Intranasal drug delivery device, system, and process

Abstract

To provide an improved intranasal delivery device that precisely locates dosage and provides comfort for a user.SOLUTION: Embodiments relate to an intranasal drug delivery device, system, and process. The drug delivery device may have a compliant / flexible soft nib. The drug delivery device may have an actuator and shot chamber. The drug delivery device may have a non-air interface mechanically pressurized fluid reservoir. The drug delivery device may have a facial or device recognition application to prevent intentional or unintentional misuse.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 656,463, filed April 12, 2018, and U.S. Provisional Patent Application No. 62 / 774,444, filed December 3, 2018, both of which are incorporated herein by reference in their entireties.

[0002] TECHNICAL FIELD The present disclosure relates entirely to the technical fields of drug delivery and intranasal devices. [Background technology]

[0003] A variety of devices are currently available for delivering medication to the nasal cavity. Examples of prior art intranasal delivery devices include: U.S. Patent Application No. 2016 / 0367774; U.S. Patent Application No. 2017 / 0072145; U.S. Patent Application No. 2016 / 0310683; U.S. Patent Application No. 2013 / 0331916; U.S. Patent Application No. 2015 / 0165139; U.S. Patent Application No. 2015 / 0080785; U.S. Patent Application No. 2016 / 0310683; U.S. Patent No. 7,799,337; U.S. Patent Application No. 2007 / 0789976; U.S. Patent Application No. 2013 / 0142868; U.S. Patent Application No. 2016 ...6 / 0331916; U.S. Patent Application No. 2016 / 0331916; U.S. Patent Application No. 2016 / 0331916; U.S. Patent Application No. 2016 / 0331916; U.S. Patent No. 014 / 0083424; U.S. Patent Application No. 2011 / 0132354; U.S. Patent Application No. 2002 / 0017294; U.S. Patent Application No. 2011 / 0088690; U.S. Patent No. 9,707,226; U.S. Patent No. 8,001,963; U.S. Patent No. 9,480,644; U.S. Patent No. 9,550,036; U.S. Patent No. 5,331,954; U.S. Patent No. 6,112,743; U.S. Patent No. 6,180,603; U.S. Patent No. 7,296,566; U.S. Patent No. 5,224,471; and U.S. Patent No. 5,307,953.

[0004] The inventors have determined that there is a need for an improved intranasal delivery device. Summary of the Invention

[0005] According to certain aspects, an intranasal drug delivery device is provided that has a soft tip that is flexible or pliable to accurately position the medication and provide comfort to the user. As used herein, the term "medication" can also be used to refer to other agents, such as vitamins, fragrances, saline solutions, or non-pharmaceutical medications.

[0006] According to one embodiment, an intranasal drug delivery device is provided having a cocking mechanism and an actuator for loading and expelling a dose.

[0007] According to certain aspects, an intranasal drug delivery device is provided with a non-pneumatic interface, mechanically pressurized fluid reservoir to allow dosing and firing chamber filling independent of orientation. In some illustrative embodiments, the reservoir can be collapsed by external pressure, including atmospheric pressure.

[0008] According to one aspect, an intranasal drug delivery device is provided that is connectable to a facial recognition or device recognition application to prevent intentional or unintentional misuse.

[0009] According to one aspect, an intranasal fluid delivery device includes a dosing tip connected to a hollow needle, a firing chamber for carrying a fluid, the firing chamber having a diaphragm at one end and a plunger at the other end, and an actuator connected to a push rod movable toward the firing chamber and having a locking mechanism, wherein pressing the actuator releases the locking mechanism and allows the push rod to press the plunger, pressurizing the fluid and forcing the needle through the diaphragm and into the firing chamber so that the fluid flows from the needle to the dosing tip.

[0010] According to one embodiment, a device for delivering fluid to a nasal volume is provided, the device including: a housing having a first end with a dosing opening and a second end with an actuation opening; a dosing tip coupled to the dosing opening; a capsule including a tube prefilled with fluid between a diaphragm and a plunger within the housing between the actuation opening and the dosing opening; and an actuator coupled to the actuation opening, the actuator including a push rod movable into contact with the plunger and a spring urging the push rod toward the plunger, the actuator secured by a locking mechanism.

[0011] According to one aspect, a method for targeted delivery of fluid into the nasal cavity is provided. The method includes inserting a flexible dispensing tip into the nasal cavity and expelling the fluid from the flexible dispensing tip to deliver a bolus of liquid in a laminar flow to a targeted region within the nasal cavity. The targeted region can be the olfactory region of the nasal cavity. Inserting the flexible dispensing tip into the nasal cavity can include inserting the flexible dispensing tip into at least the upper nostrils. Inserting the flexible dispensing tip into the nasal cavity can include positioning an end of the flexible dispensing tip in a region adjacent to the olfactory region. The flexible dispensing tip can include a cannula. Expelling the fluid can include expelling the fluid at a controlled velocity profile to limit shear stress on the fluid.

[0012] Furthermore, in various aspects, the disclosure provides corresponding systems and devices, as well as logical structures such as machine-executable coded instruction sets for implementing the devices and methods.

[0013] In this regard, before describing at least one embodiment in detail, it is to be understood that the embodiment is not limited in application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. It is also to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.

[0014] Many additional features and combinations of the embodiments described herein will occur to those skilled in the art after reading this disclosure. [Brief explanation of the drawings]

[0015] explanation [Figure 1] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 2] 1 illustrates an exemplary intranasal drug delivery device with a lid or cap, according to some embodiments. [Figure 3] A diagram of the olfactory region is shown. [Figure 4] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 5] 1 illustrates an ejection stroke and a refill stroke of an exemplary intranasal drug delivery device, according to some embodiments. [Figure 6] 1 shows an exemplary internal view of the tip and tip features of an intranasal drug delivery device, according to some embodiments. [Figure 7] 1 illustrates an exemplary intranasal drug delivery device with a removable reservoir, according to some embodiments. [Figure 8] 1 illustrates an exemplary intranasal drug delivery device with the tip inserted into the nasal cavity, according to some embodiments. [Figure 9] 1 shows a schematic of an integrated intranasal drug delivery platform. [Figure 10] 1 illustrates an exemplary disposable intranasal drug delivery device according to some embodiments. [Figure 11] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 12] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 13] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 14]1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 15] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 16] 1 illustrates an exterior view of an exemplary intranasal drug delivery device, according to some embodiments. [Figure 17] 1 illustrates an exterior view of an exemplary intranasal drug delivery device, according to some embodiments. [Figure 18] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 19a] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 19b] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 19c] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 20a] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 20b] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 20c] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 21] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 22] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 23] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 24] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 25] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 26a] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 26b] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 27a] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 27b] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 28] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 29a] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 29b] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 29c] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 30a] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 30b] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 30c] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 31] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 32] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 33a] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 33b] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 33c] 1 illustrates an exemplary intranasal drug delivery device according to some embodiments. [Figure 34] 1 illustrates an exemplary intranasal drug delivery device with a bulbous-ended dispensing tip, according to some embodiments. [Figure 35]1 illustrates an exemplary intranasal drug delivery device with a dosing tip with an alpha loop, according to some embodiments. [Figure 36] 1 shows images obtained by scanning a subject while testing a prototype device with tracer fluid. DETAILED DESCRIPTION OF THE INVENTION

[0016] Embodiments of the methods, systems, and apparatus are described through reference to the drawings.

