阅读说明：本技术 用于提供离子导入的包括阀的耳机组件 (Earphone assembly including valve for providing iontophoresis ) 是由 罗希特·吉罗特拉 埃里克·戈德法布 安德鲁·兰茨 埃尔默·伊 于 2019-01-15 设计创作，主要内容包括：本发明描述了用于将治疗性物质(诸如,麻醉剂)递送到受试者的鼓膜的系统、设备和方法。此类系统可包括具有阀的耳机,所述阀被构造成控制流体(例如,空气)流入和流出储存器。在一些实施例中,本文中描述的系统、设备和方法可包括用于减轻储存器内的负压的额外阀和特征。(Systems, devices, and methods for delivering a therapeutic substance (such as an anesthetic) to a tympanic membrane of a subject are described. Such systems may include an earphone having a valve configured to control the flow of fluid (e.g., air) into and out of the reservoir. In some embodiments, the systems, apparatus, and methods described herein may include additional valves and features for relieving negative pressure within the reservoir.)

1. An apparatus, comprising:

a body defining a channel and a reservoir in fluid communication with the channel;

an electrode disposed within the channel;

a vent path in fluid communication with the reservoir; and

a valve disposed in the vent path and configured to: (i) allow fluid to flow from within the reservoir to outside of the device, and (ii) prevent the fluid from entering the reservoir from outside of the device.

2. The device of claim 1, further comprising a sealing element disposed at the distal end of the body, the sealing element configured to form a seal against a surface of an ear canal of an ear to define a closed volume between a tympanic membrane of the ear and the device in fluid communication with a channel.

3. The apparatus of claim 2, wherein the fluid is a first fluid, and further comprising a fluid conduit in fluid communication with at least one of the channel and the reservoir and configured to fill the channel, the reservoir, and the enclosed volume with a second fluid,

the valve is further configured to allow the second fluid to flow from within the reservoir to outside of the apparatus.

4. The apparatus of claim 3, wherein the electrode is immersed in the second fluid after the fluid conduit fills the channel with the second fluid.

5. The apparatus of claim 3, wherein the first fluid is atmospheric air and the second fluid is an iontophoretic fluid containing a therapeutic substance.

6. The apparatus of claim 1, wherein the valve is an umbrella valve.

7. The apparatus of claim 1, wherein the fluid is atmospheric air.

8. An apparatus, comprising:

a body defining a channel and a reservoir in fluid communication with the channel;

an electrode disposed within the channel;

a vent path in fluid communication with the reservoir; and

a valve disposed in the vent path and configured to:

(i) allowing fluid to flow from within the reservoir to an exterior of the apparatus in response to a positive gauge pressure within the reservoir;

(ii) preventing the fluid from entering the reservoir from outside the apparatus when a differential pressure between an interior of the reservoir and an exterior of the apparatus is less than a predefined value; and

(iii) allowing the fluid to enter the reservoir from outside the apparatus when the differential pressure is greater than the predefined value.

9. The apparatus of claim 8, wherein the predefined value is 1 kilopascal.

10. The apparatus of claim 8, wherein the valve is a first valve and the fluid is a first fluid, and further comprising:

a fluid conduit in fluid communication with at least one of the channel and the reservoir and configured to fill the channel and the reservoir with a second fluid;

a connector disposed at a proximal end of the fluid conduit and configured to connect to a fluid source providing the second fluid;

a second valve disposed in one of the connector or the fluid conduit and configured to: (i) allow the second fluid to flow in a first direction toward at least one of the channel and the reservoir, and (ii) prevent the second fluid from flowing in a second direction opposite the first direction.

11. The device of claim 8, further comprising a sealing element disposed at the distal end of the body, the sealing element configured to form a seal against a surface of an ear canal of an ear to define a closed volume between a tympanic membrane of the ear and the device.

12. The apparatus of claim 11, wherein the fluid is a first fluid, and further comprising a fluid conduit in fluid communication with at least one of the channel and the reservoir and configured to fill the channel, the reservoir, and the enclosed volume with a second fluid,

the valve is further configured to allow the second fluid to flow from within the reservoir to outside of the apparatus.

13. The apparatus of claim 12, wherein the electrode is immersed in the second fluid after the fluid conduit fills the channel with the second fluid.

14. The apparatus of claim 12, wherein the first fluid is atmospheric air and the second fluid is an iontophoretic fluid containing a therapeutic substance.

15. The apparatus of claim 13, wherein the reservoir is configured to contain a pocket of the first fluid in a space separate from the electrode, the channel configured to maintain the electrode immersed in the second fluid while the pocket of the first fluid is in the reservoir.

16. The apparatus of claim 8, wherein the valve is an umbrella valve.

17. The apparatus of claim 8, wherein the fluid is atmospheric air.

18. An apparatus, comprising:

a headset, the headset comprising:

a body defining a channel and a reservoir in fluid communication with the channel;

a vent path in fluid communication with the reservoir; and

a first valve disposed in the vent path and configured to: (i) allowing a first fluid to flow from within the reservoir to outside of the apparatus, and (ii) preventing the first fluid from entering the reservoir from outside of the apparatus;

a fluid conduit in fluid communication with at least one of the channel and the reservoir and configured to fill the channel and the reservoir with a second fluid;

a connector disposed at a proximal end of the fluid conduit and configured to connect to a fluid source providing the second fluid; and

a second valve disposed in one of the connector or the fluid conduit and configured to: (i) allowing the second fluid to flow in a first direction toward at least one of the channel and the reservoir, and (ii) preventing the second fluid from flowing in a second direction opposite the first direction such that a negative gauge pressure within the reservoir remains less than a predefined value.

19. The apparatus of claim 18, wherein the first fluid is atmospheric air and the second fluid is an iontophoretic fluid containing a therapeutic substance.

