WO2014160398A1

WO2014160398A1 - Trans-tympanic antioxidant delivery system

Info

Publication number: WO2014160398A1
Application number: PCT/US2014/026493
Authority: WO
Inventors: Jeremy Heiser; Sai Bhavaraju; Ashok V. Joshi; Jessica ELWELL
Original assignee: Microlin, Llc.
Priority date: 2013-03-13
Filing date: 2014-03-13
Publication date: 2014-10-02

Abstract

A trans-tympanic antioxidant delivery apparatus. Generally, the apparatus includes a source of antioxidant. A delivery mechanism in fluid communication with the source is configured to deliver the antioxidant to a patient's ear canal. A regulator for regulating at least one of an antioxidant delivery pressure, an antioxidant delivery rate, an antioxidant delivery duration, an antioxidant delivery temperature, and an antioxidant delivery concentration. The apparatus includes a monitor for monitoring at least one of a blood-oxygen saturation level, a concentration of exhaled gas, an oxygen consumption, a blood pressure, a pulse, and a patient's cognitive interaction. A controller is in operable communication with at least one of the delivery mechanism, the regulator and the monitor and controls at least one of a delivery pressure, a delivery rate, a delivery duration, a delivery temperature, and a delivery concentration.

Description

TRANS-TYMPANIC ANTIOXIDANT DELIVERY SYSTEM

RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent No. 61/778,899 filed on March 13, 2013. This application is hereby incorporated by reference.

FIELD OF THE INVENTION

[0002] The present invention relates in general to a method and apparatus for delivery antioxidants to a patient. More specifically, the present invention relates the delivery of antioxidants to a patient through the tympanic membrane of the patient's ear.

BACKGROUND OF THE INVENTION

[0003] Oxidative stress has been demonstrated to be a primary factor in the pathology of a multitude of auditory disorders, sensorimotor disorders and dysfunctions, and the cause of hearing loss and cell death in the auditory system. Antioxidants have been demonstrated to reduce oxidative stress and associated oxidative damage to inner ear cells following a noise induced damage. A major obstacle in treating auditory disorders is the ability to deliver a therapeutic level of antioxidants to the affected area. Antioxidant agents can be delivered to the structures of the auditory system following ingestion and/or inhalation. The problem with these delivery paths however, is that they suffer from systemic dilution and removal that reduces the therapeutic concentration. Limitations to the current inhalation and ingestion delivery methods have also restricted the use of antioxidants in a clinical setting. Thus, what is needed is an apparatus and method for delivering one or more antioxidant agents to the ear canal in a way that focuses the delivery of the antioxidant molecules to the affected area with reduced systemic dilution and removal.

BRIEF SUMMARY OF THE INVENTION

[0004] A trans-tympanic antioxidant delivery apparatus includes a source of antioxidant and a delivery mechanism in fluid communication with the source. The delivery mechanism may be configured to deliver the antioxidant to a patient's ear canal. The apparatus includes a regulator for regulating at least one of an antioxidant delivery pressure, an antioxidant delivery rate, an antioxidant delivery duration, an antioxidant delivery temperature, and an antioxidant delivery concentration. The regulator may include a sensor measuring at least one of an antioxidant delivery pressure, an antioxidant delivery rate, an antioxidant delivery duration, an antioxidant delivery temperature, and an antioxidant delivery concentration. In one embodiment, the sensor is a separate component.

[0005] A monitor monitors at least one of a blood-oxygen saturation level, a concentration of exhaled gas, an oxygen consumption, a blood pressure, a pulse, and a patient's cognitive interaction. The apparatus also includes a programmable logic controller in operable communication with at least one of the delivery mechanism, the regulator, the sensor and the monitor. The programmable logic controller is configured to control at least one of a delivery pressure, a delivery rate, a delivery duration, a delivery temperature, and a delivery concentration.

[0006] In one embodiment, the trans-tympanic antioxidant delivery apparatus includes a user interface in operable communication with the programmable logic controller. The user interface can receive input from a user. The programmable logic controller is further configured to operate in response to at least one input from the user.

[0007] A method of trans-tympanic antioxidant delivery is also disclosed. The first step in the method is providing a source for at least one antioxidant. One or more antioxidants are delivered into a patient's ear canal. At least one of a delivery pressure, a delivery rate, a delivery duration, a delivery temperature, and a delivery concentration is measured. The method also includes the step of monitoring at least one of a patient's blood-oxygen saturation level, a concentration of exhaled gas, an oxygen consumption, a blood pressure, a pulse, and a patient's cognitive interaction. A programmable logic controller is used to control delivering one or more antioxidant agents to a patient using at least one of an input provided by the measuring step and an input provided by the monitoring step.

[0008] These features and advantages of the present invention will become more fully apparent from the following description and appended claims, or may be learned by the practice of the invention as set forth hereinafter.

