Intratympanic syringe device and needle for delivering drugs and method of use

Abstract

A system for delivering one or more therapeutic agents to an area within the ear, which area is inside the tympanic membrane. The system includes a catheter guide configured to be inserted into the ear canal and to cooperate with and engage the ear canal wall, and a needle assembly having a flexible shaft sized to extend through the catheter guide. The catheter guide provides alignment of the needle assembly within the ear canal relative to the tympanic membrane. The catheter guide includes a viewing cavity extending between a proximal end and a most distal end of the catheter guide and sized to remain outside the tympanic membrane. The catheter guide includes a guiding cavity extending to a distal opening near the most distal end of the catheter guide. The guiding cavity is curved from a first axis to a second axis. Related devices, systems, and methods are provided.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit of priority of U.S. Provisional Patent Application Serial No. 62 / 810,162, filed on February 25, 2019. The disclosure of the provisional application is hereby incorporated by reference in its entirety. Background of the Invention

[0003] Hearing loss can be the result of various ear diseases. The most common cause of sensorineural hearing loss (SNHL) is damage or dysfunction of cochlear hair cells or the nerve pathways from the inner ear to the brain. SNHL is typically associated with exposure to loud noise, temporal bone trauma, aging, infections, Meniere's disease, auditory and vestibular nerve tumors, drug - related ototoxicity, genetic diseases (such as Usher disease), etc.

[0004] Potential therapeutic agents for treating hearing loss have been identified. There is a need for safe, direct, and effective drug delivery devices and methods that can provide a therapeutic effect in treating hearing loss and other ear diseases, particularly middle ear and inner ear diseases. Summary of the Invention

[0005] According to a first aspect, a system for delivering one or more therapeutic agents to an ear region located inside the tympanic membrane is disclosed. The system includes a catheter guide configured to be inserted into the ear canal and matingly engage with the ear canal wall. The catheter guide includes an observation cavity that extends between a proximal end of the catheter guide and a most distal end of the catheter guide, and the most distal end of the catheter guide is sized to remain outside the tympanic membrane. The catheter guide includes a guide cavity that extends from a proximal opening near the proximal end of the catheter guide to a distal opening near the most distal end of the catheter guide. The guide cavity is curved from a first axis that extends through the proximal opening to a second axis that extends through the distal opening. The system includes a needle assembly having a flexible shaft sized to extend through the guide cavity of the catheter guide. The flexible shaft includes a fluid delivery cavity. The catheter guide provides alignment of the needle assembly within the ear canal relative to the tympanic membrane.

[0006] The flexible shaft may include a sharp tip configured to penetrate the tympanic membrane. The needle assembly may be movable relative to the catheter guide between a fully retracted position and a fully extended position. The needle assembly may further include an outer shaft through which the flexible shaft extends. The outer shaft and the flexible shaft may be movable relative to each other and relative to the catheter guide. The outer shaft may be rigid, and one or both of the flexible shaft and the outer shaft include a sharp tip configured to penetrate the tympanic membrane. The needle assembly may be between 23 gauge and 30 gauge. The outer shaft may extend from the most distal end of the catheter guide a distance of no more than about 5 mm to about 10 mm. The flexible shaft may extend from the most distal end of the catheter guide a distance of no more than about 3 mm to about 5 mm. The guide lumen of the catheter guide may be eccentric relative to the longitudinal axis of the catheter guide. When the catheter guide rotates, the guide lumen of the catheter guide may be adjusted about the longitudinal axis. The proximal end of the catheter guide may include coupling features configured to reversibly engage coupling features on the front end of the housing. The catheter guide may be adjustably attached to the housing such that the position of the guide lumen relative to the housing is adjusted by rotation. The degree of rotation of the catheter guide relative to the housing may be indicated to the user visually, auditorily, and / or haptically.

[0007] The system may further include one or more actuators configured to move the needle assembly relative to the catheter guide. The one or more actuators may include a first actuator configured to distally extend both the outer shaft and the flexible shaft relative to the most distal end of the catheter guide and immediately retract the outer shaft while the flexible shaft remains extended. The needle assembly may be actuated by a spring-loading mechanism. The flexible shaft may be steerable. The system may further include a steerable guidewire extending through a lumen of the flexible shaft. The flexible shaft may be advanced over the steerable guidewire. The catheter guide may include a conformable outer surface sized to engage the ear canal wall. The shape of the conformable outer surface may be at least partially cylindrical. The conformable outer surface may taper towards a narrower outer diameter at the most distal end. The catheter guide may include an inner layer covered by an outer compressible layer. The outer compressible layer may include a plurality of flexible flanges configured to conform to the ear canal when the catheter guide is inserted into the ear canal and advanced towards the tympanic membrane.

[0008] The catheter guide can be shaped as an otoscope. The guide lumen can extend along the curved wall of the catheter guide between a proximal opening and a distal opening. The distal opening from the guide lumen can be positioned eccentric to the longitudinal axis of the catheter guide. The most distal end of the catheter guide can be coupled to a contact tip, which is configured to abut against the outer surface of the tympanic membrane when the catheter guide is inserted and advanced through the ear canal. The contact tip can include a lumen extending from the proximal end to the distal end of the contact tip, which is configured to receive a needle assembly. The guide lumen of the catheter guide and the lumen of the contact tip can be coaxially positioned with each other. The catheter guide can be coupled to a housing. The system can also include one or more retractable external support legs, which are coupled to an area of the housing. The external support legs can be symmetrically arranged around the longitudinal axis of the catheter guide to form a stable tripod relative to the catheter guide. The external support legs can be positioned adjacent to the patient's skull, while the catheter guide is positioned within the ear canal. The flexible shaft can include visual markings on its outer surface, which are located at a certain distance close to the most distal end of the flexible shaft. The flexible shaft can include a plurality of visual markings on its outer surface. The first marking can be located distally to the second marking and can be visually distinguishable from the second marking. The needle assembly can include a large bore portion, which symmetrically tapers to the flexible shaft at the collar region. The flexible shaft can include a trans-tympanic portion located distally to the collar region. The trans-tympanic portion can be about 1.25 cm long and between 30 gauge and 33 gauge. The large bore portion can be about 2.5 cm long and between 20 gauge and 25 gauge. The needle assembly can also include an external ring, which is configured to prevent the needle assembly from being over-inserted through the tympanic membrane. The external ring can be located at or near the collar region. The needle assembly can also include a concentric vent lumen surrounding the fluid delivery lumen. The needle assembly can also include a vent lumen positioned parallel to the fluid delivery lumen. During use, the outlet from the vent lumen can be located outside the tympanic membrane, and the outlet from the fluid delivery lumen can be located inside the tympanic membrane.

[0009] The needle assembly can also include an optical conduit connecting a proximal opening and a distal opening. The optical conduit can be configured to receive an optical line, which is configured to provide illumination and / or imaging capabilities. The optical line can also include a pressure sensor and / or a position sensor configured to assist in positioning the flexible shaft. The longitudinal axis of the catheter guide can extend through the viewing lumen of the catheter guide, and the guide lumen can be eccentric to the longitudinal axis. The viewing lumen can have a viewing lens at the proximal end. The catheter guide can be coupled to the front end of the upper part of the housing, and the rear end of the upper part of the housing can include a viewing lens.

[0010] The system may further include a reservoir configured to contain one or more therapeutic agents for delivery to the ear region through the fluid delivery lumen. The reservoir may be integral with the housing or attachable to the housing. The flexible shaft may include a proximal end having an inlet in fluid communication with an outlet from the reservoir. A first axis may form an angle with a second axis, the angle being less than 90 degrees and greater than 0 degrees. The one or more therapeutic agents may include an antioxidant, an anti-inflammatory agent, an anti-microbial agent, an anti-allergy agent, a decongestant, a sympathomimetic, an anti-tumor agent, an NMDA receptor antagonist, a nootropic, an anti-apoptotic agent, a neurotrophic agent, a neuroprotective agent, a neuroprotective protein, a cannabinoid, a monoclonal antibody, gene therapy, iRNA, protein therapy, anti-VEGF, a hormonal agent, a beta-adrenergic blocker, a growth factor, and a local anesthetic.

[0011] In some variations, one or more of the following may optionally be included in any practicable combination of the above methods, devices, apparatuses, and systems. Further details of the apparatuses, systems, devices, and methods are set forth in the accompanying drawings and the description below. Other features and advantages will become apparent from the description and drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] These and other aspects will now be described in detail with reference to the following drawings. Generally, the figures are not to absolute or relative scale, but are illustrative. In addition, for clarity of illustration, the relative positions of features and elements may be modified.

[0013] Figure 1 The anatomical structure of the ear is shown in a coronal cross-section;

[0014] Figure 2A is a schematic diagram of a device having an integrated reservoir and configured for intratympanic injection;

[0015] Figure 2B is a schematic diagram of a device having a removable reservoir and configured for intratympanic injection;

[0016] Figure 2C is a block diagram showing at least a partially powered embodiment of a device and configured for intratympanic injection;

[0017] Figure 3A is an embodiment of a device configured for intratympanic injection;

[0018] Figure 3B is Figure 3A Another embodiment of the device;

[0019] Figure 3C - 3D is Figure 3A Another embodiment of the device;

[0020] Figure 3E Positioned relative to the middle ear of the ear Figure 3C Schematic diagram of the device;

[0021] Figure 3F Is Figure 3C Cross-sectional view of the distal region of the device;

[0022] Figure 3G Is Figure 3C Side view of the distal region of another embodiment of the device;

[0023] Figure 4A - 4D Various views of another embodiment of the device configured to perform intratympanic injection;

[0024] Figure 4E Is taken at the circle E-E Figure 4A Detailed view of the distal region of the device;

[0025] Figure 4F - 4I Is Figure 4E Detailed view of the device in various injection configurations relative to the tympanic membrane;

[0026] Figure 4J - 4K Is Figure 4A Partial view of another embodiment of the device;

[0027] Figure 4L - 4N Is Figure 4A Partial exploded view of another embodiment of the device, showing the connection of the reservoir cylinder;

[0028] Figure 5A Is Figure 3C Side view of an embodiment of the device having a stabilizing feature in a telescopic configuration;

[0029] Figure 5B And 5C Is Figure 5A View of the device showing the stabilizing feature in an expanded configuration;

[0030] Figure 6 Is coupled to the positioning guide Figure 3C Perspective view of the device;

[0031] Figure 7A - 7B Is Figure 3A Perspective view of an embodiment of the device having a floating delivery head relative to the positioning guide;

[0032] Figure 8 Perspective view of an embodiment of the device having a floating delivery head configured to be coupled to an otoscope handle;

[0033] Figure 9A - 9C Is combined with an aiming elementFigure 4A Various views of an embodiment of the device;

[0034] Figure 10A , 10B , 10B-1, 10C and 10C-1 are those combined with aiming elements configured to provide depth guidance Figure 4A Various views of an embodiment of the device;

[0035] Figure 11 are those combined with sensing elements configured to provide depth guidance Figure 4A Side view of an embodiment of the device;

[0036] Figure 12A - 12B are those combined with a physical proximity sensor to provide depth guidance Figure 4A View of another embodiment of the device;

[0037] Figure 13 View of a catheter guide configured to deliver a substance to the ear canal;

[0038] Figure 14A - 14B View of a temporary implant delivered from the catheter guide to the ear canal;

[0039] Figure 15A - 15C View of another embodiment of a device configured to perform an intratympanic injection;

[0040] Figure 16 Shows a kit including Figure 15A - 15C the device;

[0041] Figure 17 Shows Figure 15A - 15C an embodiment of a flexible needle used with the device;

[0042] Figure 18 Shows Figure 15A - 15C another embodiment of a flexible needle used with the device;

[0043] Figure 19A - 19F View of another embodiment of a device configured to perform an intratympanic injection;

[0044] Figure 20A - 20D Shows a single-lumen tapered needle according to some embodiments;

[0045] Figure 21A - 21D Shows a needle having concentric ventilation cavities according to some embodiments;

[0046] Figure 22A - 22D Shows a needle having parallel ventilation cavities according to some embodiments;

[0047] Figure 22EShows a top view of a needle with parallel ventilation cavities;

[0048] Figure 23A - 23C Shows a needle with parallel ventilation cavities and an optical line according to some embodiments;

[0049] Figure 23D Shows a top view of a needle with parallel ventilation cavities and an optical line according to some embodiments;

[0050] Figure 24 Shows a conventional syringe for injection according to some embodiments. Detailed embodiments

[0051] Depending on the cause, the treatment of SNHL may include pharmacotherapy for hair cell and cochlear afferent nerve regeneration, reversal of cochlear oxidative stress damage, inhibition of apoptosis, and reversal of inflammation. There are a variety of drugs in the final stages of clinical development for treating hearing loss, including: sodium thiosulfate (STS) (Fennec Pharmaceuticals) for preventing cisplatin-induced hearing loss; AM-101 (Auris Medical) for treating tinnitus; AM-111 (Auris Medical) for otoprotection in acute inner ear hearing loss; OTO-104 for treating Meniere's disease; SPI-1005 (Sound Pharmaceuticals) for treating mild to moderate acute noise-induced hearing loss and for treating Meniere's disease.

[0052] The inner ear is difficult to treat effectively. For example, the inner ear accounts for only 0.004% of the average circulating blood volume and is enclosed in one of the densest bones in the human body. These factors, combined with the presence of the blood-labyrinth barrier (BLB), limit the entry of most therapeutic drugs into the inner ear. Oral, intravenous, and intramuscular administration routes are indirect, require high doses, and have the potential risk of systemic side effects. There are also local administration methods. For example, inner ear therapies (such as drugs formulated as biocompatible gels) can enter the middle ear through intratympanic injection through the tympanic membrane (TM). The passive diffusion of the agent from the middle ear to the inner ear after intratympanic injection has different efficacies due to anatomical variations, such as the presence of a pseudomembrane covering the round window membrane, the inability of the injection preparation to contact the round window membrane, and the limited permeability of the round window and oval window membranes. In addition, the rapid clearance of the agent from the perilymph of the inner ear results in the need for repeated intratympanic injections, which is undesirable for patients and is associated with the cumulative risk of infection, inflammation, and long-term damage to the tympanic membrane, in addition to the risk of lower patient compliance. Precise placement of the preparation near the round window membrane can greatly improve the effectiveness of treatment, but it is not easily achievable with current intratympanic surgery, which is performed "blindly" without visualization of the middle ear structures.

[0053] Typically, intratympanic drug delivery is achieved by making a small incision in the anesthetized tympanic membrane and administering the drug in liquid form into the middle ear cavity near the round window. Intratympanic injection is usually performed in an outpatient clinical setting. There are various delicate structures in the middle ear, such as the malleus, incus, stapes, facial nerve, jugular bulb, and carotid artery. Accidental contact with any of these structures can result in adverse effects, which can include hearing loss, paralysis, or bleeding. Therefore, tympanic membrane perforation is usually performed in a clinical setting, sometimes surgically with expensive visual support under general anesthesia to prevent accidental penetration, over-penetration, or unwanted penetration at the wrong location.

[0054] In addition to the need to deliver therapeutic agents to middle ear and inner ear tissues in a controlled, safe, and effective manner, some therapeutic agents for treating noise-related SNHL must be delivered soon after noise exposure (e.g., within less than 24 hours after injury). The environment in which the patient is injured may not be conducive to receiving an intratympanic injection, especially within such a short time. Examples of therapeutic agents for intratympanic injection include methotrexate, gentamicin, aminoglycosides, steroids, and Apafl inhibitors such as LPT99 (see U.S. Patent 9,040,701).