[0017] Currently, disposable intranasal drug delivery devices are characterized by poor accuracy / uniformity of drug administration, a lack of design for anatomical variability, and poor design for human factors - efficacy and safety. These shortcomings severely disadvantage the following applications: direct delivery pathways to the brain (uptake via the olfactory epithelium into the CSF (cerebrospinal fluid) and action in the brain), systemically acting drugs (uptake via the mucosa into the vasculature and action systemically), vaccines (uptake and action at the mucosa), and locally acting drugs (uptake and action at the mucosa).

[0018] The following will bring the following benefits to new and existing intranasal drug delivery: lower cost, enhanced efficacy, enhanced safety (for both patients and society), and enhanced convenience (in terms of healthcare).

[0019] The following present opportunities in terms of designing for marketing in areas where access to healthcare is difficult (humanitarian impact) and designing for prevention of drug misuse.

[0020] FIG. 1 shows an illustration of an intranasal drug delivery device (100), according to some embodiments.

[0021] The device 100 has a soft, flexible tip 102 (as opposed to a rigid tip) for precise medication placement. The soft tip 102 also provides comfort for the user and may minimize blocking by the nasal wall or congestion.

[0022] A deviated nasal septum can cause a variety of health-related problems. In some embodiments, the flexible, soft tip (102) conforms to the anterior aspect of the nasal passages. In some embodiments, the soft tip (102) is biased to follow the patient's septum. This allows the tip (110) to be positioned in the nasal cavity to target olfactory region and release medication, accommodating anatomical differences in the nasal cavity.

[0023] In some embodiments, the flexible tip (102) has a kiss-cut valve near the tip (110). The valve inhibits partial release during pre- and post-actuation steps. The tip (110) also reduces or eliminates contamination from contact with air or line fill remaining in the nozzle during administration. In some embodiments, the kiss-cut is offset from the end of the tip (110) to direct the medication toward the olfactory portion of the nasal structure. The tip (102) may be an overmolded tip in some embodiments. As shown in FIG. 34, in some embodiments, the tip may have a bulbous or ball-shaped end (3400) to facilitate insertion and promote better laminar flow along the nasal ridge. As shown in FIG. 35, in some embodiments, the flexible tip utilizes an "alpha loop" (3500) to facilitate positioning the end of the dispensing tip through an obstruction. In interventional cardiology, one strategy for passing a guidewire through a stenosis or calcified obstruction is to push a flexible tip guidewire into the obstruction. The tip naturally deflects itself, and the wire finds its way through the obstruction via the leading alpha loop. The larger bearing surface helps guide the wire to the point of least resistance, and it glides through the stenosis / obstruction. This embodiment may be utilized in injuries where the integrity of the nose has been lost, and this can be shaped so that the flexible tip helps find its target.

[0024] The device 100 has an actuator 106 (e.g., a button, trigger) and a cocking mechanism 108 for reproducible dose delivery to reduce human error and variability. In certain embodiments, the use of a cocking-and-ejection mechanism promotes stable positioning during delivery and reduces the need for priming the device 100, thereby reducing the possibility of operator error. In some embodiments, actuation of a finger-press button empties the firing chamber. This method of actuating the device 100 requires little dexterity or fine motor skills, which may be particularly important for patients who may have impaired motor skills, such as those with Parkinson's disease. Priming may refer to ensuring a sufficient volume of liquid to fill a dosing / metering mechanism suitable for pumping liquid, including, but not limited to, positive displacement pumping.

[0025] In some embodiments, the device 100 has an internal reservoir that can be kept constantly pressurized to allow for orientation-independent dosing (e.g., functioning whether the user is standing or lying down). The reservoir may be a bag and can be collapsed by external pressure, including atmospheric pressure. The pressure within the reservoir may vary depending on the spring used, but it may always be under some pressure.

[0026] In some embodiments, device 100 does not have an air vent for filling, storing, or operating device 100. This allows for travel or transportation by air, particularly by decompressed or higher altitude aircraft, and may be useful for oxygen-sensitive medications, particularly in areas without cold chain infrastructure, and to extend the shelf life of certain medications. Additionally, this makes the device difficult to tamper with. In some embodiments, there may be an air vent.

[0027] In some embodiments, the shape of device 100 allows for precise nozzle positioning and an ergonomic grip that does not engage the shoulder, wrist, or any other part of the arm that does not directly manipulate device 100. The design of device 100 minimizes the use of shoulder and arm movement.

[0028] In some embodiments, the design of device 100 is highly ergonomic, taking inspiration from both the design of a larger remote controller and the design of a pen for more dexterity.

[0029] Ergonomics and considered human factors have changed the state of the art for nasal delivery devices. The design allows for targeted, repeatable, and measured dose delivery, minimizing human error. The design accommodates consumable drug reservoirs for short- to long-term use, while making the drug reservoirs low-cost consumable for a single patient. This allows for the ability to be filled with multiple drugs at the point of care or by a pharmaceutical filling line. The design, illustratively, allows for a flexible, soft tip (102) with an ultra-soft, matte-finish elastomeric shroud.

[0030] The flexible soft tip (102) of the device is placed within the intranasal cavity, using typical intranasal geometry to bring the tip close to the olfactory region. The flexible soft tip (102) rests at a distance from the olfactory region, and the expelled medication bolus is guided to the olfactory region by the natural geometry of the nasal structures. The device's mechanics support a compact, low-cost, pocket-sized form factor based on injection-moldable components.

[0031] FIG. 2 shows an illustration of an intranasal drug delivery device (100) with a lid (202) or cap, according to some embodiments.

[0032] In some embodiments, the lid 202 may be used in conjunction with or in place of the cocking mechanism 108 as part of refilling the intranasal drug delivery device 100. The addition of the lid 202 increases the grip size of the drug delivery device 100 and prevents accidental firing of the drug delivery device 100. In some embodiments, the lid 202, when attached to the bottom of the device 100, may provide extra space for grasping with the whole hand. In some embodiments, the lid 202 is shaped to increase the surface area that is not obstructed by the hand during use, so that machine-readable indicia (i.e., URL codes) can be added to the increased surface area.

[0033] In some embodiments, device 100 may include a rechargeable energy store to provide activation energy for spaced actuation. The rechargeable energy may include electrical, chemical, or pressurized fluid stores.

[0034] FIG. 3 shows a diagram of the nasal cavity (300), including the olfactory region (306), the upper nostrils (308) and the lower nostrils (310).

[0035] In local drug delivery, the drug is delivered throughout the entire mucosa (i.e., both the upper nostril (308) and the lower nostril (310)). In systemic drug delivery, the drug is delivered to the vascular system via the mucosa of the upper nostril (308). In direct drug delivery to the brain, the drug is delivered via the olfactory mucosa, primarily by diffusion in the olfactory region (306). The olfactory pathway can be short, and the drug can be carried through the cribriform plate in the cerebrospinal fluid draining from the olfactory bulb. This may also involve the trigeminal nerve.