20. The apparatus of claim 18, wherein the first valve is an umbrella valve.

21. The apparatus of claim 18, wherein the predefined value is 1 kilopascal.

22. A method, comprising:

inserting a device into an ear canal of an ear such that a sealing element of the device forms a seal against a surface of the ear canal to define a closed volume between a tympanic membrane of the ear and the device, the device including a body defining a channel and a reservoir, the channel and the reservoir being in fluid communication with the closed volume after the device has been inserted into the ear canal;

delivering a first fluid through a fluid conduit of the apparatus into at least one of the enclosed volume, the channel, and the reservoir;

expelling a second fluid from the reservoir via a vent path of the device, the vent path in fluid communication with the reservoir; and

preventing, by a valve disposed in a vent path of the device, the second fluid from entering the reservoir through the vent path when a differential pressure between an interior of the reservoir and an exterior of the device is less than a predefined value.

23. The method of claim 22, further comprising providing the second fluid through the vent path into the reservoir when the differential pressure is greater than the predefined value, thereby reducing the differential pressure.

24. The method of claim 22, wherein the predefined value is 1 kilopascal.

25. The method of claim 22, wherein the first fluid is an iontophoretic fluid containing a therapeutic substance and the second fluid is atmospheric air.

26. The method of claim 22, wherein the expelling comprises expelling the second fluid from the reservoir such that pressure within the ear canal does not increase.

Technical Field

The present disclosure relates generally to systems, devices, and methods for delivering substances to the ear of a subject using iontophoresis. More particularly, the present disclosure relates to an earphone assembly having a valve design for iontophoretic delivery of a therapeutic substance, such as an anesthetic, to the tympanic membrane of a subject.

Background

Otitis media is an inflammation of the middle ear, and is particularly common in human children due to their anatomical structure and immune function. Otitis media, if severe or untreated, can lead to tearing of the tympanic membrane, hearing loss, or intracranial complications in an individual.

Treatment of severe cases may involve placement of a pressure equalizing tube or tympanostomy tube (tympanostomy tube) through the tympanic membrane to provide adequate drainage of the middle ear by providing fluid communication between the middle ear and the outer ear. In particular, such tubes may provide a ventilation path that facilitates the drainage of fluid from the middle ear through the eustachian tube, and thus may reduce the pressure exerted on the tympanic membrane from the pressure within the middle ear. This may further reduce the likelihood of future infections and pressure induced tearing of the tympanic membrane.

In some cases, the insertion of the pressure equalization tube may be performed using general anesthesia, which may require additional resources, such as time in the operating room, the presence of an anesthesiologist, and the recovery room. Furthermore, the use of general anesthesia may include certain risks that the patient may feel comfortable or may feel uncomfortable with the procedure. To reduce these risks, local anesthesia delivery methods may be used. For example, some pressure equalization tube delivery systems and methods provide anesthetic agents to the area surrounding and including the tympanic membrane by iontophoresis.

Iontophoresis involves applying a low level current to a charged medical fluid. The current repels the similarly charged drug ions in solution and transports them across the skin or other membrane. In ear procedures, iontophoresis may be used to anesthetize the tympanic membrane prior to placement of the tympanic membrane tube through the tympanic membrane. In these procedures, a medical solution is placed in the ear canal and an electric current is applied to the solution through the electrodes, thus delivering an anesthetic within the medical solution to the tympanic membrane.

The prior and previously described iontophoresis devices and systems have certain disadvantages. For example, some devices fail to seal the drug solution in the ear canal, which would require the patient to recline and tilt their head during the iontophoresis procedure. Furthermore, prior art devices that seal medical fluids in the ear canal (such as devices that include earplugs) may not adequately conform to the curved anatomy of the ear canal and, therefore, may not form a good seal in the ear canal of at least some patients. When a seal is not formed, fluid within the ear canal may leak, resulting in bubble formation, which may interfere with contact between the iontophoresis electrode and the solution. It is therefore desirable to have an iontophoresis system that takes these and other drawbacks into account.

Disclosure of Invention

Systems, devices, and methods for delivering a substance to an ear of a subject, and in particular to a tympanic membrane of a subject, are described. The therapeutic substance may be an anesthetic, such as lidocaine, which may be used to anesthetize the tympanic membrane in preparation for membrane penetration, e.g., for myringotomy or tympanostomy, or tympanostomy.

According to some embodiments, an apparatus for delivering an anesthetic to an ear of a subject comprises: a body defining a channel; a reservoir in fluid communication with the channel; and a vent path in fluid communication with the reservoir. Electrodes may be disposed within the channel and configured to apply an electrical current to the medical fluid (i.e., the iontophoretic solution with the charged drug) within the channel and/or reservoir. The vent path may allow air and/or fluid to escape the reservoir when the reservoir is filled with medical fluid. A one-way valve may be positioned in the vent path to prevent and/or limit re-entry of air into the reservoir via the vent path, thereby reducing leakage of medical fluid from the reservoir and reducing the risk of disrupting an iontophoresis procedure. In some embodiments, the one-way valve may be an umbrella valve. In some embodiments, the one-way valve may be designed to relieve negative pressure within the channel and/or reservoir of the device. For example, the one-way valve may be designed to fail when a negative gauge pressure of 1 kilopascal (kPa) is reached and allow air to re-enter the reservoir.

In some embodiments, a fluid source may be used to supply medical fluid to the channels and/or reservoir. The fluid source may be, for example, a syringe. The device is in fluid communication with a fluid source via one or more connectors and/or conduits. The connector and/or conduit may include an adapter that prevents backflow of fluid from the device to the fluid source, thereby reducing the risk of negative pressure build-up within the device. In some embodiments, the adapter may include a one-way valve designed to allow fluid to flow forward from the fluid source to the channel and/or reservoir of the device, but prevent fluid from flowing back from the device back toward the fluid source.

It should be understood that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided that such concepts do not contradict each other) are considered a part of the inventive subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are considered part of the inventive subject matter disclosed herein. It is also to be understood that the terms explicitly employed herein, as may appear in any disclosure incorporated by reference, are to be accorded the most consistent meanings with the specific concepts disclosed herein.

Other systems, processes, and features will be or become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, processes, and features be included within this description, be within the scope of the present invention, and be protected by the accompanying claims.