[0055] Devices and systems configured to directly deliver therapeutic agents to the inner ear or middle ear cavity are described herein. The devices and systems described herein provide more effective administration of therapeutic agents by providing access through the ear canal and tympanic membrane to the middle ear, whether by intratympanic administration or intracochlear administration. The systems and devices described herein are particularly useful for first responders in a non-clinical setting to directly deliver therapeutic agents to the middle ear to prevent SNHL. However, it should be understood that the devices described herein can also be used by doctors and other medical personnel in a clinical setting. The therapeutic agents can also treat other forms of hearing loss as well as any one of other ear diseases. Although treatment of the ear is specifically mentioned below, it should also be understood that medical conditions other than these can also be treated with the devices and systems described herein. For example, the devices and systems can provide treatment for inflammation, infection, and cancerous growths. Any number of drug combinations can be delivered using any of the devices and systems described herein.

[0056] The materials, compounds, compositions, articles, and methods described herein can be more readily understood by reference to the following detailed description of specific aspects of the disclosed subject matter and the examples included therein. Before disclosing and describing the materials, compounds, compositions, articles, devices, and methods of the invention, it is to be understood that the aspects described below are not limited to a particular method or particular reagent, as they can vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.

[0057] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents, patent applications, published applications and publications, websites and other public materials mentioned throughout this disclosure are hereby incorporated by reference in their entirety unless otherwise indicated. If there are multiple term definitions herein, the definitions in this section shall prevail. When referring to a URL or other such identifier or address, it should be understood that such identifiers can change and that particular information on the Internet can come and go, but equivalent information is known and can be readily accessed, such as by searching the Internet and / or appropriate databases. The reference thereto attests to the availability and public dissemination of such information.

[0058] As used herein, relative directional terms such as front, back, proximal, distal, lateral, medial, sagittal, coronal, transverse, etc. are used throughout this disclosure. Such terms are used to describe the device and features of the device and are not intended to be limiting. For example, as used herein, "proximal" generally refers to the closest to the user of the implant device and the farthest from the target location of implantation, while "distal" refers to the farthest from the user of the implant device in the patient and the closest to the target location of implantation.

[0059] As used herein, a disease or disorder refers to a pathological condition in an organism, such as one caused by an infection or genetic defect, characterized by recognizable symptoms.

[0060] As used herein, treatment refers to any manner of improving or beneficially altering the symptoms of a disorder, condition or disease. Treatment also includes any pharmaceutical use of the devices described and provided herein.

[0061] As used herein, the improvement or alleviation of a particular disease symptom, such as by administration of a particular pharmaceutical composition, refers to any alleviation that can be attributed to or associated with the administration of the composition, whether permanent or temporary, lasting or brief.

[0062] As used herein, an effective amount of a compound for treating a particular disease is an amount sufficient to improve or in some way alleviate the symptoms associated with that disease. Such amount can be administered as a single dose or can be administered according to a regimen whereby it is effective. The amount can cure the disease, but is usually administered to improve the symptoms of the disease. Repeated dosing may be required to achieve the desired symptom improvement. The terms pharmaceutically effective amount, therapeutically effective amount, biologically effective amount and therapeutic amount are used interchangeably herein to refer to a therapeutic amount sufficient to achieve the desired result, i.e., a therapeutic effect, whether quantitative or qualitative. In particular, a pharmaceutically effective amount in vivo is an amount that results in a reduction, delay or elimination of an adverse effect (such as pathological, clinical, biochemical, etc.) in a subject.

[0063] As used herein, sustained release includes the release of an effective amount of a therapeutically active ingredient over an extended period of time. Sustained release can include first order release of the active ingredient, zero order release of the active ingredient, or other release kinetics, such as intermediate to zero order and first order, or combinations thereof. Sustained release can include the controlled release of a therapeutic agent by passive molecular diffusion driven by a concentration gradient through a porous structure.

[0064] As used herein, a subject includes any animal that is intended to be diagnosed, screened, monitored, or treated. Animals include mammals such as primates and domestic animals. Exemplary primates are humans. A patient refers to a subject, such as a mammal, primate, human, or domestic animal subject, that has a disease or disease state to be determined or a risk of a disease state to be determined.

[0065] As used herein, a therapeutic agent referred to by a trade name includes one or more therapeutic agent formulations commercially available under the trade name, the active ingredient of a commercially available formulation, the generic name of the active ingredient, or a molecule containing the active ingredient. As used herein, one or more therapeutic agents are agents that improve the symptoms of a disease or disorder or improve the disease or disorder. Therapeutic agents, therapeutic compounds, treatment regimens, or chemotherapeutic agents include conventional drugs and drug therapies, including vaccines, which are known to those of ordinary skill in the art and described elsewhere herein. Therapeutic agents include, but are not limited to, portions capable of being controlled and released into the body.

[0066] As used herein, a composition refers to any mixture. It can be a solution, suspension, emulsion, liquid, powder, paste, aqueous, non-aqueous, or any combination of these components.

[0067] As used herein, a fluid refers to any composition that is capable of flowing. Thus, fluids include semi-solids, pastes, solutions, aqueous mixtures, gels, lotions, creams, and other such forms of compositions.

[0068] As used herein, a kit is a packaged combination, optionally including instructions for use of the combination and / or other reagents and components for such use.

[0069] Now referring to the accompanying drawings, Figure 1Shows the anatomical structure of the ear, showing the outer ear, middle ear and inner ear, as well as a portion of the skull 35 and the eustachian tube 45. The outer ear includes the auricle and the ear canal 40. The tympanic membrane 5 provides a barrier between the ear canal 40 and the middle ear or tympanic cavity 30. The inner ear can be divided into the bony labyrinth and the membranous labyrinth. The structural cavities within the bony labyrinth of the inner ear include the vestibule 10, the semicircular canals 15, and the cochlea 20. The hair cells of the cochlea 20 are crucial in converting sound signals into nerve impulses. The hair cells are bathed in secreted fluids, such as perilymph provided by cells along the bony labyrinth and endolymph found within the membranous labyrinth, which help to distinguish vibrations to aid in the hearing process and maintain a sense of balance. The round window 25 includes a round window membrane, which combines with the oval window of the cochlea 20 to allow fluid movement within the cochlea 20.

[0070] Devices configured to enter the middle ear and inner ear directly through the tympanic membrane are described herein. For example, the devices described herein provide access to the middle ear for the direct delivery of one or more therapeutic agents to most effectively treat middle ear and / or inner ear disorders. A variety of devices are described, which can be used alone or in various combinations to form a system. Features described in the context of one embodiment of a device, system, or method are equally applicable to other embodiments of the devices, systems, or methods described herein, although not all such features may be explicitly described. The features of the various devices can be used in combination with any of the embodiments described herein.

[0071] Figure 2A - 2C An embodiment of a device configured to deliver a substance, such as one or more therapeutic agents, to one or more regions of the ear is schematically shown. Figure 2A Is a schematic view of a device 100 having a housing 105, the housing 105 having one or more inputs or actuators 107. The device 100 may include a catheter guide 110 protruding from a region of the housing 105, which is configured to be inserted into and matingly engage with the ear canal. The distal most end of the catheter guide 110 is sized to remain outside the tympanic membrane, and during treatment through the catheter guide 110, movement of the catheter guide 110 within the ear canal can be inhibited by sufficient force or friction. The device 100 may include a needle assembly 115, which is configured to extend distally from the catheter guide 110. The needle assembly 115 may include a flexible shaft, which is sized to be received within and slidably extend through the lumen of the catheter guide 110. The flexible shaft may include a fluid delivery lumen for delivering materials to and / or withdrawing materials from the middle ear. The catheter guide 110 may provide alignment and stabilization of the needle assembly within the ear canal relative to the tympanic membrane. The flexible shaft of the needle assembly may prevent movement from being transmitted to the tympanic membrane when the needle assembly penetrates the tympanic membrane.

[0072] The needle assembly 115 can include a rigid shaft 117 and a semi-rigid or flexible cannula 119. The device 100 can additionally include a reservoir 120 configured to contain a substance 122 to be delivered to the ear region. As Figure 2A shown, the reservoir 120 can be integral with the housing 105, or as Figure 2B shown, the reservoir 120 can be housed within a cartridge 125 configured to reversibly engage at least a portion of the housing 105. In an alternative configuration, the reservoir 120 can be within the syringe barrel of a syringe configured to connect to the needle assembly 115, which reversibly engages at least a portion of the housing 105. Actuation of the device 100 injects the substance 122 from the reservoir 120 through the fluid delivery lumen of the cannula 119 of the needle assembly 115. Each of these components can vary in structure and size, which will be described in more detail below.

[0073] The devices described herein can be purely mechanical devices (e.g., syringe-type actuation mechanisms) or can be at least partially powered instruments. In some embodiments, as will be described in more detail below, the devices incorporate one or more features that can provide stability, guidance, and / or visualization to the user, thereby allowing for better control and understanding of the relative position of the injection during the procedure such that informed choices can be made instantaneously. Figure 2C is a block diagram showing an at least partially powered embodiment of the device 100. The device 100 can include an injection module 400 in communication with an electronic module 500. The injection module 400 can vary depending on the embodiment of the device 100 but can include one or more of a needle assembly 115 configured to extend and retract via a drive element 405 and a pumping mechanism 410 configured to push fluid from the reservoir 120 towards the patient. The electronic module 500 of the device 100 can include one or more of a user interface 505 having one or more actuators 107 and a controller 510. The electronic module 500 can also optionally include a communication port 515 and one or more positioning features 520 configured to improve the aiming and / or visualization of the injection, which will be described in more detail below.

[0074] Terms such as device, system, instrument, syringe, auto-injector, drug delivery device, drug delivery system, treatment device, therapy device, etc. are terms that can be used interchangeably herein and are not intended to limit a particular embodiment of a device relative to another device. For the sake of brevity, the explicit description of each of those combinations can be omitted, although various combinations are contemplated herein. Additionally, different methods of implantation and access of the devices are described herein. Some representative descriptions of how the various devices can be used are provided; however, for the sake of brevity, the explicit description of each method for each system can be omitted.

[0075] Figure 3A - 3B Embodiments of a device 100 having a housing 105 are shown, which are similar in form factor to a syringe having a plunger. Figure 4A - 4N And Figure 15A - 15C Embodiments of a device 100 having a housing 105 are shown, which are similar in form factor to an otoscope. Figure 19A - 19F Embodiments of a device 100 having a housing 105 are shown, which are similar in form factor to an ear speculum tip. The housing 105 can be a straight body or a pistol grip type housing. The housing 105 can include one or more gripping features 127, such as indentations or ergonomic features for gripping the device 100. For example, as Figure 4A - 4D best shown, the exterior of the housing 105 can include a hand-held portion 130 coupled to an upper portion 131, such as an ergonomic pistol grip. The hand-held portion 130 can be an elongated tubular element having a gripping feature 127 that is a knurled surface facilitating single-handed gripping of the device 100. The ergonomic hand-held portion 130 can increase stability and reduce the likelihood of damage due to unintended movement. In Figure 19A - 19F the illustrated embodiment, the exterior of the housing 105 includes a gripping feature 127 having a knurled surface on opposite sides of the viewing channel.

[0076] Depending on whether the device 100 is durable or disposable, the housing 105 can be made of a high-performance engineering thermoplastic (e.g., PTFE) or a metal such as stainless steel or aluminum. The housing 105 can be an integrally molded single-piece construction, or can be formed of two or more panels configured to be coupled together. The housing 105 can include threaded or friction-fit panels configured to open to access the interior of the housing 105, such as to insert or remove a battery or a reservoir cartridge 125, which will be described in more detail below.

[0077] As described above, the housing 105 can incorporate one or more inputs or actuators 107 mounted on a portion of the housing 105, such as one or more plungers, levers, buttons, switches, keys, sliders, or combinations thereof, which are configured to be actuated such as retracted, extended, pressed, squeezed, slid, or otherwise actuated to perform a specific function of the device 100. The one or more actuators 107 can be incorporated into a portion of the housing 105 in a user-ergonomically comfortable manner, such as the hand-held portion 130. In some Figure 3A - 3B embodiments as shown, the actuator 107 can be a syringe plunger configured to push a piston head 104 through a reservoir 120 to eject a substance from the reservoir 120 through a needle assembly 115. In some Figure 4A - 4DIn other embodiments shown, the device 100 may include a pistol-grip handle portion 130 having a trigger-type actuator 107 such that the device 100 can be easily and comfortably held and actuated during use.

[0078] The pistol-grip handle portion 130 may include additional adjusters to modify the user's ergonomics relative to the patient. For example, the pistol-grip handle portion 130 may include an articulated element that allows the user to adjust the angle between the pistol-grip handle portion 130 and the upper portion 131 of the housing 105. The housing 105 may also be a straight body instrument that does not include a pistol grip.

[0079] As described above, the front end region 132 of the housing 105 may be coupled to the distal ear canal guide 110. The guide 110 may provide alignment and stability within the ear canal 40 and direct the needle assembly 115 towards the tympanic membrane 5. In some embodiments, the guide 110 includes a cylindrical portion 134 having an outer diameter configured to smoothly and comfortably insert into and engage with the ear canal 40. The cylindrical portion 134 of the guide 110 may allow a slight seal to form between the ear canal wall and the outer surface of the guide 110. The length of the cylindrical portion may vary. Figure 3A An embodiment is shown with the guide 110 where the cylindrical portion 134 has a first length, while Figure 3B Another embodiment is shown where, compared to the embodiment in Figure 3A , the cylindrical portion 134 of the guide 110 has a greater length. At least a portion of the guide 110 may taper towards the most distal end 136 such that the outer diameter near the most distal end 136 of the guide 110 is less than the outer diameter of the guide 110 near the location where it is coupled to the housing 105 (e.g., see Figure 3A - 3B , 4A-4D). The guide 110 may be similar in shape and form factor to an otoscope (see Figure 4A - 4D , Figure 15A - 15C and Figure 19A - 19F ). For example, the guide 110 may include an inclined frustoconical shape and a smooth surface that allows insertion into the ear canal 40 to a limited depth without damaging the ear. Other shapes are considered to improve the stability and aiming of the tympanic membrane 5.

[0080] Regardless of the configuration and coupling mechanism, the guide 110 may include at least a first lumen 140 extending from the proximal end 138 to the most distal end 136 of the guide 110 (see Figure 3D and 4E-4F). The cavity 140 can be a guiding cavity configured to receive, for example, the needle assembly 115 when the needle assembly 115 extends relative to the device 100. In some configurations, the catheter guide 110 can include at least a second cavity 142 extending from the proximal end 138 to the distal most end 136 of the catheter guide 110 (see Figure 4E - 4I ). In the case where the first cavity 140 of the catheter guide 110 is configured to receive the needle assembly 115, the second cavity 142 can be an observation cavity configured to allow a user to observe an object (such as the eardrum 5) through the second cavity 142. The second cavity 142 can be arranged relative to a magnifying or non-magnifying lens 143 and / or a filter assembly similar to an otoscope with an endoscope (see Figure 4C , 15A and 19B).