BRIEF DESCRIPTION OF THE SEVERAL DRAWINGS

[0009] In order that the manner in which the above-recited and other features and advantages of the invention are obtained and will be readily understood, a more particular description of the invention briefly described above will be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. Understanding that the drawings (and the various portions thereof) are not made to scale, depict only some representative embodiments of the invention, and are not therefore to be considered to be limiting of its scope, the invention will be described and explained with additional specificity and detail through the use of the accompanying drawings in which:

[0010] Figure 1 depicts a schematic diagram of a representative embodiment of a trans- tympanic antioxidant delivery apparatus;

[0011] Figure 2 depicts a schematic diagram of an alternative embodiment of the trans- tympanic antioxidant delivery apparatus of Figure 1;

[0012] Figure 3 depicts a schematic diagram of an alternative embodiment of the trans- tympanic antioxidant delivery apparatus of Figure 1;

[0013] Figure 4 depicts a schematic diagram of an alternative embodiment of the trans- tympanic antioxidant delivery apparatus of Figure 1;

[0014] Figure 5 depicts a schematic diagram of an ear interface component of a trans- tympanic antioxidant delivery apparatus;

[0015] Figure 6 depicts a schematic diagram of an alternative embodiment of the trans- tympanic antioxidant delivery apparatus of Figure 1 with a light source that is housed within the TADS unit, that shines light on the antioxidant agent conduit within the TADS;

[0016] Figure 7 depicts a schematic diagram of an alternative embodiment of the trans- tympanic antioxidant delivery apparatus of Figure 6;

[0017] Figure 8 depicts a schematic diagram of a trans-tympanic antioxidant delivery apparatus with an integrated delivery system and multipurpose patient interface;

[0018] Figure 9a depicts a front cutaway view of a patient with a patient interface; and

[0019] Figure 9b depicts a side cutaway view of a patient with a patient interface.

DETAILED DESCRIPTION OF THE INVENTION

[0020] Reference throughout this specification to "one embodiment," "an embodiment," or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases "in one embodiment," "in an embodiment," "another embodiment," and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment. Additionally, while the following description refers to several embodiments, implementations, and examples of the various components and aspects of the described invention, all of the described embodiments, implementations, and examples are to be considered, in all respects, as illustrative only and not as being limiting in any manner.

[0021] Furthermore, the described features, structures, or characteristics of the invention may be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided, such as examples of suitable anode electrodes, cathode electrodes, alkali metal intercalation materials, alkali ion conductive electrolyte membranes, etc., to provide a thorough understanding of embodiments of the invention. One having ordinary skill in the relevant art will recognize, however, that the invention may be practiced without one or more of the specific details, or with other methods, components, materials, and so forth. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of the invention.

[0022] Referring now to Figure 1, a trans-tympanic antioxidant delivery apparatus (TADS) for the controlled delivery of antioxidant agent into a patient's 8 ear canal is shown. The TADS includes an antioxidant source 1 which may comprise an antioxidant canister or antioxidant generation component that is capable of producing and/or storing antioxidant substances and/or antioxidant gas. The antioxidant source 1 may be a canister that is precharged with antioxidant or that is capable of being charged before, during or after use. The antioxidant source 1 may be stored at an elevated pressure and/or is capable of elevating the pressure within the canister for use during delivery. The antioxidant source 1 may include without limitation, an electrochemical generator, chemical generator, pre- filled chamber, pre- filled cylinder, re-fillable chamber, re- tillable cylinder, and the like. The antioxidant source may be pressurized and/or have the means to transfer the hydrogen agent to the antioxidant conduit. The antioxidant source may be permanently integrated into the system, temporarily affixed to the system, removable, interchangeable, have filling features, have evacuation features, and/or a combination of.

[0023] The antioxidant source 1 may be attached to a flexible conduit which may be part of a delivery mechanism such that when assembled, will create a sealed path for transferring the antioxidant gas from the antioxidant source 1, through regulators 3 or regulation components 3, and to the ear interface connection 10. Antioxidants may include without limitation, hydrogen, nitric oxide, carbon monoxide, hydrogen sulfide, hydrazine, flavonoids such as naringenin, tocopherol natural extracts such as rosemary extract whose volatile constituents (e,g, 1,8-Cineole) and the like. In one embodiment, the antioxidant used in the TADS may consist of gas form. In other embodiments, the antioxidant may be in the form of a liquid, suspension, oil, and/or extract.

[0024] The antioxidant conduit 2 may comprise a rigid, semi-rigid, or flexible tubing, conduit, or channel that serves as a means to contain and transport the antioxidant from the antioxidant source 1 through one or more regulators 3 and/or monitors 4 or system monitoring components 4, and into an ear interface component 9. The ear interface component 9 may include a pressure equalization tube (not shown). The pressure equalization tube may be a tympanostomy tube or a myringotomy tube or other component known to those of skill in the art to equalize pressure across the tympanic membrane of the ear.

[0025] The regulator 3 may include one or more regulation components that function to control certain aspects of the antioxidant delivery. The regulated aspects of antioxidant delivery may include a flow rate, a pressure, a volume, a duration, a humidity level, a temperature, a concentration and the like. The regulators 3 may receive information from and provide information to a controller 5 or other control system 5 as part of their regulating function. The regulators may be in operable communication with the antioxidant source 1 or conduit 2. The regulators 3 may include without limitation, pressure regulators, pressure release features, agent mixing regulators, agent concentration regulators, directional flow regulators, volume regulators, temperature regulators, and combination of these. In one embodiment the regulator includes a sensor. In another embodiment, the sensor (not shown) is separate from the regulator. The sensor senses at least one of an antioxidant delivery pressure, an antioxidant delivery rate, an antioxidant delivery duration, an antioxidant delivery temperature, and an antioxidant delivery concentration.

[0026] The TADS may include a monitor 4 or system monitoring components 4 to monitor or otherwise measure or gauge the function of various components of the TADS 4. The monitor 4 may include sensors or gauges and facilitate monitoring. Things that may be monitored by the monitor 4 include a pressure, a flow rate, a volume, a concentration, a duration, a temperatures, a humidity level, and the like. The monitors 4 may provide or receive an input to the controller 5. The regulators 3 and monitors 4 may combine create safety features to monitor the performance of the system and a patient's 8 vital signs. The monitors 4 may be in operable communication with the antioxidant source 1 or conduit 2.