Drawings

Those skilled in the art will appreciate that the drawings are primarily for illustrative purposes and are not intended to limit the scope of the inventive subject matter described herein. The figures are not necessarily to scale; in some instances, various aspects of the inventive subject matter disclosed herein may be shown exaggerated or enlarged in the drawings to facilitate an understanding of various features. In the drawings, like reference numbers generally indicate like features (e.g., functionally similar and/or structurally similar elements).

Fig. 1 illustrates an example of an iontophoresis system including a headset according to some embodiments.

Fig. 2A and 2B are illustrations of an exemplary headset according to some embodiments. Fig. 2A provides a perspective view of the headset and fig. 2B provides a cross-sectional view of the headset along line 2B-2B of fig. 2A.

Fig. 3A depicts a cross-sectional view of the earpiece of fig. 2A and 2B, in which the earpiece is positioned near the ear of the subject in a horizontal orientation, according to some embodiments.

Fig. 3B depicts another cross-sectional view of the earpiece of fig. 2A and 2B, in which the ear canal of the ear is filled with fluid and some fluid escapes through the vent path of the earpiece, according to some embodiments.

Fig. 3C depicts another cross-sectional view of the earpiece of fig. 2A and 2B, in which the ear canal of the ear is filled with a fluid and a bubble formed in the fluid, in accordance with some embodiments.

Fig. 4 depicts another cross-sectional view of the earpiece of fig. 2A and 2B, in which the ear canal of the ear is filled with fluid and there is a fluid leak between the surface of the ear and the earpiece, in accordance with some embodiments.

Fig. 5 is a schematic diagram of another example of an ion introduction system according to some embodiments.

Fig. 6 depicts a perspective view of another example iontophoresis system including a headset according to some embodiments.

Fig. 7A and 7B depict cross-sectional views of an earpiece of the iontophoresis system of fig. 6, with a one-way valve positioned in a vent path of the earpiece, according to some embodiments. Fig. 7A depicts the one-way valve in a resting configuration in which air and/or fluid from within the earphone does not flow into or out of the earphone, and fig. 7B depicts the one-way valve in a positive pressure configuration in which air and/or fluid from within the earphone may flow out through the vent path.

Fig. 8A and 8B depict additional cross-sectional views of an earpiece of the iontophoresis system of fig. 6, in which a valve is positioned in a vent path of the earpiece, according to some embodiments. Fig. 8A depicts the valve in a resting configuration in which air and/or fluid from outside the earphone cannot enter the earphone, and fig. 8B depicts the valve in a negative pressure configuration in which air and/or fluid from outside can flow into the earphone through the vent path.

Fig. 9 depicts a side perspective view of an earpiece of the iontophoresis system of fig. 6, showing one or more vent paths disposed under a valve of the earpiece, in accordance with some embodiments.

Fig. 10 depicts an example of a fluid source adapter for use in an iontophoresis system according to some embodiments.

Figures 11A and 11B depict cross-sectional views of the fluid source adapter and check valve member of figure 10 according to some embodiments. FIG. 11A depicts the check valve member in a first configuration in which fluid flows out of the fluid source, and FIG. 11B depicts the check valve member in a second configuration in which fluid cannot flow toward the fluid source.

Detailed Description

Systems, devices, and methods for iontophoresis systems are described herein. In some embodiments, the iontophoresis system may be used to anesthetize a subject's ear prior to deploying a tympanostomy tube in the subject's tympanic membrane.

A tympanic membrane tube or a pressure equalization tube may be deployed in the tympanic membrane of a subject to treat, for example, otitis media. In some embodiments, the delivery instrument can be used to insert a tympanic membrane tube into a tympanic membrane. Examples of tympanic membrane tube delivery systems are disclosed in the following documents: U.S. Pat. No. 8,052,693 entitled "System and Method for the automatic double catalysis removal of Pressure catalysis Tubes", granted on 8.11.2011; U.S. Pat. No. 8,864,774 entitled "Tympanic Membrane Pressure Tube delivery System" awarded on 21/10/2014; U.S. Pat. No. 9,320,652 entitled "Features to Imprave and sensor type polymeric Membrane application by type polymeric Tube Delivery Instrument", issued on 26.4.2016; U.S. patent No. 9,681,891 entitled "Tympanostomy tube delivery Device with Cutting simulator" awarded on 20/6/2017; U.S. patent application publication No. 2016/0038342 entitled "Campanosymy Tube Delivery Device with Rotable Flexible Shaft" published on 11.2.2016; and U.S. patent No. 9,833,360 entitled "Tympanostomy tube delivery Device with reusable form Portion," awarded on 5.12.2017. The disclosure of each of these references is incorporated herein by reference. In some embodiments, the tympanic membrane tube may be manually inserted into the tympanic membrane, for example, by forming a myringotomy incision with a cutting tool and inserting the tympanic membrane tube into the incision using forceps or the like.

In some embodiments, the iontophoresis system may include an earpiece having a flexible sealing element or earplug configured to form a fluid-tight seal against a surface of the ear of the subject. The earpiece may define a volume within the ear into which an iontophoretic fluid may be delivered. The iontophoresis system may include an electrode that may be activated to supply a current to the iontophoresis fluid to drive ions of a drug (e.g., an anesthetic) into the tympanic membrane. Examples of iontophoresis systems are disclosed in the following documents: U.S. Pat. No. 8,452,392 entitled "Systems and Methods for analysing ear tissue" granted 5, month 27, 2013; U.S. patent No. 8,840,602 entitled "Systems and methods for evaluating Ear Tissue", granted 9, 23, 2014; and U.S. patent application publication No. 2017/0014272 entitled "earplus Assembly for ionophoresis System" published on 19.1.2017. The disclosure of each of these references is incorporated herein by reference.

Fig. 1 shows an example of an ion introduction system 100 including an earphone 200. The earphone 200 communicates with a fluid source 140 (e.g., a syringe) via the connector 132 and the conduit 130. In an embodiment, the conduit 130 may be in the form of a flexible tube. The headset 200 also communicates with the control unit 170 and the ground pad 180 via the connector 152 and the cable 150. The conduit 130 and cable 150 are coupled together along a shared length extending between the clamp 120 and the earpiece 200. The shared length portion 110 of the conduit 130 and cable 150 may be coiled and may be expanded and/or contracted to adjust the distance between the clamp 120 and the earpiece 200. Clamp 120 is operable to selectively secure the combination of catheter 130 and cable 150 to clothing and/or any other suitable structure such that iontophoresis system 100 may be secured to a subject during an iontophoresis procedure.