[0081] The catheter guide 110 can be removed from the device 100. In some embodiments, the front end 132 of the housing 105 can include coupling features, such as friction fittings, snap fittings, threaded features, or other releasable connectors, including a pop-up mechanism, configured to engage and disengage with corresponding features on the proximal end of the catheter guide 110. The coupling features allow the removal of the catheter guide 110 such that the catheter guide 110 can be cleaned, disinfected, and reused, or preferably, discarded after use. The removable catheter guide 110 allows the device 100 to be customized for and used with a particular patient. For example, the overall dimensions (length and outer diameter) of the removable catheter guide 110 can vary depending on whether the device 100 is for an adult or pediatric patient.

[0082] During the process of piercing the tympanic membrane with the needle assembly, at least a portion of the catheter guide 110 can act as a proximal stabilizing anchor within the ear canal 40. The catheter guide 110 can be configured to be adjustably anchored to the ear canal 40. In some embodiments, the catheter guide 110 can have at least a portion that is configured to expand from an insertion configuration with a small outer diameter to a deployed configuration with a larger outer diameter, which is configured to hold the device in place within the ear canal 40. This engagement can exert sufficient force and / or friction on the walls of the surrounding ear canal 40 to inhibit movement of the catheter guide 110 when piercing the tympanic membrane with the needle assembly. The catheter guide 110 can incorporate any of a variety of anchoring features, including one or more rings, support legs, foam, or other anchors. At least a portion of the catheter guide 110 can be conformable or compressible such that the outer surface of the catheter guide engages, deforms, and / or assumes the shape of the ear canal 40 upon insertion. In some embodiments, the catheter guide 110 can include an inner layer covered by an outer conformable or compressible layer. The outer compressible layer can be made of any suitable material known to those skilled in the art, such as compressible foam, such as polyurethane foam, or silicone overmolded onto the inner layer, which can be harder than the compressible layer. In some embodiments, the outer compressible layer can include a plurality of flexible support rings, disks, or flanges 146 that are configured to conform to the ear canal 40 when the catheter guide 110 is inserted toward the membrane 5 (see Figure 3C - 3E ). The conformable outer surface can be at least partially cylindrical. The conformable outer surface can taper to a narrower outer diameter at the most distal end. The conformable outer surface can have an otoscope shape with inclined curved walls that taper from a larger flared outer diameter at the proximal end to a smaller narrow tubular outer diameter at the distal end.

[0083] The tympanic membrane 5 is a delicate tissue and is vulnerable to damage. However, direct contact with the membrane 5 can provide guidance for obtaining an appropriate needle depth for injection. In some embodiments, the device 100 is configured to make direct contact with the tympanic membrane 5. Figure 3C - 3E An embodiment of the device 100 is shown that includes a catheter guide 110 coupled to the front end region 132 of the housing 105 and a needle assembly 115 extending through the lumen 140. In this embodiment, the contact tip 150 is located distal to the catheter guide 110. The catheter guide 110 can provide alignment along the wall of the ear canal 40, and the contact tip 150 can abut the outer surface of the tympanic membrane 5 (see Figure 3E - 3G ). Similar to the catheter guide 110, the contact tip 150 can be a cylindrical element having a lumen 152 that extends from the proximal end 154 to the distal end 156 of the contact tip 150 and is configured to receive the needle assembly 115 (see Figure 3F)。In this way, the cavity 152 of the contact tip 150 and the first cavity 140 of the ear catheter guide 110 can be coaxially positioned with respect to each other. The combination of the catheter guide 110 and the contact tip 150 can assist in guiding the needle assembly 115 through the septum 5 and into the tympanic cavity 30 or the middle ear. In some embodiments, the distalmost end 136 of the catheter guide 110 can contact the tympanic membrane 5.

[0084] The surface of the catheter guide 110 (or the contact tip 150, if present) at its distalmost end 136 can be disposed generally in a plane perpendicular to or at an angle with respect to the front end 132 of the housing 105. For example, the surface of the catheter guide 110 can be at an angle of about 5, 10, 15, 20, 25, 30, 35, 40, 45 degrees or other angles with respect to the plane of the front end 132 of the housing 105.

[0085] The needle assembly 115 can move relative to the catheter guide 110 between a fully retracted position and a fully extended position. Referring again to Figure 3A - 3G and Figure 4A - 4I , the needle assembly 115 can extend relative to the front end 132 of the device 100. The needle assembly 115 can be fully retracted within the catheter guide 110, for example, during insertion of the catheter guide 110 into the ear canal 40 (see Figure 4F ). For example, when it is necessary to penetrate the tympanic membrane 5 (see Figure 4G - 4I ), the needle assembly 115 can extend outside the catheter guide 110. In additional embodiments, the needle assembly 115 can be completely removed from the catheter guide 110 until it is desired to penetrate the tympanic membrane 5, at which time the needle assembly 115 is coupled to the catheter guide 110 and / or extends beyond the catheter guide 110 (see Figure 15A - 15C and Figure 19A - 19F ).

[0086] The needle assembly 115 can include a shaft 117 and a cannula 119. The shaft 117 can be a substantially rigid element with a sharp tip 113 such that the shaft 117 can penetrate the tympanic membrane 5 without creating a pre-incision. The geometry of the tip 113 can vary, including any of a variety of bevels configured to cut through tissue without causing excessive damage to the tissue upon withdrawal. The cannula 119 can also include a variety of tip geometries, such as an angled tip defining an exit from the cannula 119 or a closed-tip cannula 119 with one or more side ports. The tip geometry of the cannula 119 can allow for directed flow from the cannula 119 to one or more anatomical locations, such as the round window niche. The cannula 119 can be a semi-rigid or at least partially flexible tubular element. In some embodiments, the cannula 119 can be a needle with an at least partially flexible shaft and a distal penetrating tip. The semi-rigid or flexible nature of the cannula 119 reduces unwanted movement transfer of the device 100 to ear structures such as the tympanic membrane 5. The shaft 117 can be formed of any of a variety of suitable materials, including 316 stainless steel and non-metallic materials. The cannula 119 can be formed of any of a variety of suitable materials, including polyimide, PTFE, PEEK, polyamide, or other semi-rigid or suitable flexible materials. In some embodiments, the material can be a soft, elastic, stretchable, and / or resilient biocompatible material. The flexible, soft material is intended to avoid damaging delicate middle ear structures and to avoid transferring movement to the tympanic membrane 5, even when the housing 105 moves. Instead, the flexible material bends, flexes, or otherwise deforms to avoid tearing or rupturing the membrane 5. Materials include medical-grade silicone rubber, medical-grade Teflon, and the like. The material of the structure can be flexible enough to decouple the operator from the patient such that if the operator's hand inadvertently moves, that movement will not be fully transmitted through the cannula 119 positioned through the tympanic membrane.

[0087] The configuration of the needle assembly 115 can vary. For example, the cannula 119 can extend through the lumen 114 of the shaft 117, or the shaft 117 can extend through the lumen of the cannula 119. The cannula 119 can extend through the lumen 114 of the shaft 117 and past the sharp tip 113 of the shaft 117 to access the middle ear (see Figure 3F - 3G ). In this embodiment, both the shaft 117 and the cannula 119 can be hollow tubes. Alternatively, the shaft 117 can be configured as a trocar, stylet, or obturator that extends through the lumen of a more flexible cannula 119. In this embodiment, the shaft 117 can be solid or hollow. The device 100 does not need to include a two-part needle assembly 115. For example, in some embodiments, the device 100 includes a flexible needle with a sharp tip that allows penetration of the tympanic membrane 5 and prevents movement transfer to the membrane, which will be described in more detail below (see Figure 16 - 18 ).

[0088] The shaft 117 and cannula 119 of the needle assembly 115 can both be movable elements. They can move relative to the catheter guide 110 of the device and relative to each other. As described above, the needle assembly 115 is configured to be inserted through the tympanic membrane 5 and into the tympanic cavity 30. The shaft 117 can be pushed out from the catheter guide 110 in the distal direction to penetrate the tympanic membrane 5. The cannula 119 can move with the shaft 117 in the distal direction such that it penetrates the tympanic membrane 5 by means of the shaft 117. The shaft 117 can immediately retract into the catheter guide 110, while the cannula 119 can maintain its position through the tympanic membrane 5 (see Figure 4I ).

[0089] The shaft 117 and cannula 119 can extend and / or retract upon activation of one or more actuators 107. The shaft 117 and cannula 119 of the needle assembly 115 can be extended and / or retracted relative to the catheter guide 110 manually or by electronic actuation using a drive element, which will be described in more detail below. Any of a variety of drive elements can be used to extend and / or retract the needle assembly 115 relative to the tympanic membrane 5, such as electrical, mechanical, hydraulic, pneumatic, or various combinations thereof. For example, linear actuators, screw mechanisms, electromechanical and magnetic linear actuators, hydraulic or pneumatic actuators, and many other mechanisms known to those skilled in the art. As an example, activation of the actuator 107 can cause the shaft 117 and cannula 119 to extend distally relative to the catheter guide 110 to penetrate the target. The shaft 117 can immediately retract proximally, and the cannula 119 remains extended. Retraction of the shaft 117 can occur upon further activation of one or more actuators 107, or can occur automatically without further activation. As another example, the needle assembly 115 can be actuated through the tympanic membrane 5 by a spring-loaded mechanism. The spring-loaded mechanism can include an actuator 107, such as a depressible lever, which extends the needle assembly 115 upon actuation and at least retracts the shaft 117 of the needle assembly 115 upon further actuation. Extension of the cannula 119 can be manually adjusted after retraction of the shaft 117, such as with a slider or other incremental adjuster, to achieve an optimal extension distance relative to the inner wall of the tympanic cavity 30.

[0090] The target location within the middle ear may not be perfectly aligned with the insertion location or trajectory through the tympanic membrane. A steerable guidewire located within or along the cannula 119 or shaft 117 can assist in maneuvering the needle assembly 115 towards the round window and, for example, away from the recess. For example, the catheter guide of the inner shaft 117 of the needle assembly 115 can be used to penetrate the tympanic membrane as described elsewhere herein. Once the membrane is penetrated, the shaft 117 (which can be substantially rigid) can be withdrawn, leaving the flexible cannula 119 in place through the membrane. A steerable atraumatic guidewire can be advanced through the fluid delivery lumen of the flexible cannula 119 and maneuvered to the target location. The flexible cannula 119 can then be advanced along a specified path over the steerable guidewire to the target location. Alternatively, when the shaft 117 is withdrawn from the tympanic membrane, the steerable atraumatic guidewire can remain in place and be maneuvered to the target location. The flexible cannula 119 can then be advanced over the steerable guidewire. Any of a variety of configurations are contemplated herein.

[0091] In some embodiments, the needle assembly 115 does not need to incorporate a separate steerable guidewire. The flexible cannula 119 can be remotely maneuvered by the user such that at least a portion of the needle assembly 115 itself is steerable and / or configured to articulate. For example, the flexible cannula 119 can incorporate one or more pull wires for deflecting the distal portion within a plane of curvature. Once the sharp tip of the shaft 117 has penetrated the tympanic membrane along a selected axial trajectory, the insertion trajectory may need to be slightly altered. For example, the target can be laterally or caudally away from the insertion trajectory to avoid contact with a particular anatomical site. The cannula 119 can be maneuvered to achieve a specified path that is more suitable for reaching the target location. For example, one or more internal guidewires can extend between the distal end of the cannula 119 and the proximal end of the cannula 119 such that the user can manipulate the internal guidewires to control the angle of the distal end of the cannula 119 relative to its longitudinal axis. As is known in the art, the guidewires can be placed under tension to deflect the catheter guide and maneuver the cannula 119 anywhere within a 360-degree range.

[0092] In some embodiments, the flexible cannula 119 can be manufactured to have a bend or curve along a portion of its length. For example, the material of the flexible cannula 119 can be heat-set nitinol. The shape-set cannula 119 can be inserted using a straight shaft that has a longitudinal axis and is more rigid than the flexible cannula 119. When inserted through the more rigid shaft, the bend or curve of the cannula 119 can be straightened to assume the shape of the shaft (i.e., straightened to extend parallel to the longitudinal axis of the shaft). The flexible cannula 119 can be "maneuvered" based on the degree to which the cannula 119 extends out of the distal opening of the rigid shaft and / or due to the rotation of the cannula 119 relative to the shaft during extension. When the cannula 119 extends out of the distal opening of the rigid shaft, the distal end of the cannula 119 can relax back into its bent or curved shape-set form. Rotation of the cannula 119 within the lumen of the rigid shaft can direct the distal end of the cannula 119 towards the target site of treatment.

[0093] The tympanic cavity 30 may include two parts: a tympanic cavity appropriately positioned relative to the tympanic membrane 5 and a recess or epitympanic recess located above the level of the membrane 5 (see Figure 1 ). The recess contains the upper half of the malleus and most of the incus. Including the recess, the vertical and anteroposterior diameters of the tympanic cavity are each about 15 mm. The transverse diameter is measured to be more than about 6 mm and less than 4 mm; relative to the center of the tympanic cavity, it is only about 2 mm. The tympanic cavity 30 is laterally bounded by the tympanic membrane 5, medially bounded by the lateral wall of the inner ear, bounded behind the tympanic cavity and through it with the mastoid air cells, and bounded in front of the auditory tube.

[0094] The diameter range of the needle assembly 115 can vary. In some embodiments, the maximum outer diameter of the needle assembly 115 can be between about 0.30 mm and about 0.60 mm, or between gauge 23-30, or between gauge 25-27. The shaft 117 of the needle assembly 115 can extend from the distal end of the catheter guide 110 a distance of no more than about 5-10 mm. The cannula 119 of the needle assembly 115 can extend from the distal end of the catheter guide 110 a distance of no more than about 3-5 mm. The shaft 117 can extend long enough to extend distally from the catheter guide 110 such that it can be used to penetrate the tympanic membrane 5, but not so long as to approach the otic capsule of the inner ear. The cannula 119 can extend far enough to extend distally from the shaft 117 so as to approach the otic capsule such that substances can be delivered to the medial wall of the tympanic cavity 30. In some embodiments, the needle assembly 115 can include visual guidance (such as a strip, color, marking) to inform the user of the relative extension of the needle assembly 115 through the tympanic membrane (see Figure 17 - 18 ), which will be described in more detail below.

[0095] The devices described herein assist in the stabilization and alignment of the device 100 within the ear canal 40 such that the needle assembly 115 can be used predictably, effectively, and safely for injecting substances without the typical complex visualization features of tympanocentesis performed in a clinical setting. The catheter guide 110 (and the contact tip 150, if present) assist in the stabilization and alignment of the needle assembly 115 relative to the tympanic membrane 5. In some embodiments, the needle assembly 115 extends through the lumen 140 through which the catheter guide 110 passes and is aligned with the longitudinal axis A of the catheter guide 110 (see Figure 3A - 3F ). In other embodiments, the needle assembly 115 extends through the lumen 140 through which the catheter guide 110 passes and is eccentric or offset from the longitudinal axis A of the catheter guide 110 (e.g., see Figure 3G , 4A and 4E). In other embodiments, the needle assembly 115 extends through the lumen 140 through which the catheter guide 110 passes and is eccentric from the longitudinal axis A of the catheter guide 110 and is bent from a first axis to a second axis (e.g., seeFigure 15A - 15C and 19A - 19F). This allows the catheter guide 110 to be positioned within the ear canal 40 against the wall of the ear canal 40 leading to the tympanic membrane 5, and the needle assembly 115 is used to penetrate the quadrant of the tympanic membrane 5 that is remote from the ossicular chain, thereby reducing the risk of structural damage.