[0036] Current formulations for nasal delivery use standard sprays with no specificity for the olfactory region (306), relatively small molecules are used, and the formulations are primarily water with some alcohol. A variety of functionalities are used for the inactive ingredients in formulations for nasal delivery, such as solvents, mucoadhesives, absorption enhancers, viscosity modifiers, pH buffers, antioxidants, preservatives, surfactants, etc.

[0037] Most airflow is through the lower nostrils 310. Therefore, sneezing is unlikely to displace any fluid remaining in the olfactory region 306. Nasal congestion can primarily affect the lower nostrils 310, leaving the olfactory region 306 empty.

[0038] Directly targeted drug delivery to the brain may be achieved by saturating the olfactory region (306) with an excipient / drug combination. Drugs may travel via extracellular translocation through the cribriform plate and into the central nervous system. This targeted delivery is intended to allow for safer and more effective drug delivery, sparing both local and systemic delivery.

[0039] In some embodiments, the device (100) may be adapted with the addition of a sideways atomizer tip to achieve the current state of the art of local drug delivery by saturating the entire mucosa or systemic drug delivery by targeting the upper nostrils (308).

[0040] The olfactory plateau is generally located posterior to the radix line, which correlates to the length of the nasal bridge, which is the distance from the soft tissue of the nasion to the subnasal point.

[0041] FIG. 4 shows an exemplary intranasal drug delivery device with a reservoir (402) and a soft tip (404), according to some embodiments.

[0042] Figure 5 shows an example of a release and recharge mechanism 500, according to some embodiments, that is incorporated into an intranasal drug delivery device, such as device 100.

[0043] The release and refill mechanism (500) has a reservoir (502) that contains the medication for delivery to the nasal cavity.

[0044] The discharge and refill mechanism (500) has a needle (504) for insertion into the reservoir (502).

[0045] In some embodiments, the reservoir may be a bag and may be collapsed by external pressure, including atmospheric pressure.

[0046] In some embodiments, reservoir 502 is removable, and insertion needle 504 is inserted through a silicone stopper at the top of reservoir 502 to draw material into device 100. The silicone stopper has resealing properties for air-sensitive medications. Insertion needle 504 may be left in the bottle from which the medication for the device was obtained. The filling process may eliminate the need for a separate syringe. In some embodiments, this may be called a Luer lock.

[0047] The discharge and recharge mechanism (500) is connected to an actuator (506) for releasing a spring (508).

[0048] The discharge and refill mechanism (500) includes a plunger (510), a fill valve (512), and a fill chamber (514).

[0049] The discharge and refill mechanism 500 includes a firing chamber 516, a fluid chamber 518, a discharge valve 520, and a nozzle 522. The nozzle 522 can be in fluid communication with the tip 102 such that fluid is ejected from the nozzle 522 and through the tip 102, or as described below.

[0050] In some embodiments, the discharge valve (520) may include an elongated duckbill valve at the tip to reduce and differentiate line / dead volume.

[0051] In some embodiments, reservoir 502 is held under tension by compression spring 524. A constant, predetermined fluid pressure may be maintained by compression spring 524 pushing from the bottom of the reservoir upward toward firing chamber 516, nozzle 522, and plunger 510. This constant fluid pressure fills fill chamber 514 without exposing the medication to air or metal springs, as is typical in most nasal pumps. In some embodiments, this may avoid the use of tubing between reservoir 502 and firing chamber 516. This can reduce wasted volume of medication or medication remaining in the line after use. This ensures that dosing accuracy is not compromised due to air entering firing chamber 516 and that no contents remain in firing chamber 516 or reservoir 502 after the last available medication has been dispensed. The constant pressure allows medication to be dispensed regardless of the user's orientation.

[0052] In some embodiments, the flexible, soft tip (102) is designed to emit a laminar flow, which may include a discreet slug of liquid with turbulent boundaries that is ideally suited to maximizing medication delivery to the horizontal, narrow portion of the nasal cavity leading to the olfactory region. Delivery of the laminar liquid slug assists in the capillary action required to maximize medication delivery to the olfactory region. In some embodiments, the laminar flow is generated by a tube array or hydrodynamic focusing.

[0053] In some embodiments, the design of the chamber and fluid path can facilitate high precision in the dispensed volume.

[0054] In some embodiments, the device 100 is cocked by depressing or squeezing the bottle. This method of activating the device 100 requires little dexterity or fine motor skills. This method of preparing the device for administering medication may be particularly important for patients who may have impaired motor skills, such as those with Parkinson's disease. The device can be oriented in any direction, and the reload and firing functions of the firing chamber are not affected, i.e., the device is not sensitive to gravity.

[0055] In some embodiments, the flexible soft tip (102) is extended by cocking the device. This reduces the length profile of the device for shipping, shelving, and pocketing. When in the non-use position, the device has a less 'menacing' appearance.

[0056] In some embodiments, cocking the device 100 may activate a dose counter. In some embodiments, cocking may activate a separate firing counter for each dose session.

[0057] In some embodiments, cocking may initiate a dose delay. In some embodiments, cocking may initiate a timer to remind the patient when to fire the required shots for the dose session. The delay between shots accommodates drug administration parameters including timing of maximal drug absorption through olfactory tight junctions and natural mucociliary clearance.

[0058] In some embodiments, cocking may change the exposed color (112) between the upper bottle sleeve (104) and the base (108). This, along with the extended nozzle tip (which, in some embodiments, does not engage with the lid (202) while cocked), allows the patient or caregiver to clearly see and / or feel that the device is ready for administration or storage. In some embodiments, the exposed color (112) is made of a glow-in-the-dark plastic, improving ease and convenience of nighttime use for light-sensitive patients, for example, for administering pupil-dilating medications.

[0059] In some embodiments, the nozzle has an adjustable nostril stop (114) that provides feedback to the patient when the nozzle has reached the optimal nostril depth. The nostril stop also inhibits sniffing / snorting during use.

[0060] In some embodiments, the medication may be delivered by the intranasal medication delivery device (100) by delivery of a jet, squirt, or plug of liquid, rather than a spray. In some embodiments, the design of the flexible soft tip (102), nozzle (522), and valve in the refill mechanism (500) may be designed to optimize laminar delivery of the medication.

[0061] The technology for liquid delivery is effective for a wide variety of liquid properties and can be adapted for olfactory, systemic, and topical drug delivery via the intranasal drug delivery device (100).

[0062] In some embodiments, the intranasal drug delivery device (100) utilizes the individual properties of the fluid (such as viscosity and surface tension) to ensure long-term retention of the delivered liquid in the target area (i.e., the olfactory region) through capillary bridging.

[0063] In some embodiments, the intranasal drug delivery device (100) may include excipients in the liquid formulation for delivery with specific characteristics. For example, the excipient may have thixotropic properties (higher viscosity at rest, improving residence time in the olfactory region (306), and lower viscosity under shear, improving ease of measurement and delivery) via a miscible agent such as cellulose. As a further example, the excipient used may affect the drug surface tension to promote wetting and capillary bridging in the olfactory region. As a further example, the excipient used may be pre-approved by the Federal Food and Drug Administration, allowing for shorter development times.