Fig. 2A and 2B provide detailed views of the headset 200. Fig. 2A provides a perspective view of the headset 200 and fig. 2B provides a cross-sectional view of the headset 200 taken along line 2B-2B in fig. 2A. The headset 200 may be inserted into and retained within the ear without the need for additional attachment components (e.g., a headgear). In some embodiments, the earpiece 200 may have a biocompatible pressure sensitive adhesive that may help hold the earpiece 200 in place within the ear. The headset 200 includes an insert element, such as a gripping feature 222, that can be gripped by a user and used as a handle during insertion of the headset 200 into the ear. The headset 200 also includes a take-out element, such as a pull tab 228, that can be grasped and pulled to assist in removing the headset 200 from the ear. In some embodiments, other kinds of insertion and/or removal elements may be incorporated into the headset 200. Although one earpiece 200 is shown, it is to be understood that iontophoresis system 100 may have two earpieces 200 that may be used in both ears of a subject to provide simultaneous and/or sequential delivery of therapeutic substances by iontophoresis.

The earpiece 200 includes a flexible sealing element or earplug 224 and a distally projecting nozzle 226. The sealing element 224 is configured to provide a fluid-tight seal against the surface of the ear canal when the earphone 200 is inserted into the ear. In some embodiments, a pressure sensitive adhesive is applied to the outer surface of the sealing element 224 to facilitate a fluid-tight seal to the ear canal. When the earphone 200 is inserted into the ear, the nozzle 226 is positioned to protrude into the ear canal such that the nozzle 226 is laterally spaced from the tympanic membrane (e.g., tympanic membrane TM shown in fig. 3A-3C). The nozzle 226 has a plurality of injection holes 227 and is fixed to the distal end of the rod 225. The stem 225 defines a lumen that provides a path for fluid to communicate from the catheter 130 to the jet holes 227. In an embodiment, the rod 225 may be a semi-rigid rod that may be bent and thereby adjust the injection direction of the injection holes 227. The injection holes 227 are thus in fluid communication with the fluid source 140 via the stem 225 and the conduit 130. The sealing element 224 is fixed to the rigid frame 223. The sealing element 224 and the frame 223 together define a working channel 221.

The gripping feature 222 is fixedly secured to the rigid frame 223. the gripping feature 222 and the frame 223 cooperate to define a reservoir 270. the reservoir 270 is in fluid communication with the working channel 221. the reservoir 270 and the working channel 221 thus together form L a shaped cavity L the shaped cavity operates to maintain fluid contact with the iontophoresis electrode 252 even though the ear canal undergoes a change in volume throughout iontophoresis. the frame 223 also defines at least one vent path 229, which is also in fluid communication with the reservoir 270. the vent path 229 is configured to allow fluid (e.g., air and/or liquid) to escape the reservoir 270 and the working channel 221 when the reservoir 270 and the working channel 221 are filled with an iontophoretic solution, as will be described in more detail below.

As depicted in fig. 2B, iontophoresis electrode 252 extends along the length of working channel 221. In the illustrated embodiment, the iontophoresis electrode 252 is shaped as a coil and is positioned along an inner surface of the rigid frame 223. In some embodiments, iontophoresis electrode 252 may have a different configuration. For example, iontophoresis electrode 252 may include one or more straight wires extending along the length of working channel 221. In some embodiments, the iontophoresis electrode 252 may be positioned adjacent to a wall or surface of the rigid frame 223. In other embodiments, the iontophoresis electrode 252 may be positioned within the working channel 221 spaced apart from the rigid frame 223.

Iontophoresis electrode 252 is coupled to control unit 170 via cable 150 and may be activated by control unit 170. The control unit 170 may activate the iontophoresis electrode 252 to provide a current to the iontophoretic solution to deliver the charged ions within the solution into the tympanic membrane TM. In the case of anesthetizing the tympanic membrane TM, the iontophoretic solution may include a charged anesthetic drug (e.g., lidocaine) for anesthetizing the tympanic membrane TM. The fluid source 140 may supply an iontophoretic solution containing a therapeutic substance (e.g., an anesthetic agent, such as lidocaine) to the earphone 200. And the control unit 170 may activate the iontophoresis electrode 252 to drive ions of the therapeutic substance within the iontophoretic solution into the tissue including the tympanic membrane TM.

Reservoir 270 increases the volume of space within earphone 200 that contains the iontophoretic fluid. In some embodiments, the reservoir 270 may have a volume that is at least twice the volume of the working channel 221. By increasing the volume of iontophoretic fluid within earphone 200, for example, in the event of a bubble forming within iontophoretic fluid within earphone 200, reservoir 270 reduces the risk that electrode 252 may be exposed to air. In the event that the entire electrode 252 or a substantial portion of the electrode 252 is exposed to air, the electrode 252 may not supply sufficient current to the iontophoretic fluid to deliver the therapeutic substance to the tympanic membrane TM. The reservoir 270 reduces this risk, as explained in more detail with reference to fig. 3C and 4.

The vent path 229 is positioned adjacent to the reservoir 270 such that fluid (e.g., air and/or fluid) may exit the reservoir 270 via the vent path 229. As depicted in fig. 3B, vent aperture 229 may be positioned at a lateral end of reservoir 270 such that any open space (e.g., a bubble) created by fluid exiting reservoir 270 remains within reservoir 270 adjacent its lateral end, and thus spaced apart from iontophoresis electrode 252. The vent path 229 may be integrally formed with an opening for receiving the conduit 130. Alternatively, the vent path 229 may be a separate opening formed in the earphone 200, for example, an opening formed in the gripping feature 222 that is spaced apart from the point at which the conduit 130 enters the gripping feature 222.