[0027] The controller 5 may be a computerized control component such as a programmable logic controller 5. The controller 5 may function to perform one or more of the following: system activation and deactivation; to receive treatment specific information from a user; to maintains and execute a system treatment protocol; to receive input from or provide input to a regulator 3; to receive input from or provide input to a monitor 4; to perform safety response functions, using system and patient monitoring inputs; to record a treatment history and the like.

[0028] The TADS may include a user interface 6 to provide a means for the user to: enter patient specific information, treatment specific information, select from pre-programed treatment regimens, set safety related levels, preview treatment history, control a regulator, control a monitor, and the like. The user interface 6 also allows a user to program a therapeutic regiment or select from predefined regiment settings. It may also allow a user to activate and deactivate the system.

[0029] The TADS may also include a user feedback 7 to provide a means for the user to: obtain feedback related to the program, obtain a treatment status, obtain a treatment history, obtain a monitor output, obtain a regulator output, become aware of an adverse event and the like. The user feedback 7 may include any feedback systems known in the art including a light, a sound, a display, and the like.

[0030] In one embodiment the TADS includes an ear interface component - is in communication with the antioxidant conduit 2 and provides access to and is in communication with the patient's 8 ear canal. An ear interface connection 10 creates a sealed path for transferring the antioxidant gas and/or antioxidant agent through the antioxidant conduit 2 to the ear interface connection 10.

[0031] The TADS may also include an exhalation mask 11 to allow the patient 8 to breathe ambient air. The exhalation mask 11 directs the patient's 8 exhalation to the exhalation monitoring component 28. The exhalation mask 11 may be coupled to an exhalation mask connection 12 to create a sealed path for transferring the patient's 8 exhalation from the exhalation mask 11 to an exhalation monitoring component 28.

[0032] A patient monitoring component 14 may measure one or more of the patient's 8 vital signs and relay the information to the controller 5. The patent monitoring component may for example monitor a blood oxygen saturation level, a pulse, and/or a temperature. The patient monitoring component 14 may be coupled to a patient monitoring connection 15 to provide a means to connect one or more patient monitoring components 14 to the control system 5. The patient monitoring component 14 may be attachable to a patient's 8 limb. The TADS of these and other embodiments described below may include a power source (not shown) for powering the system and its various components such as one or more monitors or regulators, to the extent they need power, the controller 5, and other components such as a light source 39, 41 discussed in connection with Figures 6 and 7 below.

[0033] Referring now to Figure 2, an embodiment of a TADS capable of delivering one or more therapeutic agents is shown. The TADS may include therapeutic agent sources 16. The therapeutic agent source 16 may be a therapeutic agent generation component or therapeutic agent canister. The therapeutic agent source 16 may be capable of producing and/or storing one or more therapeutic agents. The additional therapeutic agent source 16 may be stored at an elevated pressure and/or capable of elevating the pressure within the canister for use during delivery. An agent conduit 17 will create a sealed path for transferring the respective agent from the additional therapeutic agent source 16, through one or more regulators 3 and monitors 4, and to the ear interface component 9. An agent conduit 17 may be rigid, semirigid, or flexible tubing or channel that serves as a means to contain and transport one or more agents from the agent source 16, through one or more regulation 3 and/or system monitoring 4 components, and into an ear interface component the same or similar to the ear interface component 9 of Figure 1.

[0034] The TADS may also include a multi-agent conduit 18 that also may be rigid, semirigid, or flexible tubing or channel that serves as a means to contain one or more agents, transport one or more agents from a respective agent conduit 17 to the ear interface component 9 and/or a multi-lumen ear interface component 20, and/or mix-multiple agents for simultaneous delivery. A multi-lumen ear interface component 20 may consist of multiple lumens and/or tubes for the purpose of delivering therapeutic agents from the antioxidant conduit 2 and/or agent conduit 17 to the patient's 8 ear canal. The multi-lumen ear interface component 20 has the capability of delivering therapeutic agents individually, simultaneously, and/or a combination of in a staged sequence. The multi-lumen ear interface component 20 may also be used to transfer a light source (Figure 6) 40 into the ear canal. The multi-lumen ear interface component 20 may also be used to as part of the oxygen conduit (Figure 3) 22, exhalation conduit (Figure 3) 27, and/or evacuation conduit 34 (Figure 4)·

[0035] Returning again to Figure 2, a flow control component 19 may be a regulator 3 or other an element that functions to control the direction of flow and/or integration of one or more therapeutic agents as they are transferred from the antioxidant conduit 2, agent conduit 17, multi-agent conduit 18 or a combination of these. It will be appreciated by those of skill in the art that other regulators 3 and monitors 4 may be used to regulate and monitor the flow of therapeutic agents to a patient 8.

[0036] Therapeutic agents may include, but are not limited to metal cleating agents, efflux agents, absorption enhancers, humidified gas, pain relievers, medicines and/or tympanic membrane manipulation agents, enhancement agents, anti-swelling agents, and the like. The therapeutic agent may use the hydrogen as means to enhance its ability to cross the tympanic membrane and gain access to the structures or the auditory system. The additional therapeutic agent source may consist of but is not limited to: generated via an electrochemical reaction, generated via a chemical reaction, pre- filled chamber, pre- filled cylinder, re-fillable chamber, re-fillable cylinder, and/or a combination of. The additional therapeutic source may be pressurized and/or have the means to transfer the agent(s) to the agent conduit. The additional therapeutic agent source may be permanently integrated into the system, temporarily affixed to the system, removable, interchangeable, have filling features, have evacuation features, and/or a combination of one or more.

