and housing 185 are located within a silicone body 183 molded around those components. Electrode assembly 590 communicates with electronics in housing 185 via lead assembly 589. The lead assembly may be a silicone body molded around electrical leads extending from the electrodes to a feedthrough that engages with the housing 185, enabling signal communication from electronics within the housing to the electrical leads and thus to the electrodes. The electrode assembly, particularly its silicone body, may be separable from the silicone body encapsulating the housing 185. In this regard, in an exemplary embodiment, the lead assembly 589, together with the electrode array assembly 590, is connected to the housing 185; or more precisely, the leads of the lead assembly 589 are first attached to the feedthrough that engages with the housing 185, thereby placing the lead assembly in electrical signal communication with the receiver-stimulator assembly 580, the leads being supported by the silicone body encapsulating the leads of the lead assembly 589. Silicone is then molded around the housing 185 to form a silicone body 183, which captures or otherwise adheres the lead assembly 589 to the silicone body.

[0056] This embodiment also features a therapeutic substance delivery subsystem. In this respect, Figure 5 The embodiments are configured to deliver therapeutic material from outside the cochlea to inside the cochlea when the electrode array 590 is located in the cochlea. In this regard, the implantable portion includes the therapeutic material delivery subsystem just mentioned. This subsystem includes a reservoir 510, such as... Figure 5 As seen, it forms part of the reservoir filling assembly (the additional details of which will be described below). Figure 6Additional details of the therapeutic substance delivery subsystem are shown. Specifically, a reservoir 510 is shown in fluid communication with a conduit including a first portion 512 leading to a second portion 514. Here, the reservoir 512 is supported by a silicone body 183 encapsulating a housing. In some embodiments, the reservoir is completely contained within the silicone body 183, while in other embodiments, a portion of the reservoir extends beyond the surface of the silicone body 183 or is otherwise flush with the surface of the silicone body. The reservoir 510 may be made of titanium or a polymer stable to the therapeutic substance to be placed in the reservoir. The reservoir 510 may include a diaphragm at its top portion, which allows the reservoir to be filled with therapeutic substance. Some additional details thereof will be described below.

[0057] The conduit can be a polymer tube or constructed from a polymer tube stable to the therapeutic substance. The tube is connected to the reservoir in a manner that allows fluid to be transferred from the reservoir to the tube (e.g., using an interference fit between the reservoir's anode outlet and the tube). The tube extends from the reservoir 510 into a silicone body 516, which encapsulates an electrical lead 592 extending from the electrode. (The electrical lead may be located within the tube, while in other embodiments, the tube is "parallel" to and adjacent to the lead.) Further note that in embodiments, the tubes may be located outside the silicone body 516 and extend parallel to the silicone body (connected along the length, e.g., by a strip or some connector that holds the tubes against the body along the length of the body), or loosely arranged so that the tubes can move away from the silicone body, where the ends of the tubes then meet the electrode array (roughly similar to the operation of the old Chesapeake Bay Bridge tunnel—the bridges are separate but joined together / meet at the tunnel—here, the tubes and the body may meet at the array, such that only one opening enters the cochlea). In this regard, in an exemplary embodiment, portions of the reservoir 510 and tube 512 extending into the silicone body 516 can be molded within the silicone body 183 during a molding process of the silicone body 183 around the housing 185. At least some of the tube portions 514 and 512 can be placed together with the electrical leads 592, and then the silicone can be molded around both simultaneously to establish the body 516. In embodiments, there is no explicitly defined tube structure itself, but rather a conduit within the silicone, i.e., a hollow space therein. For example, the hollow space could be the hollow space left after removing a mandrel around which the leads are molded. In embodiments, the silicone can be removed, for example, by excavating the hollow space. In some embodiments, any means, systems, and / or methods capable of creating a channel within the implant that achieves the teachings herein can be used, provided that the process and / or end result is achievable in the art. Therefore, in embodiments, the implant is "tubeless" entirely or partially relative to the therapeutic material delivery system (e.g., portions 514 and / or 518 may be tubeless, but portion 512 may be, for example, a tube). Any portion may be tubeless or constructed from a tube.

[0058] Consistent with the embodiments described above, electrode assembly 590 is located at the end of lead assembly 589. A tube extends into the illustrated electrode array portion. A portion 518 of the tube extending into the electrode array portion extends to the tip of electrode array 590. Commonly, portions 518, 514, 512, and the reservoir form an implantable therapeutic material reservoir. In embodiments, portion 518 is configured to be flexible. In embodiments, all or most of the therapeutic material delivery system located within the cochlea is flexible when fully implanted. In embodiments, the portion located within the cochlea is at least as flexible as an electrode array without portion 518. Therefore, in some embodiments, portion 518 is even more flexible than an electrode array without portion 518.

[0059] The plug 530 is located at the end of the tube (e.g., interference fit inside the tube, or attached to the tube). The plug provides a bacterial seal at the tube portion 518 and thus at the reservoir assembly, but allows therapeutic material in the reservoir to pass through and thus enter the cochlea. Additional details thereof will be described below.

[0060] In view of the above, in an embodiment, there is a device, such as an implantable portion of a cochlear implant, comprising an array of electrodes and an implantable therapeutic substance reservoir. The device is configured such that, when the device is fully implanted in the recipient, the therapeutic substance reservoir extends from a location behind the ear canal between the mastoid bone and the skin of the person to the cochlea. In this respect, as described above, a reservoir, which is part of the reservoir, is adjacent to the receiver-stimulator 580. When the implant is implanted in the head of a person, the reservoir 510 is located behind and / or above the ear canal, or at least a portion thereof is positioned in this manner. In an embodiment, at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% (when viewed from below the coil) of the total area contained in the reservoir is positioned in this manner. Further note that, in the embodiment, when viewed directly from the side of the head (90 degrees from the front), for a 60-year-old 50th percentile engineered individual born in the United States, the implantable portion is configured such that any one or more of the aforementioned characteristics of reservoir 510 also apply to the area not obscured by the person's auricle (e.g., 100% unobscured, or at least 20% unobscured). Note that this is not a subjective characteristic of the given person. This is an objective characteristic relating to the qualifying facts related to the aforementioned 50th percentile. That is, in the exemplary embodiment, this can be a subjective value for the given person.

[0061] about Figure 8A quadrant system exists centered on the recipient's ear canal 106. It can be seen that this is established by a vertical line 99 and a horizontal line 98 centered on the center of the ear canal 106. These lines establish four quadrants around the ear canal: Q1, Q2, Q3, and Q4. As will be understood, these quadrants generally follow a 12-hour clock, with quadrant 1 falling between the 12 o'clock and 3 o'clock positions, quadrant 2 between the 3 o'clock and 6 o'clock positions, quadrant 3 between the 6 o'clock and 9 o'clock positions, and quadrant 4 between the 9 o'clock and 12 o'clock positions. In an embodiment, the reservoir falls entirely within quadrant Q4. Therefore, in an exemplary embodiment, there exists a hearing prosthesis device comprising a reservoir having a portion falling within quadrant 4. When viewed directly from the side (90 degrees from the front), these quadrants are established by the outermost opening of the ear canal 106. These are established at the outermost portion of the ear canal, which forms a closed circle or oval shape in cross-section.

[0062] Note that alternating quadrants may exist. In an exemplary embodiment, a quadrant may be established by lines 94 / 96, which are the uppermost and lowermost tangents to the ear canal 106 (the opening of the ear canal); lines 99 and 98, which correspond to the center of the opening of the ear canal, as just detailed; and lines 95 and 97, which correspond to the uppermost and lowermost tangents to the ear canal (again, relative to the opening). The features just mentioned can be applied to any quadrant of a quadrant established by any of these lines. (Quadrants may include quadrants based on lines 97 and 94—all lines may be mixed and matched.) Note further that, in the exemplary embodiments, there may be a basis based on and Figure 8 The quadrant of any one or more lines parallel to the lines shown, wherein these lines are to the left or right of the given line, or above or below, any value or range of values ​​in increments of 1 mm, of 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 cm. Any of the above characteristics may be applied to such a quadrant.

[0063] In an embodiment, at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or more of the total volume of the reservoir, or any value or range of values ​​in increments of 1% (e.g., 33%, 54%, 31 to 94%, etc.), may be located behind (where the person's face is in front) and / or above (where the person's feet are below) any one or more of the lines just mentioned.

[0064] In this embodiment, the reservoir is fully integrated into the implantable portion of the cochlear implant. For example, as detailed above, the reservoir 510 is located within the silicone body of the encapsulating housing 185, and the tube portions 512, 514, and 518, as well as the plug 530, are all within the boundary of the lead assembly that forms with the electrode assembly.

[0065] In an exemplary embodiment, at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% of the total outer surface area of ​​the components constituting the reservoir (e.g., the reservoir and tubing, and plugs, if present)) is in direct contact with silicone, which forms the silicone body of the encapsulating housing and the silicone body of the lead assembly including the electrode assembly. Some portions of the reservoir (e.g., a diaphragm that allows the reservoir to be filled) may be located outside the silicone body of the encapsulating housing or otherwise flush with the surrounding silicone body.

[0066] Figure 7 A lead assembly 789 is shown prior to the connection of the lead assembly to the receiver-stimulator of the cochlear implant. In an exemplary embodiment, this lead assembly is manufactured separately from the receiver-stimulator. As seen at the right end of the lead assembly 789, a T-shaped member 777 is present. It should be noted that some embodiments do not utilize the T 777.

[0067] Figure 7 The non-repulsive features associated with the conduit of the lead assembly are also shown. In particular, two different tubes are used. Here, there is a first tube with portions 714 and 712, which is a silicone tube. This tube can be easily bent or deformed to establish portions 714 and 712 without permanently kinking the tube or otherwise adversely affecting the flow of the therapeutic material therein.

[0068] In one embodiment, the carrier member 146 of the electrode array is molded itself around the tube 718, or is molded by connecting the tube 718 to the tube 714. In another embodiment, the carrier member 146 of the electrode array is molded around the portion 518. Subsequently, the silicone body 516 of the lead assembly is molded around the tube 714 (and / or a portion of the tube 718, depending on the length of the tube 718) / around the portion 714. That is, in this embodiment, the carrier member is built together with the silicone body 516, so these portions are integral with each other.

[0069] In the embodiments, there is an electrode array including tube 718 and / or portion 518. Figure 7AA tube, or more precisely, a lumen and reservoir of silicone without a lead body / silicone body, is shown (in some embodiments, the lumen is constructed from different tubes coated with a silicone body / wherein the silicone body is molded onto the tube, and in other embodiments, the lumen is formed within the silicone body). Furthermore, an embodiment without a stopper 530 is shown (the embodiment may include a closure device and may not have one).

[0070] We now distinguish the lead assembly from the lead portion of the implantable component. The lead assembly is the component attached to the housing and receiver-stimulator during manufacturing and can be identified after manufacturing; the bracket welded to the pressure vessel can also be distinguished from the pressure vessel thereafter. The inference from this is that the implantable component has a lead portion after the implantable component is manufactured or after a complete implantable component for implantation is obtained by a physician, surgeon, or healthcare professional (the surgeon does not attach the lead assembly to the receiver-stimulator; these components are delivered as a single device in a fully implantable form). The lead portion is the portion of the external component extending from the feedthrough (to which the electrical leads are attached) of the housing 185 to the furthest end of the electrode assembly 590, and this can take, for example, the portion encapsulating the silicone body of the electrical leads, and in this embodiment, can take, for example, the portion of the reservoir 510 and the tube 712. In an exemplary embodiment, such as where the feedthrough is located on the left side of the housing 185, directly facing the lead assembly 589 (rather than on the bottom, top, or side of the housing), the lead portion of the implantable component would be the portion to the left of the reference line 599. Therefore, if the leads extend from the silicone body of the lead assembly before the silicone body 183 is constructed, this will include a portion of the encapsulation housing 185 of the silicone body 183 (e.g., which will also encapsulate portions of the electrical leads). Furthermore, there are feedthroughs located at the bottom or top of the housing 185 or on the side of the housing (in... Figure 5 In some embodiments of the arrangement (relative to the side facing the electrode array 590), the lead portion of the implantable component may extend to the right side of the reference line 599 (rather than ending there), but within a potentially narrow channel (which may or may not be obvious) surrounding the lead assembly 589. In practice, in embodiments, a channel providing space for the electrical leads may exist in the bottom of the housing 185. The lead portion will be at least a portion of the electrical leads in this channel, as well as a filling channel of the silicone body, to secure the leads relative to the housing 185 between the feedthrough and the silicone body of the lead assembly 589. Therefore, when viewed from the side, it may have a dog-leg-shaped sub-portion extending downwards from the front of the housing 185 (from the left side of the reference line 599) and then extending below the housing 185. Note that in these embodiments, the lead portion will include everything to the left of the reference line 599.

[0071] Therefore, the embodiments include relative to Figure 5 The embodiment is located entirely to the left of line 599, which represents the leftmost portion of housing 185. In the exemplary embodiment, at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of the total internal volume of the reservoir, or any value or range of values ​​in increments of 1%, are located to the left of line 599, and therefore to the left of the leftmost portion of housing 185.

[0072] refer to Figure 5 The leftmost part of the housing 185 is in the direction of the longitudinal axis of the implantable part opposite to the antenna 181. Figure 5 The part that extends in the horizontal direction.

[0073] By rough analogy, the portion of the silicone body 185 discussed, which is part of the lead wire section, can be considered analogous to the mounting portion of an antenna. For example, the base of an antenna, including a mounting device that allows the antenna to be attached to, for example, the fuselage of an aircraft, is still considered the antenna section.

[0074] Furthermore, note again that the various parts of the silicone body 183 may overlap with the silicone body of the lead assembly 589.

[0075] Therefore, we see embodiments in which the reservoir is fully integrated into the lead portion of the cochlear implant, the lead portion including an array of electrodes.

[0076] In embodiments, the memory has values ​​less than, greater than, and / or equal to (including all endpoints or excluding endpoints) 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. The volume can be 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 110, 120, 130, 140, or 150 microliters, or any value or range of values ​​in increments of 0.01 microliters (e.g., 9.03, 22.22, 5.01 to 19.31 microliters, etc.). Therefore, in embodiments, the reservoir has a volume not exceeding any of these values ​​(e.g., not exceeding 20 microliters, not exceeding 10 microliters, not exceeding 0.73 microliters, etc.). "Not exceeding" includes smaller volumes. Specifications require that the volume must not exceed this amount. And this volume corresponds to the amount of therapeutic material that can be received.

[0077] In the embodiments, the reservoir has an internal volume (fluid capacity) less than, greater than and / or equal to 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 110, 120, 130, 140 or 145 microliters or a range of values ​​in increments of 0.005 microliters. In the embodiments, tube 714 (alone or including portion 712) has the following values: 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4. 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55 or 60 μL or any value or range of values ​​in increments of 0.005 μL. In the embodiment, tube 718 has the following properties: 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.30, 0.35, 0.4, 0.5, 0.6, 0.7, 0.8. 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 μL, or any value or range of values ​​in increments of 0.001 μL, or any value of internal volume (fluid capacity) that can be calculated using the data herein.In the embodiments, the length of tube 718 is less than, greater than and / or equal to 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 or 40 mm, or any value or range of values ​​in increments of 0.1 mm, or any value that can be calculated using the data herein. In embodiments, the length of tube 714 (alone or including portion 712) is less than, greater than and / or equal to 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, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190 or 200 mm, or any value or range of values ​​in increments of 0.1 mm. The outer diameter of the storage tank may be less than, greater than and / or equal to 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 4, 4.5, 5, 5.5, 6, 6.5 or 7 mm, or any value or range of values ​​in increments of 0.05 mm. In the embodiments, the inner diameter of tube 718 is less than, greater than and / or equal to 0.01, 0.015, 0.2, 0.25, 0.3, 0.35, 0.4, 0.045, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19 or 0.2 mm, or any value or range of values ​​in increments of 0.001 mm. In the embodiments, the inner diameter of tube 714 and / or portion 712 is less than, greater than and / or equal to 0.1, 0.15, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 0.32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, 0.4, 0.41, 0.42, 0.43, 0.44, 0.45 mm, or any value or range of values ​​in increments of 0.001 mm.

[0078] The embodiments include an integrated septum configured to receive the end of an syringe so that therapeutic material can be delivered to a reservoir, and which provides a bacterial seal between the reservoir and the external environment of the device after the end is removed. Figure 9 An exemplary embodiment is shown, which is about Figure 5 A view of section 9-9. Here, additional details of an exemplary reservoir according to an exemplary embodiment are described. The reservoir 510 includes a titanium shell wall 912, to which a support and fixing device 920 is attached, the support and fixing device being a titanium ring welded to the top of the cylindrical wall 912 of the reservoir.