[0064] In some embodiments, the intranasal drug delivery device (100) may include measuring methods or accessories for determining the ideal flexible soft tip (102) size or nozzle (522) type.

[0065] In some embodiments, the intranasal drug delivery device (100) may include a mechanical or electronic timer and / or locking mechanism to prevent overdosing. The intranasal drug delivery device (100) may incorporate the use of mobile technology to identify users and track usage to prevent overdosing. The intranasal drug delivery device (100) may incorporate the use of a cocking-and-releasing mechanism to stabilize positioning during drug delivery. These additions aid in patient compliance.

[0066] In some embodiments, the intranasal drug delivery device (100) may be used for one or more of the following applications: 1) drugs that target the brain directly via the olfactory region, 2) drugs that act systemically (e.g., better systemic bioavailability or less degradation than via the GI tract), 3) vaccine agents that induce a mucosal immune response, and 4) drugs that act locally.

[0067] In some embodiments, the intranasal drug delivery device (100) may have one or more of the following features: 1) is handheld, 2) can be used with one hand, 3) is designed for ambidextrous use, 4) the priming mechanism is simple and intuitive for the user, 5) there is a clear indication when the dose is filled, 6) the configuration encourages proper positioning in the nasal cavity, 7) is designed to require a single user action to deliver the filled dose, 8) is designed to prevent the user from dispensing a partial dose, and 9) is usable for multiple administrations.

[0068] In some embodiments, the intranasal drug delivery device (100) is intended to be filled by a pharmacist or other medical professional, hi some embodiments, the intranasal drug delivery device (100) will include a means for preventing unintentional refilling of the reservoir (502).

[0069] In some embodiments, the intranasal drug delivery device (100) is designed for multiple uses. In some embodiments, the intranasal drug delivery device (100) uses a disposable or refillable reservoir (502). In some embodiments, the flexible soft tip (102) is disposable.

[0070] In some embodiments, the intranasal drug delivery device (100) is designed with a removable gasket within the disposable or reusable reservoir (502).

[0071] In some embodiments, the drug delivery device (100) may be integrated with systems involving mobile technology, such as facial recognition and location tracking, gyroscopic location tracking of the device and correlation with facial location, use of NFC to track firing counts, etc.

[0072] In some embodiments, the drug delivery device (100) may enable electrically activated drug delivery, such as iontophoresis. In some embodiments, the drug delivery device (100) may include application of an ionic charge to promote translocation of drug molecules. In some embodiments, the drug delivery device (100) may include telescoping tips.

[0073] In some embodiments, the intranasal drug delivery device (100) is designed to use foam as a vehicle to allow air passage while ensuring residence time in the target area.

[0074] In some embodiments, the intranasal drug delivery device (100) has a hook to lock the gasket at the end of the travel to prevent misuse by refilling.

[0075] In some embodiments, the intranasal drug delivery device (100) has a piston that registers on the wall of the chamber, moving to the top of the reservoir with each actuation, which disables the device after one use.

[0076] In some embodiments, the intranasal drug delivery device (100) is a multi-dose device with a sterile barrier to prevent contamination.

[0077] FIG. 6 shows an exemplary intranasal drug delivery device (100) according to some embodiments, including a liquid chamber (602), a nozzle (604), a flexible soft tip (606), an actuator (608), an exposed collar (610), and a base (612).

[0078] 7 shows exemplary intranasal drug delivery devices (700), (708), (710) with the base (702) connected to the intranasal drug device (700), the base (702) removed and the removable reservoir (704) inserted into the intranasal drug delivery system (708), and the removable reservoir (704) partially removed from the intranasal drug delivery system (710), according to some embodiments. In some embodiments, a latching mechanism (706) retains the removable reservoir (704) in the device.

[0079] 8 shows an intranasal drug delivery device (100) inserted into a patient's nasal cavity with the tip touching the olfactory region (306). In some embodiments, a speculum may be used as an attachment to open the nostrils. In some embodiments, the device (100) includes an attachment to guide the tip.

[0080] The flexible soft tip (102) of the device enters the intranasal cavity and uses a typical intranasal geometry to self-guide the flexible soft tip (102) to the olfactory region, where it is held against the lateral and lateral nasal walls via the adjacent medial septum.

[0081] In some embodiments, when the device (100) is activated, the internal measuring chamber expels a repeatable, measured dose into the superior / posterior aspect of the olfactory region. To ensure that the expelled dose is delivered to the target area rather than being spread throughout the intranasal space, a laminar flow is generated, rather than a traditional atomization or spray. Due to the Coanda effect, the expelled excipient adheres to the medial, lateral, and superior aspects of the olfactory passages, but remains in motion.

[0082] When the kinetic energy of the expelled liquid dissipates, capillary movement of the opposing walls allows the excipient to coat the entire olfactory cortex, due to a combination of excipient surface tension (due to cohesion within the excipient) and the mucoadhesive properties of the excipient-to-olfactory mucosal wall interface.

[0083] To achieve this residence time, and as a result of capillary action, the excipient is held in the olfactory passage by a capillary bridge effect caused by the opposing walls of the inner, outer, and upper lateral sides of the olfactory passage, thus preventing the excipient from flowing out to the lower lateral side of the nasal vault. A suitably high viscosity, or thixotropic property, of the excipient helps to extend the residence time.

[0084] In one embodiment, the proposed method for targeted drug administration using device (100) is as follows: 1) applying the flexible tip to the anterior lateral side of the olfactory passage; 2) ejecting the excipient from the tip in a "moderately" laminar jet toward the posterior lateral side of the olfactory passage; 3) due to the Coanda effect, the jet ejection causes the excipient to adhere to the inner, lateral, and upper lateral sides of the olfactory passage while still in motion; 4) when the kinetic energy of the ejected liquid dissipates, capillary movement of the opposing walls causes the excipient to coat the entire olfactory cortex. This is due to a combination of excipient surface tension (due to cohesion within the excipient) and mucoadhesive properties between the excipient and the olfactory mucosal wall; 5) to achieve a residence time and as a result of capillary action, the excipient is retained in the olfactory passage by the capillary bridge effect caused by the opposing walls of the inner, outer, and upper lateral sides of the olfactory passage. Thus, the excipient is prevented from flowing down the lateral side of the nasal vault. A reasonably high viscosity, or thixotropic property, of the excipient helps to increase residence time.

[0085] FIG. 9 illustrates an integrated intranasal drug delivery platform including an intranasal drug delivery system (902), a mobile device (904), an intranasal device software application (906), a core application program interface (908), and device-generated data (910) that may be shared with interested parties (912).

[0086] The device (902) can connect to a software application (906) installed on the mobile device (904) for data logging to flag or track misuse and for medication adherence. For example, the intranasal device software application (906) can capture images up the nasal cavity to flag misuse, perform user biometric authentication for medication adherence, capture medication timing data for medication adherence, provide alerts or reminders to the user, etc.

[0087] In some embodiments, software applications will be available in cooperation with the device (100) to form an integrated hardware and software intranasal drug delivery platform (900), which will include a database for storing data generated from the device (100), which will serve as the basis for expansion into a permission-based personal data ecosystem platform.