[0037] Turning now to Figure 3, a TADS capable of delivering pulmonary agents such as supplemental oxygen to the oral and/or nasal cavity is illustrated. The TADS may include a pulmonary agent 21 or supplemental oxygen source 21 (hereinafter together a supplemental oxygen source 21), which in one embodiment is an oxygen generation component. In other embodiments the supplemental oxygen source 21 may include an oxygen canister that is capable of producing and/or storing supplemental oxygen. The supplemental oxygen source 21 may be stored at an elevated pressure and may also be capable of elevating the pressure within the canister for use during delivery. The supplemental oxygen source 21 may be coupled with an pulmonary agent conduit 21 or oxygen conduit 22 (hereinafter together an oxygen conduit 22) to create a sealed path for transferring the oxygen from the oxygen source 21 to a patient 8. The oxygen may be delivered to the patient through an ear interface component similar to the ear interface component of Figure 1. The TADS may include and oxygen regulator 23 and an oxygen monitor 24, both in communication with the oxygen conduit. The oxygen may flow to a pulmonary interface component 25 for delivery oxygen to the patient 8.

[0038] The oxygen conduit 22, like other conduits in the TADS, may be rigid, semi-rigid, or flexible tubing or other channels that serve as a means to contain and transport supplemental oxygen from the oxygen source 21, through one or more regulation 23 and/or system monitoring 24 components, and into the pulmonary interface component 25. An oxygen regulator 23 is in operable communication with the oxygen conduit 22 and functions to control the aspects of supplemental oxygen delivery, measure aspects of the delivery, and provide input to the control system 5. Regulated and monitored aspects of delivery may include concentration, flow rate, pressure, volume, duration, and temperature.

[0039] An oxygen monitor 24 or monitoring components 24 may measuring aspects of the oxygen delivery and provide input to the control system - measuring and/or gauge components 24 that functions to measure aspects of the oxygen delivery (examples being: concentration, pressure, flow rate, volume, temperature) and/or provide input to the control system 5. [0040] A pulmonary interface component 25 may allow the patient 8 to breathe supplemental oxygen and directs the patient's 8 exhalation to an exhalation monitoring component 28. The pulmonary interface component 25 may include a means to control the direction of flow for the supplemental oxygen and/or exhalation. The pulmonary interface component 25 may interface with the oral cavity, the nasal cavity, or a combination thereof. An oxygen supply interface 26 may include one or more lumens, tubes, and/or channels that serve as a means to contain and transport supplemental oxygen from the oxygen conduit 22, to the patient's 8 oral cavity and/or nasal cavity.

[0041] Where oxygen is described throughout, other pulmonary agents known to those of skill in the art may be substituted therefor.

[0042] The TADS may also include an exhalation conduit 27 that includes one or more lumens, tubes, and/or channels and that serves as a means to contain and transport the patient's 8 exhalation from the patient 8 to an exhalation monitoring component 28. The exhalation conduit 27 may contain a volumetric component (example being an inflatable bag) as necessary to perform exhalation gas measurements. The exhalation monitoring component 28 may measure aspects of the patient's 8 exhalation, for example a concentration, a pressure, a flow rate, a volume, and the like. The exhalation monitoring component 28 may provide input to the control system 5. A pulmonary interface connection 29 facilitates a sealed path for transferring oxygen to the patient's 8 oral or nasal cavity and a sealed path for transferring exhalation from the pulmonary interface component 25 to the exhalation monitoring component 28.

[0043] Thus, the TADS comprises a delivery mechanism in fluid communication with the source of antioxidant, the source of oxygen or supplemental oxygen, or the source of therapeutic agent. The delivery mechanism is configured to deliver the antioxidant and other products to a patient's ear canal. The delivery mechanism may include at least the antioxidant conduit 2, the agent conduit 17, the multi agent conduit 18, and the oxygen conduit 22. The delivery mechanism is also comprised of interfaces and interface connections such as the ear interface component 9, the ear interface connectionlO, the multilumen ear interface component 20 the pulmonary interface component 25 and the oxygen supply interface 26. The delivery mechanism also includes all regulators 3 and monitors 4, including without limitation the flow control component 19, the oxygen regulator 23 and the oxygen monitoring component 24. The delivery mechanism may include heaters, pressure equalization tubes and light sources 38, 39, 41 (see Figures 5, 6, and 7 respectively). In short, the delivery mechanism may include all components of the TADS between a source such as the antioxidant source 1, the therapeutic agent source 16 or the supplemental oxygen source 21 and the patient 8.

[0044] The connection 10, 12, 15, 29 and other connections between conduits, regulators, monitors and system components may be permanent, temporary, or a combination of. The connection method may consist of, but is not limited to: threaded, luer, quick-disconnect, snap, barb, adhesive, solvent, weld, and/or a combination of.

[0045] The antioxidant, therapeutic agents or pulmonary agents such as oxygen may be delivered to the right ear only, left ear only, and/or both ears independently, simultaneously, in a staged independent sequence, in a staged simultaneous sequence, in combinations of the foregoing, and the like.

[0046] Turning now to Figure 4, the TADS is capable of delivering one or more therapeutic agents to the ear canal, as well as removing one or more substances and/or agents from the ear canal. The TADS may include a canal evacuation outlet 30 that functions in part as a controlled exit port for the evacuation of gases following their removal from the patient's 8 ear canal. The canal evacuation outlet 30 may incorporate a filtering mechanism and/or valve system to control the direction of gas exchange.