[0096] Figure 4F The distal end 136 of the catheter guide 110 is shown, with the needle assembly 115 substantially retracted, thereby preventing the sharp tip 113 of the shaft 117 from inadvertently penetrating the ear tissue. The distal end 136 of the catheter guide 110 is shown located within the ear canal 40 adjacent to the tympanic membrane 5 such that the quadrant of the membrane 5 that is remote from the ossicular chain is the target for penetration by the needle assembly 115. Figure 4G The shaft 117 of the needle assembly 115 extending through the tympanic membrane 5 is shown. Figure 4H The inner delivery cannula 119 is shown extending through the shaft 117 and the membrane 5 such that the distal end of the cannula 119 is located within the middle ear. Figure 4I The shaft 117 of the retracted needle assembly 115 and the inner delivery cannula 119 held within the middle ear extending through the tympanic membrane 5 are shown. The shaft 117 can be used as a guide to thread the delivery cannula 119 into the middle ear before the less rigid delivery cannula 119 rapidly retracts into the lumen 140 of the catheter guide 110. The off - axis needle assembly 115 relative to the longitudinal axis A of the catheter guide 110 reduces damage to the delicate structures near the recess. When the needle assembly 115 is in the injection position, the semi - rigid or flexible nature of the inner delivery cannula 119 reduces the risk of tympanic membrane damage in the event of unwanted inadvertent movement within the housing 105 of the device 100.

[0097] The catheter guide 110 can be attached to the housing such that the position of the guide lumen relative to the housing can be adjusted by the user. The attachment between the catheter guide 110 and the housing can be a rotatable attachment. In some embodiments, the relative position of the needle assembly 115 extending distally from the catheter guide 110 about the longitudinal axis A of the catheter guide 110 can be adjusted. Figure 4J - 4KAn embodiment of an ear catheter guide 110 configured to rotate about a longitudinal axis A relative to a front end 132 of an upper portion 131 of a housing 105 is shown. A lumen 140 through which a needle assembly 115 extends is eccentric or offset from the longitudinal axis A of the catheter guide 110 such that when the catheter guide 110 rotates, the position of the lumen 140 changes its position about axis A. This adjustment allows a user to select the most comfortable or convenient ergonomic positioning while still controlling the position of the needle assembly 115 relative to the central axis of the ear canal 40. The catheter guide 110 and the lumen 140 may rotate about the longitudinal axis A in degree increments between 0 degrees and 360 degrees. The degree of rotation of the catheter guide relative to the housing may be indicated to the user visually, auditorily, and / or tactually. In some embodiments, the degree increments of rotation may be felt as a series of clicks between preset adjustments or may be observed by the user as a series of relative markings. In some embodiments, the rotation of the catheter guide 110 is fully customizable to achieve an infinite number of degrees of rotation. The catheter guide 110 may also include one or more markings 163 visible to the user during use that identify the position of the lumen 140 when the catheter guide 110 rotates. The markings 163 may indicate the relative anatomical position for an optimal target for the tympanic membrane 5, such as an upper marking 163a that identifies where the patient's nose should be relative to the device 100 and another marking 163b that points to where the patient's feet should be relative to the device 100 (see Figure 4J ). Any of a variety of markings 163 may be incorporated.

[0098] Embodiments of the devices described herein deliver a drug solution and / or drug suspension, as well as powders, liquids, gels, dispersions, and aerosols contained within a reservoir 120, through a cannula 119 having a catheter guide within the tympanic cavity 30. At least a portion of the housing 105 may be configured to receive at least a portion of a reservoir 120 configured to contain a substance 122 to be delivered. The reservoir 120 may be integral with the housing 105 (see Figure 3A - 3D ), or the reservoir 120 may be a detachable element, such as a cartridge 125 containing the reservoir 120 (see Figure 4L - 4N ). In some embodiments, the housing 105 may include one or more windows 164 configured to expose at least a portion of the reservoir 120 from the exterior of the housing 105 such that a user can easily and quickly determine whether the device is ready for injection (see Figure 3A - 3D and Figure 4A ). The window 164 may be a transparent or translucent feature extending through the housing 105.

[0099] Regardless of the configuration, the proximal end of the flexible shaft or cannula 119 can include an inlet configured to be operatively and fluidly coupled to an outlet from a reservoir 120, and a distal region of the cannula 119 can include an outlet configured to be positioned within the middle ear 30. Substance 122 from reservoir 120 can be delivered to the patient through cannula 119, for example by activating actuator 107.

[0100] Cartridge 125 can include a housing 175 having an inner chamber forming reservoir 120, which is configured to store a quantity of substance 122 to be delivered by device 100. Reservoir 120 can be a container surrounded or formed by a flexible material or bag that can expand and be contained within a relatively rigid housing 175. Reservoir 120 can have any suitable shape and size configured to receive a fluid substance, such as through a fill port. The reservoir volume can vary, for example between about 50 ul and about 250 ul, or between about 75 ul and about 200 ul, or between about 100 ul and about 150 ul. The housing 175 of cartridge 125 can be any of a variety of suitable materials, particularly a moldable material, including polymers and specific materials such as polycarbonate and the like. The flexible material contained within housing 175 can also be any of a variety of suitable materials, such as polymers like PET, SiO, linear low density polyethylene, and the like. The drug cartridge 125 can be manufactured as a pre-filled element, or can be filled by the user at the time of use. In some embodiments, reservoir 120 is a separate syringe device configured to be coupled to needle assembly 115, which in turn is inserted through catheter guide 110 to effect an injection.

[0101] In some embodiments, housing 105 (such as handpiece 130) can be at least partially hollow such that cartridge 125 can be removably and operatively secured within housing 105 of device 100 (see Figure 4L - 4N ). Housing 105 can include a receiving slot 177, for example in the lower end region of handpiece 130. The receiving slot 177 can be opened, such as by unscrewing or otherwise separating cap element 178. Cap element 178 can include an internal cradle 179 having an inner diameter configured to receive the outer diameter of cartridge 125. The user can slide cartridge 125 into cradle 179 and replace cap element 178 onto the lower end region of housing 105 such that internal cradle 179 is inserted within receiving slot 177. When cap element 178 is coupled to housing 105, cartridge 125 can be operatively connected to device 100 such that substance 122 from reservoir 120 can be delivered out through needle assembly 115 upon activation of actuator 107.

[0102] The housing 175 of the cartridge 125 and / or the housing 105 of the device 100 may include one or more corresponding alignment or attachment mechanisms such that the cartridge 125 can be reversibly attached to and detached from the housing 105 of the device 100. The alignment or attachment mechanism may include a tapered needle or similar element within the receiving slot 177 configured to penetrate a septum or other penetrable feature at the upper end of the cartridge 125 to place the reservoir 120 within the cartridge 125 in fluid communication with the proximal end of the inner cannula 119. When installing and coupling the cartridge 125 to the housing 105, the tapered needle may penetrate the septum of the cartridge 125.

[0103] The device 100 may include a pumping mechanism configured to push a substance from the reservoir 120 into the cannula 119 for delivery to a patient when the actuator 107 is activated. The pumping mechanism may be a mechanical mechanism including the actuator 107, such as Figure 3A - 3B the piston plunger of the syringe shown. The pumping mechanism may also be an electric pumping mechanism including a positive displacement pump configured to be driven by any one of a variety of drive mechanisms including hydraulic, pneumatic, piezoelectric, stepper motor, continuous motor, etc. configured to push fluid out of the reservoir 120. In one embodiment, the pumping mechanism is a spring-driven plunger without any active electronics to cause the pumping to occur. In this embodiment, the pumping mechanism is a single-use or limited-use pump suitable for a disposable syringe device.

[0104] In some embodiments, the entire device 100 is disposable and discarded after a single use, similar to how a syringe may be used. In other embodiments, the entire device 100 is reusable and configured to be autoclaved or sterilized. In some embodiments, certain components of the device 100 are durable and reusable after use, while other components are configured to be removed from the durable portion and discarded after use. For example, one or more of the cartridge 125, the needle assembly 115 including the shaft 117 and the cannula 119, and the catheter guide 110 may be removed from the housing 105 and discarded after use. Each of the various components may be manufactured such that they are sterile. One or more components may be manufactured as a kit in a sterile package. Figure 16 An embodiment of a kit 1605 is shown including a sterile package 1610 containing an otoscopic viewing element 300 configured to be coupled to a positioning guide 200 having a scope-like catheter guide 110, and a needle assembly 115 configured to be inserted through the catheter guide 110 and configured to be coupled to a reservoir cartridge 125 such as a pre-filled syringe.

[0105] Figure 5A - 5CAn embodiment showing optional stabilizing features is presented, which can provide support and assist in aligning the needle assembly 115 with the eardrum 5 to further reduce the risk of middle ear injury due to inadvertent needle movement. The device 100 can include one or more retractable outer support legs 182 that are coupled to an area of the housing 105. In one embodiment, three retractable legs 182 can be coupled to an area of the housing 105 such that, when extended, they form a stable tripod relative to the ear canal guide 110. The legs 182 can be symmetrically arranged about the longitudinal axis A of the device 100. Each leg 182 can extend outward at an angle θ relative to the axis A. The angle θ and the length of the legs 182 in the extended configuration can allow the legs 182 to rest against the patient. For example, the first leg 182a can be located in front of the patient's mandible, the second leg 182b can be located at the caudal side of the patient's skull near the neck, and the third leg 182c can be located at the cranial side of the patient's skull near the top of the head. Each leg 182 can include a foot member 184 that is movably coupled to the distal end of the leg 182 and is configured to fold outward ( Figure 5B - 5C ) when the leg 182 is in the extended configuration and fold inward ( Figure 5A ) when the leg 182 is in the retracted configuration. The legs 182 can snap into the extended configuration so that they avoid inadvertent retraction. The degree of extension of each leg 182 can be selected between a plurality of preset angles relative to the longitudinal axis A. Each foot member 184 can rotate about its attachment to provide a customized fit with the patient as the legs 182 move between the inward and outward folded configurations, thereby providing better stability. In some embodiments, the foot member 184 is coupled to its leg 182 by a barrel hinge-type coupler having at least 2 degrees of freedom. In other embodiments, the foot member 182 is coupled to its leg 182 by a ball-and-socket coupler that provides any degree of freedom.

[0106] Figure 6Another embodiment showing alternative stabilizing features is configured to provide additional stability of the device during injection, thereby reducing the risk of middle ear damage due to inadvertent needle movement. The device 100 may be removably coupled to a positioning guide 200. The positioning guide 200 may include a front end 205 and a rear end 210, with the front end 205 configured to couple to the device 100. The rear end 210 may be held by a user during injection, such as by a handle 215. The front end 205 of the positioning guide 200 may include a bore 220 extending between a receiving portion 225 of the front end 205 and the most distal end 230 of the front end 205. The receiving portion 225 is configured to receive and mate with a catheter guide 110 of the device 100. When the catheter guide 110 and the receiving portion 225 are coupled, the bore 220 of the positioning guide 200 is aligned with the position where the needle assembly 115 projects from the catheter guide 110. When the needle assembly 115 is in a retracted configuration, the device 100 and the positioning guide 200 may be coupled together. The device 100, which is coupled to the distal end of the positioning guide 200, may be inserted through the ear canal 40 while the needle assembly 115 remains retracted. Once positioned, the device 100 may be actuated to extend the needle assembly 115 out of the ear catheter guide 110 and through the bore 220 of the positioning guide 200 until the most distal end of the needle assembly 115 extends past the most distal end 230 of the positioning guide 200 and penetrates the tympanic membrane 5. In other embodiments, the positioning guide 200 may be positioned within the ear canal 40 without being coupled to the device 100. For example, the front end 205 of the positioning guide 200 may be inserted into the ear canal 40 and into a bore 220 disposed relative to the tympanic membrane 5 such that the quadrant to be punctured is targeted. When the positioning guide 200 is aligned within the ear canal 40, the most distal end 230 of the front end 205 of the positioning guide 200 is positioned near the tympanic membrane 5, and the receiving portion 225 of the positioning guide 200 remains outside the ear. The user may insert the needle assembly 115 through the bore 220 of the positioning guide 200 through the receiving portion 225 until the most distal end of the needle assembly 115 extends past the most distal end 230 of the front end 205 of the positioning guide 200 and through the tympanic membrane 5 (see Figure 6)。The user can also insert the catheter guide 110 through the receiving portion 225 while the needle assembly 115 remains retracted. Once the catheter guide 110 and the receiving portion 225 are properly positioned and coupled together, the user can actuate the device 100 to extend the needle assembly 115 through the catheter guide 110 and through the aperture 220 of the positioning element 200. The guide 200 can be pre-positioned in the ear, and the already extended needle is inserted therethrough to perform the injection. The guide 200 can also be pre-positioned in the ear, and the device is inserted into the proximal end of the guide 200 while the needle is in the retracted position. Once the guide 200 and the device 100 are properly aligned with each other, the needle can be extended for injection. It should be understood that although the needle assembly 115 need not be movable and can be in a fixed position relative to the housing 105. When used with the fixed needle assembly 115, the guide 200 can provide protection for the ear canal.

[0107] Figure 7A - 7B An embodiment of the device 100 is shown, where the housing 105 includes a floating delivery head 106 coupled to the proximal body 108 by a flexible sleeve 109. The floating delivery head 106 can provide enhanced positioning control and stability and reduce the risk of accidental movement transfer from the proximal body 108. The needle assembly 115 and the catheter guide 110 can be part of the floating delivery head 106. The user can position the delivery head 106 alone within the ear canal 40 without moving or even holding the proximal body 108. The positioning guide 200 can optionally be used to insert the delivery head 106 into the appropriate position within the ear canal 40, as described in more detail above.

[0108] In some embodiments, the floating delivery head 106 can include the needle assembly 115 and an ear catheter guide 110 (see Figure 8 ). In this embodiment, the reservoir 120 can be contained within a syringe-type barrel proximal body 108 coupled to the floating delivery head 106 by a flexible sleeve 109. The proximal body 108 can be configured to inject a substance from the reservoir 120 to the patient through the flexible sleeve 109 coupled to the needle assembly 115 that can protrude from the catheter guide 110. The proximal end 138 of the catheter guide 110 can be coupled to an otoscope handle 300 for positioning and guiding. Thus, the device 100 can include a drug delivery syringe having a plunger-driven or spring-loaded injection mechanism directly connected to the catheter guide 110 and the needle assembly 115 and an otoscope viewing element 300. This embodiment separates the otoscope viewing from the delivery syringe to reduce the risk that unwanted movement due to delivery initiation is inadvertently transmitted to the trans-tympanic element and membrane damage.