[0088] In some embodiments, the software application may be expanded to become a platform for broader data aggregation and permission-based sharing. Personal patient data is collected and exchanged with permission from all parties with a role and responsibility in administering intranasal procedures (as authorized and applied). The data exchange portal will provide patient insights aimed at consistent, ongoing, and impactful positive action. The expansion facilitates smartphone-based sharing of various types of personal data with various stakeholders, including other patients, parents, doctors, clinics, clinical trial studies, healthcare professionals, patient health insurance companies, doctor insurance companies, healthcare insurance companies, drug developers, pharmacies, patient peer support groups, disease / disability researchers, disease / disability NGOs, government policymakers, and law enforcement / first responders. Privacy and control of personal data are important. Users may wish to share data in certain situations based on incentives or favors.

[0089] In some embodiments, the integrated intranasal drug delivery platform (900) may include an intranasal drug delivery device (902) that ineluctably links a designated medication to an individual patient through device-to-patient authentication; an intranasal drug delivery system (902) that provides machine-readable signals (origin markers) at the time of script creation, script filling, patient dosing, patient retention, and device retrieval (i.e., patient lifecycle events); continuous data collection, transport, storage, and retrieval capabilities; aggregation and anonymization of personal data into mineable and usable datasets, for example, for reporting, analytics, gamification, rewards, etc.; and personal data for the optimization of the patient's real-time and ongoing healthcare and a permission-based sharing system.

[0090] Categories of data that the integrated intranasal drug delivery platform (900) may utilize are patient profiles; stakeholder profiles for managing data shared with stakeholders; non-medical passive personal data (recovery may be ongoing); medical / biometric personal data (recovery may be ongoing); event-driven personal data at the time of script creation, script filling, patient medication, patient retention, and device retrieval (i.e., patient lifecycle); and event-driven prompting to influence current behavior.

[0091] In one example of an integrated intranasal drug delivery platform (900) for a user prescribed a medication to be administered using an intranasal drug delivery system (902), 1) the user receives an alert on their mobile device (904) indicating it is time to administer the scheduled dose of the medication, 2) the user unlocks the mobile device (904) using traditional ID authentication (passcode, fingerprint, or facial recognition), and the intranasal device software application (906) opens on the mobile device, 3) the user activates the intranasal drug delivery system (902) by touching the mobile device (904) or using another form of recognition, 4) the user uses the mobile device (902) for facial recognition authentication, and 5) the intranasal device software application (906) receives a short video capture (video capture) to determine pre-operational / biometric indicators (relevant metrics may be determined by a clinician, e.g., cognitive surveys, HR measurements, emotional state / disorders, etc.). capture); 6) the user completes any input required to complete pre-activation testing; 7) the intranasal device software application (906) determines that the intranasal drug delivery system (902) is activated (activation may be time-stamped and recorded, and methods of confirming activation include Bluetooth connectivity and visual images, sounds, color changes, and artificial intelligence to recognize activation); 8) the intranasal device software application (906) prompts the user for post-activation biometric measurements (relevant metrics may be determined by a clinician); 9) the user is taken back to the dashboard, a portion of the interface controlled by the software application (906), where they can track various metrics and manage permissions (who can see what data).

[0092] 10 shows an exemplary disposable intranasal drug delivery device (1000), a pump (1002) incorporating a reservoir, a pump locking mechanism (1004), and a flexible, soft tip (1008) with a tip locking mechanism (1006), a firing chamber (1010), and a spray tip (1012). In some embodiments, the pump (1002) is a spring-activated piston, and the pump locking mechanism (1004) will lock the tip locking mechanism (1006).

[0093] In some embodiments, the device can include an olfactory marker included with the excipient / drug to provide biofeedback to the user. This can take the form of an olfactory active marker that can inform the user that the drug / excipient has been delivered to the olfactory region. This can include, but is not limited to, feedback of off-target, under-deployed, deployed, or over-deployed drug / excipient. The marker can be included in the drug / excipient formulation or, in some embodiments, added during the release process. In some embodiments, the marker can be included without the active drug to provide feedback to the user, and application and administration (without the drug) can be successful to solicit a psychological response.

[0094] 11 shows an exemplary intranasal drug delivery device (1100), according to some embodiments. The device (1100) includes an outer chassis (1108) with a dosing opening at a first end and an actuation opening at a second end. A dosing tip is coupled to the dosing opening, and an actuator (1130) is coupled to the actuation opening. As described below, fluid can be delivered to a nasal volume through the dosing tip by depressing the actuator (1130).

[0095] In some embodiments, device 1100 is configured to receive carpule 1120 (which includes diaphragm 1110, tube 1112, firing chamber 1114, and plunger 1116 as described) and is pre-filled with a fluid, such as a pharmaceutical fluid. In the example of FIG. 11, device 1100 is slidably received within outer chassis 1108 and includes enclosure 1122 configured to receive carpule 1120.

[0096] The carpule (1120) includes a tube (1112) with an internal firing chamber (1114) that contains a fluid. In some embodiments, the firing chamber (1114) may be loaded with an anesthetic agent, such as ketamine or other pharmaceutical formulations, for delivery to the patient's nasal passages or olfactory region. The firing chamber (1114) has a plunger (1116) at one end and a diaphragm (1110) at the end opposite the plunger (1116). The device (1100) is configured so that when a user activates the actuator (1130), the fluid in the firing chamber (1114) is delivered through the dispensing tip with predetermined flow characteristics. In the embodiment illustrated in FIG. 11, the dispensing tip includes a flexible cannula, or tip (102), configured to deliver a slug of liquid in a laminar flow, as previously described.

[0097] In some embodiments, plunger 1116 may be engaged by push rod 1124. In the embodiment of FIG. 11 , push rod 1124 is located at the bottom of enclosure 1112, and spring 1134 is compressed between push rod 1124 and push button 1132. Locking mechanism 1128 retains push rod 1124 and prevents it from engaging plunger 1116 until push button 1132 is depressed. In the illustrated embodiment, locking mechanism 1128 includes a pair of pivotable tabs with inner ends that engage the push rod and outer ends that extend past the outer edge of enclosure 1122, such that when enclosure 1122 is pushed into chassis 1108 by depressing push button 1132, the tabs pivot to release push rod 1124. In other embodiments, the locking mechanism may include one or more tabs of locking material that can be broken by depressing a push button (1132).

[0098] Diaphragm 1110 is pierceable by needle 1106. Needle 1106 connects to channel 1104 in flexible tip 102, which is inserted into the nasal cavity for fluid delivery as described above. When actuated, fluid in firing chamber 1114 is forced through needle 1106 and channel 1104 and into the nasal cavity. Arm 1126 can assist a user in gripping device 1100 and engaging push button 1132.

[0099] In some embodiments, to assemble device 1100, carpule 1120 may be inserted into carpule enclosure 1122. Carpule enclosure 1122 may then be inserted into outer chassis 1108. In the illustrated embodiment, chassis 1108 includes a resilient lip 1109, and the actuator opening deforms slightly to accommodate carpule enclosure 1122 and carpule 1120, then retaining them within chassis 1108. In other embodiments, a seal may be added to aid in tamper detection.