[0047] The TADS includes a canal evacuation canister 31 in operable communication with the canal evacuation outlet 30. The canal evacuation canister 31 is configured to contain one or more substances and/or agents following their removal from the patient's ear canal. The canal evacuation canister 31 may incorporate one or more filtering mechanisms and/or agent neutralization elements. An evacuation regulator - one or more regulation and/or gauge components 32 that function to control the aspects of the removal of one or more substances and/or agents from the ear canal (examples being: concentration, flow rate, pressure, volume, duration), measure aspects of the evacuation, provide input to the control system 5, and/or provide safety related functions. The TADS may use evacuation monitoring components 33 to measure aspects of the evacuation process, including a pressure, a flow rate, a volume, a tube occlusion level, and the like. The monitoring component or monitor 33 may provide input to the control system 5.

[0048] An evacuation conduit 34 may include one or more lumens, tubes, and/or channels that serve as a means to contain and transport the patient's 8 evacuation substances and/or gasses from the delivery/evacuation ear interface component 36 to the canal evacuation canister 31 and/or canal evacuation outlet 30. The evacuation conduit 34 may contain safety release valve features to protect the patient from excessive negative pressure. An evacuation flow control component 35 may be in communication with the evacuation conduit 34 or canister 31 to control the direction of flow and/or integration of one or more evacuation elements. The evacuation conduit 34 may be attached to an evacuation ear interface component 36, which may be a tube consisting of one or more lumens that allows for the evacuation of one or more substances and/or agents to and from the patient's 8 ear canal. In one embodiment, the delivery of antioxidant, therapeutic agents, oxygen and/or enhancement agents may be through the same conduit 2, 17, 18, 22 as each other and or as the evacuation conduit 34. Thus the delivery and evacuation functions of the TADS may occur independent of each other, simultaneously, and/or a combination of each other. In one embodiment, these functions occur in a staged sequence. A delivery and/or evacuation interface connection 37 may be positioned between the evacuation conduit and the delivery/evacuation ear interface to create a sealed path for transferring therapeutic agents, enhancement agents, humidified gas, oxygen and/or antioxidant to and/or removing one or more substances and/or gasses from the patient's 8 ear canal.

[0049] Turning now to Figure 5, an ear interface component 9 is shown that incorporates a canal light source 38 that shines light within the ear canal. The canal light source 38 may be integrated in the ear interface component 9 and positioned to provide heat to the patient's 8 ear canal.

[0050] With reference now to Figure 6, the TADS may include a system or internal light source 39 that is housed within the TADS unit, that shines light on one or more of the antioxidant, therapeutic agent or oxygen conduits 2, 17 (Figure 2) 18 (Figure 2) 22 (Figure 3) within the TADS. In one embodiment the TADS contains an exposure window 40 to allow the light from the internal light source 39 to interact with one or more of the antioxidant, agents and oxygen. The exposure window 40 may be a section of a conduit 2, 17, 18, 22 that is transparent and/or semi-transparent. The light exposed antioxidant, agents and/or oxygen may then enter the ear of the patient 8 through an ear interface component such as ear interface component 9 (see Figure 1).

[0051] Referring now to Figure 7, another embodiment of the TADS is illustrated. The TADS may include a light source 41 within the TADS that can transmit light to the patient's ear canal. In one embodiment the transmittable light source 41 is in communication with a light tube 42 that allows for the transmission of the light along the ear interface component and shine into the patient's 8 ear canal. The light tube 42 may be housed in a multi-lumen ear interface component 20, such that the light interacts with one or more of an antioxidant, oxygen, or other therapeutic agent as they pass through the tube to the patient's 8 ear canal by way of an ear interface component such as ear interface component 9 (see Figure 1). [0052] It will be appreciated by those of skill in the art that the light sources 38, 39, 41 provide light with can activate the antioxidant molecules (or oxygen or therapeutic agents) to increase their oxygen free radical capturing potential and/or improve their ability to penetrate the nasal cavity and enter the brain. The light can also elevate the internal temperature of the ear canal and/or tympanic membrane to help promote the uptake of the antioxidant molecules, oxygen or therapeutic agents. The light sources 38, 39, 41, may consist of, but are not limited to: incandescent lamp, electroluminescent lamp, light-emitting diode, light- emitting electrochemical cell, halogen lamps, gas discharge lamps, fluorescent lamps, plasma lamps, ultraviolet, and filament based bulbs.

[0053] Figure 8 illustrates an embodiment of a TADS with an integrated delivery system 44 and multipurpose patient interface 43. In this embodiment, the components and features of the TADS embodiments described in connection with Figures 1-7 are integrated into a headset or other mobile device such as an arm band and the like. The integrated delivery system 44 may have an on board power source (not shown) such as a battery that allows the TADS to function without being connected to fixed power source. The integrated delivery system 44 is operably connected to a multipurpose patient interface 43. The multipurpose patient interface 43 may include features such as with headphones, ear buds, noise canceling headphones, earmuffs, headband, ear covers, hat, and/or a headphone-like system that creates a sealed or partially sealed environment on or around the pinna of the ear. These features may also be included in the ear interface components 9, 36 discussed in connection with Figures 1 - 5 above. In one embodiment the ear interface components 9 and 36 are the same and are the same as those shown in each embodiment illustrated in Figures 1-10. The ear interface components 9, 36 and multi- purpose interface 43 described herein (hereinafter ear interface components), and which can be used in some or all of the embodiments illustrated and described herein, may function to deliver one or more antioxidant agents and/or additional therapeutic agents to the patient such that the delivery is independent, simultaneous, a staged independent sequence, a staged simultaneous sequence, and/or a combination of. Such ear interface components may mix one or more antioxidant agents, therapeutic agents and/or metal cleating agents, efflux agents, absorption enhancers, humidified gas, and/or tympanic membrane manipulation agents. These ear interface component may consist of a single lumen or multi-lumen tube or channel that can be positioned to deliver one or more antioxidants and/or additional therapeutic agents to a single or a variety of locations, including, but not limited to: the opening of the ear canal opening, extend into the ear canal, extend to the tympanic membrane and deliver one or more agents into the nasal cavity, extend into the sinus cavity, and/or a combination of. The ear interface components may have geometry that closes the canal opening from the ambient environment, does not effectively block the ear canal, restricts the ear canal's communication with the external environment, and or a combination of. The ear interface components may have features that engage with the patient's anatomy and/or clothing for the purpose of creating and maintaining orientation and/or positioning during use; including, but not limited to: loops, contours, clip, snaps, Velcro, ties, straps, and/or a combination of. The ear interface components may incorporate a valve feature that allows for the release of pressure within the ear canal. The valve feature would function to protect the ear canal and tympanic membrane from elevated pressures and allow for the evacuation of gas and/or fluid within the ear canal without the removal of the ear interface component. The evacuation process can result from the delivery of gas to the ear canal and/or re-positioning of the ear interface component during use.