[0109] In addition to the above-described stabilization features, the devices described herein may incorporate one or more features that facilitate visualization, aiming, and hitting of the needle assembly 115 to prevent inadvertent penetration and damage to delicate structures in the ear during injection. As described above and as Figure 8 shown, the catheter guide 110 of the needle assembly 115 having a needle extending therethrough and fluidly coupled to the reservoir 120 may be configured to couple to a separate otoscope viewing element 300. Alternatively, the device 100 itself may have an otoscope form factor and incorporate one or more visualization features typical of an otoscope. Referring again to Figure 4A , the front end 132 of the upper portion 131 may be coupled to the catheter guide 110, which is configured to be inserted into the ear canal similar to an endoscope tip. The rear end 133 of the upper portion 131 may incorporate an observation lens 143 similar to an otoscope lens for the user to view the target area of the injection. The first cavity 140 passing through the catheter guide 110 may be eccentric or offset from the longitudinal axis A of the catheter guide 110 such that the user may view an object through the second cavity 142 using the lens 143. For example, the user may see the tympanic membrane 5 through the second cavity 142 before, during, and / or after advancing the needle assembly 115 through the first cavity 140. The visualization feature may enhance the safety of the device by allowing the user to view the tympanic membrane 5 as the needle assembly 115 advances toward the tympanic membrane. Endoscopes, video visualization devices, and other viewing elements may also be used with the device. The device may also incorporate one or more lighting elements, such as LEDs, lenses, light pipes, filters, etc., that improve visibility through the device during use.

[0110] Figure 15A - 15C Another embodiment of the device 100 is shown having an otoscope viewing element 300 configured to couple to a positioning guide 200. The viewing element 300 may include a handheld portion 130 and an upper portion 131. The positioning guide 200 may include a proximal receiving portion 225 configured to engage the upper portion 131 of the viewing element 300 and a catheter guide 110 configured to be inserted into the ear canal similar to an endoscope tip. The catheter guide 110 of the positioning guide 200 may include an observation cavity 142 and a guide cavity 140, and in Figure 15A - 15C the embodiment of, the guide cavity 140 is a single flexible needle shaft. The needle assembly 115 may be inserted into the guide cavity 140 through a proximal opening 1505 in the cavity 140 on the positioning guide 200. The guide cavity 140 may extend from the proximal opening 1505 to a distal opening 1510 located at the distal end 136 of the catheter guide 110. The guide cavity 140 may have a curved shape corresponding to the taper of the outer wall of the catheter guide 110. The proximal opening 1505 may have a receiving entrance that is enlarged relative to the inner diameter of the guide cavity 140 to facilitate insertion of the needle assembly 115 into the guide cavity 140 (see Figure 19F)。The inner diameter of the guiding cavity 140 may be sufficient to accommodate the outer diameter of the needle assembly 115. Thus, the inner diameter of the guiding cavity 140 may be between about 0.4 mm and about 1.0 mm. In contrast, the inner diameter of the viewing cavity 142 may be significantly larger.

[0111] As described above, the guiding cavity 140 may extend between the proximal opening 1505 and the distal opening 1510, and the distal opening 1510 is curved along the inclined wall of the catheter guide 110. The guiding cavity 140 may be eccentric or offset from the longitudinal axis A of the catheter guide 110, such that the user can observe an object through the viewing cavity 142 using the lens 143. Thus, the distal opening 1510 of the guiding cavity 140 may be disposed on one side of the distal opening of the viewing cavity 142. The rear end 133 of the upper portion 131 may include the viewing lens 143 to allow the user to observe the injection target area through the viewing cavity 142 of the positioning guide 200. After positioning the catheter guide 110 in the ear canal, the needle assembly 115 may be inserted through the guiding cavity 140 until it extends past the most distal end 136 of the catheter guide 110, as described elsewhere herein. The catheter guide 110 may have a tapered inclined shape, where the proximal outer diameter of the catheter guide 110 is greater than the distal outer diameter. The guiding cavity 140 may extend along the curved wall of the catheter guide 110 between the proximal opening 1505 and the distal opening 1510. The distal opening 1510 of the guiding cavity 140 may be positioned eccentric or offset from the longitudinal axis A of the catheter guide 110. The curve of the guiding cavity 140 may be from a first axis to a second axis. The first axis may extend through the proximal opening 1505 into the guiding cavity 140, and the second axis extends from the guiding cavity through the distal opening 1510. The first axis may be arranged at an angle with respect to the second axis and / or the longitudinal axis A of the conduit guide 110. The second axis may be parallel to (and eccentric to) the longitudinal axis A. The angle between the first axis and the second axis may be greater than 0 degrees but less than 90 degrees. Thus, the first axis is preferably not parallel to the second axis and preferably not perpendicular to the second axis. In some embodiments, the angle between the first axis and the second axis is about 5 - 85 degrees, about 10 - 80 degrees, about 15 - 75 degrees, about 20 - 70 degrees, about 25 - 65 degrees, including about 45 degrees. The guiding cavity of any of the embodiments described herein may also be curved. For example, Figure 3C - 3F the cavities 140 and 152 of the contact tip 150 shown in need not be straight and may curve from a first axis to a second axis that is at an angle to the first axis, as described above.

[0112] The guide lumen 140 can have an inner diameter adapted to receive the outer diameter of the needle assembly described herein. In some embodiments, the needle assembly includes a small gauge needle shaft having a gauge between about 30g and about 33g. The guide lumen 140 can in turn have an inner diameter that is at least as large as the small gauge needle (e.g., at least 0.22 mm). The inner diameter of the guide lumen 140 can be between about 0.170 mm and about 1.00 mm or between 0.22 mm and about 0.65 mm. Some of the needle assemblies described herein include a larger proximal bore portion. The large bore portion can be 20g to 25g. Thus, the lumen 140 can have an inner diameter that is at least as large as that which accommodates the larger bore portion (e.g., up to about 0.95 mm). The inner diameter of the guide lumen 140 need not be uniform and can vary along its length. In some embodiments, the guide lumen 140 can have a distal region near the distal opening 1510 with a smaller inner diameter sized to receive a smaller gauge shaft (e.g., 30g - 33g) and a proximal region near the proximal opening 1505 with a larger inner diameter sized to receive a larger gauge shaft (e.g., 20g - 25g). The reduction in the inner diameter of the guide lumen 140 near the distal opening 1510 can help prevent over-insertion of the shaft through the guide lumen 140.

[0113] The proximal opening 1505 can be positioned relative to the catheter guide 110 in a location that permits easy entry of the needle assembly 115 into the guide lumen 140. In some embodiments, such as Figure 15A shown, access to the proximal opening of the guide lumen 140 can be obtained on one side of the catheter guide 110. As seen through the viewing lens 143 at the proximal end of the catheter guide 110 from the user's perspective, the proximal opening 1505 of the guide lumen 140 can be located between about 3 o'clock and about 5 o'clock, or between about 7 o'clock and about 9 o'clock, on a first side of the viewing lens 143. In other embodiments, such as Figure 19A - 19D the embodiment shown, the proximal opening 1505 into the guide lumen 140 can be located at about 6 o'clock or on the lower side of the catheter guide 110 between the gripping features 127 on either side of the viewing lens 143. The foregoing are examples of more ergonomically comfortable configurations. Any of a variety of configurations are contemplated herein.

[0114] The positioning guide 200 can be removed from the upper portion 131 of the viewing element 300. The cross-section of the receiving portion 225 of the positioning guide 200 can be generally C-shaped so as to slide onto or snap onto the upper portion 131 such that the central axis of the guide lumen 140 is generally aligned with the viewing lens 143. Any of a variety of coupling mechanisms are contemplated herein.

[0115] The needle assembly 115 may include a needle 1515 having a proximal connector 1520 and a distal sharp tip 1525. The shape of the tip 1525 may vary as known for a needle bevel. The shaft of the needle 1515 may be flexible such that when the flexible shaft or cannula is inserted through the first lumen 140, the needle 1515 may bend along the path of the guide lumen 140 (see Figure 15A - 15C ). The needle 1515 may include a visual marker 1530 on its outer surface, located at a distance proximate to the tip 1525. The marker 1530 may be visualized during use (i.e., through the second lumen 142) to ensure proper insertion depth of the shaft of the needle 1515. For example, the user may align the marker 1530 with the tympanic membrane 5 (see Figure 17 ) to ensure proper penetration depth (arrow). Preferably, the tip 1525 of the needle 1515 reaches a location within the middle ear near but not contacting the medial wall of the tympanic cavity 30. The marker 1530 may be positioned on the shaft of the needle 1515 to achieve this optimal distance. Figure 18 A further embodiment of the needle 1515 having a plurality of visual markers 1530 is shown. The plurality of visual markers 1530 may include a first marker 1530a located distally of a second marker 1530b. The plurality of markers 1530 may be unique to one another such that they are distinguishable to the user. The markers 1530 may be distinguishable colors (e.g., red, yellow, green, etc.), or distinguishable in number or shape (e.g., rectangular strip, fan-shaped strip, triangular strip, etc.). In one embodiment, the distal marker 1530a is red and indicates the portion of the needle that must be fully inserted into the tympanic cavity 30. The proximal marker 1530b is green and indicates the portion of the needle that must remain fully visible within the ear canal and near the tympanic membrane 5. The first marker 1530a and the second marker 1530b may be separated from one another by a distance such that the tympanic membrane 5 is aligned with that portion of the needle shaft between the markers, which may form a third marker 1530c. The first marker 1530a may indicate the portion of the needle shaft that must be fully inserted through the tympanic membrane 5, and the second marker 1530b may indicate the portion of the needle shaft that must not be inserted through the tympanic membrane 5 and remain visible to the user. The relative alignment of the markers 1530 with the tympanic membrane 5 may ensure that the user achieves an optimal depth of entry into the tympanic cavity 30. The markers 1530 on the needle shaft may provide a user-visible graduated surface that directly measures the insertion of the needle shaft through the tympanic cavity 30.

[0116] Figure 16An embodiment of kit 1605 is shown, the kit 1605 having a sterile package 1610 that includes an observation element 300, a positioning guide 200 having a catheter guide 110, a needle assembly 115, and a reservoir barrel 125. In this embodiment, the reservoir barrel 125 is a syringe body having a plunger actuator 107 (e.g., pre-filled with a therapeutic agent or empty and configured to be filled with a therapeutic agent). The needle assembly 115 may include a needle 1515 having one or more visual markers 1530, a proximal connector 1520, and a sharp tip 1525.

[0117] Figure 19A - 19F Another embodiment of a device 100 for performing an intratympanic injection is shown, which does not need to include a conventional pistol-grip type handle portion. In this embodiment, the device 100 is generally tubular and designed to be held between the thumb and index finger of a single hand. A pair of gripping features 127 may be located on opposite sides of the device 100. The device 100 may include an integrated viewing lens 143 at the proximal end and a cannula-shaped catheter guide 110 at the front end. As in Figure 15A - 15C the embodiment, the catheter guide 110 may include a guide lumen 140 and an observation lumen 140. The guide lumen 140 may extend from a proximal opening 1505 to a distal opening 1510 along the curve of the catheter guide 110 and be configured to receive the needle assembly 115. The guide lumen 140 may be eccentric or offset from the axis of the observation lumen 142 such that a user can visualize the injection through the observation lumen 142 using the viewing lens 143.

[0118] Figure 20A A side view of an embodiment of the needle assembly 115 is shown, which includes a single-lumen tapered needle 900 having a standard luer connector 901 for intratympanic injection. The needle assemblies described herein may be long enough and flexible enough, depending on the specifications of the curved guide lumen 140 to be inserted through as described above and as Figure 19F shown. In one embodiment, the needle assembly 115 may include a needle 900 that is 25 gauge and has a length of up to about 13.0 cm. The needle 900 includes a longitudinally extending cylindrical shaft 921a ( Figure 20C ), which has a smooth outer surface diameter, a distal end, a proximal end, and an inner surface diameter defining fluid lumens 906a, 906b. A portion of the shaft tapers symmetrically about the longitudinal axis of the shaft at a collar region 907a, the collar region 907a having a gradually decreasing outer surface diameter and a gradually decreasing inner surface diameter towards the distal end ( Figure 20D ). The total needle length may be about 3.5 - 4.0 cm long, measured from the distal penetrating tip 903 to the attachment point at the luer connection point 902. The luer connection 901 may in turn be attached to a plurality of standard syringes ( Figure 24 ), modified syringes ( Figure 3A - 3G, 5A - 5C), an improved otoscope( Figure 4A - 4N ), or other such devices. In some embodiments, the overall length allows the needle 900 to travel down the ear canal 40 (e.g., through the guiding lumen 140 of the catheter guide 110) and pierce the tympanic membrane 5( Figure 1 ). The large - bore portion 905 can be approximately 1 inch (i.e., 2.5 cm) long and can be between 20 - 25 gauge needles to reduce flow restriction, thus enabling faster injection into the middle ear. The diameter of the needle can be reduced (i.e., symmetrically tapered) in the collar region 907a of the needle. The trans - tympanic portion 904 can be located distal to the collar region 907a (between the penetrating tip 903 and the collar region 907a) and can measure approximately 0.5 inch (i.e., 1.25 cm) long. Relative to the large - bore portion 905, the trans - tympanic portion can have a reduced diameter (i.e., 30 - 33 gauge) to form a smaller hole through the tympanic membrane. The large - bore portion can be symmetrically tapered to the flexible trans - tympanic portion 904 at the collar region. The trans - tympanic portion 904 can be flexible to prevent movement transfer to the tympanic membrane when the needle assembly penetrates the tympanic membrane. This minimizes trauma to the tympanic membrane, reduces tympanic membrane scarring, and promotes healing. The configuration of the trans - tympanic portion makes it more flexible and capable of being pushed through a curved working channel on an endoscope, especially an endoscope with an offset needle entry, for easier positioning in the middle ear. Figure 20B is an enlarged view of the conical region 907a and the trans - tympanic portion 904. For example, the collar region 907a can be located at any position along the length of the needle, just proximal to the penetrating tip 903, to accommodate anatomical differences.

[0119] Figure 20C shows a cross - sectional view similar to Figure 20A . A single fluid lumen 906a, 906b is shown extending along the length of the needle 900 of the needle assembly 115 and tapering in the transition region of the collar region 907a. Figure 20D is Figure 20C an enlarged cross - sectional view of a portion of

[0120] Figure 21A including the large - bore portion 905, the conical trans - tympanic portion 904, and the collar region 907a. During use, the distal penetrating tip 903 and a portion of the trans - tympanic portion 904 can penetrate the tympanic membrane into the middle ear. In some embodiments, the needle 900 can include an outer ring or shoulder positioned around the needle shaft at or near the collar 907a. The outer diameter of the outer ring can be sized to prevent the needle 900 from being over - inserted into the tympanic membrane. The outer ring can be made of a substantially soft material to avoid damage to ear tissue and can prevent the large - bore portion 905 from passing through the tympanic membrane. shows a needle assembly 115 having concentric ventilation lumens. More specifically, a concentric ventilation needle 910 for penetrating the tympanic membrane 911 to deliver a therapeutic agent to a patient's middle ear (and reduce the pressure therein) is shown(Figure 21A - 21D )。The longitudinally extending cylindrical shaft 921b has a smooth first outer surface diameter 919, a smooth second outer surface diameter 920, a distal end terminating in a penetrating tip 903, a proximal end terminating in a Luer connection 901, a first inner surface diameter 917, and a second inner surface diameter 918. Both the first and second inner surface diameters 917, 918 define a fluid chamber 916. A portion of the shaft may taper symmetrically about the longitudinal axis of the shaft at the collar region 907b. The collar region 907b gradually transitions from the first outer surface diameter 919 to the second outer surface diameter 920 distally. The first outer surface diameter 919 may be greater than the second outer surface diameter 920. The proximal end 902 may be attached to the Luer connector 901, which may be attached to a plurality of standard syringes( Figure 24 ), improved syringes( Figure 3A - 3G , 5A - 5C), improved otoscopes( Figure 4A - 4N ) or other such devices containing a therapeutic agent.