Fig. 3A-3C illustrate an earphone 200 for use in an iontophoresis procedure. As shown in fig. 3A, the earpiece 200 may be positioned in the ear canal EC of a subject. The sealing element 224 is positioned such that it rests against the surface of the ear canal EC. The sealing element 224 may secure the earpiece 200 to the ear and form a fluid seal against the surface of the ear canal EC. The sealing of the ear canal EC creates a cavity between the drum membrane TM and the earpiece 200, which cavity can receive an iontophoretic fluid. In some embodiments, a pressure sensitive adhesive may be disposed on the sealing element 224. The backing strip 220 (shown in fig. 1) may be covered with a pressure sensitive adhesive during placement of the earpiece 200 in the ear canal EC. The backing strip 220 may be removed to expose the pressure sensitive adhesive so that the pressure sensitive adhesive may adhere to the surface of the ear canal EC, further ensuring that the earpiece 200 remains secured to the ear canal EC and forms a fluid seal between the flexible sealing element 224 and the ear canal EC.

Once the earpiece 200 is secured in the ear canal EC, the user may begin to apply iontophoretic fluid into the ear canal EC through the nozzle 226. A user may connect the fluid source 140 to the catheter 130 and use the fluid source 140 to supply the iontophoretic fluid. When supplied with ionic fluid, ear canal EC, working channel 221 and reservoir 270 may be filled with fluid and air expelled from ear canal EC, working channel 221 and reservoir 270 will flow out to the exterior of earphone 200 through vent path 229. The user may continue to supply iontophoretic fluid until fluid 320 is observed to flow out through vent path 229, as shown in fig. 3B. Fluid 320 flowing out through ventilation path 229 indicates to the user that ear canal EC, working channel 221, and reservoir 270 are full of iontophoretic fluid and that electrode 252 may be activated. In some embodiments, gripping feature 222 may be transparent to enable a user to observe that reservoir 270 is being filled with an iontophoretic fluid.

The user may remove the fluid source 140 prior to activating the electrodes 252. In some cases, removal of fluid source 140 may result in loss of iontophoretic fluid from working channel 221 and reservoir 270. For example, removing the fluid source 140 may result in a 0.04cc or milliliter iontophoresis fluid loss. Accordingly, a corresponding volume of air pockets 330 may be formed in the reservoir 270, as shown in fig. 3C. Due to the shape of reservoir 270, air pocket 330 is spaced away from iontophoresis electrode 252 so that iontophoresis electrode 252 remains fully immersed in the iontophoretic fluid.

In some cases, fluid may escape from reservoir 270 prior to and/or during an iontophoresis procedure in general, fluid may escape prior to an iontophoresis procedure through ventilation path 229 or due to a non-ideal fit of earphone 200 in the ear canal (e.g., when flexible sealing element 224 does not form a fluid-tight seal against the surface of the ear canal). for example, movement of the subject (e.g., due to coughing, speaking, swallowing, crying, yawning, or other activity) may result in a change in the volume of ear canal EC.

However, in some cases, a leak may form between the surface of the ear canal EC and the flexible sealing element 224. When a leak develops between the surface of ear canal EC and flexible sealing element 224, iontophoretic fluid from ear canal EC, working channel 221, and reservoir 270 may leak, which may interrupt the iontophoresis process. For example, as shown in fig. 4, a gap or opening 304 may be formed between the flexible sealing element 224 and a surface 302 of the ear canal EC. The gap 304 may be formed when the doctor or the patient pushes or pulls on a portion of the earphone 200 (e.g., when adjusting the earphone 200), due to movement of the patient (e.g., talking, crying, yawning, eating, or moving his chin), or due to a non-ideal fit of the earphone 200 within the ear canal (e.g., when the flexible sealing element 224 does not form a fluid-tight seal against the surface of the ear canal EC). The gap 304 may be formed before or during the ion implantation process. When the gap 304 is formed, the iontophoretic fluid may leak out of the gap 304 and be replaced by air flowing into the reservoir 270 through the vent path 229. The size of the air pocket 330 may increase as the iontophoretic fluid leaks out of the gap 304, as shown in FIG. 4. In some cases, air pockets or bubbles may also migrate to the surface of iontophoresis electrode 252. If the leak is not addressed, the iontophoretic fluid may continue to leak from ear canal EC until iontophoresis electrode 252 is exposed to air, e.g., due to an increase in the size of air pocket 330 or migration of the air pocket to the surface of iontophoresis electrode 252. Such exposure to air may cause the iontophoresis procedure to be delayed or interrupted. Before the iontophoresis procedure can begin or resume, the leak will need to be addressed (e.g., gap 304 will need to be blocked so that fluid can no longer leak out of reservoir 270) and reservoir 270 is refilled with iontophoretic fluid. In some cases, the earpiece 200 may need to be replaced with a new earpiece that may form a new fluid seal against the surface of the ear canal EC. The additional work of addressing leaks and/or replacing the earphone 200 may extend the amount of time required for the iontophoresis procedure and require additional interaction or contact between the physician and the patient. Extended periods of time and/or additional contact between the physician and the patient can lead to discomfort, frustration, and impatience, which can lead to behavioral challenges, especially in younger patients.

To provide some resistance to fluid leakage, the vent path 229 and/or other openings in the earpiece 200 that allow air to enter the earpiece 200 may be closed so that air does not readily displace fluid that leaks out through the gap 304. In an embodiment, the user may manually close the vent path 229 to prevent air from entering the earpiece 200 and displace fluid that leaks out through the gap 304. For example, the user may cover the vent path 229 with their fingers, or the user may close the vent path 229 using a plug, tape, or other mechanism. The user may keep the vent path 229 closed until the iontophoresis procedure is complete and/or until the gap 304 is plugged. However, in some cases, it may be difficult for a user to close the vent path 229 and/or keep the vent path 229 closed. For example, the vent path 229 may be positioned on the earphone 200 in a location that is difficult for a user to access, or the vent path 229 may have a size and/or configuration that makes it difficult for a user to close (e.g., the vent path 229 may be formed in a recess). In some embodiments, vent path 229 may be sized and/or configured to prevent it from being easily closed or blocked, as it is undesirable for vent path 229 to be covered when earphone 200 is filled with an iontophoretic fluid. For example, if the vent path 229 is blocked when the earphone 200 is filled with iontophoretic fluid, pressure may build up within the ear canal EC and cause discomfort and/or injury to the patient.