[0054] Figures 9a and 9b show a partial cutaway front view and side view respectively of a patient 8. A multipurpose patient interface 43 or ear interface component 9, 36 may gains access to the structures of the auditory system via one or more of the patient's Eustachian tubes. A Eustachian tube access channel 45 is in communication with or part of the interfaces 9, 36, 43 and with a Eustachian tube interface 46. The Eustachian tube interface 46 is configured to fit proximate or within one or more of the patient's 8eustachian tubes. The Eustachian tube interface may have geometry that closes the Eustachian tube opening from the ambient sinus environment, does not effectively block the Eustachian tube, restricts the e Eustachian tube's communication with the sinus environment, and or a combination of. The Eustachian tube interface may have features that engage with the patient's anatomy for the purpose of creating and maintaining orientation and/or positioning during use; including, but not limited to: loops, contours, clip, snaps, suchers, ties, expansion features, and/or a combination of. The Eustachian tube interface component may incorporate a valve feature that allows for the release of pressure within the Eustachian tube and/or middle ear. The valve feature would function to protect the structures of the auditory system from elevated pressures and allow for the evacuation of gas and/or fluid within the Eustachian tube and/or middle ear without the removal of the Eustachian tube interface component. The evacuation process can result from the delivery of gas to the Eustachian tube and/or disengaging the connection during use.

[0055] The trans-tympanic delivery of antioxidant agents has the ability to access the structures of the auditory system. This will allow for the improved use of antioxidant agents in the therapeutic treatment of oxygen stress within the auditory system. In the auditory system, oxidative stress results in oxidative damage.

[0056] Delivering antioxidant agent(s) to the ear canal will allow for the use of the tympanic membrane as a pathway to directly access the structures of the auditory system. Manipulation of the ear canal may be used to enhance the antioxidant delivery and/or absorption into one or more of the targeted structures, allow for extended delivery periods, allow for increased treatment frequency and/or efficacy, and/or allow for the administration of a higher antioxidant concentration; examples include but are not limited to: the use of a light source to activate antioxidant molecules, the use of a heat source to promote facile transfer of the gas into the structures of the auditory system, induced constriction of the Eustachian tube (tube that links the nasopharynx to the middle ear), induced dilation of auditory nerve, agents to increase the uptake of an antioxidant, agents to breakdown wax buildup within the ear canal, and/or surgical intervention.

[0057] The trans-tympanic delivery of one or more antioxidant agents will allow the antioxidant molecules to readily enter the auditory system and function to reduce oxidative stress. While it is uncertain whether oxidative stress is the initiating cause of damage to the auditory system, a growing body of evidence indicates its involvement in the propagation of cellular damage that leads to the neuropathology of host of auditory and sensorimotor disorders; including but not limited to: tinnitus, sensorimotor disorders, and noise, drug, age and trauma induced hearing loss. In tinnitus, oxidative stress has been thought of to be a contributing factor to the degradation of neurological function. It has also been shown that neurodegeneration is not necessarily a cascade of events, but rather a reoccurring cycle of events, of which oxidative stress is a primary factor. The trans-tympanic delivery of antioxidants will serve to reduce oxidative stress; which in turn, will serve to interrupt the destructive cycle and delay, or stop, the progression of the respective disorder.

[0058] Trans-tympanic antioxidant delivery can also be used to protect the structures of the auditory system from oxidative stress that results from a medical procedure. Diagnostic testing, pharmacological treatments, surgical intervention, and radiation/chemo therapy can cause various levels of injury to the structures of the auditory system. The auditory system has a unique series of responses to injury. In addition to acute cell death, medical procedures have been shown to induce an intrinsic recovery/repair response in the auditory system. This response results in secondary reactive processes that generate persistent oxidative stress. The oxidative stress may cause additional damage and result in secondary complications and/or procedural side-effects. The trans-tympanic delivery of one or more antioxidant agents will serve as a means to administer the antioxidative properties of the respective agents to the structures of the auditory system to reduce the oxidative stress that results from a medical procedure; thereby, protecting the auditory system for further damage. This same mode of protection could be used as a treatment modality for a patient following a noise induced damage or other physical trauma.

[0059] The disclosed TADS may also incorporate a feature to further activate the antioxidant molecules to increase their oxygen free radical capturing potential and/or improve their ability to access the structures of the auditory system. Light has been demonstrated to activate antioxidant molecules to increase their oxygen free radical capturing potential and/or enable photolysis and create hydrogen radicals. Hydrogen radicals are very effective in capturing oxygen radicals.