[0121] The penetrating tip 903 may be located at the distal end and define a fluid outlet in communication with the fluid delivery chamber 916 such that the therapeutic agent may longitudinally exit the fluid chamber 916 and enter the middle ear after the tympanic membrane 911 is penetrated. The ventilation portion 914a may be concentrically located near the collar region 907b. The ventilation portion 914a has at least one distal vent 912a and at least one proximal vent 913a, and ventilation paths 915a and / or 915b are located between the proximal vent and the distal vent. The ventilation paths 915a and / or 915b extend parallel to each other along the length of the fluid path 916. When the needle may be inserted into the tympanic membrane 911, the path vents air and / or fluid from the patient's middle ear, and when the distal vent 912a and the proximal vent 913a are on opposite sides of the tympanic membrane, the therapeutic agent may be injected into the middle ear( Figure 21B , 21D ). Although the path vents air since the tympanic cavity is filled with air, there may be liquefied effluent, for example, in the case of a pre - existing middle ear infection. Thus, fluid may also be vented if desired. As the therapeutic agent is injected into the middle ear, the pressure may increase, and this concentric ventilation needle allows for a more comfortable experience for the patient during the treatment of ear diseases.

[0122] Any needle assembly described herein may include features for achieving ventilation or pressure balance, such as the vents described above and / or ventilation through the annular space between the inner and outer shafts of the needle assembly described elsewhere herein.

[0123] The first inner surface diameter 917 can be greater than the second inner surface diameter 918, and the first and second inner surface diameters can transition at a location near the ventilation portion. The distal and proximal ventilation ports are in a geometric planar shape and can be, for example, circular, elliptical, square, rectangular, triangular, rhombic, trapezoidal, or a combination thereof.

[0124] Figure 22A The needle assembly 115 is shown, which includes parallel ventilation needles 929 for penetrating the tympanic membrane to deliver a therapeutic agent to the middle ear of a patient and reduce the pressure therein. The needle includes a longitudinally extending cylindrical shaft 921c having a smooth first outer surface diameter 919, a smooth second outer surface diameter 920, a distal end, a proximal end, a first inner surface diameter 917, and a second inner surface diameter 918. Both the first and second inner surface diameters can define a fluid chamber. A portion of the shaft can symmetrically taper about the longitudinal axis of the shaft at a collar region 907c, and the collar region 907c gradually transitions from the first outer surface diameter 919 towards the distal end to the second outer surface diameter 920. The first outer surface diameter 919 can be greater than the second outer surface diameter 920. The proximal end can be configured to be attached to a Luer connector 901, and the Luer connector 901 is attached to a syringe containing a therapeutic agent. This can include a standard syringe ( Figure 24 ), an improved syringe ( Figure 3A - 3G , 5A - 5C), an improved otoscope ( Figure 4A - 4N ), or other such devices containing a therapeutic agent. The penetrating tip 903 located at the distal end defines a fluid outlet to communicate with the fluid chamber such that the therapeutic agent can longitudinally exit the fluid chamber and enter the middle ear after the tympanic membrane 911 is penetrated. The ventilation portion 914b can be positioned parallel to the cylindrical shaft 921c. The ventilation portion 914b has at least one distal ventilation port 912b and at least one proximal ventilation port 913b and a ventilation path 915c therebetween, and the ventilation path 915c extends parallel to the length of the fluid path 916 respectively. The ventilation path 915c is configured to discharge air and / or fluid from the middle ear of the patient when the needle can be inserted into the tympanic membrane 911, and can deliver the therapeutic agent such that at least one distal ventilation port 912b and at least one proximal ventilation port 913b are located on opposite sides of the tympanic membrane 911 ( Figure 22D ).

[0125] Figure 22E A top view of the needle with parallel ventilation chambers is shown. The ventilation path 915c extends parallel to the length of the fluid path 916 respectively.

[0126] Figure 23A - 23C The needle assembly 115 according to some embodiments is shown, which includes a needle 930 having parallel ventilation chambers and an optical line. Note that Figure 23B is Figure 23AThe magnified portion rotates about an axis (arrow 928) to show additional details of the optical component and other elements. More specifically, a parallel ventilation needle with an optical component penetrates the tympanic membrane 911 to deliver a therapeutic agent to the patient's middle ear, reduce the pressure therein, and visualize it. The needle includes a longitudinally extending cylindrical shaft 921d. The shaft 921d has a smooth first outer surface diameter 919, a smooth second outer surface diameter 920( Figure 23B ), a first inner surface diameter 917, and a second inner surface diameter 918. Both the first and second inner surface diameters 917, 918 define a fluid chamber( Figure 23C ). A portion of the shaft may taper symmetrically about the longitudinal axis of the shaft at the collar region 907d, which gradually transitions from the first outer surface diameter 919 towards the distal piercing tip 903 to the second outer surface diameter 920. The first outer surface diameter 919 may be greater than the second outer surface diameter 920. The proximal end of the shaft 902 is attached to a Luer connector 901, which in turn may be attached to a syringe containing a therapeutic agent. This may include a standard syringe( Figure 24 ), an improved syringe( Figure 3A - 3G , 5A - 5C), an improved otoscope( Figure 4A - 4N ), or other such device containing a therapeutic agent. The piercing tip 903 may be located at the distal end of the shaft, defining a fluid outlet in communication with the fluid chamber such that the therapeutic agent can longitudinally exit the fluid chamber and enter the middle ear after the tympanic membrane 911 is penetrated by the tip 903( Figure 23C ).

[0127] The optical portion 926 is positioned parallel to the cylindrical shaft 921d. The optical portion 926 has a distal opening 922 and a proximal opening 923 and a duct 924( Figure 23B ) connecting the proximal opening 922 and the distal opening 923( Figure 23C ). The optical portion 926 and the associated duct 924 extend parallel to the length of the fluid path 916 but are separate from the fluid path 916. The duct 924 encloses the optical line 925a. The optical line has a proximal end 925c and a distal end 925b. When the needle tip 903 can be inserted (i.e., penetrate) the tympanic membrane 911, the distal end 925b of the optical line 925a exits the distal opening 922 and enters the patient's middle ear, such that the distal opening 922 and the proximal opening 923 are on opposite sides of the tympanic membrane 911( Figure 23C ). The optical line 925a may be an optical fiber line that provides real - time illumination and / or imaging capabilities. The proximal end of the optical line 925c may be connected to a camera, a computer monitor, a television, or other similar device 927. The optical line 925a may include a pressure sensor and / or a position sensor. For example, the position sensor can assist in positioning the needle. The optical line 925a may include acrylate - coated or polyimide - coated fibers, and the needle can be sterilized in an autoclave or other such.

[0128] The ventilation portion 914c can be positioned parallel to the cylindrical axis 921c ( Figure 23A and 23C ). The ventilation portion 914c has at least one distal ventilation port 912c and at least one proximal ventilation port 913c and a ventilation path 915c therebetween, the ventilation path 915c extending parallel along the length of the fluid path 916 respectively. The ventilation path 915c is configured to discharge air and / or fluid from the middle ear of the patient when the needle can be inserted into the tympanic membrane 911 and the therapeutic agent can be delivered, such that at least one distal ventilation port 912c and at least one proximal ventilation port 913c are located on opposite sides of the tympanic membrane 911 ( Figure 23C ).

[0129] Figure 23D A top view of a needle having a parallel ventilation cavity and an optical line according to some embodiments is shown. The ventilation path 915c extends parallel along the length of the fluid path 916 and can be separate from the fluid path 916. The conduit 924 also extends parallel along the lengths of the fluid path 916 and the ventilation path 915c, but can be a conduit separate from the other paths. The optical line 925a shown in the middle of the conduit 924 enclosed in Figure 23D the conduit 924

[0130] Now turning to Figure 24 , a standard (i.e., general, conventional, typical) syringe 931 can be filled with a selected volume of the therapeutic agent 933 for use, for example, with the intratympanic needle 900 ( Figure 20A ), 910 ( Figure 21A ), 929 ( Figure 22A ) or 930 ( Figure 23A) is injected into the middle ear. The distal end 932 of the syringe 931 can receive a Luer connector 901 to attach any one of the needles 900, 910, 929, or 930. The Luer connection 901 can receive a Luer lock tip (i.e., a fixed screw-type connection), a slip tip (i.e., a slip or push-on connection), an eccentric tip (i.e., an off-center tip), a catheter tip (i.e., a long tapered slip tip), or other connections known to those skilled in the art. Depending on a series of factors or the requirements of a procedure, one needle can be interchanged, replaced, or changed to a similar or different needle. In this way, needles can be added 932 or removed 933 from the syringe 931. For example, if it is important to observe the middle ear and / or inner ear during injection, the needle 930 can be used because it includes an optical component. Any combination of the needles 900, 910, 929, or 930 and / or the syringe 931 can be single-use (i.e., disposable) or multi-use (i.e., after sterilization). It should be understood that the various needles described herein (e.g., 900, 910, 929, 930, 1515, etc.) can incorporate one or more features of any other needle described herein.

[0131] Referring again to Figure 2C , the device 100 can be at least partially powered instrument that includes an injection module 400 operably communicating with an electronic module 500. The injection module 400 can vary depending on the implementation of the device 100, but can include one or more of a needle assembly 115 configured to extend and retract via a drive element 405 and a pumping mechanism 410 configured to push fluid from a reservoir 120 towards the patient. The electronic module 500 of the device 100 can include one or more of a user interface 505 having one or more actuators 107 and a controller 510. The electronic module 500 can also optionally include a communication port 515 and one or more positioning features 520 configured to improve the aiming and / or visualization of the injection, which will be described in more detail below.

[0132] The user interface 505 can receive manual input from the user and can include one or more actuators 107, including buttons, keypads, touchscreens, or other inputs. The configuration of the one or more actuators 107 can vary. Various features of the device can include separate actuators 107 for activation. For example, the extension of the needle assembly 115 can be achieved by activating a first actuator, and the retraction of the needle assembly 115 can be achieved by activating a second actuator. Alternatively, both the extension and retraction of the needle assembly 115 can be achieved by activating a single actuator, which is a two-stage actuator such that the direction of the achieved movement depends on the degree of actuation of the actuator 107. The extension can be achieved by a first activation of the actuator 107, and the retraction can be achieved by a second activation of the actuator 107. Additionally, during a single activation of the actuator 107, the extension and retraction can be achieved in a two-step manner. The user interface 505 can also include one or more inputs that change the actuation achieved when activating the one or more actuators 107. For example, Figure 4L the cap element 178 (or another input on the housing 105) shown in

[0133] can be used as an adjustment knob configured to change the degree of extension of the needle assembly 115 achieved when activating the actuator 107. The cap element 178 can be used to change the length of the shaft extension, the activation of the shaft, and / or the deployment of the inner cannula. One or more of the inputs or actuators 107 can be mechanical or electrical. Although the above describes the user using a "lever" or "actuator" to cause a specific action of the device to occur, actuation can also occur by programming the device to perform a specific action through the user interface on the instrument.

[0134] Still referring to Figure 2C, the controller 510 may include at least one processor and a memory device. The memory may be configured to receive and store user input data as well as data acquired during the use of the device 100. The memory may be any type of memory capable of storing data and transmitting the data to one or more other components of the device, such as the processor. The memory may be one or more of flash memory, SRAM, ROM, DRAM, RAM, EPROM, dynamic memory, etc. The memory may be configured to store user information, usage history, administered injections, etc.

[0135] In some embodiments, one or more components of the device 100 may be powered by a battery. The battery may be a removable battery that may be encapsulated within a portion of the device housing 105. The battery may have different chemical compositions or characteristics. For example, the battery may include lead acid, nickel cadmium, nickel metal hydride, silver oxide, mercury oxide, lithium ion, lithium ion polymer, or other lithium chemistries. These instruments may also include rechargeable batteries that are recharged using a DC power port, induction, solar cells, etc. Power systems known in the art for powering medical devices used in an operating room will be considered herein. It should be understood that other power systems known outside the field of medical devices will also be considered herein.

[0136] Still referring to Figure 2C , the device 100 may optionally include a communication port 515 that may be configured to communicate with another device. In some embodiments, the communication port 515 may communicate with the removable cartridge 125. In some embodiments, the communication port 515 may communicate with an external computing device 600. The communication port 515 of the device 100 may be a wired communication port, such as an RS22 connection, a USB connection, a Firewire connection, a proprietary connection, or any other suitable type of hardwired connection configured to receive information and / or transmit information to the external computing device 600. Alternatively or additionally, the communication port 515 may include a wireless communication port such that information may be fed between the instrument 100 and the external computing device 600 via a wireless link. The wireless connection may use any suitable wireless system, such as Bluetooth, Wi-Fi, radio frequency, ZigBee communication protocol, infrared, or a cellular phone system, and may also use encoding or authentication to verify the source of the received information. The wireless connection may also be any of a variety of proprietary wireless connection protocols. In some embodiments, the device 100 does not have a user interface 505 and communicates with an external computing device 600 configured to display information related to the instrument 100. It should be understood that the external computing device 600 with which the instrument 100 communicates may vary and include, but is not limited to, a desktop computer, a laptop computer, a tablet computer, a smartphone, or other device capable of displaying information and receiving user input.

[0137] The communication port 515 of the device 100 can communicate with the cartridge 125. In some embodiments, the communication port 515 can communicate with a transceiver or other data element 176 configured to communicate with the communication port 515, such as an encoder or a bar code type strip on the housing 175 of the cartridge 125. As an example, the element 176 can store data about the cartridge 125, such as the substance, volume, concentration, manufacturing date contained in the reservoir 120, and any other information about the substance or the cartridge 125. The data can be stored within the element 176 and transmitted to and received by the controller 510 of the instrument 100 when the element 176 on the cartridge 125 is "read". For example, the cartridge 125 can be a bar code such that the device 100 reads what substance 122 is loaded in the device. The controller 510 can use the identification of the cartridge 125 to set or adjust certain parameters. The data can be received as part of the setup procedure and preparation of the actual instrument being used. This can be automatically initiated by software run by the controller 510 of the instrument 100 without any user input. Alternatively, the user can manually enter information about the substance 122 on the user interface 505 of the device 100. The device 100 can also be used without any substance being introduced.

[0138] The communication can be one-way or two-way wireless communication. The communication can be wireless communication, such as a transmitter and / or receiver, a radio frequency (RF) transceiver, a WI-FI connection, an infrared or a Bluetooth communication device. The data element 176 of the cartridge 125 can include an encoder or a bar code type strip configured to be scanned and read by a corresponding reader device of the instrument 100, which is operably communicable with the controller 510. The data element 176 can alternatively be an RFID chip or the like that transmits data to a reader such as a data receiving processor. Such an encoder device includes the ability to securely transmit and store data, such as by encryption, to prevent unauthorized access to or tampering with such data. The memory of the controller 510 can be configured to maintain a record of a particular cartridge 125. For example, the record can indicate when the cartridge 125 expires such that it should not be used for injection.