In some embodiments, a valve may be used to prevent air from entering the earphone (e.g., earphone 200) via the vent path. The valve may allow air to exit the earphone when the earphone is filled with fluid, but prevent air from returning into the earphone when a leak develops. As schematically shown in fig. 5, iontophoresis system 400 may include valve 440. The valve 440 may restrict fluid (e.g., air and/or liquid) flow through the vent path 429. In some embodiments, the iontophoresis system 400 may optionally include an additional valve 434 that may control the flow of fluid (e.g., iontophoresis fluid) between the fluid source 402 and the reservoir 470 of the iontophoresis system 400.

Similar to iontophoresis system 100, iontophoresis system 400 may include iontophoresis electrode 452, reservoir 470, vent path 429, fluid source 402, and controller or control unit 404.

The iontophoresis system 400 may be positioned within the ear canal EC of a subject. In particular, a portion of the body 422 of the iontophoresis system 400 may be positioned within the ear canal EC. Body 422 of iontophoresis system 400 may include one or more rigid, semi-rigid, or flexible components. For example, body 422 may include a flexible sealing element similar to flexible sealing element 224 of iontophoresis system 100, which may secure iontophoresis system 400 to ear canal EC and form a seal against the surface of ear canal EC. In some embodiments, a pressure sensitive adhesive may also be disposed on the flexible sealing element to help secure the ion introduction system 400 to the ear canal EC. When iontophoresis system 400 is secured to ear canal EC, a portion of body 422 (e.g., a flexible sealing element) may define enclosed volume 410 outside of the tympanic membrane TM within ear canal EC.

Body 422 defines a reservoir 470 that can receive iontophoretic fluid IF. The reservoir 470 is in fluid communication with the enclosed volume 410. Electrode 452 may be used to supply an electrical current to iontophoresis fluid IF to drive drug ions in iontophoresis fluid IF into tympanic membrane TM. The electrode 452 may be coupled to the reservoir 470 or separate from but engageable with the reservoir. In some embodiments, the electrodes 452 may be disposed within the body 422 within and/or adjacent to the reservoir 470. The electrode 452 may have any general shape (e.g., wound wire, straight line, mesh, etc.).

In some embodiments, the electrodes 452 can have different configurations to increase surface area and facilitate iontophoresis. For example, the electrodes 452 may include one or more of the following: a plurality of wires similar to a brush head configuration, a plurality of concentric tubes of staggered diameter nested within one another, a silver mesh mass similar to a steel wool configuration, a molded polymer matrix plug having a sponge-like structure and a metallic plating or deposition layer (e.g., a pure silver plating or deposition layer), a metallic coated woven fabric, a honeycomb structure, a coiled structure, a mass having a plurality of petals or limbs (e.g., flower-shaped), a flexible bag structure, one or more cavities or recesses with a metallic coated surface, a textured surface (e.g., cross-hatch, etched, sandblasted), a laser cut tube with cavities or recesses, and the like. In some embodiments, electrode 452 may be coupled to controller 404, which supplies power to electrode 452 and controls when electrode 452 applies current to iontophoresis fluid IF. The controller may include safety features that prevent electrode 452 from activating and applying current until iontophoresis system 400 is properly positioned within ear canal EC and filled with iontophoresis fluid IF. For example, electrode 452 may include a sensor that informs controller 404 when electrode 452 is immersed in iontophoretic fluid IF before allowing a user to actuate controller 404 and apply a current.

In some embodiments, the electrode 452 can include multiple metals, with one metal (e.g., zinc) serving as a galvanic or sacrificial anode. In some embodiments, the electrode 452 may include a conveyor system (e.g., a flexible belt) that can be actuated during the iontophoresis procedure to supply a new electrode surface. In some embodiments, the electrode 452 can include a wiping or cleaning mechanism that can be actuated to clean the surface of the electrode 452. In some embodiments, the electrode 452 may include a protective coating to help prevent corrosion.

The valve 440 may be a one-way valve. The valve 440 may be configured to restrict fluid flow through the vent path 429. In some embodiments, the valve 440 may be a flow control valve, i.e., a valve that provides a substantially constant flow regardless of the pressure drop across the valve. In other embodiments, the valve 440 may be a pressure controlled valve, i.e., a valve that opens and/or closes beyond a predetermined pressure threshold.

As depicted, a valve 440 may be disposed in the vent path 429. In other embodiments, the valve 440 may be disposed adjacent or proximate to the vent path 429. The valve 440 is configured to allow fluid (e.g., air and/or liquid) to flow out of the reservoir 470 with low resistance, but restrict fluid (e.g., air and/or liquid) from flowing into the reservoir 470. Specifically, during use of iontophoresis system 400, valve 440 may be configured to allow air and/or excess iontophoresis fluid IF to flow out of reservoir 470 such that pressure does not build up within reservoir 470 when reservoir 470 is being filled with iontophoresis fluid IF. The valve 440 may also be configured to restrict the flow of air (or other fluid substance) back into the reservoir 470. The valve 440 may be an umbrella valve, or any other suitable type of valve that restricts fluid flow in one direction (e.g., duckbill valve, dome valve, seat valve, ball check valve). The valve 440 may reduce fluid leakage from the reservoir 470 and/or ear canal EC by preventing air from flowing into the reservoir 470 and displacing fluid that has leaked from the reservoir 470 and/or ear canal EC.

In some embodiments, the valve 440 may be designed to provide negative pressure relief. For example, the valve 440 may be designed to open when the pressure drop across the valve is greater than a preset level. The valve 440 may prevent fluid (e.g., air and/or liquid) from flowing into the reservoir 470 unless and/or until the pressure within the reservoir 470 is below a certain gauge pressure, thereby allowing fluid to flow into the reservoir 470. By allowing fluid to flow into reservoir 470, valve 440 may relieve negative pressure within reservoir 470 and relieve patient discomfort caused by the negative pressure. When a clinician inadvertently applies suction via a syringe (e.g., a fluid source) connected to the fluid delivery path 430, negative pressure may build up within the reservoir 470. To prevent the patient from experiencing discomfort due to the applied suction, the valve 440 may be designed to fail and allow fluid to enter the reservoir 470 before the pressure reaches a threshold of discomfort (e.g., -1 kilopascal).