[0060] The versatility of trans-tympanic antioxidant delivery allows the treatment to be used in conjunction with other treatment modalities, therapeutic agents, metal cleating agents, efflux agents, absorption enhancers, tympanic membrane manipulation agents, modifiers of the enzymes involved in reactive oxygen species generation and/or metabolism, agents to breakdown wax buildup within the ear canal and/or on the tympanic membrane, the use of a light source to activate antioxidant molecules, the use of a heat source to promote facile transfer of the gas into the structures of the auditory system, induced constriction of the Eustachian tube, induced dilation of auditory nerve, agents to increase the uptake of an antioxidant, or a combination of.

[0061] The disclosed TADS would be used for the therapeutic treatment of oxidative stress and oxidative damage within the middle ear, inner ear, and/or cochlear nerve. Oxidative stress is a contributing factor to the pathology of a host of auditory and sensorimotor disorders and dysfunctions; including but not limited to: noise induced trauma, age related hearing loss, hearing loss, tinnitus, oxidative damage secondary to a medical procedure and/or pharmacological event. Antioxidants function to reduce the free radicals that cause oxidative stress, including the excess production of reactive oxygen and reactive nitrogen species. The primary obstacle in using antioxidants to treat auditory system disorders is the ability to deliver a therapeutic concentration of the antioxidant to the affected location. The disclosed TADS utilizes the delivery of an antioxidant across the tympanic membrane; thereby, allowing it to come in direct contact with the structures of the inner ear, middle ear, an cochlear nerve. Trans-tympanic delivery may consist of either the passing of agents through the tympanic membrane, the passing of agents through a tympanostomy tube (also known as a grommet, ear tube, pressure equalization tube, PE tube or myringotomy tube), or a combination of. Once the antioxidant passes the tympanic membrane and enters the ear, the antioxidant will serves as a free radical scavenger and function to reduce oxidative stress and associated oxidative damage.

[0062] In one embodiment, the components of the TADS may be interchangeable and disposable. For example, the ear interface may have disposable ear buds. The canisters may be configured to be exchanges for pre-charged canisters when they become empty. The ability to interchange components such as the ear interface component allows for the prolonged repeat use of the core system and flexibility in sizing for optimal patient fit.

[0063] The disclosed TADS consists of single use and/or multi-use components and may incorporate a programmable therapy regiment and/or one or more safety features; example being a control feedback system that maintains the antioxidant delivery within the therapeutic target and/or protects the user from adverse events. The TADS may deliver one or more antioxidants in a continuous or intermittent manner. The TADS may have a feature to further activate the antioxidant molecules to increase their oxygen free radical capturing potential and/or improve their ability to enter the central nervous system. The versatility of disclosed TADS allows for the delivery of a variety of antioxidants.

[0064] In addition, the disclose TADS allows an antioxidant treatment to be used in conjunction with other treatment modalities, therapeutic agents, metal chelating agents, modifiers of the enzymes involved in reactive oxygen species generation and/or metabolism, and/or efflux agents. Additional therapeutic agent sources may be incorporated into the TADS and delivered to the patient's ear canal in a simultaneous, staged and/or cyclical manner. Agents may also be incorporated into the system that modify and/or enhance the ear canal, tympanic membrane, middle ear, inner ear, and/or cochlear nerve's compatibility with therapeutic agent exposure and/or ability to transfer the administered therapeutic agents to the affected area.

[0065] The TADS may incorporate patient monitoring components to measure aspects of the patient vital signs and/or therapy monitoring and provide information to the control system. Patient monitoring component may consist of, but are not limited to: blood oxygen saturation level, pulse, finger oximeter component, pulse oximetry unit, reflectance pulse oximetry unit, arterial blood gas test, cognitive interaction system, free radicals in blood, and/or a combination of. Each patient monitoring component may incorporate one or more patient monitoring connections. The patient monitoring connects will function to provide and/or receive signals from the respective patient monitoring component and allow for communication between the respective monitoring component and the control system. [0066] The TADS may deliver an agent specific dose volume of one or more antioxidant agents and/or one or more additional therapeutic agents, deliver a patient specific dose volume of one or more antioxidant agents and/or one or more additional therapeutic agents, deliver a treatment specific dose volume of one or more antioxidant agents and/or one or more additional therapeutic agents, and/or a combination of. The TADS may incorporate a control system that performs functions that include, but are not limited to: delivery activation, delivery deactivation, receive treatment specific information from the user and/or medical care provider, maintain and execute the system's treatment protocol, receive input from one or more delivery regulation components, receive input from one or more system monitoring components, receive input from one or more patient monitoring components, perform performance analysis operations, perform safety analysis operations, perform performance response functions, perform safety response functions, record treatment history, interface with external computer devices, and/or a combination of. The TADS control system may be used to provide a means for the user to enter patient specific information, treatment specific information, select from pre-programed treatment regimens, set safety related levels, preview treatment history, and or a combination of. The control system may incorporate a computer based system, including but not limited to a programmable logic controller and/or central processing unit. In addition, the TADS control system may function to provide feedback to the user and/or medical care provider; including, but not limited to: program inputs, treatment status, and/or treatment history. The control system feedback may include, but is not limited to: one or more touch screens, display screens, lights, audible sounds, vibration sequences, and/or a combination of.