[0139] The processor, memory, storage device, and input / output device can be interconnected by a system bus. The processor is capable of processing instructions executed within the system. Such an executed instrument can implement one or more processes related to the use of the instrument described herein. For example, one or more signals from a first sensor can be transmitted and converted into one or more processed signals that represent or provide information related to what is sensed, including but not limited to one or more of the following: torque, energy, power, cumulative power, time, material strength, material density measurement, spindle speed, depth, feed control, force, 3D orientation of penetration, drilling energy, pull-out force, screw insertion energy, etc.

[0140] The processor of the controller 510 can be a single-threaded processor or a multi-threaded processor. The processor of the controller 510 is capable of processing instructions stored in the memory and / or storage device to display information to the user, such as on a graphical display or other user interfaces provided via the input / output device. It should be understood that the graphical display does not have to be on the device 100, but can be on an external computing device 600 in communication with the device 100. Alternatively, it should be understood that the output does not have to be graphical and can be any of a variety of indicators (light, sound, tactile feedback).

[0141] As described above, the electronic module 500 can also optionally include one or more aiming features 520 configured to improve the aiming and / or visualization of the injection. In some embodiments, the aiming features 520 include one or more sensing elements 525, including but not limited to proximity sensors, aiming elements 530 configured to project one or more aiming beams, illumination elements 535, and any of a variety of other visualization aids, including but not limited to LEDs, lenses, light pipes, filters, etc.

[0142] Figure 9A - 9C An embodiment of the device 100 is shown having a catheter guide 110 incorporating one or more aiming elements 530 configured to provide visual cues or feedback to the user before, during, and / or after penetration of the membrane 5. In one embodiment, one or more aiming elements 530 can direct at least one aiming beam 531 towards an object of interest (i.e., the tympanic membrane 5) so that the user can see the location where the needle assembly 115 will strike before actuating the device. The beam 531 can be a very narrow beam projected onto the object of interest and aligned with the point 532 where the axis 117 of the needle assembly 115 will strike. The beam 531 generated by the aiming element 530 can provide various visual cues, including one or more dots, boxes, dashed lines, crosshairs, or other visual cue configurations at the point 532. The visual cues can be static, dynamic, or responsive. For example, the visual cues can be pulsed, strobing, continuous, or semi-continuous flashes, changing brightness, or a combination thereof. Additionally, the visual cues can change patterns to provide feedback to the user, such as indicating the optimal distance or angle relative to the target of interest. Proper positioning of the device can provide faster, more effective, and safer results for a successful injection. Figure 9C A view through the viewing lens 143 of the device 100 when using the aiming element 530 is shown. The visible point 532 of light helps to overcome the loss of depth perception due to monocular vision.

[0143] The aiming element 530 can include any of a variety of one or more optical elements, including an aiming light source, a lens, a pinhole element, a light pipe, a condensing element with or without a diffusing element, an optical waveguide, a blocking element, an optical collimator, etc. The aiming light source of the aiming element 530 can include, for example, an LED, an OLED, a laser diode, etc. configured to be electrically connected to a printed circuit board (PCB). The aiming element 530 can be optimized for an LED light source, for example, including a light pipe to collect, guide, and diffuse the projected light. The shape of the light beam 531 and the shape of the visible point 532 can vary, including circular, square, cross-shaped, or "x" shaped, and the user will see its outline projected onto the target position.

[0144] The shape of the light beam 531 projected by the aiming element 530 onto the target position can change according to the distance of the catheter guide 110 from the target. Figure 10A - 10C An embodiment of the aiming element 530 is shown, in which more than a single light beam 531 can be directed at the target (e.g., the eardrum 5). The aiming element 530 can direct a first light beam 531a at a first angle relative to the catheter guide 110 and a second light beam 531b at a second angle relative to the catheter guide 110. The angles can be such that the first and second light beams 531a, 531b pass through a distance D from the distal end of the catheter guide 110. The two light beams 531a, 531b allow the user to measure the proximity of the target 5 relative to the distal end of the catheter guide 110 based on whether two light spots 532 are projected or one light spot 532. When the catheter guide 110 is positioned too far (or too close) from the target 5, the user will see the first and second light beams projected onto the target 5 as two points 532 (see Figure 10A and 10C and 10C-1). When the catheter guide 110 is at the optimal distance D from the target 5, the user will see a single light beam projection point 532 (see Figure 10B and 10B-1 ). It should be understood that a "point" can be any of the various shapes described above.

[0145] Now referring to Figure 11 , additionally or alternatively, the device 100 can include one or more sensing elements 525 to improve the aiming of the eardrum 5. In one embodiment, the sensing element 525 is a proximity sensor. The sensing element 525 can be an infrared sensor configured to record infrared radiation (IRR) emitted by the membrane, a pressure sensor configured to detect contact, a laser distance sensor, an electrode sensing tissue contact, for example, to distinguish the eardrum 5 from other tissues in the ear.

[0146] Signals from the proximity sensor 525 can be processed into one or more processed signals that represent the relative distance between the catheter guide 110 and the target (e.g., the tympanic membrane 5). The sensor 525 can transmit information related to the relative distance to the controller 510 of the electronic module 500. The transmitted information can be provided to the user in real time via the user interface 505, for example, which in turn can provide the user with visual, auditory, and / or tactile cues regarding the preparation for injection into the membrane 5. In some embodiments, information from the sensing element 525 (and / or the aiming element 530) can communicate with the controller 510 of the device such that the controller 510 automatically triggers injection and aiming at an appropriate proximity without any input from the user.

[0147] The proximity sensor 525 can be an optical, acoustic, or another type of sensor. The proximity sensor 525 can be electronic or entirely mechanical. In one embodiment, the proximity sensor 525 is a physical proximity sensor configured to instantaneously determine the optimal depth of the device 100 (see Figure 12A - 12B ). The proximity sensor 525 can include a post 527 that extends distally from the catheter guide 110 for a distance. The post 527 can transmit a signal to the device upon physical engagement between the distal end of the post 527 and the tympanic membrane 5. The device 100 can in turn provide visual, tactile, and / or auditory cues related to the contact with the membrane 5 to the user. The user can then actuate the injection, or the device can automatically actuate the injection. The post 527 can be a semi-flexible contact sensor tip that cannot pierce or damage the tympanic membrane upon contact.

[0148] Throughout the description, devices are configured to penetrate a target to deliver a substance through a cannula into a cavity such as the tympanic cavity 30. It should be understood that the devices described herein can deliver treatment to other parts of the ear, such as the ear canal 40. Figure 13 An embodiment of the catheter guide 110 is shown that is configured to deliver treatment from its distal end 136 in addition to delivering treatment through the needle assembly 115. At least a portion of the catheter guide 110 and / or the contact tip 150, if present, can be coated or impregnated with a substance, such as a topical anesthetic compound or an antibacterial compound, to reduce the risk of patient discomfort and / or infection. The catheter guide 110 can include a dispenser 160 that extends through a region of the catheter guide 110 and is configured to deliver a substance stored in an additional reservoir (not shown) into the ear canal 40. The reservoir can be an internal reservoir of the device 100 or an external reservoir that is in fluid communication with the device 100. The substance can be a liquid, powder, gel, dispersion, aerosol, or other formulation known in the art.

[0149] The dispenser 160 can have a nozzle 162 at the most distal end 136 of the catheter guide 110, which is configured to produce at least one stream of material for delivery in the region adjacent to the most distal end 136. The dispenser 160 can be fluidly connected to an additional reservoir through a tube 166 that extends through the region of the device 100. The catheter guide 110 in this configuration can include three cavities: a first cavity 140 through which the needle assembly 115 extends, a second cavity 142 through which the user can observe the target through the lens 143, and a third cavity for the nozzle 162. The fluid delivery from the dispenser 160 can be controlled in combination with the same or additional actuators 107 such that the fluid from the reservoir can be pumped, injected, jetted, dripped, sprayed, or otherwise delivered from the nozzle 160 into the ear canal 40.

[0150] The device 100 can also deliver a substance to the ear canal 40 by dispensing a temporary implant 800 impregnated with the substance into the ear canal 40 (see Figure 14A - 14B ). In some embodiments, the implant 800 can be removably coupled to a region of the catheter guide 110. The implant 800 can be impregnated with a therapeutic substance, such as a topical anesthetic and / or a preservative configured to reduce patient discomfort and / or injection risk. The implant 800 can be an annular element that is configured to engage and surround the distal region of the catheter guide 110. The implant 800 can be positioned on the catheter guide 110 before use and can be separated from the catheter guide 110 when the catheter guide 110 is inserted into the ear canal 40. The implant 800 can remain in place in the ear canal 40 near the tympanic membrane 5 for a period of time. The therapeutic substance can elute from the implant 800 over a period of time. The material of the implant 800 can vary and include any of a variety of biocompatible drug-release materials, including but not limited to porous materials such as polymers or collagen sponges, wicking materials, permeable silicone, packed beds, microporous structures or fritted glass, porous coatings, nano-coatings, rate-limiting membranes, matrix materials, sintered fritted glass, permeable membranes, semi-permeable membranes, capillaries or tortuous channels, nanostructures, nano-channels, sintered nanoparticles, etc. The implant 800 can be biodegradable or bioabsorbable such that it does not need to be removed after being positioned in the ear canal 40. The implant 800 can also fall off on its own after a period of time or be removed by a doctor during a follow-up visit.

[0151] Method of Use

[0152] In one embodiment, the device 100 (which may be pre-filled with the substance 122 in the reservoir 120 for immediate delivery or filling prior to use, such as by inserting the cartridge 125) has a needle assembly 115 in a fully retracted configuration. In some embodiments, the device 100 may be powered on and acquire data related to the injection. The user may insert the front end of the catheter guide 110 into the patient's ear canal 40. The positioning, alignment, and aiming of the device 100 within the ear canal 40 may vary as described herein. For example, in some embodiments, the device 100 may be inserted without any visualization or alignment aids. In other embodiments, the device 100 may be aligned by positioning the tympanic membrane 5 through the viewing lens 143 of the device 100 or a separate otoscope handle 300. The catheter guide 110 may be positioned at a distance from the target or in direct contact with the target to be injected. After achieving the appropriate insertion distance and rotational alignment with the target, the user may activate the actuator 107, such as a spring release element, to cause the needle assembly 115 to extend from the distal end of the catheter guide 110. The shaft 117 may penetrate the target portion of the tympanic membrane 5, which may simultaneously cause the cannula 119 extending through the lumen of the shaft 117 to be positioned through the tympanic membrane 5. The shaft 117 may immediately retract into the catheter guide 110 such that it no longer extends through the membrane 5 leaving the cannula 119 in place. Alternatively, the user may activate the same or a different actuator 107 to retract the shaft 117 into the catheter guide 110. The user may adjust the catheter guide of the cannula 119 within the tympanic cavity 30 (e.g., the length of protrusion and / or rotation about the longitudinal axis A of the catheter guide 110) to ensure its positioning at the desired location for therapeutic delivery. The substance 122 from the reservoir 120 may be automatically injected when the needle assembly 115 is actuated or upon additional activation of an actuator 107 (the same or a different actuator 107) to cause fluid to flow out of the distal region of the cannula 119 located within the middle ear 30. The device 100 may be similarly used a second time on the same patient, e.g., in the other ear. One or more components of the device 100 may be discarded after use, including but not limited to the cartridge 125, the needle assembly 115, the catheter guide 110, or the entire device itself.

[0153] Treatment and disease

[0154] The treatment devices described herein can be used to treat and / or prevent a variety of other conditions, including but not limited to hearing loss, including hidden hearing loss, noise-induced hearing loss, age-related hearing loss, drug-induced hearing loss, such as chemotherapy-induced hearing loss or aminoglycoside-induced hearing loss, sudden sensorineural hearing loss (SNHL), etc. Any one of a variety of ear diseases can be treated using the devices described herein. The treatment devices described herein can be used to treat other ear diseases, such as tinnitus. The treatment devices described herein can be used to treat balance disorders, including vertigo, Meniere's disease, vestibular neuronitis, labyrinthitis, etc.

[0155] Examples of therapeutic agents that can be delivered by the treatment devices described herein and / or described in the applications incorporated herein by reference are provided below.

[0156] Therapeutic agents that can be delivered from the devices described herein include but are not limited to antioxidants, anti-inflammatory agents, steroids, antimicrobials, NMDA receptor antagonists, nootropics, anti-apoptotic agents, neurotrophic agents, neuroprotective agents, neuroprotective proteins such as CNTF, BDNF, PEDF, nerve growth factor, etc., cannabinoids, monoclonal antibodies, other proteins, gene therapies such as iRNA and protein therapies such as anti-VEGF. Gene therapies can include DNA, RNA, iRNA, siRNA, etc., antisense oligonucleotides, stereopure nucleic acids, viruses, adeno-associated viruses (AAV), non-viral gene therapies, toxoids, liposomes, CRISPR cas9-mediated homology-independent targeted integration (HITI) or homology-directed repair (HDR) to alter the genetic components of various ear diseases. Treatment methods can include anti-VEGF, such as Avastin (bevacizumab), Lucentis (ranibizumab), Caprelsa (vandetanib), Inlyta (axitinib), Votrient (pazopanib), and Eylea (aflibercept).

[0157] As an example, the therapeutic agent can include, but is not limited to, antibacterial agents such as antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, cephalexin, oxytetracycline, chloramphenicol, kanamycin, rifampicin, ciprofloxacin, tobramycin, gentamicin, erythromycin and penicillin; antifungal agents such as amphotericin B and miconazole; antibacterial drugs such as sulfonamides, sulfadiazine, sulfacetamide, sulfamethoxazole and sulfisoxazole, nitrofurazone and sodium propionate; antiviral drugs such as idoxuridine, trifluridine, acyclovir, ganciclovir and interferon; antiallergic drugs such as sodium cromoglycate, antazoline, methapyrilene, chlorpheniramine, pyribenzamine, cetirizine and dipyridamole; anti-inflammatory agents such as hydrocortisone, hydrocortisone acetate, dexamethasone, dexamethasone 21-phosphate, fluocinonide, medrysone, prednisolone, prednisolone 21-phosphate, prednisolone acetate, flumethasone, betamethasone and triamcinolone acetonide; non-steroidal anti-inflammatory drugs such as salicylates, indomethacin, ibuprofen, diclofenac, flurbiprofen and piroxicam; decongestants such as phenylephrine, naphazoline and tetrahydrozoline; miotics and anticholinesterases such as pilocarpine, salicylates, acetylcholine chloride, physostigmine, eserine, carbachol, diisopropyl fluorophosphate, phospholine iodide and demecarium bromide; antiallergic drugs such as atropine sulfate, cyclopentolate, homatropine, scopolamine, tropicamide, atropine and hydroxyamphetamine; sympathomimetic drugs such as adrenaline; antitumor drugs such as carmustine, cisplatin and fluorouracil; immunological drugs such as vaccines and immunostimulants; hormonal drugs such as estrogen, estradiol, progesterone, progestin, insulin, calcitonin, parathyroid hormone and peptides and vasopressin hypothalamic releasing factors; β-adrenergic blockers such as timolol maleate, levobunolol HCl and betaxolol HCl; growth factors such as epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor β, growth hormone and fibronectin; carbonic anhydrase inhibitors such as dichlorphenamide, acetazolamide and methazolamide, and other drugs such as prostaglandins, anti-prostaglandins and prostaglandin precursors; antioxidants, NMDA receptor antagonists, nootropics, anti-apoptotic agents, neurotrophins, neuroprotective agents, cannabinoids, monoclonal antibodies, other proteins and gene therapy. Other therapeutic agents known to those skilled in the art that can be controlled and continuously released into the ear in the manner described herein are also applicable to the embodiments of the device described herein.