[0079] A support and fixing device holds the diaphragm 930 in place. The diaphragm material is sandwiched between the various parts of the titanium ring 920 or otherwise bonded to the inner wall of the ring 920.

[0080] Embodiments may include the use of a self-healing septum. The septum 930 is configured to allow at least one puncture (and in some embodiments, repeated punctures) and subsequent healing via the end of the syringe. The end can be inserted through the septum, allowing therapeutic material to be injected into a reservoir, and thus “filling” or otherwise delivering the material into a receptacle. That is, in embodiments, the septum may be a disposable / single-use septum. And in this respect, in exemplary embodiments, the receptacle or other therapeutic material delivery system is a single-use system. In embodiments, it is used for some chronic diseases or other chronic conditions.

[0081] Furthermore, while the above embodiments focus on filling the container shortly before implantation using a filling or filling device or otherwise, in another embodiment, the therapeutic substance may be located in a reservoir while the therapeutic substance is located in a package and otherwise aseptically sealed in the package.

[0082] In practice, embodiments include selecting a specific type of therapeutic substance to be delivered by the implantable portion, and then filling the implantable portion within the defined timeframe herein. Further note that embodiments may include packaging two or more different types of therapeutic substances, rather than just a single therapeutic substance. In this exemplary embodiment, this allows healthcare professionals to select which therapeutic substance to use shortly before implantation. Furthermore, multiple identical therapeutic substances may be provided at different concentrations to allow healthcare providers to select the concentration to be delivered. A corollary to this is that in some embodiments, the therapeutic substance can be such that the substance itself determines the diffusion rate. For example, the same therapeutic substance may be provided in a mixture that diffuses more slowly than the same therapeutic substance provided in another mixture. All of these can be selected shortly before implantation.

[0083] Still, embodiments include shipping the therapeutic material and the implantable portion together, whether in the same package or in separate packages but together.

[0084] The diaphragm seals the top of the reservoir and, in other ways, establishes a barrier between the reservoir and the internal portion of the body, specifically the tissue above the mastoid bone or the proximal portion of the lead portion near the implantable component. In an exemplary embodiment, the diaphragm 930 is configured to receive and, in other ways, allow the tip of a syringe (e.g., the syringe of a hypodermic syringe) to pass through it in a manner similar to or otherwise identical to that of a liquid medical container including a diaphragm (a self-healing diaphragm) that allows the tip of the syringe to pass through it to access a liquid therapeutic substance within the container. In at least some exemplary embodiments, in some embodiments any means, systems, and / or methods capable of repeatedly and sealingly entering from the outside of an external component (whether implanted in some embodiments or not in others (and both need not be mutually exclusive, but can be)) may be utilized—as described below—to enable filling of the reservoir prior to implantation.

[0085] In view of the above, in an exemplary embodiment, there is a device comprising an implantable therapeutic substance reservoir, a plurality of electrodes (e.g., electrode 148), and a silicone carrier body (e.g., carrier 146) supporting the plurality of electrodes. Furthermore, the device includes a stimulator assembly comprising a housing and stimulator electronics. In this embodiment, the device may include a receiver-stimulator, such as the receiver-stimulator 580 described above, or may include only a stimulator, or some other components besides a stimulator. The key point is that the device requires only a stimulator. And as mentioned above, the embodiment can be applied to pacemakers, etc., where, for example, its receiver component may not be present. In this regard, unless otherwise stated, any disclosure relating to a receiver-stimulator corresponds to the disclosure of alternative embodiments of the stimulator and / or receiver, provided that it is possible to implement in the art. In other words, any reference to a receiver-stimulator includes alternative embodiments with only a receiver or only a stimulator, or with a stimulator and some other components or multiple additional components but without a receiver. The inference from this is that a receiver-stimulator or receiver may include components having additional functions beyond that of a receiver-stimulator, as long as the functions of a receiver-stimulator are present.

[0086] In this embodiment, the device includes a filling port (e.g., a diaphragm) in fluid communication with a reservoir, the filling port being configured to deliver therapeutic material into the reservoir (e.g., via the tip of a syringe that punctures the diaphragm), and the filling port is located between the housing and a plurality of electrodes. In this embodiment, "between" refers to the relative position with respect to the longitudinal axis of the device (in...Figure 5 In the middle, the longitudinal axis is horizontal with its view.

[0087] Examples include arrangements that provide a desired release rate of drug molecules from one or more openings in an elongated lumen filled with a drug solution to the body fluids of a target organ (as an example, not a limitation, such as the cochlea). This can be achieved by providing a device with specific lumen dimensions (e.g., total lumen length and cross-sectional area over its length). Examples include geometry-controlled passive diffusion local drug release. Examples include an arrangement that provides controlled release of drug molecules through a tubular device from an implanted reservoir to a distant location (e.g., scala tympani) within the patient body via passive diffusion of drug molecules driven by a concentration gradient of a solvent (e.g., water). Examples include net movement without solvent / virtually net movement without solvent / substantially net movement without solvent. The desired (target / designed) release rate of drug molecules from the device at a distant location (e.g., the cochlea) can be adjusted (designed, e.g., as opposed to real-time adjustment) by the drug molecule size, the concentration of the drug solution used to fill the device, and / or the device's geometry (including the length and / or inner diameter of the tube).

[0088] In embodiments, no more than 30%, 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the total amount of solvent contained in the reservoir is transferred from the reservoir to the environment upon completion of filling and / or upon contact of the outlet with bodily fluids and / or upon completion of implantation (e.g., after closure). In embodiments, the aforementioned diffusion qualifier occurs after the outlet first contacts bodily fluids and / or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours after refilling.

[0089] In one embodiment, the lumen device containing the drug solution (sometimes referred to herein as a delivery tube device) can be made of a series of lumens of different lengths and / or cross-sectional areas, such as... Figure 7As shown in the diagram. Here, there are two lumens, lumen 7144 and lumen 7188, which are established by tubes 714 and 718, respectively. Lumen 7144 is connected to a “lumen” 5100 established by a reservoir 510. In short, this text will use the phrase “lumen length / lumen length,” which refers to the distance a therapeutic substance molecule travels as it travels from the reservoir to the outlet. This length is an extrapolated length or, alternatively, a length that would exist if the lumen and reservoir, etc., were positioned linearly. As an example, if the lumen is shaped like a U, the length is the length obtained if the U is flattened into a straight shape, or alternatively, the distance from the top of the U on the left to the top of the U on the right. The result will be described below. In practice, the lumen is likely not straight. For example, regarding the extension from the portion between the skin on the lateral side of the mastoid bone to the middle ear cavity (in the case of cochlear implants, by the portion of bone that is removed to enter the middle ear), an arcuate shape would exist. The overall geometry of the lumen can have any shape that can be of practical value. Furthermore, the tubes that define the lumen may need to be "converged," coiled, serpentine, or spiraled. For example, if the overall length of the device cannot exceed a certain number due to anatomical reasons, the tubes may be coiled. Moreover, even when using "straight" tubes, the internal lumen can be spiraled much longer than the tube itself to meet desired diffusion rates / performance. For example, suppose the length of tube 714 is X mm. The internal lumen can be equal to or greater than X by 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 times or more to achieve different desired diffusion rate / performance characteristics, exceeding the conventional 1:1 relationship between the lumen and tube lengths.

[0090] Figure 10 Exemplary functional arrangements of various lumens are depicted, and here, for analytical purposes, reservoir 510 (or more precisely, the volume established by reservoir 510) is considered as a short and wide lumen 5100 (by rough analogy, this can be likened to the structure between the jet engine mounts on an aircraft being considered incompressible / having very high stiffness / strength (and therefore impractical) in a finite element analysis of the buckling of an aircraft wing during flight). In practice, the reservoir will be arranged such that its axial direction extends perpendicular to or relatively perpendicular to the extension direction of tube 714, as shown in the attached figure above (corresponding to the cylindrical shape of the internal volume of the reservoir). Again, in this example, there is reservoir 510, which is relatively short but has a relatively large cross-sectional area, and therefore a relatively large internal volume. The volume established by reservoir 510 and the additional lumen have a diameter ID 30, as shown... Figure 10 As shown in the diagram. A tube 714, commonly referred to as tube 1 or the first tube, is attached to the reservoir 510. Therefore, a lumen 7144 is attached to a "lumen" 5100, as... Figure 10 As seen in the image. Lumen 7144 has a smaller inner diameter ID 10 compared to ID 30, which is described in detail below.

[0091] As described above, a second tube 718 is attached to tube 714. This is commonly referred to as tube 2 or the second tube. Tube 714 has a lumen 7188 having an inner diameter ID 20, which may be the same as or different from ID 10. Note that the tubes may overlap relative to their longitudinal direction. In this respect, as... Figure 7 As seen, a portion of tube 718 is actually located inside tube 714 (in an exemplary embodiment where the outer diameter of tube 714 is slightly larger than ID 10, tube 714 may be interference-fitted into tube 718). However, note that in an alternative embodiment, tube 714 terminates where tube 718 begins. Therefore, in this respect, the length of lumen 7144 will be less than the total length of the lumen because a portion of that length (again, where length refers to the path of the therapeutic substance) is occupied by lumen 7188.

[0092] In an exemplary embodiment, the end of tube 718 is in fluid communication with a target (here, the perilymph of the scala tympani in the human cochlea). In an exemplary embodiment, a filter may be present at the outlet of tube 718. This will be described in more detail below. In an embodiment, no filter is present at the outlet or anywhere else in this regard.

[0093] In an embodiment, the outlet has a cross-sectional area on a plane perpendicular to the longitudinal extension direction of the lumen 7188, the cross-sectional area being the same as the mean, median, and / or mode of the cross-sectional area on the plane perpendicular to the longitudinal direction, and / or the same as the maximum or minimum area. In some embodiments, the cross-sectional area is constant along the length of the lumen 7188 or does not vary from the maximum value by more than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% along the length, respectively. (Note that these values ​​may also be the case for the lumen 7144, where in some embodiments, the "outlet" will be the portion of the tube 714 located therein.) In an exemplary embodiment, tube 718 may be replaced, or alternatively, tube 718 may be selected for use with the device. By way of example only and not limitation, tube 718 may be attached to tube 714 shortly before implantation and / or during surgery to implant the device. In an exemplary embodiment, tube 718 may be interference-fitted into tube 714. In an exemplary embodiment, there is a method of selecting tube 718 from a plurality of tubes available to a surgeon or other healthcare professional and attaching the selected tube 718 to tube 714 such that performance characteristics associated with that tube, disclosed herein, are achieved. Thus, for example, if a higher release rate is desired, a tube having a cross-section and / or length that will achieve the desired release rate is selected and attached to tube 714 such that, after implantation, the desired result is achieved. In an exemplary embodiment, tubes may be color-coded or otherwise placed in different containers such that tubes can be distinguished from each other and / or additionally, make it possible to determine the performance characteristics of a given tube without having to measure the tube's size. In embodiments, instead of tube 718 being located inside the carrier or a second lumen being located within the carrier, tube 718 may be attached to an outlet on the carrier, and then tube 718 will extend along with the electrode array. This facilitates the "replacement" of the desired tube 718 or otherwise attaching it to tube 714.

[0094] In an exemplary embodiment, the lumen 7188 may be enlarged or otherwise sized to determine the maximum size detailed herein, at least relative to the cross-sectional area, and the exemplary embodiment includes placing "filler material" into the lumen to reduce the cross-sectional area. By way of example only and not limitation, a cylindrical body may fit into the opening and extend downward into the lumen 7188. The cylindrical body itself may have a precisely controlled cross-sectional area that reduces the effective cross-sectional area of ​​the lumen 7188. This can be in a manner with standardized equipment that can be modified for unique or other specific performance characteristics, modifications which, in at least some exemplary embodiments, can be performed in the field or at least at a distribution site.

[0095] The entire lumen, formed by the reservoir lumen, tube 1 lumen, and tube 2 lumen, can initially be filled with a solution containing a certain concentration of the drug (a solution containing the active pharmaceutical ingredient, API). For example, when the tip of tube 2 comes into contact with the perilymph, a fluid bridge is formed between the API-containing fluid contained in lumen 2 and the perilymph. This allows API molecules to diffuse out of the device and into the perilymph following a concentration gradient from a high concentration inside the device to a lower concentration outside the device. In an exemplary embodiment, the highest API release rate occurs at the start of therapeutic delivery. Over time, the API release rate decreases until it stabilizes at a moderate release rate because the concentration gradient inside the device changes only relatively slowly. From then on, the concentration gradient inside the device changes only relatively slowly as API molecules are continuously supplied from the reservoir into tube 714.

[0096] The release rate over time (dn / dt) depends on the API molecule diffusion coefficient D, the cross-sectional area of ​​(multiple) lumens, and the concentration gradient dc / dx along the length. By adjusting the design combination of drug molecules and the device design, the desired drug release rate over time can be achieved in the resulting implantable device.

[0097] In the embodiments, the movement of the API from position x to position y at a distance z can be controlled (design controlled) by one or more of the following factors: the concentration gradient (driving force) between x and y; the distance between x and y; the cross-sectional area defined by the drug impermeable boundary between x and y; the solvent (diffusion medium) filling the volume between x and y (the solvent may be, for example, water, hydrogel, or polymer); the drug molecule; the size and polarity of the molecule defining its diffusion coefficient and / or the addition of diffusion-limiting components in the diffusion path between x and y.

[0098] Figures 11 to 15 Exemplary design data for an exemplary device according to an exemplary embodiment are shown. Here, the Y-axis is a logarithmic axis and the X-axis is a linear axis. In the exemplary embodiment, the cross-sections of the lumens of tube 1 and tube 2 are circular, but other shapes may be utilized in other embodiments. For convenience, the cross-section of the volume established by the reservoir can be considered as a constant cross-section over a certain distance, here 4 mm or 8 mm, shown only as an example and not as a limitation. The lumens of tube 1 and tube 2 can be considered as the geometry of the driving performance, provided that the internal volume of the reservoir is large enough. The distance (X-axis) is the aforementioned linearized length from the portion of the reservoir furthest from the outlet to the reservoir at the outlet.

[0099] Figures 16-19Exemplary design data for an exemplary device according to an exemplary embodiment are shown, wherein the cross-sectional area of ​​the lumen of tube 2 is different for different designs, while the cross-sectional area of ​​the lumen of tube 1 remains constant. In short, it should be noted that the provided graphics are exemplary, and embodiments include data shown in the graphics (these and others) plus or minus any value or range of values ​​(e.g., 4.1%, 19.5%, 7.7% to 23.3%, etc.) in increments of 0.1% or higher, represented 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%, or such values) provided for textual economy. Figure 20 The diagram shows the various cross-sections of the lumen of pipe 2 with respect to its constant length and the constant distances and cross-sections of the lumen of pipe 1 (e.g., one or more of those discussed above and / or below, such as the lumen length of pipe 2 being 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mm or any value or range of values ​​in increments of 0.1 mm, and the lumen length of pipe 1 being 50, 60, 70, 80, 90, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 11...). 5, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, or 130 mm, or any value or range of values ​​in increments of 0.1 mm, wherein the cross-sectional area of ​​the lumen of pipe 1 is 0.15, 0.14, 0.13, 0.12, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.0009, 0.0008, 0.0007, 0.006, 0.0005, 0.0004, 0.0003, 0.0002, or 0.0001 mm. 2 Or within a range of 0.00001mm 2 (any value or range of values ​​for the increment), an exemplary release rate from device to person over a period of several days, where the value of the curve is related to the cross-sectional area of ​​lumen 2 (mm²). 2 The value of ) is adapted to. The figure shows the release rate of an exemplary dexamethasone from a device having a constant reservoir size, a constant tube 1 size, and a tube 2 with a constant length but varying inner diameter over time.

[0100] Figure 21The concentration gradient along the path is shown for some of the exemplary embodiments described above. Unlabeled curves correspond to the regions shown in the graph according to... Figure 20 The figure shows an exemplary concentration gradient within the reservoir (4 mm initially), tube 1, and then tube 2 (the transition occurs at the dashed line), established seven (7) days after the delivery of the therapeutic substance to the human body, to account for the changing inner diameter of tube 2, where the y-axis shows the dexamethasone concentration of the fluid within the lumen in mg / mL. In this embodiment, the cross-sectional area of ​​the lumen of tube 2 is circular.