[0100] The use of carpules can be advantageous in certain situations because carpules are commonly manufactured containers for drugs and are made of a material that is non-reactive with drugs, such as glass.

[0101] FIG. 12 illustrates an exemplary intranasal drug delivery device 1100, according to some embodiments, in which the carpule 1120 is inserted into the carpule enclosure 1122, and the carpule enclosure 1122 is inserted into the outer chassis 1108, but the actuator 1130 is not engaged by a user, and the locking mechanism 1128 holds the push rod 1124 so that the plunger 1116 is not engaged, and the fluid in the firing chamber 1114 is not pressurized. The arm 1126 may be folded outward or inward relative to the outer chassis 1108. The device 1100 may be stored with the fluid in the firing chamber 1114 not under pressure. The flexible tip 102 may be placed in a patient's nasal cavity before the actuator 1130 is engaged by a user.

[0102] FIG. 13 shows an exemplary intranasal drug delivery device 1100, according to some embodiments, in which a user has engaged a push button 1132, for example, by pressing it with their thumb. The user may hold the device 1100 in their hand with the arms 1126 in an outwardly deployed orientation. When the user presses the push button 1132, a locking mechanism 1128 releases the push rod 1124. In some embodiments, the locking mechanism may include one or more tabs that break off to release the push rod 1124, making the device 1100 a one-time use device. In other embodiments, the locking mechanism may include one or more tabs that fold over or cantilevers that are released to release the push rod 1124. When the locking mechanism 1128 is engaged, it prevents the push rod 1124 from applying pressure to the plunger 1116.

[0103] When push rod 1124 presses against plunger 1116, it pressurizes the fluid in firing chamber 1114 and moves carpule 1120 toward the needle. In some embodiments, spring 1134 is included to ensure that push rod 1124 applies even pressure to plunger 1116, and once locking mechanism 1128 is released, spring 1134 may move carpule 1120 further into outer chassis 1108 toward needle 1106 until needle 1106 pierces diaphragm 1110. In some embodiments, the user continues to press push button 1132 to move carpule 1120 into outer chassis 1108 until needle 1106 pierces diaphragm 1110.

[0104] In some embodiments, actuator (1130) may be a push button located on the bottom of device (1100), while in other embodiments, actuator (1132) may be located on the side of outer chassis (1108).

[0105] In some embodiments, device (1100) may be designed for one-time use with a locking mechanism (1128) that includes a break-off tab or other sacrificial fastener or structure, such that carpule enclosure (1122) cannot be removed from outer chassis (1118) to replace spent carpule (1120) with a new carpule (1120) without damaging device (1100).

[0106] 14 shows an exemplary intranasal drug delivery device (1100), according to some embodiments, in which the actuator (1130) is depressed by a user, causing the needle (1106) to pierce the diaphragm (1110) and the tip of the needle (1106) to contact fluid in the firing chamber (1114). Fluid in the firing chamber (1114) is under pressure from the plunger (1106), enters the needle (1106), and may flow through the channel (1104) in the tip (102). The fluid may flow through the channel (1104), which is placed in the patient's nasal cavity or olfactory region.

[0107] FIG. 15 shows an exemplary intranasal drug delivery device (1100), according to some embodiments, in which the actuator (1130) is pressed by a user, causing the push rod (1124) to push the plunger (1116) until it reaches the diaphragm (1110), terminating the ejection of fluid.

[0108] 16 shows an exterior view of an exemplary intranasal drug delivery device 1100, in which arms (1126) are hingedly connected by hinges (1602) and may be folded toward an outer chassis (1108) for storage, packaging, and transportation, according to some embodiments. For example, hinges (1602) may be living hinges made of thin material.

[0109] 17 shows an exterior view of an exemplary intranasal drug delivery device (1100), according to some embodiments, in which arms (1126) are deployed outward from an outer chassis (1108) to provide a grip for a user when using the device (1100). In its deployed state, arms (1126) may provide a grip for a user wearing gloves or a user with impaired dexterity.

[0110] FIG. 18 shows an exemplary intranasal drug delivery device (1100), according to some embodiments, in which the dispensing tip includes an atomizer (1103) designed to deliver a spray of fluid to the nasal cavity, rather than a laminar slug of liquid.

[0111] 19a-19c show an exemplary intranasal drug delivery device (1900) in which a two-stage trigger mechanism is activated with a single button press, according to some embodiments.

[0112] When the actuator 1902 is first pressed by the user, the carpule 1904 is forced into the needle 1906. The needle 1906 penetrates the diaphragm 1908 (i.e., the carpule septum) and opens a fluid pathway through the channel 1910 (cannula), as shown in FIG. 19b. The actuator 1902 is directly connected to the plunger 1914. When the actuator 1902 is pressed a second time by the user, the spring 1912 releases and compresses the plunger 1914, expelling fluid through the channel 1910, as shown in FIG. 19c.

[0113] As shown in Figures 19b and 19c, spring 1912 may be released by breaking shear pin 1916 into pieces 1918 and 1920. In other embodiments, spring 1912 may be released when an injection-molded breakoff point or wings on plunger 1914 are broken off. In other embodiments, spring 1912 may be released by a ball-detent mechanism, a molded snap-fit ​​component that activates upon reaching a preset force, or other mechanism. In yet another embodiment, spring 1912 may be released by a compressive force that separates a magnet on the plunger from a magnet in the main system.

[0114] The movement of the plunger 1914 is limited by a stop mechanism 1904 to set the total dose, which may include an actuator protrusion 1922 that engages the base 1924 of the carpule.

[0115] Figures 20a through 20c show an exemplary intranasal drug delivery device (1900A), according to some embodiments, in which a two-stage trigger mechanism is activated with a single press. In this embodiment, actuator (1902A) is connected to spring (1912A), which is connected to plunger (1914A). After actuator (1902A) is pressed by a user, carpule (1904A) is pressed into needle (1906A), which penetrates diaphragm (1908A) and opens a fluid pathway through channel (1910A) (cannula), as shown in Figure 20b. Further pressure on actuator (1902A) builds up spring force in the user's hand (or other means used to press the button). When sufficient spring force is achieved, actuator (1902A) is released. As described above, actuator 1902A may be released in several different ways. The spring force built up behind actuator 1902A then rapidly compresses spring 1912A, which is between actuator 1902A and plunger 1914A. Spring 1912A then dispenses fluid from channel 1910A.

[0116] In some embodiments, the device includes a dampening mechanism, examples of which are further described below with respect to Figures 21 through 33. Elements such as a dispensing tip, a needle that pierces a diaphragm, an outer body, etc., are not shown in all figures but may be included in some embodiments. In each of these exemplary embodiments, device 2100 / 2200 / 2300 / 2400 / 2500 / 2600 / 2700 / 2800 / 2900 / 3000 / 3100 / 3200 / 3300 is configured to eject a jet of fluid with a controlled velocity profile through the channel. This helps limit shear to the delivered agent, although some of the delivered agent may be compromised by shear. For example, in some embodiments, the device is configured to begin ejecting a fluid jet with a high initial velocity, but at the end of the jet dispense the jet velocity slows linearly to near zero.