[0158] Therapeutic agents can include, but are not limited to, sodium thiosulfate to prevent cisplatin-induced hearing loss; NMDA receptor antagonists (AM-101; Auris Medical) for the treatment of tinnitus; AM-111 containing the synthetic peptide D-JNKI-1 (D-stereoisomer of c-Jun N-terminal kinase inhibitor 1; Auris Medical) for otoprotection in acute inner ear hearing loss; dexamethasone for the treatment of Meniere's disease; D-methionine (Southern Illinois University) for protection against noise-induced hearing loss; LY411575 (a selective γ-secretase inhibitor that blocks Notch activation); and the neurotrophin NT-3.

[0159] Therapeutic agents can include, but are not limited to, local anesthetics for delivery into the ear canal, including benzocaine, antipyrine, butamben, dibucaine, lidocaine, oxybuprocaine, pramoxine, prilocaine, propanocaine, and tetracaine.

[0160] The various pharmaceutically acceptable carriers for the therapeutic agents described herein can include, for example, solids such as starch, gelatin, sugars, natural gums such as gum arabic, sodium alginate, and carboxymethylcellulose; polymers such as silicone rubber; liquids such as sterile water, saline, dextrose, dextrose in water or saline; condensation products of castor oil and ethylene oxide, liquid triglycerides of lower molecular weight fatty acids; lower alkanols; oils such as corn oil, peanut oil, sesame oil, castor oil, etc., having emulsifiers such as monoglycerides or diglycerides of fatty acids, or phospholipids such as lecithin, polysorbate 80, etc.; diols and polyalkylene glycols, including P407 and other combinations of polyethylene glycol and polypropylene glycol; aqueous media in the presence of suspending agents, such as sodium carboxymethylcellulose, sodium hyaluronate, sodium alginate, poly(vinylpyrrolidone), and similar compounds, or alone, or with suitable dispensing agents such as lecithin, cyclodextrin, polyoxyethylene stearate, etc. The carrier can also contain adjuvants such as preservatives, stabilizers, wetting agents, emulsifiers, or other related materials.

[0161] The devices described herein are preferably used to deliver therapeutic agents within a short time after exposure to noise in the environment where the injury occurs, which is a non-clinical type of environment. The ease of use of the devices described herein allows for the delivery of the agent within a time frame that permits the prevention of permanent ear damage. The therapeutic agents can vary and include LPT99, methotrexate, gentamicin, aminoglycosides, or steroids. The time frame can also vary and include less than 24 hours, less than 36 hours, less than 48 hours, less than 60 hours, or less than 72 hours after exposure to noise.

[0162] The volume of the drug solution or suspension injected into the tympanic cavity can vary and includes 0.2, 0.5, 0.75, 1, 1.5, 2, 3, 4, and 5 mL. The drug solution can be administered to the tympanic cavity in volumes within the ranges of 0.2 to 5, 0.5 to 4, 0.75 to 3, and 1 to 2 mL.

[0163] Aspects of the subject matter described herein can be implemented in digital electronic circuitry, integrated circuitry, specially designed ASICs (application specific integrated circuits), computer hardware, firmware, software, and / or combinations thereof. These various embodiments can include embodiments in one or more computer programs that are executable and / or interpretable on a programmable system including at least one programmable processor, which may be special purpose or general purpose, coupled to receive signals, data, and instructions from, and to send signals, data, and instructions to, a storage system, at least one input device, and at least one output device.

[0164] These computer programs (also referred to as programs, software, software applications, or code) include machine instructions for a programmable processor and can be implemented in high-level procedural and / or object-oriented programming languages and / or assembly / machine languages. As used herein, the term "machine-readable medium" refers to any computer program product, apparatus, and / or device (e.g., a disk, optical disk, memory, programmable logic device (PLD)) used to provide machine instructions and / or data to a programmable processor, including a machine-readable medium that receives machine instructions as a machine-readable signal. The term "machine-readable signal" refers to any signal used to provide machine instructions and / or data to a programmable processor.

[0165] Although this specification contains many details, these details should not be construed as limiting the scope of what is claimed or of what may be claimed, but rather as descriptions of specific features of particular embodiments. Certain features that are described in the context of separate embodiments in this specification may also be implemented in combination within a single embodiment. Conversely, various features that are described in the context of a single embodiment may also be implemented separately in multiple embodiments or in any suitable sub-combination. Moreover, although features may have been described above as acting in certain combinations and even initially claimed as such, in some cases, one or more features from a claimed combination may be excluded from the combination, and the claimed combination may be directed to a sub-combination or a variant of a sub-combination. Similarly, although operations may be described in the drawings in a particular order, this should not be understood as requiring that the operations be performed in the particular order shown or in sequential order, or that all of the illustrated operations be performed, to achieve desirable results. Only multiple examples and embodiments are disclosed. Variations, modifications, and enhancements of the described examples and embodiments and other embodiments are possible based on the disclosed content. The claimed subject matter has been described in connection with its detailed description, and the foregoing description is intended to illustrate rather than limit the scope of the claimed subject matter of the appended claims.

[0166] In the foregoing description and claims, phrases such as "at least one" or "one or more" may appear after a list of elements or features joined by "and". The term "and / or" may also appear in a list of two or more elements or features. Unless implicitly or explicitly contradicted by the context in which it is used, such phrases are intended to mean any element or feature listed individually, or any combination of any listed element or feature with any other listed element or feature. For example, the phrases "at least one of A and B;" "one or more of A and B;" and "A and / or B" are each intended to mean "A alone, B alone, or A and B together." A similar interpretation applies to lists containing three or more items. For example, the phrases "at least one of A, B, and C;" "one or more of A, B, and C;" and "A, B, and / or C" are each intended to mean "A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B, and C together."

[0167] In the foregoing and in the claims, the use of the term "based on" is intended to mean "at least in part based on", such that features or elements not recited are also permissible.

Claims

1. A system for delivering one or more therapeutic agents to an ear region located inside the tympanic membrane, the system comprising: A catheter guide (110) configured to be inserted into the ear canal and matingly engage with the ear canal wall, the catheter guide comprising: An observation cavity (142) extending between the proximal end of the catheter guide and the distal most end of the catheter guide, the distal most end of the catheter guide being sized to remain outside the tympanic membrane; and A guide cavity (140) extending from a proximal opening near the proximal end of the catheter guide to a distal opening near the distal most end of the catheter guide, wherein the guide cavity is curved from a first axis extending through the proximal opening to a second axis extending through the distal opening; and A needle assembly (115) comprising a flexible shaft (119) sized to extend through the guide cavity (140) of the catheter guide (110), the flexible shaft comprising a fluid delivery cavity, wherein the catheter guide (110) provides alignment of the needle assembly (115) within the ear canal relative to the tympanic membrane; A positioning guide (200) configured to assist in positioning and guiding the needle assembly (115) into the ear canal and correctly aligning it with the tympanic membrane (5), the positioning guide including a front end (205) and a rear end (210), wherein the front end (205) is configured to receive and mate with the catheter guide (110), and the rear end (210) is held by the user during the injection process.

2. The system according to claim 1, wherein The needle assembly is movable relative to the catheter guide between a fully retracted position and a fully extended position.

3. The system according to claim 1, wherein The needle assembly further includes an outer shaft through which the flexible shaft extends.

4. The system according to claim 3, wherein, The outer shaft and the flexible shaft are movable relative to each other and relative to the catheter guide.

5. The system according to claim 3, wherein The outer shaft is rigid, and one or both of the flexible shaft and the outer shaft include a sharp tip configured to penetrate the tympanic membrane.

6. The system according to claim 3, wherein The needle assembly is between 23 gauge and 30 gauge.

7. The system according to claim 3, wherein, The outer shaft can extend from the distal most end of the catheter guide a distance of no more than 5 mm to 10 mm.

8. The system according to claim 7, wherein, The flexible shaft can extend from the distal most end of the catheter guide a distance of no more than 3 mm to 5 mm.

9. The system according to claim 1, wherein The flexible shaft includes a sharp tip configured to penetrate the tympanic membrane.

10. The system according to any one of the preceding claims, wherein, The guide cavity of the catheter guide is eccentric with respect to the longitudinal axis of the catheter guide.

11. The system according to claim 10, wherein, When the catheter guide is rotated, the guide cavity of the catheter guide can be adjusted about the longitudinal axis.

12. The system according to any one of claims 1-9, wherein, The proximal end of the catheter guide includes a coupling feature configured to reversibly engage with a coupling feature on the front end of the housing.

13. The system according to claim 12, wherein The catheter guide is adjustably attached to the housing such that the position of the guide cavity relative to the housing is adjusted by rotation.

14. The system according to claim 13, wherein, The degree of rotation of the catheter guide relative to the housing is indicated to the user visually, auditorily, and / or haptically.

15. The system according to any one of claims 1-9, wherein, The system further includes one or more actuators configured to move the needle assembly relative to the catheter guide.

16. The system according to claim 15, wherein The one or more actuators include a first actuator configured to extend both the outer shaft and the flexible shaft of the needle assembly distally relative to the distal most end of the catheter guide and immediately retract the outer shaft while the flexible shaft remains extended.

17. The system according to any one of claims 1-9, wherein, The needle assembly is actuated by a spring-loading mechanism.

18. The system according to any one of claims 1-9, wherein, The flexible shaft is manipulable.

19. The system according to any one of claims 1-9, further comprising a manipulable guide wire extending through the fluid delivery lumen of the flexible shaft, wherein the flexible shaft is advanceable over the manipulable guide wire.

20. The system according to any one of claims 1-9, wherein, The catheter guide includes a conformable outer surface sized to engage the ear canal wall.

21. The system according to claim 20, wherein, The shape of the conformable outer surface is at least partially cylindrical.

22. The system according to claim 20, wherein, The conformable outer surface tapers towards a narrower outer diameter at the most distal end.

23. The system according to any one of claims 1-9, wherein, The catheter guide includes an inner layer covered by an outer compressible layer.

24. The system according to claim 23, wherein, The outer compressible layer includes a plurality of flexible flanges configured to conform to the ear canal when the catheter guide is inserted into the ear canal and advanced towards the tympanic membrane.

25. The system according to any one of claims 1-9, wherein The catheter guide is shaped as an otoscope.

26. The system according to any one of claims 1-9, wherein, The guide lumen extends along the curved wall of the catheter guide between the proximal opening and the distal opening.

27. The system according to any one of claims 1-9, wherein, The distal opening from the guide lumen is positioned eccentric to the longitudinal axis of the catheter guide.

28. The system according to any one of claims 1-9, wherein The most distal end of the catheter guide is coupled to a contact tip configured to abut the outer surface of the tympanic membrane when the catheter guide is inserted and advanced through the ear canal.

29. The system according to claim 28, wherein The contact tip includes a lumen extending from the proximal end to the distal end of the contact tip and configured to receive the needle assembly.

30. The system according to claim 29, wherein, The guide lumen of the catheter guide and the lumen of the contact tip are coaxially positioned with respect to each other.

31. The system according to any one of claims 1-9, wherein, The catheter guide is coupled to a housing.

32. The system according to claim 31, wherein, The system further includes one or more retractable external support legs coupled to an area of the housing.

33. The system according to claim 32, wherein, The external support legs are symmetrically arranged about the longitudinal axis of the catheter guide to form a stable tripod relative to the catheter guide.

34. The system according to claim 32, wherein, The external support legs are positioned adjacent to the patient's skull while the catheter guide is positioned within the ear canal.

35. The system according to any one of claims 1-9, wherein The flexible shaft includes visual markings on its outer surface, the visual markings being located at a distance proximal to the most distal end of the flexible shaft.

36. The system according to any one of claims 1-9, wherein, The flexible shaft includes a plurality of visual markings on its outer surface, wherein a first marking is distal to a second marking and is visually distinguishable from the second marking.

37. The system according to any one of claims 1-9, wherein, The needle assembly includes a large bore portion that symmetrically tapers to the flexible shaft at the ferrule region.

38. The system according to claim 37, wherein, The flexible shaft includes a trans-tympanic portion distal to the ferrule region.

39. The system according to claim 38, wherein, The trans-tympanic portion is approximately 1.25 cm long and between 30 gauge and 33 gauge.

40. The system according to claim 39, wherein The large bore portion is approximately 2.5 cm long and between 20 gauge and 25 gauge.

41. The system according to claim 39, wherein, The needle assembly further includes an external ring configured to prevent over-insertion of the needle assembly through the tympanic membrane.

42. The system according to claim 41, wherein, The external ring is located at or near the ferrule region.

43. The system according to any one of claims 1-9, wherein The needle assembly further includes a concentric vent lumen surrounding the fluid delivery lumen.

44. The system according to claim 43, wherein, The needle assembly further includes a vent lumen positioned parallel to the fluid delivery lumen.

45. The system according to claim 43, wherein During use, the outlet from the vent lumen is located external to the tympanic membrane and the outlet from the fluid delivery lumen is located internal to the tympanic membrane.

46. The system according to any one of claims 1-9, wherein The needle assembly further includes an optical conduit connecting a proximal opening and a distal opening.

47. The system according to claim 46, wherein, The optical conduit is configured to receive an optical line configured to provide illumination and / or imaging capabilities.

48. The system according to claim 47, wherein, The optical line further includes a pressure sensor and / or a position sensor configured to assist in positioning the flexible shaft.

49. The system according to any one of claims 1-9, wherein The longitudinal axis of the catheter guide extends through the viewing cavity of the catheter guide, and the guiding cavity is eccentric with respect to the longitudinal axis.

50. The system according to any one of claims 1-9, wherein, The viewing cavity has a viewing lens at the proximal end.

51. The system according to claim 50, wherein, The catheter guide is coupled to the front end of the upper housing, and wherein the rear end of the upper housing includes the viewing lens.

52. The system according to claim 31, further comprising a reservoir configured to contain one or more therapeutic agents for delivery to the ear region through the fluid delivery cavity.

53. The system according to claim 52, wherein, The reservoir is integral with or attachable to the housing.

54. The system according to claim 52 or 53, wherein, The flexible shaft includes a proximal end having an inlet in fluid communication with an outlet from the reservoir.

55. The system according to claim 52 or 53, wherein, The one or more therapeutic agents are selected from the group consisting of antioxidants, anti-inflammatory agents, anti-microbial agents, anti-allergy agents, decongestants, sympathomimetics, anti-tumor agents, NMDA receptor antagonists, nootropics, anti-apoptotic agents, neurotrophic agents, neuroprotective agents, cannabinoids, monoclonal antibodies, gene therapy agents, protein therapy agents, anti-VEGF, hormonal agents, beta-adrenergic blockers, growth factors, and local anesthetics.

56. The system according to any one of claims 1-9, wherein, The first axis forms an angle with the second axis that is less than 90 degrees and greater than 0 degrees.

57. The system according to claim 55, wherein, The protein therapy agent is a neuroprotective protein and the gene therapy agent is iRNA.

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