[0101] The embodiment may include a lumen of a second tube having a diameter as a mm 2 The value or range of any of the following values ​​or values ​​between them, per unit cross-sectional area (located in a plane perpendicular to the longitudinal axis of the lumen / direction of the lumen), and these may be used for the entire length of the second lumen or for the average (mean, median, and / or mode) over the entire length and / or for any value or range of values ​​less than, greater than, and / or equal to 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or in increments of 1%, and may be any value or range of values ​​between them (percentage difference): Note that the embodiments may have a cross-sectional area different from those described above (larger or smaller). The embodiments also include variations in the length of the lumen of tube 2. Figures 22-24 Exemplary design data for an exemplary device according to an exemplary embodiment are shown, wherein the length of the lumen of tube 2 is different for different designs, wherein the cross-sectional areas of the lumens of tube 1 and tube 2 remain constant, but the length of the lumen of tube 1 varies when the length of the lumen of tube 2 is shortened. In short, it should be noted that the provided graphics are exemplary, and embodiments include data shown in the graphics (these and others) plus or minus values ​​represented by any value or range of values ​​in increments of 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%, or between these values, provided for textual economy. Figure 25The diagram shows the various lengths of the lumen of tube 2 with respect to its constant cross-sectional area and the constant cross-sectional area of ​​the lumen of tube 1, but the length of the lumen of tube 1 varies as described above with different lengths of lumen 2 (e.g., one or more of those discussed herein) at exemplary release rates from device to person over a period of several days, wherein the values ​​of the curves are presented to be adapted to the length of lumen 2 (in mm).

[0102] Figure 26 The concentration gradient along the path is shown for some of the exemplary embodiments described above. Unlabeled curves correspond to lengths shown in the graph in 5-mm increments.

[0103] The embodiment may include a lumen of a second tube having any of the following values ​​or any range of values ​​between them as a length in mm, or may be greater than or less than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% or any value or range of values ​​between them in increments of 1%, and may be any value between them or any range of values ​​between them (percentage difference).

[0104] Note that the embodiments may have lengths different from those described above (larger or smaller). Figures 27-29 Exemplary design data for an exemplary device according to an exemplary embodiment are shown, wherein the cross-sectional area of ​​the lumen of tube 1 is different for different designs, and the cross-sectional area of ​​the lumen of tube 2 remains constant. In short, it should be noted that the provided graphics are exemplary, and embodiments include data shown in the graphics (these and others) plus or minus any value or range of values ​​(e.g., 4.1%, 19.5%, 7.7% to 23.3%, etc.) in increments of 0.1% or higher, represented 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%, etc., provided for textual economy.

[0105] Figure 31The diagram shows the various cross-sections of the lumen of pipe 1 with respect to its constant length, and the constant distances and cross-sections of the lumen of pipe 2 (e.g., one or more of those discussed above, such as the lumen length of pipe 2 being 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mm or any value or range of values ​​in increments of 0.1 mm, and the lumen length of pipe 1 being 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119). The cross-sectional area of ​​tube 2 is 0.15, 0.14, 0.13, 0.12, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.0009, 0.0008, 0.0007, 0.006, 0.0005, 0.0004, 0.0003, 0.0002, or 0.0001 mm. (The values ​​are listed as 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, or 130 mm, or any value or range thereof in increments of 0.1 mm.) 2 Or within a range of 0.00001mm 2 (any value or range of values ​​for the increment), an exemplary release rate from device to person over a period of several days, where the value of the curve is related to the cross-sectional area of ​​lumen 1 (mm²). 2 The values ​​are adapted to the given values. The figure shows the release rate of an exemplary dexamethasone from a device having a constant reservoir size, a constant tube 2 size, and a tube 1 with a constant length but varying inner diameter over time.

[0106] Figure 30 The concentration gradient along the path is shown for some of the exemplary embodiments described above. Unlabeled curves correspond to the diameter of the circular cross-sectional region of the lumen decreasing in 0.1 mm increments. The figure shows an exemplary concentration gradient within the reservoir (4 mm initially), tube 1, and then tube 2 (the transition occurs at the dashed line), established seven (7) days after the delivery of the therapeutic substance to the human body, for the changing inner diameter of tube 2, where the y-axis shows the dexamethasone concentration of the fluid within the lumen in mg / mL. In the embodiment, the cross-sectional region of the lumen of tube 2 is circular, and as noted, the lumen of tube 1 is circular.

[0107] The embodiment may include a lumen of a first tube having a diameter as a mm 2The values ​​described above for the lumen of the second tube, in units of cross-sectional area (for the sake of textual economy—these values ​​do not need to be identical, again, this is merely textual economy) or any range of values ​​between them (located in a plane perpendicular to the longitudinal axis of the lumen / direction of the lumen), and these may be used for the entire length of the first lumen or as an average (mean, median, and / or mode) over the entire length and / or as less than, greater than, and / or equal to 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or any value or range of values ​​in increments of 1%, and may be any value between them or any range of values ​​between them (percentage difference).

[0108] Note that embodiments may have cross-sectional areas different from those described above (larger or smaller). Also note that in some embodiments, the values ​​just listed above may be used for the lumen of tube 1. Embodiments may have a wall thickness (forming the body of the lumen, e.g., tube 1) less than, greater than, and / or equal to 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% or more, or any value or range of values ​​in increments of 0.1%, of the diameter or radius of the lumen.

[0109] The embodiment also includes variations in the length of the lumen of tube 1. Figures 32-34 Exemplary design data for an exemplary device according to an exemplary embodiment are shown, wherein the length of the lumen of tube 1 is different for different designs, wherein the cross-sectional areas of the lumens of tube 1 and tube 2 remain constant, and the length of the lumen of tube 2 is constant. In short, it should be noted that the provided graphics are exemplary, and embodiments include data shown in the graphics (these and others) plus or minus values ​​represented by any value or range of values ​​in increments of 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%, or between, in 0.1% increments, provided for textual economy. Figure 35 The exemplary release rate from device to person over a period of several days is shown for the various lengths of the lumen of tube 1 with respect to its constant cross-sectional area and for the constant cross-sectional area of ​​the lumen of tube 2, where the length of the lumen of tube 2 is constant.

[0110] Figure 36 The concentration gradient along the path is shown in some of the exemplary embodiments described above. The length corresponds to...Figures 34-36 The length.

[0111] The embodiment may include a lumen of a first tube having a length in mm for the lumen of a second tube of any of the above values ​​(for the sake of text economy—these values ​​do not need to be the same, again, this is just for the sake of text economy) or any of the following values ​​or any range of values ​​therebetween, or may be greater than or less than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or any value or range of values ​​therebetween in increments of 1%, and may be any value therebetween or any range of values ​​therebetween (percentage difference).

[0112] Note that the embodiments may have lengths different from those described above (larger or smaller).

[0113] In view of the foregoing, it can be seen that, in exemplary embodiments, there exists a device, such as the aforementioned therapeutic substance delivery device alone or in combination with a cochlear implant electrode array or some other medical device (such as any of those detailed herein), which includes a reservoir and, in some embodiments, includes therapeutic substance contained within a volume. In this exemplary embodiment, the reservoir may correspond, for example, to a pool plus one or more of the tubes detailed above. In embodiments, the device is configured to deliver the therapeutic substance to its recipient via diffusion-controlled release (controlled by the precise implementation of the reservoir's dimensions to provide precise control (passive control)).

[0114] The embodiments do not elute the drug or therapeutic substance, or more precisely, this is not a principle of drug delivery (described in detail later), but rather allows the substance to diffuse through a barrier or diffuse without a barrier (in some embodiments, the opening corresponds to the diameter of the lumen of the second tube). That is, in some embodiments, the outlet may be open. However, regarding the outlet(s) with a barrier, the barrier has pores that allow a direct fluid connection between the liquid (drug solution) inside the therapeutic substance delivery system and the external liquid (e.g., perilymph). This allows therapeutic substance molecules to diffuse freely from the inside of the device through the barrier to the outside following a concentration gradient. That is, the therapeutic substance molecules do not need to dissolve, absorb, or adsorb into a third matrix (considering the therapeutic substance solvent inside the device as the first matrix and the perilymph (or other bodily fluids) as the second matrix). The barrier (if present) may be used to prevent pathogens such as viruses, bacteria, protozoa, prions, viroids, and / or fungi from leaving and entering the device (e.g., bacterial filters with a pore size of 0.22 micrometers or smaller are used in some embodiments). In some embodiments, the barrier also provides mechanical mechanisms to increase flow resistance between the lumen inside the device and the external environment (i.e., perilymph in the implanted state). This allows for the containment of a therapeutic solution within the device after initial induction (filling) during manipulation and implantation. In the implanted state, the barrier's flow resistance helps prevent significant fluid loss or inflow into the delivery system due to pressure changes inside or outside the device, such as from body movement or impacts, or in cases where only the device is manipulated during implantation.

[0115] In embodiments, the therapeutic material may undergo some minor diffusion and / or elution through the tube and / or through the silicone body of the lead assembly (rather than exiting the device through an outlet). This is undesirable in at least some exemplary embodiments, but is not a problem due to the limited effective amount. In exemplary embodiments, therapeutic material used to fill or fill the reservoir diffuses and / or elutes through the tube and / or silicone body at a concentration not exceeding 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.25%, or 0.1%, or any value or range of values ​​in increments of 0.1%. It should be noted that some of the above values ​​may not be desirable or permissible, while in other embodiments they may be permissible. In exemplary embodiments, the delivery rate is based at least substantially on diffusion through the outlet (regardless of the presence of different barriers at the outlet). In an exemplary embodiment, at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, or any value or range of values ​​in increments of 0.1%, of the therapeutic substance leaving the reservoir and entering the body is the result of diffusion (including diffusion through different barriers) within any one or more time ranges (or all) detailed herein.

[0116] In this embodiment, the therapeutic substance is water-based and diffuses out, while water remains in the delivery system, and salts diffuse into the reservoir to resolve concentration gradients. In this embodiment, the movement of purified water into the device (osmosis) is avoided. In this embodiment, an isotonic therapeutic solution is used to match the molar osmotic pressure concentration of the perilymph, thereby preventing osmosis.

[0117] This contrasts with the operation of, for example, membranes through openings, where the therapeutic substance or other active ingredient actually exits the water, enters the membrane, and then returns to the water, for example, in the cochlea. The embodiments taught herein ensure that, when filled with therapeutic substance, the therapeutic substance does not leave the water located in the reservoir. The diffusion is the diffusion of the therapeutic substance, which differs from the operating principle of the membrane. In the embodiments, there is no semi-permeable membrane for the reservoir / enclosing the reservoir. In the embodiments, a 100-micrometer-thick membrane is present, which does not affect the release rate, or reduces the rate from the rate without the membrane by up to 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%, or any value or range of values ​​in increments of 0.1%. In fact, in the embodiments, the device is completely hydrogel-free. In an embodiment, at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% (by mass and / or by volume) of all therapeutic substances delivered to a person by the device are delivered to the person without the use of a hydrogel.

[0118] The embodiments include sound pressure wave mitigation and / or prevention. In the embodiments, there is practical value in scenarios where acoustic energy traveling through the skin and impacting the tube and / or generating pressure waves within the reservoir of a therapeutic substance delivery device due to the movement of perilymph or other fluid motion waves within the cochlea. In the embodiments, pressure damping devices can therefore be present, for example, at or near the outlet or somewhere along the length of the tube assembly. That is, in exemplary embodiments, a pressure gradient can be applied to the reservoir, said pressure gradient being sufficiently large to overwhelm the effect of any pressure generated, for example, by sound waves.

[0119] In some embodiments, the same amount of water molecules still exchange through the outlet, but to compensate for the drug diffusion out (efflux) into the perilymph, it can be assumed that it is not water molecules moving in, but rather solutes (e.g., sodium and chloride) from the perilymph diffuse in (flow) to maintain the same molar osmotic concentration. Therefore, in embodiments, the therapeutic substance solution is water-based, and the therapeutic substance remains dissolved in water, diffusing from the reservoir into the perilymph following a gradient from the higher therapeutic substance concentration in the water-based therapeutic substance solution to the lower therapeutic substance concentration in the water-based perilymph (efflux).

[0120] In an embodiment, the total water volume of the therapeutic substance delivery system at implantation is within the range of any value or increment of 0.05% of the water volume value at which 80%, 85%, 90%, or 95% of the therapeutic substance has diffused from the system into the body.

[0121] In embodiments, at least after the implantable component is implanted in the human body, there is no pressure gradient that would cause the therapeutic material to diffuse out or otherwise leave the reservoir. In exemplary embodiments, the system is configured to avoid overpressure (or underpressure) of any one or more amounts detailed herein. As briefly noted above, in some embodiments, the initial filling pressure will cause the therapeutic material to leak from or otherwise leave the barrier, and this can be used to determine whether the reservoir is full or whether additional therapeutic material has reached the tip of the electrode array, but after the filling process, the pressure inside the reservoir should be approximately room pressure or any local ambient pressure. That is, the reservoir is not a pressurized system. The operating principle of therapeutic material delivery is generated by the concentration gradient of the therapeutic material present inside the reservoir relative to the outside of the reservoir (specifically, the cochlea in embodiments where the device is a cochlear implanted electrode array). In this respect, initially, for example within the first few minutes after the electrode array is inserted into the cochlea, the outlet will come into contact with the perilymph of the cochlea or other bodily fluids about another body cavity. Therefore, a gradient will exist between the outside and inside of the reservoir (relative to the outlet). Over time, as the system “desires” to balance the chemical states inside and outside the reservoir, this gradient will decrease to a 1:1 ratio or approximately a 1:1 ratio. In an exemplary embodiment, after the initial contact with perilymph or related bodily fluids upon entry into the cochlea / exit, the gradient will decrease to a 1:1 ratio or approximately a 1:1 ratio. (The remaining text appears to be a series of numbers and symbols, possibly related to a specific timeframe or sequence of events.) Within 500, 3000, 3500, 4000, 4500, or 5000 hours, when the therapeutic substance in the reservoir comes into contact with bodily fluids at an outlet (whether or not there is a barrier, and if there are more outlets, starting from the first and / or last outlet), at least and / or no more than 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, or 95%, or any value or range of values ​​in increments of 1%, is retained in the reservoir due to the diffusion of the therapeutic substance through different barriers into the cochlea or associated body cavity or body space. In embodiments, any present barrier does not control the release rate. In embodiments, any present barrier reduces the flow rate by up to 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%, or any value or range of values ​​in increments of 0.1%, relative to the flow rate that would be present without a barrier. In embodiments, the barrier is an invisible barrier.

[0122] Still, in some embodiments, there is no barrier at the end of tube 2, and in some embodiments, the fluid is held therein by capillary action.

[0123] In an embodiment, the filter can be considered as a third tube having a minimum cross-sectional area. In practice, in an embodiment, the effective cross-sectional area of ​​the barrier is at most 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the cross-sectional area of ​​the second lumen, or any value or range of values ​​in increments of 0.1%.

[0124] It should also be noted that in some embodiments, the barrier is a flow limiter, rather than something that controls diffusion. In fact, the filter has almost nothing to do with controlling the delivery rate.

[0125] In an exemplary embodiment, the therapeutic substance delivery system is a valveless system and / or an unlimited flow system (in addition to the physical barriers (multiple) that are considered flow limiters).

[0126] In exemplary embodiments, no part of the lead assembly is impregnated with the therapeutic substance and / or no part of the implantable portion is impregnated with the therapeutic substance, which in at least some exemplary embodiments may be in addition to a barrier (if present) or at least a portion of the barrier.

[0127] In this embodiment, the silicone or other material of the lead assembly and / or any tube is not porous and / or not gas-filled.

[0128] As seen above, in some embodiments, the memory and lead assembly are part of a single unit. It can also be seen that, in embodiments, the electrode array and memory are part of a single unit.

[0129] Consistent with the foregoing teachings, in an embodiment, the device's reservoir includes a first sub-reservoir and a second sub-reservoir, the second sub-reservoir being contracted relative to the first sub-reservoir, and molecules of the therapeutic substance moving from the first sub-reservoir to the second sub-reservoir during delivery of the therapeutic substance to the recipient. In an embodiment, the first sub-reservoir may be a reservoir, and the second sub-reservoir may be a first tube or a second tube. In an embodiment, the first sub-reservoir may be a first tube, and the second sub-reservoir may be a second tube. However, in this embodiment, the cross-sectional area of ​​the lumen of the second tube cannot be the same as or greater than the cross-sectional area of ​​the lumen of the first tube; otherwise, the second sub-reservoir would not be a contracted sub-reservoir. The phrase "sub-reservoir" indicates that they differ from each other by, for example, size or by structural differences. This differs from a single tube that is arbitrarily divided into segments that are merely single sub-reservoirs. In an embodiment, the reservoir includes a third sub-reservoir, and the third sub-reservoir is configured relative to the second sub-reservoir, and molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir to the third sub-reservoir during delivery of the therapeutic substance to the recipient. In an embodiment, there are 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more sub-reservoirs, or any value or range of values ​​in increments of 1, and at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more sub-reservoirs, or any value or range of values ​​in increments of 1, are contracted relative to the "upstream" sub-reservoir.