[0117] FIG. 21 shows an exemplary intranasal drug delivery device (2100), according to some embodiments, in which a plunger (2102) is pushed by a spring (2104). In the embodiment of FIG. 21, the speed of the plunger (2102) is controlled by an eddy current brake connected to the end of travel of the spring (2104). In the embodiment of FIG. 21, the dampening mechanism includes a magnet (2106) connected to the plunger (2102) that moves through a conductive jacket (2108), generating eddy currents to limit the maximum speed of the plunger. In another embodiment, the speed of the plunger (2102) may be controlled by having the magnet (2106) turned by a helix on a shaft connected to the end of travel of the spring (not shown).

[0118] 22 illustrates an exemplary intranasal drug delivery device 2200, according to some embodiments, in which the speed of movement of the plunger 2202 is controlled by a dampening mechanism necessarily formed from the structure and materials selected for the device 2200. For example, in some embodiments, part tolerances and material variations are controlled to provide friction in the plunger 2202 and K values ​​in the spring 2204 configured to ensure a desired jet velocity profile.

[0119] FIG. 23 shows an exemplary intranasal drug delivery device 2300, according to some embodiments, in which the speed of a plunger 2302 is controlled by a dampening mechanism including a viscous dampener 2304 connected to the end of travel of a spring 2306. The dampener 2304 is filled with air or a viscous liquid (e.g., oil). The dampener 2304 controls the speed of the end of travel of the spring 2306. The maximum speed is limited by the dampener 2304, and as the spring 2306 extends, its driving force decreases. This results in a faster initial speed and a slower speed throughout the dose.

[0120] 24 shows an exemplary intranasal drug delivery device 2400, according to some embodiments, in which the speed of a plunger 2402 is controlled by a dampening mechanism attached to the rear of the device 2400 and including a sealed chamber 2404 connected to a spring 2408, which is connected to the plunger 2402. To allow the plunger 2402 to advance, air must be drawn into the chamber 2404, but airflow into the chamber 2404 is restricted by either 1) a flow control valve (not shown) or 2) a simple flow restriction 2406 (e.g., a narrow channel, orifice plate).

[0121] FIG. 25 shows an exemplary device 2500, according to some embodiments, in which the dampening mechanism includes a spring 2502 that is used to compress a volume of air (e.g., push against a bellows, a diaphragm, or a piston) into a sealed chamber 2504. The compressed air flows through a flow restrictor 2506, which controls the rate at which the air flows into the device 2500. The outside of the body of the device 2500 (e.g., an O-ring seal) seals the sealed chamber 2504. The air then pushes against the backside 2508 of the piston 2510, forcing the medication out of the channel 2512. The rate at which the air flows is controlled by the flow restrictor 2506, which in turn controls the rate at which the piston 2510 moves. The flow restriction (2506) can be as simple as an orifice plate, narrow tubing, or narrow drilled hole, but it can also be a pneumatic device such as a pressure relief valve or flow control valve.

[0122] 26a and 26b illustrate an exemplary intranasal drug delivery device 2600, according to some embodiments, in which control over the velocity of the plunger 2602 is achieved by a dampening mechanism including a container of compressed gas 2604 (e.g., a sealed canister of CO canister, air, N, etc.). The container of compressed gas 2604 is connected to a flow restriction 2606 by piercing a membrane 2608 or septum, or by connecting to a valve. Leak points may be added to the chamber so that pressure applied to the device 2600 dissipates over time. This provides a decreasing velocity profile for the fluid jet. The compressed gas container may be connected to the chamber of the device 2600 by piercing a membrane on the canister, by a valve, or similar mechanism.

[0123] 27a and 27b show an exemplary intranasal drug delivery device 2700, according to some embodiments, in which the dampening mechanism includes a piston 2702, a sealed chamber 2704, and a pin and ball valve 2706. In this embodiment, the piston 2702 is moved, and compressed gas in the sealed chamber 2704 is momentarily delivered through the use of a mechanically operated valve 2706, such as a pin and ball valve. When the piston 2702 reaches the top of the chamber 2704, a pin 2708 is pushed by the piston 2702, opening a ball valve 2710 to release pressure into a firing chamber 2712.

[0124] FIG. 28 shows an exemplary intranasal drug delivery device (2800), according to some embodiments, in which a plunger (2802) is pushed by an electric motor (2804) (e.g., a stepper motor, DC motor, brushless motor, etc.), providing both the actuation force and the dampening mechanism. Circuitry on the electric motor (2804) controls the speed of the plunger (2802) to set a desired ejection flow rate profile. Control of the electric motor (2804) can be open-loop or closed-loop. The motor (2804) can be a linear motor or a rotary motor combined with gearing, linkage, cam, lead screw, or other mechanical elements to drive the plunger (2802).

[0125] 29a-29c show an exemplary intranasal drug delivery device (2900), according to some embodiments, in which a controlled jet rate is provided by a dampening mechanism including an elastomeric chamber (2902). This occurs in two steps. First, the plunger (2904) is depressed to fill the elastomeric chamber (2902), as shown in FIG. 29b. Second, a fluid path to the channel (2906) opens, whereupon the spring force built up within the stretched elastomeric chamber (2902) forces fluid out of the channel (2906), as shown in FIG. 29c.

[0126] To provide a controlled jet velocity profile, the fluid resistance of the fluid path from the elastomeric chamber 2902 is matched to the stiffness of the elastomeric chamber 2902. When the elastomeric chamber 2902 relaxes, the pressure on the fluid decreases, thus providing a jet velocity that is fast at the start and then slows down.

[0127] 30a through 30c show an exemplary intranasal drug delivery device 3000, according to some embodiments, in which the carpule 3002 is depressed to fill the elastomeric chamber 3004 and open the fluid path to the channel 3006 in one motion. In this embodiment, as shown in FIG. 30a, the needle 3008 is partially embedded in the septum 3010 to seal the end of the needle 3008. First, as the plunger 3016 moves, the diaphragm 3012 is pierced. As the plunger 3016 continues to move, as shown in FIG. 30b, the elastomeric chamber 3004 is filled with fluid. A spring 3014 prevents movement of the carpule 3003 until the plunger 3016 is fully depressed. Third, plunger 3016 stops moving, spring 3014 is compressed, and septum 3010 is pierced by needle 3008, as shown in FIG. 30c. Fourth, elastomeric chamber 3004 forces fluid out through channel 3006. As the pressure in elastic elastomeric chamber 3004 decreases, the velocity profile decreases. The chamber geometry can be modified to create a linear or non-linear decreasing velocity profile.

[0128] 31 shows an exemplary intranasal drug delivery device 3100, according to some embodiments, in which a large spring 3102 with limited initial travel is used to overcome static friction in the piston 3106, and a secondary spring 3104 provides the power to fully dispense the drug. The large spring 3102 is a stronger power spring than the secondary spring 3104. The fluid path from the channel 3108 is long enough so that the high velocity travel by the large spring 3102 does not force the fluid away from the channel 3108.