In some embodiments, the iontophoresis system optionally includes a second valve, e.g., valve 434. The valve 434 may be disposed between the fluid source 402 and the fluid delivery path 430, or at some point along the fluid delivery path 430. Valve 434 may be designed to allow fluid (e.g., iontophoretic fluid IF) to flow from fluid source 402 in the direction of reservoir 470, but prevent fluid from flowing back toward fluid source 402. When fluid source 402 is a syringe, valve 434 prevents the clinician from applying suction via the syringe, thereby avoiding negative pressure within reservoir 470. Similar to valve 440, valve 434 may be a one-way valve.

Fig. 6 depicts an example of an iontophoresis system including a valve. Specifically, iontophoresis system 500 includes components similar to iontophoresis system 100, but also includes one-way valve 580 (depicted in fig. 7A-8B). Iontophoresis system 500 includes a headset 520. The earphone 520 communicates with a fluid source (not shown) via one or more connectors (e.g., connector 532) and conduits (e.g., conduits 530, 564). The headset 520 also communicates with a control unit (not shown) and a ground pad (not shown) via a connector and cable 550. The conduit 530 and cable 550 may be coupled together along a shared length extending between the earphone 520 and the clamp. The shared length portion 510 of the conduit 530 and cable 550 may be coiled such that it may be expanded and/or contracted to adjust the distance between the clamp and the earpiece 520.

Iontophoresis system 500 may include adapter 560. The adapter 560 can be connected to a fluid source, such as a syringe 540 (shown in fig. 10). As described in further detail below with reference to fig. 10, 11A, and 11B, the adapter 560 may include a valve for controlling the flow of fluid from the fluid source. The adapter 560 may be connected to the connector 532 via a conduit 564. The conduit 564, in conjunction with the conduit 530, may provide a path for delivering fluid from a fluid source to the earphone 520.

Although one earphone 520 is shown in fig. 6, it is to be understood that iontophoresis system 500 may have two earphones 520 that may be used in both ears of a subject to provide simultaneous and/or sequential delivery of therapeutic substances via iontophoresis.

Fig. 7A, 7B, 8A and 8B show cross-sectional views of a portion of the headset 520 within the area a circled in fig. 6. The headset 520 comprises housing parts 522, 523. The housing portions 522, 523 may cooperate to define a reservoir 570. Reservoir 570 is in fluid communication with conduit 530 such that a fluid, e.g., an iontophoretic fluid, may be delivered to reservoir 570 via conduit 530. The housing portion 522 may define a gripping feature that may be gripped by a user and used as a handle during insertion of the earpiece 520 into the ear of a subject.

As depicted, the earpiece 520 includes an umbrella valve 580. In other embodiments, the earpiece 520 may include a different type of valve, such as a duckbill valve, a dome valve, a seat valve, or a ball check valve. The valve 520 may be formed of a flexible material such as an elastomer. The valve 520 may be configured to restrict flow through one or more vent paths 529. The vent path 529 may be formed as an opening in the housing portion 522. In other embodiments, ventilation path 529 can have a different size and/or configuration. In some embodiments, the valve 520 may be releasably coupled to the housing portion 522. For example, the valve 520 may include a portion 518 (depicted in fig. 7A) that is insertable into an opening in the housing portion 522. The portion 518 of the valve 520 may be sized to maintain a coupling between the valve 520 and the housing portion 522. Portion 518 of valve 520 may be deformed when inserted into housing portion 522 and then return to its resting configuration to retain portion 518 in housing portion 522. In other embodiments, the housing portion 522 may be permanently attached to the housing portion 522 or integrally formed therewith.

During an iontophoresis operation, a fluid source (e.g., syringe 540) may be used to fill reservoir 570 with iontophoretic fluid. Valve 580 may be configured to allow air from within reservoir 570 to flow out of reservoir 570 via vent path 529 and one or more openings 584 (shown in fig. 9) when reservoir 570 is filled with iontophoretic fluid. For example, in response to a slight positive pressure increase within reservoir 570, the umbrella portion of valve 580 may move and expose vent path 529, allowing air to flow out of reservoir 570, as indicated by arrow 586 in fig. 7B.

The valve 580 is also configured to prevent air or another gas and/or liquid from flowing back into the reservoir 570. For example, as shown in fig. 8A, when a slight negative pressure builds within the reservoir 570 and/or a positive pressure acts on the valve 580 in the direction 588, the umbrella portion of the valve 580 closes at the vent path 529 such that air from outside the earphone 520 is prevented from flowing into the reservoir 570 via the vent path 529. The valve 580 may reduce fluid leakage by preventing air from flowing back into the reservoir 570. For example, when a gap is formed such that iontophoretic fluid from the ear and/or within the reservoir 570 can leak through the gap, the valve 580 can prevent air from flowing into the reservoir 570 such that air does not readily displace any fluid that leaks through the gap. Thus, the valve 580 may provide a degree of resistance to fluid leakage by restricting the flow of fluid into the reservoir 570.

In some embodiments, the valve 580 may be configured to provide negative pressure release, for example, when suction is applied (e.g., inadvertently by a clinician) to the reservoir 570 by a fluid source (e.g., the syringe 540) connected to the catheter 530 by, for example, a clinician. Suction may cause a negative pressure to build within reservoir 570. At certain levels, negative pressure may cause discomfort and/or injury to the patient. Thus, to prevent discomfort and/or injury, the valve 580 may be designed to open or fail when the gauge pressure within the reservoir 570 is below a certain pressure threshold to allow air to enter the reservoir 570, thereby reducing the negative pressure within the reservoir 570. As depicted in fig. 8B, when the valve 580 fails, the umbrella portion of the valve 580 may flare outward, exposing the vent path 529 to allow air to enter the reservoir 570, as indicated by arrow 590 (depicted in fig. 8B). In embodiments, the valve 580 may be designed to fail at a negative gauge pressure in excess of 1 kilopascals, or when the pressure differential between the interior of the earphone 520 (i.e., the pressure within the reservoir 570) and the exterior of the earphone 520 is greater than 1 kilopascal.