[0130] In an embodiment, the reservoir is constructed of at least a reservoir and a conduit assembly (e.g., commonly tubes 714 and 718). In an embodiment, the conduit assembly includes a first conduit segment having a first cross-sectional area perpendicular to the extension direction of the first conduit segment (or perpendicular to the direction of molecular movement during delivery to the recipient), the first cross-sectional area being larger than a second cross-sectional area of ​​a second conduit segment perpendicular to the extension direction of the second conduit segment (or perpendicular to the direction of molecular movement during delivery to the recipient). In an embodiment, the cross-sectional area of ​​the second conduit segment is such that the release rate of the therapeutic substance from the device on and / or after day Y of release into the recipient (“on” is a Y-day marker (e.g., 7 days – the 7-day marker requirement must be met), “after” is Y days and later (e.g., 7, 8, 9, 10, 11, 12 days, etc. – the requirement of day Y or later must be met, whether day 7 or day 10 is included)) is less than X% of the release rate that would exist if the first and second cross-sectional areas were the same, all other conditions being equal, where Y is 2, 3, ... 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100, or any value or range of values ​​in increments of 1 therein, and X is 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21. 20, 19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4. 4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1, or any value or range of values ​​in increments of 0.01.In this regard, for example, if the lengths of the first catheter segment and the second catheter segment are constant (consistent with the teachings above, they may be different), and the cross-sectional area of ​​the first catheter segment is constant, and the type of therapeutic substance in the reservoir is the same, and there is no pressure gradient or pressure change relative to the comparison case, and there is no temperature change, etc., then the above-mentioned release rate will be obtained for different second cross-sectional areas relative to the case where the second cross-sectional area is the same as the first cross-sectional area.

[0131] The first duct segment has a first cross-sectional area perpendicular to the direction of extension (molecular movement), and the first cross-sectional area is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100, or any value or range of values ​​in increments of 1, of the second cross-sectional area of ​​the second duct segment. In embodiments where the first catheter segment has a first length greater than the second length of the second catheter segment, the length of the second catheter segment is such that the release rate of the therapeutic substance from the device after Y days of release into the human body is less than 90, 85, 80, 75, 70, 65, 60 times the release rate of the first length being 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 times the second length, or any value or range of values ​​in increments of 1 (all other conditions being equal), respectively. 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8 0.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1 or 3.0 or any value or range of values ​​in increments of 0.01.

[0132] In one embodiment, there is a device comprising a reservoir and a delivery tube. Again, the device is an implantable therapeutic substance delivery device. In another embodiment, the delivery tube is a diffusion delivery tube. The device is configured such that therapeutic substance located in the reservoir travels to the delivery tube for delivery to a person with an implanted device.

[0133] In one embodiment, the reservoir has an internal volume at least one order of magnitude larger than the internal volume of the delivery tube.

[0134] In an embodiment, the delivery tube device has a first section, the first cross-sectional area of ​​which, perpendicular to its extension direction, is larger than the second cross-sectional area of ​​a second section of the delivery tube device, the second cross-sectional area being perpendicular to the extension direction of the second section. In an embodiment, the first cross-sectional area is such that the release rate of the therapeutic substance from the device after Y days of release into the human body is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.5, 4, 4.5, or 5 times, or intermediately, the release rate of the therapeutic substance after Y days of release from the device, provided that the first and second cross-sectional areas are the same and all other conditions are identical. 0.01 is any value or range of values ​​in increments, and / or is any value or range of values ​​not exceeding 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.5, 4, 4.5, 5, 5.5, or 6 times, or in increments of 0.01, for the same first and second cross-sectional areas and all other conditions being equal.

[0135] In an embodiment, the first cross-sectional area is such that the release rate of the therapeutic substance from the device after Y days of release into the human body is 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 or 30% of the release rate under the condition that the first and second cross-sectional areas are the same, or any value or range of values ​​in increments of 0.1%.

[0136] In an embodiment, the delivery tube device has a first segment having a first length greater than a second length of a second segment of the delivery tube device, and the first segment having a first cross-sectional area perpendicular to the extension direction of the first segment, the first cross-sectional area being at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100, or any value or range of values ​​in increments of 1 among the second cross-sectional areas of the delivery tube device perpendicular to the extension direction of the second segment. The length of the first segment is at least four times the length of the second segment, and the length of the first segment is such that the release rate of the therapeutic substance from the device seven days after release into the human body will be within the range of 20%, 19%, 18%, 17%, 16%, 15%, 14%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the length of the first segment or any value or range of values ​​in increments of 0.1%, provided that the length of the first segment is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17%, 18%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the length of the second segment or any value or range of values ​​in increments of 0.1%.

[0137] In an embodiment, the delivery tube device has a first segment having a first length greater than the second length of a second segment of the delivery tube device. Again, as described above with respect to some embodiments, the first segment has a first cross-sectional area perpendicular to its extending direction, which is greater than the second cross-sectional area of ​​the second segment of the delivery tube device perpendicular to its extending direction. Here, the second cross-sectional area is such that the release rate of the therapeutic substance is less than X% of the release rate present when the first cross-sectional area and the second cross-sectional area are the same, at or after 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours after the therapeutic substance is released from the device into the human body. In an embodiment, the second cross-sectional area is such that the release rate of the therapeutic substance 12 hours after it is released from the device into the human body and / or thereafter will be within X% of the existing release rate if the second cross-sectional area is at least one of 1 / 5, 1 / 6, 1 / 7, 1 / 8, 1 / 9, 1 / 10, 1 / 11, 1 / 12, 1 / 13, 1 / 14, 1 / 15, 1 / 16, 1 / 17, 1 / 18, 1 / 19 or 1 / 20, or 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 times larger.

[0138] The embodiments include a device, such as any of the devices described herein, or other implantable medical devices, comprising a first at least partially bounded volume (e.g., the lumen or reservoir of tube 1) and a second at least partially bounded volume (e.g., the lumen of a second tube). In the embodiments, at least one device outlet is present at the second bounded volume (e.g., an outlet at the end of the second tube). Again, consistent with the teachings herein, the device is an implantable therapeutic substance delivery device. In this embodiment, the device effectively delivers the therapeutic substance to its recipient entirely due to a concentration gradient. This differs from pressurized delivery, etc.

[0139] In this embodiment, the device provides passive diffusion of the local therapeutic substance release, which is entirely controlled by the geometry (e.g., the geometry detailed above). And note that this control is passive. The geometry is designed and then set during the manufacture or otherwise assembly of the device (described in detail below). This is not, for example, active control, where, for example, the outlet diameter changes one, two, three, or four days after the device is implanted in the recipient, for example, after the delivery of the therapeutic substance. In embodiments, the control is "controlled" or maintained or otherwise kept constant for at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 500, 600, 700, 800, 900, 1000, 1250, 1500, 2000, 2500, 3000, 3500, 4000 or more days or a range of values ​​in increments of one day. That is, in exemplary embodiments, the control remains constant or is otherwise maintained throughout the lifespan of the implant or, additionally, for as long as possible while the implant provides the therapeutic substance.

[0140] Consistent with the above embodiment with two tubes, this embodiment has a third, at least partially bounded volume, wherein the third, at least partially bounded volume is the movement of substance located between the first and second volumes. "Movement of substance located between..." refers to the movement of molecules of the therapeutic substance along the direction of travel during delivery, which can occur over a process of days, weeks, or months. For example, this is movement from a reservoir to an outlet. This would be the opposite of the movement of salt or other molecules into the reservoir to balance the movement of molecules that have been removed from the reservoir.

[0141] In short, while embodiments typically focus on a single outlet rather than a single outlet point, multiple outlet points can exist. Outlet points can have different cross-sectional areas to account for concentration variations within the device. For example, the cross-sectional area of ​​the outlet can increase with increasing distance from the reservoir to achieve uniform or quasi-uniform drug release. This can be practical because the concentration gradient across the outlet can decrease with increasing distance from the reservoir. The following discussion... Figures 40-42 An exemplary embodiment of a plurality of outlets arrangement is shown. In an embodiment, the outlets may also be radially positioned. In an embodiment, the size and dimensions of the outlets are set to account for a concentration gradient, for example, variation along the length of tube 718, and the outlets provide a release rate that is axially spaced from each other / provides the same delivery at a given location as at a considerable number of other locations: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 outlets, or at least 50%, 60%, 70%, 80%, or 90% of the outlets, or all outlets at 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 3 0%, 29%, 28%, 27%, 26%, 25%, 24, 23%, 22, 21%, 20%, 19%, 18, 17%, 16%, 15, 14%, 13%, 12%, 11%, 10%, 8%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%, or any value or range of values ​​in increments of 0.1% (e.g., there may be two outlets at a length of 119 mm, and they may be different—the total release rate can be used at that location and compared with the total release rate at another location). The mean / median and / or mode can be used to calculate the average value for any value or range of values ​​spaced apart from each other by 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.5, or 5 mm, or in increments of 0.01 mm. The average value can be distributed among these values. The flow rate just mentioned can be used for any time value in this document, such as 7 days after delivery and / or thereafter.

[0142] In this embodiment, the volume of the first volume is at least Z times the volume of the third volume, and the third volume is at least AA times the volume of the second volume (and the value of Z does not need to be the same), where Z can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, or 400, or any value or range of values ​​in increments of 1 therebetween, and AA can be 1, 2, 3, 4, 5, 6, 7, 8, 9... 10, 11, 12, 13, 14, 15, 16, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 500, 600, 700, 800, 900, 1000, 1250, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 7000, 8000, 9000, 10000, or any value or range of values ​​incremented by 1.

[0143] In an embodiment, the first cross-sectional area of ​​the first volume located on a plane perpendicular to the material movement direction from the first volume to the second volume is at least AA times (and / or AA multiplied by 10) times the second cross-sectional area of ​​the third volume located on a plane perpendicular to the material movement direction from the first volume to the second volume. Furthermore, the third cross-sectional area of ​​the second volume located on a plane perpendicular to the material movement direction from the first volume to the second volume is at least Z times (or Z multiplied by 10) of the second cross-sectional area.

[0144] In an embodiment, the second at least partially bounded volume is a lumen having a diameter, and the lumen has a release rate at and / or after seven days or any time period detailed herein when the therapeutic substance is released into the human body, such that the release rate increases with diameter by a factor 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, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, or 500. Or any value or range of values ​​incremented by 1 within any interval (all other conditions being equal) increasing by an amount between 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, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, or 500 times, or any value or range of values ​​incremented by 1 within any interval (e.g., between 8 and 15, between 5 and 67, between 22 and 122, etc.). In embodiments, the release rate decreases as the length of the second at least partially bounded volume increases by any of the aforementioned ranges.

[0145] The embodiments include methods. Figure 38 An exemplary flowchart of an exemplary method (method 3800) is shown, the method including action 3810, which includes entering the interior of the human body, such as a cavity within the human body. In embodiments, this could be the cochlea, or semicircular canals, as described above. Note that this does not require a definitive action of opening a passage into the cavity or moving a device (e.g., the end of tube 2) into the cavity. This can be satisfied, for example, by having an outlet present in the cavity (an outlet can be placed in the cavity by another participant). Action 3810 is satisfied if, for example, the outlet is in the cavity, and the therapeutic substance can move through the outlet. Method 3800 includes method action 3820, which includes the action of treating a person's disease by controllably delivering a therapeutic substance delivered from an implantable therapeutic substance delivery device, wherein the controllably delivering the therapeutic substance is performed passively. In embodiments, this control is based on controls such as the size of the therapeutic substance and / or the selection of the size of the therapeutic substance. There are no metering or pressure variations or valve adjustments for controlling the delivery of the therapeutic substance. In embodiments, this control is entirely based on any one or more features detailed herein that implement this control.

[0146] In an exemplary embodiment, a fluid bridge exists between the therapeutic substance and the body fluids of the person. In an exemplary embodiment, this is a result of method action 3810. In practice, in an exemplary embodiment, there may be method actions to establish the fluid bridge. In an exemplary embodiment, this bridge allows molecules of the therapeutic substance to diffuse from the therapeutic substance delivery device into the human body. Consistent with the foregoing teachings, the body fluids may be perilymph, but may also be another type of body fluid, such as fluid in the semicircular canals.

[0147] In an exemplary embodiment, after an initial period in which the release rate of the therapeutic substance steadily decreases from a relatively high rate, the release rate quasi-stabilizes at a lower rate. In this embodiment, this may correspond to the performance associated with the release rate detailed above.

[0148] In the embodiments, there are a first release period and a second release period. The first release period may be in which the amount released decreases from the initial release amount (maximum and / or average (mean, median and / or mode)) by more than and / or equal to 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 38%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 6% within a specific time (e.g., 1, 2 or 3 hours from initial implantation). 0%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, or 96%, or any value or range of values ​​in increments of 0.1%, and there may be an initial gap from implantation (e.g., waiting 1 hour). In an embodiment, the second time period can be such that the release rate does not change by more than 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%, or any value or range of values ​​in increments of 0.1%. In an embodiment, the initial time period and / or the first time period are less than and / or equal to 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 45, or 50 hours, or any value or range of values ​​in increments of 0.1 hours. In this embodiment, the second time period and / or quasi-stable period is greater than and / or equal to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200 days or more, or any value or range of values ​​in increments of 1 hour. Note that the first time period may be continuous with the second time period, or may be discontinuous. Note that the first time period does not need to be the same as the initial time period described above, and the second time period does not need to be the same as the quasi-stable period.

[0149] In this embodiment, the quasi-steady release rate is attributed to a slowly varying concentration gradient of the substance within the device. In this embodiment, the slowly varying concentration gradient is attributed to the continuous supply of therapeutic substance molecules from a large volume region of the device to a smaller volume region. In this embodiment, the controlled delivery of the therapeutic substance is controlled by Fick's law.

[0150] In embodiments, the quasi-stable release rate and / or the second time period cause the change in the concentration gradient to be no greater than and / or equal to 50%, 45%, 40%, 35%, 30%, 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%, or any value or range thereof in increments of 0.1%. In embodiments, the first time period and / or the reduction period cause the change in the concentration gradient to be greater than and / or equal to 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, or 30%, or any value or range thereof in increments of 0.1%.

[0151] The embodiments include those by Figure 39 The flowchart illustrates the method. Here, there is a method, method 3900, which includes method action 3910 requiring entry into the human body. This has been described in detail above. Method 3900 also includes method action 3920, which includes treating a person's disease by controllably delivering a therapeutic substance from an implantable therapeutic substance delivery device, wherein the controllably delivering the therapeutic substance is performed effectively without any net movement of the solvent in which the therapeutic substance is present from the volume of the device containing the therapeutic substance to the surrounding environment outside the device. As detailed above, in some embodiments, a filter or plug is present at the outlet, while in other embodiments, such a filter or plug is not present at the outlet. Embodiments include implementing the method with or without a filter or plug at the outlet.

[0152] In this embodiment, there is only one medium.

[0153] In embodiments, the second lumen is a performance limiting factor. In exemplary embodiments, changing the length and / or cross-sectional area of ​​the second lumen by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, 250%, 300%, 350%, or 400%, or any value or range of values ​​in 1% increments therein, will alter the performance (e.g., rate or concentration gradient) more than changing a similar value of lumen 1 by that amount and / or by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, or 200% (e.g., if the change is 20%, then the change in lumen 1 will be 20% plus 20% of 20% or 100% or 150%).

[0154] Note that in the embodiments, any value in this document may be a maximum value.

[0155] For example, even though diffusion control elements are not required in at least some embodiments, the use of a flow restrictor (sometimes referred to herein as a filter or plug—not necessarily a flow restrictor) at the tip / end of tube 2 may have practical value. In embodiments, this can be useful in reducing / avoiding scenarios of direct pressure transfer from the reservoir (e.g., the pool) to the cochlea during refilling or in the event of a shock. Moreover, the risk can be mitigated by a porous material that provides flow resistance between the reservoir and the tube. This can be achieved by selecting the cross-sectional area, pore size, density, and / or length. The pores can be small enough to also serve as a bacterial filter (e.g., 0.22 μm or less in some embodiments). Thus, the filter can be located at the outlet of the pool and / or at the end of tube 1, where it connects to the pool (thus, one could say that the pool is a closed volume—without the filter, this volume would be a partially closed / enclosed volume).