[0067] The TADS may incorporate an ear canal evacuation system and/or Eustachian tube evacuation system. This system may be used to flush one or more antioxidant agents and/or additional therapeutic agents from the user's ear canal. The ear canal may be utilized to extend the functional reach of the evacuation system such that it allows for the removal of agents and/or substances from the middle ear and/or inner ear via a tympanostomy tube, opening in the tympanic membrane, and/or through a needle component. The evacuation system my function independently, in combination with a gaseous supply in a simultaneous operation, staged operation, and/or a combination of. The TADS may incorporate an aspirator feature to assist in removing fluid and/or loose wax from the ear canal; thereby, improving the tympanic membrane's exposure to the antioxidant(s) and/or additional therapeutic agent(s). The aspiration feature may consist of a mechanical ear aspirator pump, an electric ear aspirator system, and/or a combination of. The canal evacuation system and the ear aspirator feature may consist of the same components, may consist of independent components, or a combination of. The ear interface component may deliver agents at a point that is further into the ear canal than the evacuation point, closer to the opening of the ear canal than the evacuation point, or a combination of.

[0068] While specific embodiments and examples of the present invention have been illustrated and described, numerous modifications come to mind without significantly departing from the spirit of the invention and the scope of protection is only limited by the scope of the accompanying claims.

Claims

CLAIMS:

1. A trans-tympanic antioxidant delivery apparatus, comprising:

a source of antioxidant;

a delivery mechanism in fluid communication with the source configured to deliver the antioxidant to a patient's ear canal;

a regulator for regulating at least one of an antioxidant delivery pressure, an

antioxidant delivery rate, an antioxidant delivery duration, an antioxidant delivery temperature, and an antioxidant delivery concentration; a monitor for monitoring at least one of a blood-oxygen saturation level, a

concentration of exhaled gas, an oxygen consumption, a blood pressure, a pulse, and a patient's cognitive interaction; and

a controller in operable communication with at least one of the delivery mechanism, the regulator and the monitor, said controller configured to control at least one of a delivery pressure, a delivery rate, a delivery duration, a delivery temperature, and a delivery concentration.

2. The trans-tympanic antioxidant delivery apparatus of claim 1, further comprising a user interface in operable communication with the controller, said user interface configured to receive input from a user, and wherein the controller is further configured to operate in response to at least one input from said user.

3. The trans-tympanic antioxidant delivery apparatus of claim 1, wherein the delivery mechanism comprises a flexible conduit attached to the source of antioxidant.

4. The trans-tympanic antioxidant delivery apparatus of claim 1, wherein the delivery mechanism comprises an ear interface.

5. The trans-tympanic antioxidant delivery apparatus of claim 4, wherein the ear

interface is removably attached to a flexible conduit.

6. The trans-tympanic antioxidant delivery apparatus of claim 1, wherein the delivery mechanism comprises a pressure equalization tube.

7. The trans-tympanic antioxidant delivery apparatus of claim 1, further comprising a light source in communication with the antioxidant.

8. The trans-tympanic antioxidant delivery apparatus of claim 1, further comprising a heater configured to elevate the internal temperature of the ear to promote the uptake of antioxidant.

9. The trans-tympanic antioxidant delivery apparatus of claim 1, wherein the user interface provides a user with feedback from at least one of the regulator, the monitor and the delivery mechanism.

10. The trans-tympanic antioxidant delivery apparatus of claim 1, further comprising a therapeutic agent source in fluid communication with a delivery mechanism configured to deliver the therapeutic agent to a patient's ear canal.

11. The trans-tympanic antioxidant delivery apparatus of claim 1, further comprising a pulmonary agent source in fluid communication with a delivery mechanism configured to deliver the pulmonary agent to a patient's ear canal.

12. The trans-tympanic antioxidant delivery apparatus of claim 1, further comprising a sensor for sensing at least one of an antioxidant delivery pressure, an antioxidant delivery rate, an antioxidant delivery duration, an antioxidant delivery temperature, and an antioxidant delivery concentration.

13. A method of trans-tympanic antioxidant delivery, comprising:

providing a source for at least one antioxidant;

delivering one or more antioxidants into a patient's ear canal;

measuring at least one of a delivery pressure, a delivery rate, a delivery duration, a delivery temperature, and a delivery concentration;

monitoring at least one of a patient's blood-oxygen saturation level, a concentration of exhaled gas, an oxygen consumption, a blood pressure, a pulse, and a patient's cognitive interaction; and

using a controller to control delivering one or more antioxidant agents to a patient using at least one of an input provided by the measuring step and an input provided by the monitoring step.

14. The method of claim 13, further comprising heating the internal temperature of the ear to promote the uptake of antioxidant.

15. The method of claim 13, further comprising providing input to the logic controller through a user interface.

16. The method of claim 13, further comprising receiving feedback from at least one of the measuring step and the monitoring step through a user interface.

17. The method of claim 13, wherein providing a source for an antioxidant comprises one of providing a container comprising pre-charged antioxidant and generating an antioxidant.

18. The method of claim 13, wherein the antioxidant comprises at least one of hydrogen, nitric oxide, carbon monoxide, hydrogen sulfide, hydrazine, naringenin, tocopherol, and natural extracts.

19. The method of claim 13, further comprising activating the antioxidant with energy from a light source.

20. The method of claim 13, wherein delivering one or more antioxidants into a patient's ear canal comprises delivering multiple antioxidants in one or more of an independent, simultaneous, or staged manner.

21. The method of claim 13, wherein delivering one or more antioxidants into a patient's ear canal comprises continuous delivery.

22. The method of claim 13, wherein delivering one or more antioxidants into a patient's ear canal comprises intermittent delivery.

23. The method of claim 13, further comprising delivering a therapeutic agent into the patient's ear canal.