[0129] FIG. 32 shows an exemplary intranasal drug delivery device (3200), according to some embodiments, in which the flow rate of the jet is controlled by a flow restrictor device (3202) between the carpule (3204) and the channel (3206). The flow restrictor device (3202) may be long and gentle to maintain a laminar flow profile. This avoids excessive shear on the delivered drug (e.g., protecting the efficacy of a vaccine agent). The flow restrictor device (3202) may also be more compact, but still generate turbulence. This may make a more compact device suitable for delivering large amounts of drug. The flow restrictor device (3202) may also replace an active element, such as a constant-velocity flow control valve, a pressure relief valve, or a pressure control valve.

[0130] Figures 33a through 33c show an exemplary intranasal drug delivery device 3300, according to some embodiments, in which a plunger 3302 is driven by a spring 3304, while the speed of the piston is controlled by an air-filled bellows 3306. As the piston 3302 moves, the bellows 3306 is compressed, and air is forced through a flow restriction 3308 (e.g., a simple orifice plate, a small drilled hole, a pressure control valve, or a flow rate control valve). The rate at which the bellows 3306 can deform is controlled by the rate at which air flows through the flow restriction 3308. This can be achieved by an arrangement in which the air is contained within a diaphragm 3310, a rolling diaphragm, or the piston, as shown in Figures 33b and 33c. It can also be achieved with the same configuration as shown in Figure 33a, but with a diaphragm, rolling diaphragm, or piston.

[0131] The air may be vented externally from the device, or, to avoid the need for external venting, it may be vented into a secondary chamber.

[0132] A prototype device including a cannula and dampening mechanism was tested to demonstrate targeted fluid bolus delivery. The test involved inserting a cannula into the upper nostril of a patient and ejecting a laminar flow of fluid through the cannula. In the test, technicium-99 was used as the tracer fluid. As shown in Figure 36, a scan of the patient taken after ejection of the laminar flow of fluid indicates that the fluid was deposited in the patient's olfactory region (3600). In the scan shown in Figure 36, the presence of technicium-99 appears as a region of light.

[0133] The foregoing discussion provides many exemplary embodiments of inventive subject matter. While each embodiment represents a single combination of inventive elements, the subject matter is considered to include all possible combinations of the disclosed elements. Thus, if one embodiment includes elements A, B, and C and a second embodiment includes elements B and D, the subject matter is considered to include any remaining combination of A, B, C, or D, even if not explicitly disclosed.

[0134] The device, system, and method embodiments described herein may be implemented in a combination of both hardware and software, and may be implemented on programmable computers, each including at least one processor, a data storage system (including volatile or non-volatile memory or other data storage elements or a combination thereof), and at least one communication interface.

[0135] The program code is adapted to input data, perform the functions described herein, and generate output information. The output information is adapted to one or more output devices. In some embodiments, the communication interface may be a network communication interface. In embodiments where elements may be combined, the communication interface may be a software communication interface, such as for inter-process communication. In yet other embodiments, there may be a combination of a communication interface implemented as hardware, software, and a combination thereof.

[0136] Throughout the foregoing discussion, numerous references are made to servers, services, interfaces, portals, platforms, or other systems formed from computing devices. It should be recognized that use of such terms is deemed to refer to one or more computing devices having at least one processor configured to execute software instructions stored on a computer-readable, tangible, non-transitory medium. For example, a server can include one or more computers operating as a web server, database server, or other type of computer server in a manner that fulfills the described roles, responsibilities, or functions.

[0137] The technical solutions of the embodiments may take the form of a software product. The software product may be stored on a non-volatile or non-transitory storage medium, which may be a compact disc-based read-only memory (CD-ROM), a USB flash disk, or a removable hard disk. The software product includes a number of instructions that enable a computing device (personal computer, server, or network device) to perform the methods provided by the embodiments.

[0138] The embodiments described herein are implemented by physical computer hardware, including computing devices, servers, receivers, transmitters, processors, memory, displays, and networks. The embodiments described herein provide useful physical machines and individually configured computer hardware arrangements.

[0139] Although embodiments have been described in detail, it should be understood that various changes, substitutions, and alterations can be made thereto.

[0140] Moreover, the scope of the present application is intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification.

[0141] It will be understood that the above-described and illustrated embodiments are intended to be exemplary only.

Claims

1. A fluid delivery device for delivering a fluid to a subject's nasal cavity, the fluid delivery device comprising: a dispensing tip for dispensing the fluid; and a damping mechanism for producing a controlled velocity profile of the fluid as it exits the dispensing tip, the fluid comprising a laminar flow; the dispensing tip comprising a flexible, flexible, soft tip configured to conform to the subject's nasal cavity while being self-guided through the subject's intranasal geometry to a location adjacent to the olfactory region within the subject's nasal cavity.

2. A fluid delivery device as described in claim 1, characterized in that the dispensing tip is coupled to a chamber for containing the fluid to be dispensed.

3. A fluid delivery device as described in claim 2, characterized in that the chamber is a firing chamber.

4. The fluid delivery device of claim 2, further comprising an actuator operably coupled to the chamber such that, when actuated, the fluid flows from the chamber and out of the dispensing tip.

5. The fluid delivery device of claim 1, wherein the dispensing tip further comprises a nostril stop configured to (I) limit the depth of insertion of the dispensing tip into the subject's nasal cavity, and (II) provide feedback to the subject when the dispensing tip reaches a location adjacent the olfactory region within the subject's nasal cavity.

6. A fluid delivery device as described in claim 4, characterized in that the actuator is charged by a spring.

7. A fluid delivery device as described in claim 6, characterized in that the spring is coincident with the plunger.

8. A fluid delivery device as described in claim 7, characterized in that when the fluid delivery device is actuated, the plunger applies pressure to the chamber and pushes the fluid flow out of the chamber.

9. The fluid delivery device of claim 1, characterized in that it is handheld, usable with one hand, designed for ambidextrous use, promotes proper positioning in the nasal cavity, requires only a single user action to deliver the filled dose, prevents dispensing of a partial dose, or a combination thereof.

10. The fluid delivery device of claim 1, configured to deliver multiple doses.

11. The fluid delivery device of claim 1, wherein dispensing the fluid from the fluid delivery device as a liquid jet includes a separate liquid slug.

12. The fluid delivery device of claim 1, further comprising a housing, the housing defining an outer body of the fluid delivery device.

13. The fluid delivery device of claim 12, wherein the housing includes a dosing opening.

14. The fluid delivery device of claim 1, wherein the dispensing tip is deflected to follow the subject's septum.

15. The fluid delivery device of claim 14, wherein the dispensing tip is configured to conform to the anterior aspect of the nasal passage.

16. The fluid delivery device of claim 15, further comprising a removable reservoir containing the fluid.

17. The fluid delivery device of claim 16, characterized in that the reservoir includes a fluid reservoir that is mechanically pressurized with a non-air interface to enable medication administration independent of the orientation of the subject.

18. The fluid delivery device of claim 16, wherein the reservoir comprises a disposable reservoir.

19. The fluid delivery device of claim 16, wherein the reservoir comprises a refillable reservoir.

20. The fluid delivery device of claim 1, characterized in that the damping mechanism includes at least one of a magnet, a spring, a viscous damper, a sealed chamber with airflow restriction, a compressed gas container, a valve, a motor, an elastomeric chamber, a flow restriction device, and a plunger and firing chamber configuration.

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