[0156] In an embodiment, the volume has a total distance extending from the exit of the volume into the human body to the furthest point from the exit. The size and dimensions of the volume are set such that, seven days after delivery and / or thereafter, the concentration gradient of the molecules of the therapeutic substance such that, for at least a first segment along the total distance of the volume, the concentration varies from a maximum value not exceeding 50%, 45%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19.5%, 19%, 18.5%, 18%, 17.5%, 17%, 16.5%, 16%, 15%. 0.5%, 15%, 14.5%, 14%, 13.5%, 13%, 12.5%, 12%, 11.5%, 11%, 10.5%, 10%, 9.75%, 9.5%, 9.25%, 9.0%, 8.75%, 8.5%, 8.25%, 8.0%, 7.75%, 7.5%, 7.25%, 7.0%, 6.75%, 6.5%, 6.25%, 6.0%, 5.75%, 5.5%, 5.25%, 5.0%, 4.9%, 4.8%, 4.7%, 4.6%, 4.5%, 4.4%, 4.3%, 4.2%, 4.1%, 4.0%, 3.9%, 3.8%, 3.7%, 3.6%, 3.5%, 3.4%. 3.3%, 3.2%, 3.1%, 3.0%, 2.9%, 2.8%, 2.7%, 2.6%, 2.5%, 2.4%, 2.3%, 2.2%, 2.1%, 2.0%, 1.9%, 1.8%, 1.7%, 1.6%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1% or 1%, or any value or range of values ​​in increments of 0.1%, wherein the first segment has at least 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 2 3%, 22%, 21%, 20%, 19.5%, 19%, 18.5%, 18%, 17.5%, 17%, 16.5%, 16%, 15.5%, 15%, 14.5%, 14%, 13.5%, 13%, 12.5%, 12%, 11.5%, 11%, 10.5%, 10%, 9.75%, 9.5%, 9.25%, 9.0%, 8.75%, 8.5%, 8.25%, 8.0%, 7.75%, 7.5%, 7.25%, 7.0%, 6.75%, 6.5%, 6.25%, 6.0%, 5.75%, 5.5%, 5.25%, 5.0%, or any value or range of values ​​in increments of 0.1%.In an embodiment, the size and dimensions of the volume are set such that the concentration gradient of the molecules of the therapeutic substance during and / or after seven days of substance delivery or any time period herein is such that the concentration is effectively constant and / or substantially constant with respect to the distance.

[0157] In embodiments, the size and dimensions of the volume are set such that, seven days after substance delivery (or any time period described herein) and / or thereafter, the concentration gradient of the molecules of the therapeutic substance causes the concentration to decrease by at least 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19.5%, 19 %, 18.5%, 18%, 17.5%, 17%, 16.5%, 16%, 15.5%, 15%, 14.5%, 14%, 13.5%, 13%, 12.5%, 12%, 11.5%, 11%, 10.5%, 10%, 9.75%, 9.5%, 9.25%, 9.0%, 8.75%, 8.5%, 8.25%, 8.0%, 7.75%, 7.5%, 7.25%, 7.0%, 6.75%, 6.5%, 6.25%, 6.0%, 5.75%, 5.5%, 5.25%, 5 The quantity of any value or range of values, or increments of 0.0% or in increments of 0.1%, in the second segment having a total distance of 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19.5%, 19%, 18.5%, 18%, 17.5%, 17%, 16.5%, 16%, 15.5%, 15 The distance between any value or range of values ​​in increments of 0.1% is %, 14.5%, 14%, 13.5%, 13%, 12.5%, 12%, 11.5%, 11%, 10.5%, 10%, 9.75%, 9.5%, 9.25%, 9.0%, 8.75%, 8.5%, 8.25%, 8.0%, 7.75%, 7.5%, 7.25%, 7.0%, 6.75%, 6.5%, 6.25%, 6.0%, 5.75%, 5.5%, 5.25%, 5.0%, or any value or range of values ​​in increments of 0.1%, wherein the second segment is continuous with the first segment.

[0158] In this embodiment, the therapeutic substance is delivered within 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, or 35 days after delivery, specifically within 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 days after delivery. The release rate during the 28, 29, or 30-day period was less than 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19.5%, 19%, 18.5%, 18%, 17.5%, 17%, 16.5%, 16%, 15.5%, 15%, 14.5%, 14%, 13.5%, and 13% of the maximum release rate, respectively. 12.5%, 12%, 11.5%, 11%, 10.5%, 10%, 9.75%, 9.5%, 9.25%, 9.0%, 8.75%, 8.5%, 8.25%, 8.0%, 7.75%, 7.5%, 7.25%, 7.0%, 6.75%, 6.5%, 6.25%, 6.0%, 5.75%, 5.5%, 5.25%, 5.0%, 4.9%, 4.8%, 4.7%, 4.6%, 4.5%, 4.4%, 4.3%, 4.2% 4.1%, 4.0%, 3.9%, 3.8%, 3.7%, 3.6%, 3.5%, 3.4%, 3.3%, 3.2%, 3.1%, 3.0%, 2.9%, 2.8%, 2.7%, 2.6%, 2.5%, 2.4%, 2.3%, 2.2%, 2.1%, 2.0%, 1.9%, 1.8%, 1.7%, 1.6%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1% or 1%, or any value or range of values ​​in increments of 0.1%.

[0159] Figure 20 and 21 The graphic is used for the lumen of pipe 2 with a diameter of 15 mm. The equivalent lumen length of the reservoir is 4 mm. The lumen of pipe 1 occupies the difference in total length (the total length can be 134 mm). The cross-sectional area of ​​the lumen of pipe 1 is a circular cross-sectional area of ​​0.3 mm over the entire length of the lumen of pipe 1. Figure 30 and 31 The figure has a lumen of the same length as just mentioned, wherein the cross-sectional area of ​​the lumen of tube 1 changes from the cross-sectional area of ​​a circle with a diameter of 0.5 mm to 0.1 mm by a reduction of 0.1 mm (the bottom curve is used for the diameter of 0.1 mm). Figure 35 and 36The diagram is used for the lumen of tube 2 with a diameter of 15 mm, the equivalent lumen length of the reservoir is 4 mm, the lumen of tube 1 is 60, 80, 100, 114 or 131 mm or any value or range of values ​​in increments of 1 mm, and the cross-sectional area of ​​the lumen of tube 1 is a circular cross-sectional area of ​​0.3 mm over the entire length of the lumen of tube 1.

[0160] In embodiments, the device is configured such that the release rate at and / or after 7 days of release of the therapeutic substance or any time period detailed herein increases by at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, or 500, or any value in increments of 1 therebetween, relative to the weight of the formulation. The range is reduced by at least 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, 250%, 300%, 350%, 400%, 450%, or 500%, or any value or range of values ​​in increments of 1% therebetween.

[0161] Figure 37 Release graphs of per-molecule size at different times are presented for the exemplary embodiments disclosed above. Below is a table of various release rates for delivery over 7 days and / or any time period herein, and / or thereafter, according to exemplary embodiments of the herein. Embodiments may include devices for delivery at these release rates, which have a range of any of the following values ​​or values ​​between them, as values ​​in ng / hr, and / or may be greater than or less than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or any value or range of values ​​in increments of 1%, and may be any value or range of values ​​between them (percentage difference).

[0162] Note that the embodiments may have values ​​different from those described above (larger or smaller).

[0163] In the examples, the BDNF MW (molecular weight in grams per mole) is 28,109. Some values ​​in this document assume an application concentration of 10,000 μg / mL. In the examples, a Dex release rate of 24% (4% by weight, moles) can be achieved. In the examples, dexamethasone disodium phosphate (as can be used in a 10 mg / mL injection solution) has a MW of 516 g / mol. Therefore, it is much smaller than Dex, which will result in a lower diffusion rate of BDNF, which in turn can lead to a smaller / lower release rate. When comparing the mass of BDNF released over time, it can be 24% of the mass of dex released in the same time, or when considering the number of BDNF molecules released, it can be 4% of the number of dex molecules released in the same time. This is while keeping size, temperature, solvent, and diffusion time constant.

[0164] In embodiments, the release rate with respect to FW can be linear, decreasing from 30 ng / hr to 3 ng / hr, from 100 to 500 Da or any value or range of values ​​in increments of 0.1 Da (e.g., a 200 Da molecule can have a release rate of 20 ng) to 10,000 to 500,000 Da or any value or range of values ​​in increments of 0.1 Da.

[0165] The embodiment may include a lumen and a reservoir that can establish a concentration gradient along a direction of movement as shown in the figure above. As an example, the concentration gradient may vary along its length from the unitized and / or real values ​​shown below, thereby tracking the curve presented above, and may differ from any values ​​shown below, and / or may be any value or range of values ​​differing from (or between and including) those values ​​by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or in increments of 1%, and may be any value or range of values ​​between them (percentage difference).

[0166] Note that the graphics presented herein have a precision that ends at a certain point, consistent with any printed graphics. In this regard, embodiments include designs with values / performance characteristics corresponding to "approximately" those presented in the graphics. That is, reference is made only as an example. Figure 20 The figure shows the release rate over time, 0.00785 mm.2 The area curve represents the publicly disclosed release rate of approximately 11 ng / hr at 7 days.

[0167] The inference is that the values ​​for the design and performance characteristics described above have been given. For the purpose of precision, these values ​​can be mapped to those along the graph. As an example, we have disclosed a release rate of 11.5 ng / hr above. If more precision is required, this can be mapped to... Figure 20 0.00785mm 2 The value on the curve.

[0168] Figure 39A Performance graphs for passive diffusion-based local drug delivery of small molecules, such as dexamethasone, are shown in exemplary embodiments having any one or more features disclosed herein. Note that the embodiments include applications of the teachings herein to macromolecular drugs (e.g., brain-derived neurotrophic factor-BDNF) that can be dissolved in aqueous or other solvents. Figure 39A The graph illustrates exemplary performance data on the release rate of dexamethasone phosphate into physiological saline at 37 degrees Celsius over time using a device having one or more of the features detailed above.

[0169] The graphics presented herein are for some exemplary embodiments, and other embodiments may have values ​​different from those presented in the graphics. In this regard, embodiments include values ​​less than, greater than, and / or equal to 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the values ​​presented in the graphics, or any value or range of values ​​in increments of 1%. Furthermore, the embodiments include values ​​less than, greater than, and / or equal to 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 225%, 250%, 275%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 700%, 800%, 900%, 1000%, 1250%, 1500%, 1750%, 2000%, or any value or range of values ​​in increments of 1%.

[0170] Note that, unless otherwise stated, the values ​​above are for Dex drugs (e.g., dexamethasone phosphate) and are presented at the concentrations described above.

[0171] In embodiments, the teachings herein are used in conjunction with any or more of the teachings in U.S. Patent Application Serial No. 63 / 399613, filed August 19, 2022, entitled "Substance Delivery Inside Mammals," inventor Daniel Smith. In embodiments, any or more of the design features and / or performance features detailed herein are used in any or more of the devices detailed herein, provided that they are achievable in the art. In embodiments, any or more of the method actions and / or method results and / or method prerequisites / qualifiers detailed herein are used in any or more of the methods detailed herein, provided that they are achievable in the art. In practice, embodiments include employing the entire implantable device disclosed herein and providing a lumen having one or more features disclosed herein. In embodiments, any or more of the packaging and / or filling arrangements disclosed herein are used in conjunction with the devices disclosed herein.

[0172] In an exemplary embodiment, at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, or 95% of the total internal volume of the reservoir (the volume of the therapeutic substance), or any value or range of values ​​in increments of 1%, are located no more than 1.5, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.8, 0.7, 0.6, or 0.5 cm from the reference line 599 or the leftmost portion of the housing 185, and / or any one or more percentages of the internal volume of the reservoir as detailed above are located to the left of the reference line 599.

[0173] Consistent with the teachings of the diaphragm described above, the filling port includes a resealable diaphragm configured to receive the end of the syringe, wherein the diaphragm is configured to provide a barrier against bacteria when the syringe is removed from the diaphragm after the therapeutic substance has been delivered to the reservoir.

[0174] Furthermore, note that in the exemplary embodiment, when the reservoir is full, the therapeutic substance may "eject" from the opening of tube 718. In the exemplary embodiment, the pressure buildup during filling and filling can cause continued attempts to transfer the therapeutic substance from the reservoir once full to result in pressure buildup, causing fluid to flow out of the outlet at least in a beaded manner. This can provide healthcare professionals with an indication that the reservoir is full. Additionally, this can provide a protective mechanism to prevent the reservoir from "bursting" or otherwise damaging it.

[0175] Furthermore, in some embodiments where a stopper is present in the outlet, the stopper 530 may be configured to be porous enough that increased pressure will cause the therapeutic substance to "leak" from the stopper. In practice, in exemplary embodiments, this could be how a healthcare provider determines how the reservoir is filled. In exemplary embodiments of this particular embodiment, care may be taken to avoid increasing the pressure to a level where leakage cannot keep up with the pressure increase.

[0176] Therefore, in an embodiment, there is a component comprising an implantable portion and a reservoir filling assembly in fluid communication with the reservoir via a filling port, wherein the reservoir filling assembly is configured to be at least substantially filled with a therapeutic material to fill the reservoir, and the reservoir filling assembly is removable from the filling port, allowing the device to be implanted without the reservoir filling assembly. In an embodiment, when the reservoir filling assembly is removed from the filling port, the implantable portion is prepared to be implanted into the recipient at least relative to an action associated with closing the filling port, because in this embodiment, the filling port is self-sealing and / or self-closing. That is, in an alternative embodiment, the filling port may be “filled” with another material, such as fast-curing silicone or adhesive, or such material may be injected or otherwise placed in the channel to further enhance the sealing and fixation. In an embodiment, unlike the diffuser material used for the outlet, the other material used for the filling port does not allow for material diffusion. The degree of diffusion present is far less than that of the diffuser material used for the outlet.

[0177] In embodiments, compression can be applied after the terminal is removed, or alternatively, a component (e.g., a spring) can be positioned within the silicone body. This allows the terminal to open the channel when pressed against the tube, but then, once the terminal is removed, the component compresses the silicone to close the channel. That is, the presence of a spring is not necessarily required. Alternatively, a relatively rigid or stiff C-shaped body can be located on either side of the channel, where the simple fact that the silicone fills the interior of the seal is sufficient to cause the channel to self-heal or otherwise close when the terminal is removed. In other words, the terminal presses the silicone against the side (inside) of the C-shaped body, thereby opening the channel, and then, when removed, the silicone expands back to its original state, thus closing the channel.

[0178] In an exemplary embodiment, the filling action of the reservoir, as detailed herein, occurs within any value or range of 24, 18, 12, 6, 5, 4, 3, 2, or 1 hour, or in increments of one minute, prior to placing at least a portion of the implantable portion into the recipient's body through an artificially created opening in the recipient's skin. In an embodiment, the filling action of the reservoir, as detailed herein, occurs within any value or range of 90, 80, 70, 60, 50, 40, 30, 25, 20, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 minute, or in increments of one second, prior to placing at least a portion of the implantable portion into the recipient's body through an artificially created opening in the recipient's skin. In an exemplary embodiment, the portion that can be placed into the recipient can be a receiver-stimulator when it is placed above the mastoid bone through an incision in the skin of the head above the mastoid bone.

[0179] The embodiments include the action of implanting an implantable portion into the human body after providing a therapeutic substance. In the embodiments, no further therapeutic substance is provided to the therapeutic substance delivery system after the action of providing the therapeutic substance. In this exemplary embodiment, this may correspond to a single filling, wherein no further therapeutic substance is provided to the reservoir or implantable portion after implantation. That is, as described above, the embodiments may include, after implantation, puncturing the skin above the septum of the implantable reservoir with the tip of a syringe after a certain period of time to refill with therapeutic substance or provide a different therapeutic substance.

[0180] The inference from this is that the embodiments include selecting a specific type of therapeutic substance to be delivered by the implantable portion or otherwise placed in the reservoir before filling or otherwise filling the reservoir. Therefore, the embodiments can make it possible to select a wide variety of therapeutic substances during surgery or at any time associated with the first portion of the implant being in the human body. For example, therapeutic substance A can be selected for some patients, and therapeutic substance B can be selected for other patients, all of which can be selected during or during the procedure. In one embodiment, the therapeutic substance is dexamethasone. However, it should be noted that other types of therapeutic substances may also be used / included in the reservoir, such as systemic steroids, anticoagulants, clot dissolving agents, antifibrotic agents, antiproliferative agents, or NSAIDs. Therapeutic substances include pharmaceuticals, but also include non-pharmaceutical substances. In an exemplary embodiment, the therapeutic substance includes steroids (such as those just mentioned and / or biologics). Therapeutic substances may also include minerals, etc. Any disclosure herein regarding pharmaceuticals or the inclusion or delivery of pharmaceuticals also corresponds to another embodiment that relates to an embodiment involving a therapeutic substance. That is, generally, the term pharmaceutical as used herein is an abbreviation for therapeutic substance. Therefore, unless otherwise indicated, the embodiments include the present disclosure, wherein the term "medicine" is used in place of the term "therapeutic substance".