As shown in fig. 7A-8B, valve 580 and vent path 529 may be disposed within a recess 582 defined in earphone 520. The depression 582 can reduce the risk of a user accidentally covering the one or more openings 584, which can impair the operation of the vent path 529. Multiple openings 584 may also be provided to reduce the risk that operation of vent path 529 may be compromised.

Fig. 9 depicts a rear side view of the headset 520. As shown, similar to the headset 200 described above, the headset 520 includes a removal element (e.g., a pull tab 528) and a flexible sealing element 524.

In some embodiments, the earphone 520 may include a valve defining a vent path. In such embodiments, it may not be necessary to form a separate vent path (e.g., vent path 529 as shown in fig. 7A-8B) in the housing of earphone 520. The valve may include a stem or ball and a base element (e.g., a seat ring or disk), where the base element includes an opening that acts as a vent path, and the stem or ball is configured to close the opening to prevent fluid flow into the earphone 520. In other embodiments, the earpiece 520 may include an electrically actuated component that operates as a one-way valve.

Fig. 10, 11A, and 11B provide more detailed views of the adapter 560. Fig. 10 provides a perspective view of an adapter 560, wherein a syringe 540 can be coupled to the adapter 560. Fig. 11A and 11B provide cross-sectional views of the adapter 560. The adapter 560 may be connected to a conduit 564, which may be connected to one or more other conduits (e.g., conduit 530) to provide a fluid flow path between the syringe 540 and the reservoir 570. Syringe 540 may be used to supply iontophoretic fluid to reservoir 570. The syringe 540 may be similar to a standard syringe and may include a shaft 544 having a plunger 546 disposed within the barrel 540. The syringe 540 may be releasably coupled to the end 562 of the adapter 560 by its luer tip 542. The end 562 of the adapter 560 can be shaped to receive and mate with the luer tip 542 of the syringe 540. While a syringe 540 having a luer tip 542 and an adapter 560 having an end 562 shaped to engage the luer tip are shown, one of ordinary skill in the art will appreciate that other types of connections may be used between a syringe or other type of fluid source and an adapter.

The adapter 560 can include a valve 566. Valve 566 can allow fluid (e.g., iontophoretic fluid) to flow out of syringe 540 in a first direction 561, but prevent fluid from flowing back toward syringe 540 in a second, opposite direction 563. As depicted in fig. 11A and 11B, the valve 566 may be formed by a disk movable between an open position (fig. 11A) and a seated position (fig. 11B). When the valve 566 is in the open position, the valve 566 is disengaged from the seat post 568 such that fluid from within the syringe 540 may flow out of the syringe 540. And when the valve 466 is in the seated position, the valve 566 may be seated against the seat post 568 such that fluid cannot flow back into the syringe 540. By preventing backflow of fluid into the syringe 540, the valve 566 may prevent suction from being applied to the reservoir 570 by the syringe 540, thereby reducing the risk of negative pressure buildup within the reservoir 570. By adding the valve 580 to the earpiece 520, the clinician may inadvertently create a negative pressure within the reservoir 570 and ear canal if the clinician withdraws the syringe 540. As described above, the valve 580 may be designed to fail to reduce the negative pressure within the earpiece 520. Additionally or alternatively, the valve 566 may be used to prevent negative pressure from being created within the reservoir 570 by the addition of the valve 580.

While various inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the function and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto; and that embodiments of the invention may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the scope of the present disclosure.

Furthermore, various inventive concepts may be embodied as one or more methods, examples of which have been provided. The actions performed as part of the method may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts concurrently, even though shown as sequential acts in illustrative embodiments.

All definitions, as defined and used herein, should be understood to govern dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms.

The indefinite articles "a" and "an", as used in the specification and in the claims, are understood to mean "at least one" unless explicitly indicated to the contrary.

The clauses "and/or" as used in the specification and claims are to be understood as meaning "one or both" of the elements so combined, i.e., elements that are present in combination in some cases and are present in isolation in other cases. Multiple elements listed with "and/or" should be interpreted in the same manner, i.e., "one or more" of the elements so combined. In addition to elements explicitly identified by the "and/or" clause, other elements may optionally be present, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, when used in conjunction with open-ended language (e.g., "including"), references to "a and/or B" may refer in one embodiment to a alone (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than a); in yet another embodiment to both a and B (optionally including other elements); and so on.

As used herein in the specification and claims, "or" should be understood to have the same meaning as "and/or" as defined above. For example, when items in a list are separated, "or" and/or "should be interpreted as inclusive, i.e., including at least one of a plurality of elements or a list of elements, but also including more than one, as well as (optionally) other unlisted items. Merely explicitly stating the opposite terms, such as "only one" or "exactly one," or "consisting of …" when used in the claims, will mean that only one element of a plurality or list of elements is included. In general, as used herein, the term "or" preceded by an exclusive term (e.g., "any," "one of," "only one of," or "exactly one of") should be interpreted as indicating an exclusive alternative.

As used herein in the specification and claims, the phrase "at least one," when referring to a list of one or more elements, should be understood to mean that any one or more elements selected from the list of elements does not necessarily include at least one of each element specifically listed in the list of elements, and does not exclude any combination of elements in the list of elements. This definition also allows that, in addition to the elements explicitly identified in the list of elements to which the phrase "at least one" refers, other elements may optionally be present, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, "at least one of a and B" (or, equivalently, "at least one of a or B," or, equivalently "at least one of a and/or B") may refer, in one embodiment, to at least one, optionally including more than one, a, absent B (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, no a is present (and optionally including elements other than a); in yet another embodiment, refers to at least one, optionally including more than one, a, and at least one, optionally including more than one, B (and optionally including other elements); and so on.