[0181] The therapeutic substance can be a corticosteroid, such as betamethasone, clobetasol, difluralasone, fluocinolone, triamcinolone, its salts, esters, or combinations thereof.

[0182] In one embodiment, there is a device, such as an implantable portion of a cochlear implant or its lead assembly, comprising an implantable electrode array including a plurality of electrodes supported by a silicone body. In this exemplary embodiment, the electrode array includes a therapeutic substance delivery channel (e.g., tube portion 518 or tube 718), the therapeutic substance delivery channel including at least one port (e.g., a distal portion of portion 581 or tube 718). In an exemplary embodiment, the port includes different barriers made of a material that maintains a bacterial barrier before the channel is filled with a water-based substance. In an exemplary embodiment, the barrier is a plug 530.

[0183] Figure 40 An alternative exemplary embodiment of a different barrier relative to electrode array 1890 is presented. Here, element 1830 is a cap fitted onto the distal end of tube 718 (rather than being inside the tube like a plug). In this exemplary embodiment, tube 718 extends outward by a small amount so that the cap can be fitted onto the tube. Figure 18 In the embodiment shown in A, the cap 1830 is the front surface of the array. In some embodiments, the cap protrudes slightly from the silicone body, which is the silicone carrier 146 encapsulating the tube 718. Conversely, Figure 41An exemplary electrode array 1990 is shown, wherein the material of the carrier 146 extends beyond the cap 1830. This can be of practical value with respect to the protective cap, in addition to the fact that the foremost surface is a relatively flexible and soft silicone forming the body of the carrier 146. Any arrangement that can implement the teachings detailed herein can be utilized in at least some exemplary embodiments.

[0184] In the embodiments, the different barriers have pores. For example, the pore size of the different barriers is no greater than 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.09, 0.08, 0.07, 0.06, 0.05 micrometers or any value or range of values ​​in increments of 0.005 micrometers (but note that some of these may not establish a bacterial barrier—some embodiments do not establish a bacterial barrier).

[0185] The barrier can be PVDF. Note that micropores or tiny pores may be used depending on the embodiment.

[0186] A different barrier is a component that differs from other components immediately adjacent to it in material and / or size and / or arrangement. For example, a barrier may differ from the silicone used to build the carrier in material and size. The barrier may also differ from tube 718 in material and size. In embodiments, a rolled silicone filter or a porous silicone filter may be used.

[0187] In an exemplary embodiment, the different barriers are made entirely of polyvinylidene fluoride and may be made of Durapore®.

[0188] In embodiments, different barriers are configured to operate at pressures not exceeding 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9.5, and 9 at pressures not exceeding 0.1 atmospheres after implantation into the body, and / or at pressures in the reservoir caused by implantation after surgery (where the reservoir is filled at 1 atmosphere). Dexamethasone diffuses at rates of 8.5, 8, 7.5, 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.75, 1.5, 1.25, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, or 0.2 ng / h (the mean, median, and / or mode and / or maximum rate over any one or more time periods detailed herein) or any value or range of values ​​in increments of 0.05 ng / h. (This does not mean that filling must be completed at 1 atmosphere. This means that when it is completed at 1 atmosphere, this is what happens.) In the embodiments, the therapeutic substance diffuses through the barrier and is replaced by NaCl. As the concentration of the therapeutic substance decreases over time, the release rate also decreases.

[0189] In embodiments, the different barriers are also configured such that overpressure in the channel relative to the external environment will cause dexamethasone to be expelled from the plug, while retaining the plug for subsequent use as different diffusion barriers. In exemplary embodiments, the overpressure can be any value or range of values ​​of 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, 250%, 300%, 350%, or 400% or more, or in increments of 1%, where the denominator is the pressure before the overpressure. This can be practically valuable relative to the presence of overpressure during the filling operation of the reservoir. The idea is that it is practical for the cap or plug not to "pop" or break. In embodiments, the reservoir(s) are also configured such that overpressure in the reservoir retains the reservoir for subsequent use when implanted in the human body. In embodiments, a valve is present that is configured to eject the substance upon overpressure. This can be positioned along the lead wire and / or at the reservoir. This can be positioned away from / to be positioned within the electrode array / partially located in the cochlea upon full implantation. In embodiments, a lift valve may be present to pop out in the event of overpressure. The lift valve may be configured such that it must be replaced or a new lift valve placed in the position of the old one. A spare lift valve may be provided with the implant in the package. In embodiments, the valve / lift valve ensures or otherwise reduces the possibility of damage to the material delivery system by overpressure. In a sense, the lift valve can be a sacrificial component.

[0190] In this embodiment, minimal mass transfer occurs when the therapeutic material is delivered to the recipient. All, substantially all, or effectively all deliveries are performed by diffusion. In this embodiment, delivery of at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, or any value or range thereof in increments of 0.1%, is performed by diffusion. In this embodiment, the diffusion qualifier mentioned above occurs after the outlet first comes into contact with bodily fluids and / or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours after refilling (considering the fact that some amount of mass transfer may occur, for example, during the implantation and / or surgical procedure or refilling process, such as due to pressure applied to the reservoir during implantation).

[0191] While the above embodiments focus on a single outlet for therapeutic substances, embodiments include reservoirs with multiple outlets. In this respect, Figure 42 An exemplary electrode array 2888 is shown, including outlets located on the sidewall-facing side of the electrode array. In this embodiment, each outlet includes a plug 2030, which may not be present in other embodiments and may correspond to the plugs detailed above. Various placements of the plugs are also shown. It can be seen that some plugs may be located inside the outermost portion of the outlet, and some plugs may extend into the tube 718. Any arrangement can be utilized as long as the therapeutic material can be transferred from the tube to the surrounding environment after implantation. It should also be noted that the outlets may have various sizes and / or dimensions, and they may differ from one another. In an exemplary embodiment, the plug 2030 is adhesively bonded to the tube 718 and / or the silicone body that forms the carrier. In this embodiment, the tube 718 has an orifice positioned along its length, and the plug 2030 fills the orifice. In an embodiment, the plug is interference-fitted to the orifice to retain the plug within the orifice. In an embodiment, an adhesive or some other bonding technique is again used.

[0192] In an exemplary embodiment, the reservoir is a non-expandable reservoir. By way of example only and not limitation, in an exemplary embodiment, the reservoir may be made of an elastomeric material, but the reservoir is configured to minimize elasticity. In an exemplary embodiment, under a 1 atm pressure, the reservoir establishes a first internal volume. As an example, when subjected to pressure (e.g., any one or more of the pressures described above), depending on the pressure, the reservoir establishes a second internal volume that is no more than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% larger than the first internal volume.

[0193] Note that the phrase "filling" as used herein is not an absolute term. It refers to the act of placing material from a location outside the reservoir into the reservoir. The reservoir does not need to be filled to capacity, although embodiments do include filling the reservoir to capacity.

[0194] Some embodiments of therapeutic substances can be pharmaceuticals. Therefore, embodiments relate to drug delivery systems. Therapeutic substances include pharmaceuticals, but also non-pharmaceutical substances. In exemplary embodiments, therapeutic substances include steroids and biological agents. Therapeutic substances may also include minerals, etc.

[0195] In an exemplary embodiment, the barrier described above has a dual function as both a flow limiter and a bacterial barrier.

[0196] In view of the foregoing, it can be seen that, in an exemplary embodiment, there exists a device comprising, for example, a cochlear implant electrode array and an implantable drug reservoir. In this exemplary embodiment, the device is configured such that the drug reservoir is part of the electrode array, and when the cochlear implant electrode array is fully implanted in the recipient, the drug reservoir is at least substantially located outside the middle ear space and outside the inner ear space. (Note that "reservoir" is a relative term. Due to the relatively small size of the reservoir, the conduit of the lead assembly including the electrode array is considered a reservoir. Conversely, if the reservoir is much larger than at least some of the exemplary embodiments disclosed herein, the conduit of the lead assembly will not be considered a reservoir.) In the above embodiments, when the cochlear implant electrode array is fully implanted in the recipient in both a relaxed state and a fully operational inflated state, the reservoir is entirely located outside the middle and inner ear. In at least some embodiments, the reservoir is a non-elastic shell other than a septum or a completely non-elastic shell.

[0197] In an exemplary embodiment, under 1 atm pressurization, the reservoir establishes a first internal volume. As an example, when subjected to pressurization (e.g., any one or more of the pressurizations described above), depending on the pressurization, the reservoir establishes a second internal volume that is no more than 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% larger than the first internal volume. In an embodiment, if the diaphragm is rigidly retrained to prevent expansion, the reservoir establishes a second internal volume that is no more than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% larger than the first internal volume.

[0198] In some embodiments, the teachings detailed herein implement a device configured to deliver, without refilling, at an average value of 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, 35, 40, 45, 50, 55, or 60 nanograms per hour, or any value or range of values ​​in increments of 0.05 nanograms per hour, during a first time period within a second time period. In an exemplary embodiment, the first time period is 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, 35, 40, 45, 50, 55, or 60 hours or days, or any value or range of values ​​in increments of one hour or one day therebetween. The second time period is any value or range of values ​​ranging from 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300 hours or days, or in increments of one hour or one day. In embodiments, different barriers act as both bacterial filters and controls / determines the delivery rate of the therapeutic substance. Different barrier constructions (e.g., porosity) can be selected to obtain different diffusion rates. In embodiments, the barriers are designed to be relatively thin, thin enough that they have a relatively small effect on the diffusion rate. In other embodiments, other barriers may be easier to rate control. In embodiments, the concentration in the reservoir can be changed / adjusted to change / control the delivery rate. For example, high concentration can be equated to faster diffusion, at least initially, and vice versa. Alternatively and / or in addition, the cross-sectional area of ​​the long tubes (tubes 718 and / or 714) can be changed / modified to at least approximately achieve the desired rate.

[0199] Furthermore, in some embodiments, as detailed, the device is configured such that the reservoir can be refilled or refilled without surgery.

[0200] In an exemplary embodiment, the pressure at which the drug is located is a pressure not exceeding the ambient pressure inside the cochlea and / or the statistically average atmospheric pressure at sea level in Washington, D.C. for the 2021 calendar year based on Dulles Airport data and / or any value or range of 1.01, 1.02, 1.03, 1.04, 1.05, 1.06, 1.07, 1.08, 1.09, 1.1, 1.12, 1.14, 1.16, 1.18, or 1.2 times greater than or in increments of 0.01 times, all other conditions being equal. In this embodiment, different barriers may be configured to prevent pressures exceeding any one or more of the aforementioned pressures.

[0201] Unless otherwise specified, any arrangement disclosed herein may be a refillable and / or refillable arrangement. Similarly, other embodiments include implantable portions that are at least not refillable or refillable after implantation.

[0202] The embodiment includes an apparatus configured to be fully charged or otherwise activated for a period of time not exceeding 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 minute or a range of values ​​in increments of 1 second.

[0203] It should be noted that any disclosure regarding one or more embodiments detailed herein may be practiced in conjunction with any other disclosure regarding one or more other embodiments detailed herein. That is, some exemplary embodiments include any one or more of the teachings detailed herein in combination with any one or more of the other teachings detailed herein, unless otherwise stated, provided that it is possible to implement them in the art. It should also be noted that any disclosure herein regarding any feature corresponds to the disclosure of an exemplary embodiment that explicitly excludes that given feature from use with any one or more other features detailed herein, unless otherwise stated, provided that it is possible to implement them in the art.

[0204] It should be noted that any disclosure of any method action herein corresponds to a disclosure of an apparatus and / or system capable of implementing that method action. It should be noted that any disclosure of any method for manufacturing, further developing, or producing the apparatus disclosed herein corresponds to a disclosure of the apparatus resulting from that method. It should be noted that any disclosure of any device and / or system herein corresponds to a disclosure of providing and / or manufacturing that device and / or system. It should be noted that any disclosure of any function herein corresponds to an apparatus and / or system configured to provide that function. It should be noted that any disclosure of any device and / or system herein corresponds to a disclosure of a method utilizing that device and / or system.

[0205] In this regard, it should be noted that any disclosure of the apparatus and / or system herein corresponds at least in terms of utilizing its functionality to the disclosure of the apparatus and / or system detailed herein. Furthermore, it should be noted that any disclosure of the manufacturing method corresponds to the disclosure of the apparatus and / or system produced by said manufacturing method. It should also be noted that any disclosure of the apparatus and / or system herein corresponds to the disclosure of manufacturing the apparatus and / or system.

[0206] While various embodiments have been described above, it should be understood that they are presented by way of example only and not as limiting. It will be apparent to those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention. Therefore, the breadth and scope of the invention should not be limited to any of the exemplary embodiments described above, but should be defined only by the following claims and their equivalents.

Claims

1. An apparatus comprising: Storage container; as well as The therapeutic substance located in the storage container, wherein The device is an implantable therapeutic substance delivery device, and The device is configured to deliver the therapeutic substance to its recipient via diffusion-controlled release.

2. The device according to claim 1, wherein: The storage device includes a first sub-storage and a second sub-storage, the second sub-storage being retracted relative to the first sub-storage; and During the delivery of the therapeutic substance to the recipient, molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir.

3. The device according to claim 1, wherein: The storage device includes a first sub-storage, a second sub-storage, and a third sub-storage, wherein the second sub-storage is contracted relative to the first sub-storage, and the third sub-storage is contracted relative to the second sub-storage; During the delivery of the therapeutic substance to the recipient, molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir and then to the third sub-reservoir.

4. The device according to claim 1, 2 or 3, wherein: The storage device is constructed at least of a reservoir and a conduit system; The catheter device includes a first catheter segment having a first cross-sectional area perpendicular to its extension direction, the first cross-sectional area being larger than a second cross-sectional area of ​​a second catheter segment perpendicular to its extension direction; and The cross-sectional area of ​​the second catheter segment is such that the release rate of the therapeutic substance from the device seven days after being released into the recipient and / or thereafter is less than one-third of the release rate that would exist if the first and second cross-sectional areas were the same, all other things being equal.

5. The device according to claim 1, 2 or 3, wherein: The storage device is constructed at least of a reservoir and a conduit system; The catheter device includes a first catheter segment having a first cross-sectional area perpendicular to the extension direction of the first catheter segment, the first cross-sectional area being larger than a second cross-sectional area of ​​a second catheter segment perpendicular to the extension direction of the second catheter segment. and The cross-sectional area of ​​the second catheter segment is such that the release rate of the therapeutic substance from the device after seven days and / or thereafter is less than 10% of the release rate under the same conditions as the first and second cross-sectional areas.

6. The device according to claim 1, 2 or 3, wherein: The storage device is constructed at least of a reservoir and a conduit system; The catheter device includes a first catheter segment having a first cross-sectional area perpendicular to the extension direction of the first catheter segment, the first cross-sectional area being at least five times larger than a second cross-sectional area of ​​a second catheter segment perpendicular to the extension direction of the second catheter segment. The first catheter segment has a first length, which is greater than the second length of the second catheter segment; and The length of the second catheter segment ensures that the release rate of the therapeutic substance from the device is less than 50% of the release rate under the condition that the first length is 25 times the second length, all other things being equal.

7. The device according to claim 1, 2 or 3, wherein: The storage device is constructed at least of a reservoir and a conduit system; The catheter device includes a first catheter segment having a first cross-sectional area perpendicular to the extension direction of the first catheter segment, the first cross-sectional area being at least five times larger than a second cross-sectional area of ​​a second catheter segment perpendicular to the extension direction of the second catheter segment. The first catheter segment has a first length, which is greater than the second length of the second catheter segment; and The length of the second catheter segment ensures that the release rate of the therapeutic substance from the device is less than 70% of the release rate under conditions where the length of the second segment is 25 times the second length and all other conditions are equal.

8. An apparatus comprising: Storage tank; as well as Delivery tube device, wherein The device is an implantable therapeutic substance delivery device. The delivery tube device is a diffusion delivery tube device, and The device is configured such that therapeutic material located in the reservoir travels to the delivery tube for delivery to a person with the device implanted.

9. The device according to claim 8, wherein: The reservoir has an internal volume that is at least an order of magnitude larger than the internal volume of the delivery tube.

10. The device according to claim 8 or 9, wherein: The delivery tube device has a first section having a first cross-sectional area perpendicular to its extending direction, the first cross-sectional area being larger than a second cross-sectional area of ​​a second section of the delivery tube device, the second cross-sectional area being perpendicular to the extending direction of the second section; and The first cross-sectional area ensures that the release rate of the therapeutic substance from the device seven days after release into the human body and / or thereafter is at least twice the release rate under the same conditions as the first and second cross-sectional areas.

11. The device according to claim 8 or 9, wherein: The delivery tube device has a first section having a first cross-sectional area perpendicular to its extending direction, the first cross-sectional area being larger than a second cross-sectional area of ​​a second section of the delivery tube device, the second cross-sectional area being perpendicular to the extending direction of the second section; and The first cross-sectional area ensures that the release rate of the therapeutic substance from the device after seven days and / or thereafter is within 20% of the release rate under the same conditions as the first and second cross-sectional areas.

12. The device according to claim 8 or 9, wherein: The delivery tube device has a first section, the first section having a first length that is greater than the second length of the second section of the delivery tube device; The first segment has a first cross-sectional area perpendicular to its extending direction, and this first cross-sectional area is at least five times larger than the second cross-sectional area of ​​the second segment of the delivery tube device perpendicular to its extending direction; and The length of the first segment is at least four times the length of the second segment, and the length of the first segment is such that the release rate of the therapeutic substance from the device seven days after release into the human body and / or thereafter is within 10% of the release rate that would exist if the length of the first segment were at least six times the length of the second segment, all other things being equal.

13. The device according to claim 8 or 9, wherein: The delivery tube has a first section, the first section having a first length greater than the second length of the section of the delivery tube; The first segment has a first cross-sectional area perpendicular to its extending direction, and this first cross-sectional area is at least five times larger than the second cross-sectional area of ​​the second segment of the delivery tube device perpendicular to its extending direction; and The length of the first segment is at least four times the length of the second segment, and the length of the first segment is such that the release rate of the therapeutic substance from the device after seven days and / or thereafter is within 10% of the release rate that would exist if the length of the first segment were at least eight times the length of the second segment, all other things being equal.

14. The device according to claim 8 or 9, wherein: The delivery tube device has a first section, the first section having a first length that is greater than the second length of the second section of the delivery tube device; The first segment has a first cross-sectional area perpendicular to its extending direction, and this first cross-sectional area is larger than the second cross-sectional area of ​​the second segment of the delivery tube device perpendicular to its extending direction; and The second cross-sectional area is such that, 12 hours after the therapeutic substance is released from the device into the human body, and / or thereafter, the release rate of the therapeutic substance is less than 60% of the release rate that would exist if the second cross-sectional area were the same as the second cross-sectional area; and The second cross-sectional area is such that, 12 hours after the therapeutic substance is released from the device into the human body, the release rate of the therapeutic substance will be within 10% of the existing release rate if the second cross-sectional area is at least one-tenth or ten times larger.

15. A method comprising: Entering the human body; as well as The disease of the human body is treated by controllably delivering therapeutic substances from an implantable therapeutic substance delivery device, wherein... The action of passively and controllably delivering the therapeutic substance is performed.

16. The method of claim 15, wherein: A fluid bridge exists between the therapeutic substance and the bodily fluids in the human body.

17. The method of claim 16, wherein: The bridge allows molecules of the therapeutic substance to diffuse from the device into the human body.

18. The method according to claim 15, 16 or 17, wherein: Body fluids are perilymph.

19. The method according to claim 15, 16, 17 or 18, wherein: After an initial period in which the release rate of the therapeutic substance steadily decreases from a relatively high rate, the release rate of the therapeutic substance quasi-stabilizes at a lower rate.

20. The method of claim 19, wherein: The quasi-stable release rate is attributed to the slowly changing concentration gradient of the substance within the device.

21. The method of claim 20, wherein: The slowly changing concentration gradient is attributed to the continuous supply of molecules of the therapeutic substance from a large volume region to a smaller volume region of the device.

22. The method according to claim 15, 16, 17, 18, 19, 20 or 21, wherein: The controlled delivery of the therapeutic substance is governed by Fick's Law.

23. An apparatus comprising: The first at least partially bounded volume; The second at least partially bounded volume; as well as At least one device outlet at the second bounded volume, wherein The device is an implantable therapeutic substance delivery device, and The device delivers the therapeutic substance effectively to the recipient entirely due to the concentration gradient.

24. The device according to claim 23, wherein: The device provides passive diffusion of locally therapeutic substances with fully controlled geometry.

25. The device according to claim 23 or 24, further comprising: The third at least partially bounded volume, in which The third, at least partially bounded volume, is the movement of matter between the first and second volumes. The volume of the first volume is at least 5 times the volume of the third volume, and the volume of the third volume is at least 5 times the volume of the second volume.

26. The device according to claim 23 or 24, further comprising: The third at least partially bounded volume, in which The third, at least partially bounded volume, is the movement of matter between the first and second volumes. The first cross-sectional area of ​​the first volume located on a plane perpendicular to the material movement direction from the first volume to the second volume is at least 8 times the second cross-sectional area of ​​the third volume located on a plane perpendicular to the material movement direction from the first volume to the second volume, and The third cross-sectional area of ​​the second volume, located on a plane perpendicular to the direction of material movement from the first volume to the second volume, is at least one-sixth of the second cross-sectional area.

27. The device according to claim 23 or 24, further comprising: The third at least partially bounded volume, in which The third, at least partially bounded volume, is the movement of matter between the first and second volumes. The second at least partially bounded volume is a lumen having a diameter, and the lumen having a release rate seven days after the release of the therapeutic substance into the human body, such that the release rate increases by 8 to 15 times with an increase of 2 to 5 times in diameter, all other things being equal.

28. The device according to claim 23 or 24, further comprising: The third at least partially bounded volume, in which The third, at least partially bounded volume, is the movement of matter between the first and second volumes. The second at least partially bounded volume is a lumen having a length, and the lumen having a release rate seven days after the release of the therapeutic substance into the human body, such that the release rate decreases by a factor of 2 to 5 as the length increases by 4 to 8 times, all other things being equal.

29. The device according to claim 23, 24, 25, 26, 27 or 28, further comprising: The device is configured such that the release rate at 7 days and / or thereafter is reduced by at least 70% for an increase of at least 100 times in the weight of the formulation, all other things being equal.

30. A method comprising: Entering the human body; as well as Treating human diseases by controllably delivering therapeutic substances from an implantable therapeutic substance delivery device, wherein The action of controllably delivering the therapeutic substance is performed effectively without any net movement of the solvent in which the therapeutic substance is present from the volume of the device containing the therapeutic substance to the surrounding environment outside the device.

31. The method according to claim 30, wherein: The volume has a total distance extending from the exit of the volume into the human body to the furthest point from the exit, and the size and dimensions of the volume are set such that, seven days after substance delivery and / or thereafter, the concentration gradient of the molecules of the therapeutic substance is such that, for at least a first segment along the total distance of the volume, the concentration varies from a maximum value by no more than 5%, the first segment having at least one-third of the total distance.

32. The method according to claim 30 or 31, wherein: The size and dimensions of the volume are set such that, seven days after delivery and / or thereafter, the concentration gradient of the molecules of the therapeutic substance causes the concentration to decrease by at least 20% over a second segment along the total distance of the volume, the second segment having a distance of half the total distance, the second segment being continuous with the first segment.

33. The method according to claim 30 or 31, wherein: The size and dimensions of the volume are set such that, seven days after delivery and / or thereafter, the concentration gradient of the molecules of the therapeutic substance causes the concentration to decrease by no more than 20% over a second segment along the total distance of the volume, the second segment having a distance of 1 / 3 of the total distance, the second segment being continuous with the first segment.

34. The method according to claim 30 or 31, wherein: The size and dimensions of the volume are set such that, seven days after substance delivery and / or thereafter, the concentration gradient of the molecules of the therapeutic substance causes the concentration to decrease by no more than 20% over a second segment along the total distance of the volume, the second segment having a distance of 1 / 2 of the total distance, the second segment being continuous with the first segment.

35. The method according to claim 30, 31, 32, 33 or 34, wherein: The release rate during a 5-day period within the first 8 days of delivery of the therapeutic substance is less than 20% of the maximum release rate.

36. The method according to claim 30, 31, 32, 33 or 34, wherein: The release rate during a 5-day period within the first 8 days of delivery of the therapeutic substance is less than 10% of the maximum release rate.

37. The method according to claim 30, 31, 32, 33 or 34, wherein: The release rate during a 5-day period within the first 8 days of delivery of the therapeutic substance is less than 5% of the maximum release rate.

38. An implantable therapeutic substance delivery device, comprising: Storage tank; as well as Delivery tube device, wherein The delivery tube device includes a tubular device comprising a first lumen and a second lumen that is distinctly different from the first lumen. The delivery tube device is a diffusion delivery tube device. The first lumen is in fluid communication with the storage tank, and the second lumen is in fluid communication with the first lumen. The device is configured such that therapeutic material located in the reservoir travels to the delivery tube for delivery to a person with the device implanted.

39. An apparatus wherein at least one of the following is true: The device includes a storage unit; The device includes a therapeutic substance located in the reservoir; The device is an implantable therapeutic substance delivery device; The device is configured to deliver the therapeutic substance to its recipient via diffusion-controlled release; The storage device includes a first sub-storage and a second sub-storage, wherein the second sub-storage is contracted relative to the first sub-storage; During the delivery of the therapeutic substance to the recipient, molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir; The storage device includes a first sub-storage, a second sub-storage, and a third sub-storage, wherein the second sub-storage is contracted relative to the first sub-storage, and the third sub-storage is contracted relative to the second sub-storage; During the delivery of the therapeutic substance to the recipient, molecules of the therapeutic substance move from the first sub-reservoir to the second sub-reservoir and then to the third sub-reservoir; The storage device is constructed at least of a reservoir and a conduit system; The catheter device includes a first catheter segment having a first cross-sectional area perpendicular to the extension direction of the first catheter segment, the first cross-sectional area being larger than a second cross-sectional area of ​​a second catheter segment perpendicular to the extension direction of the second catheter segment. The cross-sectional area of ​​the second catheter segment is such that the release rate of the therapeutic substance from the device seven days after being released into the recipient and / or thereafter is less than 1 / 3 of the release rate that would exist if the first and second cross-sectional areas were the same, all other conditions being equal. The storage device is constructed at least of a reservoir and a conduit system; The catheter device includes a first catheter segment having a first cross-sectional area perpendicular to the extension direction of the first catheter segment, the first cross-sectional area being larger than a second cross-sectional area of ​​a second catheter segment perpendicular to the extension direction of the second catheter segment. The cross-sectional area of ​​the second catheter segment ensures that the release rate of the therapeutic substance from the device seven days after its release into the human body and / or thereafter is less than 10% of the release rate under the same conditions where the first and second cross-sectional areas are identical. The storage device is constructed at least of a reservoir and a conduit system; The catheter device includes a first catheter segment having a first cross-sectional area perpendicular to the extension direction of the first catheter segment, the first cross-sectional area being at least five times larger than a second cross-sectional area of ​​a second catheter segment perpendicular to the extension direction of the second catheter segment. The first catheter segment has a first length, which is greater than the second length of the second catheter segment; The length of the second catheter segment ensures that the release rate of the therapeutic substance from the device seven days after its introduction into the human body is less than 50% of the release rate under the condition that the first length is 25 times the second length, all other things being equal. The storage device is constructed at least of a reservoir and a conduit system; The catheter device includes a first catheter segment having a first cross-sectional area perpendicular to the extension direction of the first catheter segment, the first cross-sectional area being at least five times larger than a second cross-sectional area of ​​a second catheter segment perpendicular to the extension direction of the second catheter segment. The first catheter segment has a first length, which is greater than the second length of the second catheter segment; The length of the second catheter segment ensures that the release rate of the therapeutic substance from the device seven days after and / or thereafter is less than 70% of the release rate under conditions where the length of the second segment is 25 times the second length and all other conditions are equal. Storage tank; as well as Delivery tube device; The device is an implantable therapeutic substance delivery device; The delivery tube device is a diffusion delivery tube device; The device is configured such that therapeutic material located in the reservoir travels to a delivery tube for delivery to a person with the device implanted. The reservoir has an internal volume that is at least an order of magnitude larger than the internal volume of the delivery tube; The delivery tube device has a first section, the first section having a first cross-sectional area perpendicular to the extending direction of the first section, the first cross-sectional area being larger than the second cross-sectional area of ​​a second section of the delivery tube device, the second cross-sectional area being perpendicular to the extending direction of the second section; The first cross-sectional area ensures that the release rate of the therapeutic substance from the device after seven days and / or thereafter is at least twice the release rate under the same conditions as the first and second cross-sectional areas. The delivery tube device has a first section, the first section having a first cross-sectional area perpendicular to the extending direction of the first section, the first cross-sectional area being larger than the second cross-sectional area of ​​a second section of the delivery tube device, the second cross-sectional area being perpendicular to the extending direction of the second section; The first cross-sectional area ensures that the release rate of the therapeutic substance from the device after seven days and / or thereafter is within 20% of the release rate under the same conditions as the first and second cross-sectional areas. The delivery tube device has a first section, the first section having a first length that is greater than the second length of the second section of the delivery tube device; The first segment has a first cross-sectional area perpendicular to its extending direction, and this first cross-sectional area is at least five times larger than the second cross-sectional area of ​​the second segment of the delivery tube device perpendicular to its extending direction; and The length of the first segment is at least four times the length of the second segment, and the length of the first segment is such that the release rate of the therapeutic substance from the device after seven days and / or thereafter is within 10% of the release rate that would exist if the length of the first segment is at least six times the length of the second segment, all other things being equal. The delivery tube has a first section, the first section having a first length greater than the second length of the section of the delivery tube; The first section has a first cross-sectional area perpendicular to the extending direction of the first section, and the first cross-sectional area is at least five times larger than the second cross-sectional area of ​​the second section of the delivery tube device perpendicular to the extending direction of the second section; The length of the first segment is at least four times the length of the second segment, and the length of the first segment is such that the release rate of the therapeutic substance from the device after seven days and / or thereafter is within 10% of the release rate that would exist if the length of the first segment is at least eight times the length of the second segment, all other things being equal. The delivery tube device has a first section, the first section having a first length that is greater than the second length of the second section of the delivery tube device; The first section has a first cross-sectional area perpendicular to the extending direction of the first section, and the first cross-sectional area is larger than the second cross-sectional area of ​​the second section of the delivery tube device perpendicular to the extending direction of the second section; The second cross-sectional area is such that, 12 hours after the therapeutic substance is released from the device into the human body, and / or thereafter, the release rate of the therapeutic substance is less than 60% of the release rate that would exist if the second cross-sectional area were the same as the second cross-sectional area. The second cross-sectional area is such that, 12 hours after the therapeutic substance is released from the device into the human body, and / or thereafter, the release rate of the therapeutic substance will be within 10% of the existing release rate if the second cross-sectional area is at least one-tenth or ten times larger. The device is configured to perform an action of treating a disease in the human body by controllably delivering a therapeutic substance from an implantable therapeutic substance delivery device, wherein the action of controllably delivering the therapeutic substance is performed passively; A fluid bridge exists between the therapeutic substance and the bodily fluids in the human body; The bridge allows molecules of the therapeutic substance to diffuse from the device into the human body; The fluid in question is perilymph; After an initial period of time during which the release rate of the therapeutic substance stabilizes at a relatively high rate, the release rate of the therapeutic substance quasi-stabilizes at a lower rate. The quasi-stable release rate is attributed to the slowly changing concentration gradient of the substance within the device; The slowly changing concentration gradient is attributed to the continuous supply of molecules of the therapeutic substance from a large volume region to a smaller volume region of the device; The controlled delivery of the therapeutic substance is governed by Fick's Law; The device includes a first at least partially bounded volume; The device includes a second at least partially bounded volume; The device includes at least one device outlet at the second bounded volume; The device is an implantable therapeutic substance delivery device; The device effectively delivers the therapeutic substance to its recipient entirely due to the concentration gradient; The device provides passive diffusion of locally therapeutic substances with fully controlled geometry; The device includes a third, at least partially, bounded volume, wherein The third at least partially bounded volume is the movement of matter between the first volume and the second volume; The volume of the first volume is at least 5 times the volume of the third volume, and the volume of the third volume is at least 5 times the volume of the second volume; The device includes a third, at least partially, bounded volume; The third at least partially bounded volume is the movement of matter between the first volume and the second volume; The first cross-sectional area of ​​the first volume located on a plane perpendicular to the material movement direction from the first volume to the second volume is at least 8 times the second cross-sectional area of ​​the third volume located on a plane perpendicular to the material movement direction from the first volume to the second volume; The third cross-sectional area of ​​the second volume located on a plane perpendicular to the direction of material movement from the first volume to the second volume is at least one-sixth of the second cross-sectional area; The third at least partially bounded volume is the movement of matter between the first volume and the second volume; The second at least partially bounded volume is a lumen having a diameter, and the lumen has a release rate seven days after the release of the therapeutic substance into the human body and / or thereafter, such that the release rate increases by 8 to 15 times with an increase of 2 to 5 times in diameter, all other things being equal. The third at least partially bounded volume is the movement of matter between the first volume and the second volume; The second at least partially bounded volume is a lumen having a length, and the lumen has a release rate seven days after the release of the therapeutic substance into the human body, such that the release rate decreases by 2 to 5 times as the length increases by 4 to 8 times, all other things being equal. The device is configured such that the release rate of the therapeutic substance at 7 days and / or thereafter is reduced by at least 70% for a formulation weight increase of at least 100-fold, all other things being equal. The device is configured to perform the action of treating a disease in a human body by controllably delivering a therapeutic substance from an implantable therapeutic substance delivery device; The action of controllably delivering the therapeutic substance is performed effectively without any net movement of the solvent in which the therapeutic substance is present from the volume of the device containing the therapeutic substance to the surrounding environment outside the device; The volume has a total distance extending from the exit of the volume into the human body to the furthest point from the exit, and the size and dimensions of the volume are set such that the concentration gradient of the molecules of the therapeutic substance seven days after delivery and / or thereafter is such that for at least a first segment along the total distance of the volume, the concentration changes from a maximum value by no more than 5%, the first segment having at least 1 / 3 of the total distance. The size and dimensions of the volume are set such that, seven days after material delivery and / or thereafter, the concentration gradient of the molecules of the therapeutic substance causes the concentration to decrease by at least 20% over a second segment along the total distance of the volume, the second segment having a distance of ½ of the total distance, the second segment being continuous with the first segment. The size and dimensions of the volume are set such that, seven days after substance delivery and / or thereafter, the concentration gradient of the molecules of the therapeutic substance causes the concentration to decrease by no more than 20% over a second segment along the total distance of the volume, the second segment having a distance of 1 / 3 of the total distance, the second segment being continuous with the first segment. The size and dimensions of the volume are set such that, seven days after substance delivery and / or thereafter, the concentration gradient of the molecules of the therapeutic substance causes the concentration to decrease by no more than 20% over a second segment along the total distance of the volume, the second segment having a distance of 1 / 2 of the total distance, the second segment being continuous with the first segment. The release rate during a 5-day period within the first 8 days of delivery of the therapeutic substance is less than 20% of the maximum release rate; The release rate during a 5-day period within the first 8 days of delivery of the therapeutic substance is less than 10% of the maximum release rate; The release rate during a 5-day period within the first 8 days of delivery of the therapeutic substance is less than 5% of the maximum release rate; The device includes a first tube and a second tube, wherein the second tube is interference-fitted into the first tube; The device includes a tube, wherein one end of the tube is in communication with a target fluid; The target is the perilymph of the scala tympani in the human cochlea; The device includes a filter at the outlet of the pipe; The outlet has a cross-sectional area on a plane perpendicular to the longitudinal extension direction of the lumen, the cross-sectional area being the same as the mean, median, and / or mode of the cross-sectional area on the plane perpendicular to the longitudinal direction, and / or the same as the maximum or minimum area, and / or the cross-sectional area being constant along the length of the lumen, and / or not changing more than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 90%, 95%, or 100% from the maximum value along the length. The tube can be replaced, or tube 718 can be selected for use with the device. The device is configured such that one tube can be attached to another tube shortly before implantation and / or during the surgical procedure in which the device is implanted to select a delivery protocol; The device is configured such that if a higher release rate is desired, a tube having a cross-section and / or length that will achieve the desired release rate is selected and attached to another tube, so that the desired result is achieved after implantation. The tubes are color-coded; The lumen length of tube 2 is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mm or any value or range of values ​​in increments of 0.1 mm. The lumen length of tube 1 is 50, 60, 70, 80, 90, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129 or 130 mm or any value or range of values ​​in increments of 0.1 mm. The cross-sectional areas of the lumen of pipe 1 are 0.15, 0.14, 0.13, 0.12, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.0009, 0.0008, 0.0007, 0.006, 0.0005, 0.0004, 0.0003, 0.0002, and 0.0001 mm. 2 Or within a range of 0.00001mm 2 Any value or range of values ​​that is an increment; The cross-sectional areas of the lumen of pipe 2 are 0.15, 0.14, 0.13, 0.12, 0.11, 0.10, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.0009, 0.0008, 0.0007, 0.006, 0.0005, 0.0004, 0.0003, 0.0002, and 0.0001 mm. 2 Or within a range of 0.00001mm 2 Any value or range of values ​​that is an increment; The lumen of the second tube can have a diameter of mm. 2 The value or range of any of the above values ​​or any values ​​between them are for the unit cross-sectional area (located in a plane perpendicular to the longitudinal axis of the lumen / direction of the lumen), and these can be used for the entire length of the second lumen or for the average (mean, median and / or mode) over the entire length and / or for any value or range of values ​​less than, greater than and / or equal to 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% or in increments of 1%, and can be any value or range of values ​​between them (percentage difference). The device does not wash away drugs or therapeutic substances; The principle of drug delivery by the device is not elution; The principle of drug delivery is that the device allows the substance to diffuse through a barrier or diffuse without a barrier (in some embodiments, the opening corresponds to the diameter of the lumen of the second tube). The outlet of the device is open; The outlet of the device includes a filter; The exit is protected; The barrier has pores that allow direct fluid connection between the liquid (drug solution) inside the therapeutic substance delivery system and the external liquid (e.g., perilymph). The device allows therapeutic substance molecules to diffuse freely from the inside of the device through the barrier to the outside, following a concentration gradient. The device is configured such that the therapeutic substance molecules do not need to be dissolved, absorbed, or adsorbed into a third matrix (the therapeutic substance solvent inside the device is considered the first matrix and the perilymph (or other body fluids) is considered the second matrix). The barrier (if present) can be used to prevent pathogens such as viruses, bacteria, protozoa, prions, viroids and / or fungi from leaving and entering the device; The device includes a bacterial filter with a pore size of 0.22 micrometers or smaller; The barrier also provides a mechanical mechanism to increase the flow resistance between the lumen inside the device and the external environment; The barrier contains the therapeutic substance solution inside the device after initial arousal (filling) during manipulation and implantation of the implant; In the implanted state, the barrier increases the degree to which pressure changes inside or outside the device, such as those caused by body movement or impact, or prevent large amounts of fluid from leaving or entering the delivery system when only the device is manipulated during implantation; The device is configured such that in the therapeutic substance used to fill or fill the reservoir, a range of any value or value not exceeding 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.25%, or 0.1%, or in increments of 0.1%, of the therapeutic substance diffuses and / or elutes through the tube and / or silicone body. The device is configured such that, upon leaving the reservoir and entering the body, at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, or any value or range of values ​​in increments of 0.1%, of the therapeutic substance is the result of diffusion (including diffusion through different barriers) within any one or more time ranges (or all) detailed herein. The therapeutic substance is water-based, and the device is configured such that the therapeutic substance diffuses out while water is retained in the delivery system, and salts diffuse into the reservoir to resolve the concentration gradient. The device is configured to prevent clean water from entering the device (osmosis). The device includes a treatment solution that utilizes isotonicity to match the molar osmotic pressure concentration of perilymph, thereby preventing osmosis. There is no membrane passing through the opening, wherein the therapeutic substance or other active ingredient actually comes out of the water and then enters the membrane and then returns to the water in the cochlea; When the therapeutic substance is filled, the therapeutic substance does not leave the water located in the reservoir; The diffusion refers to the diffusion of the therapeutic substance, which differs from the operating principle of the membrane. In this embodiment, there is no semi-permeable membrane used in or surrounding the reservoir; The device includes a 100-micrometer-thick membrane that does not affect the release rate, or reduces the rate from the rate present when the membrane is not present to a value or range of values ​​of up to 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%, or in increments of 0.1%. The device is completely hydrogel-free. In an embodiment, at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% (by mass and / or by volume) of all therapeutic substances delivered to a person by the device are delivered to the person without the use of hydrogel; The device includes sound pressure wave mitigation and / or prevention; The device is configured to prevent acoustic energy traveling through the skin and impacting the tube and / or acoustic energy that generates the movement of the perilymph or other fluid motion waves within the cochlea from generating pressure waves within the reservoir of the therapeutic substance delivery device. The device is configured such that, at implantation, the total water volume of the therapeutic substance delivery system is within a range of 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4.5%, 4%, 3.5%, 3%, 2.5%, 2%, 1.5%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, or 0.5% of the water volume value at which 80%, 85%, 90%, or 95% of the therapeutic substance has diffused from the system into the body, or any value in increments of 0.05%. The device is configured such that upon initial entry into the cochlea / exit and contact with the perilymph or related bodily fluids, the following sequence of numbers appears: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 550, 600, 700, 800, 900, 1000, 1250, 1500, 1750, 2000, 2250, 2500. Within 3000, 3500, 4000, 4500, or 5000 hours, when the outlet (whether or not it has a barrier, and if there are more outlets, starting from the first and / or last outlet) comes into contact with the body fluid, at least and / or no more than 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, or 95%, or any value or range of values ​​in increments of 1%, of the therapeutic substance in the reservoir is retained in the reservoir due to the diffusion of the therapeutic substance through different barriers into the cochlea or associated body cavity or body space; The barrier reduces the flow rate by up to 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%, or any value or range of values ​​in increments of 0.1%, relative to the flow rate that would exist without the barrier. The barrier is an invisible barrier; The device is configured such that the fluid is held therein by capillary force / action; The device is configured such that the effective cross-sectional area of ​​the barrier is at most 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1% of the cross-sectional area of ​​the second lumen, or any value or range of values ​​in increments of 0.1%. The therapeutic substance delivery system is a valveless system and / or an unlimited flow system (other than the (multiple) physical barriers that are considered flow limiters). The device includes a lead assembly, and no portion of the lead assembly is impregnated with a therapeutic substance and / or no portion of the implantable portion is impregnated with a therapeutic substance, which in at least some exemplary embodiments may be in addition to a barrier (if present) or at least a portion of the barrier; In an embodiment, the silicone of the lead assembly and / or any tube, or the material of the tube, is not porous and / or not gas-filled; The device includes a catheter assembly, the catheter assembly including a first catheter segment having a first cross-sectional area perpendicular to the extension direction of the first catheter segment (or perpendicular to the direction of molecular movement during delivery to the recipient), the first cross-sectional area being larger than a second cross-sectional area of ​​a second catheter segment perpendicular to the extension direction of the second catheter segment (or perpendicular to the direction of molecular movement during delivery to the recipient). The cross-sectional area of ​​the second catheter segment is such that the release rate of the therapeutic substance from the device on and / or after day Y ("on" is a Y-day marker (e.g., 7 days - the 7-day marker requirement must be met), and "after" is the Y-day and later (e.g., 7, 8, 9, 10, 11, 12 days, etc. - the Y-day or later requirement must be met, whether day 7 or day 10 is included)) is less than X times the release rate that would exist if the first cross-sectional area were the same as the second cross-sectional area, all other conditions being equal. %, where Y is any value or range of values ​​of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100, or any value in increments of 1 therebetween, and X is 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23. 22, 21, 20, 19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25, 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1, or any value or range of values ​​in increments of 0.01; The device is configured such that if the lengths of the first catheter segment and the second catheter segment are constant (consistent with the above teachings, they can be different), and the cross-sectional area of ​​the first catheter segment is constant, and the type of therapeutic substance in the reservoir is the same, and there is no pressure gradient or pressure change relative to the comparison case, and no temperature change, etc., then the above-mentioned release rate will be obtained for a different second cross-sectional area relative to the case where the second cross-sectional area is the same as the first cross-sectional area; The device is configured such that the first catheter segment has a first cross-sectional area perpendicular to the direction of extension (molecular movement), the first cross-sectional area being at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100, or any value in increments of 1 for the second cross-sectional area of ​​the second catheter segment. The range is larger than a factor of 1, and the first catheter segment has a first length greater than the second length of the second catheter segment, wherein the length of the second catheter segment is such that the release rate of the therapeutic substance from the device after Y days of release into the human body is less than a factor of 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 of the first length or any value or range of values ​​in increments of 1 thereof, 90, 85, 80, 75 of the release rate under all other conditions being equal. 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19.5, 19, 18.5, 18, 17.5, 17, 16.5, 16, 15.5, 15, 14.5, 14, 13.5, 13, 12.5, 12, 11.5, 11, 10.5, 10, 9.75, 9.5, 9.25 9.0, 8.75, 8.5, 8.25, 8.0, 7.75, 7.5, 7.25, 7.0, 6.75, 6.5, 6.25, 6.0, 5.75, 5.5, 5.25, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1 or 3.0 or any value or range of values ​​in increments of 0.01; The reservoir has an internal volume that is at least an order of magnitude larger than the internal volume of the delivery tube; The delivery tube device has a first section having a first cross-sectional area perpendicular to the extending direction of the first section, the first cross-sectional area being larger than a second cross-sectional area of ​​a second section of the delivery tube device, the second cross-sectional area being perpendicular to the extending direction of the second section. In an embodiment, the first cross-sectional area is such that the release rate of the therapeutic substance from the device after Y days of release into the human body is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.5, 4, 4.5, or 5 times, or more, the release rate of the same first and second cross-sectional areas under the same conditions. Any value or range of values ​​in increments of 0.01, and / or a release rate not exceeding 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.5, 4, 4.5, 5, 5.5, or 6 times, or any value or range of values ​​in increments of 0.01, assuming the first cross-sectional area is the same as the second cross-sectional area and all other conditions are the same. The first cross-sectional area allows the release rate of the therapeutic substance from the device after Y days of release into the human body to be 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%, or 30%, or any value or range thereof in increments of 0.1%, where the first cross-sectional area is the same as the second cross-sectional area and all other conditions are the same. The delivery tube device has a first section having a first length greater than a second length of a second section of the delivery tube device, and the first section having a first cross-sectional area perpendicular to the extending direction of the first section, the first cross-sectional area being at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100, or any value or range of values ​​in increments of 1. The length of the first segment is at least four times the length of the second segment, and the length of the first segment is such that the release rate of the therapeutic substance from the device seven days after release into the human body is within a range of 20%, 19%, 18%, 17%, 16%, 15%, 14%, 12%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the length of the first segment (which is the length of the second segment) or any value or value in increments of 1, all other things being equal. The delivery tube device has a first section, the first section having a first length that is greater than the second length of the second section of the delivery tube device; The first section has a first cross-sectional area perpendicular to the extending direction of the first section, and the first cross-sectional area is larger than the second cross-sectional area of ​​the second section of the delivery tube device perpendicular to the extending direction of the second section; The second cross-sectional area is such that, if the release rate of the therapeutic substance is less than X% of the first cross-sectional area and the second cross-sectional area at or after 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours after the therapeutic substance is released from the device into the human body, and / or thereafter, the release rate will be the same. The second cross-sectional area is such that, 12 hours after the therapeutic substance is released from the device into the human body and / or thereafter, the release rate of the therapeutic substance is within X% of the release rate present when the second cross-sectional area is at least one of 1 / 5, 1 / 6, 1 / 7, 1 / 8, 1 / 9, 1 / 10, 1 / 11, 1 / 12, 1 / 13, 1 / 14, 1 / 15, 1 / 16, 1 / 17, 1 / 18, 1 / 19 or 1 / 20, or 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 times larger. The outlet(s) can be positioned radially along the second pipe; The size and dimensions of the outlet are set to take into account the variation of the concentration gradient along the length of the second tube; or The release rate provided by the outlets is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 outlets spaced axially from each other / providing the same delivery at a given location as at a considerable number of other locations, or at least 50% or 60% or 70% or 80% or 90% of the outlets, or all outlets within any value or range of 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 29%, 28%, 27%, 26%, 25%, 24, 23%, 22, 21%, 20%, 19%, 18, 17%, 16%, 15, 14%, 13%, 12%, 11%, 10%, 8%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1%, or in increments of 0.1%.

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