Intranasal drug delivery devices, systems, and processes

Abstract

To provide an intranasal drug delivery device, system, and process.SOLUTION: An intranasal drug delivery device 100 has an elastic or flexible soft tip 102 (as opposed to a hard tip) for accurate dosing positioning. A soft tip may also provide comfort for the user and minimize blocking due to nasal walls or congestion. The device has an actuator 106 (e.g., button or trigger) and a cocking mechanism 108 for releasing a reproducible dose to reduce human error / variability.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] Cross-Reference to Related Applications This application claims the benefit of priority from U.S. Provisional Patent Application No. 62 / 656,463 filed on April 12, 2018, and No. 62 / 774,444 filed on December 3, 2018, both of which are incorporated herein by reference in their entireties.

[0002] The present disclosure relates generally to the technical field of drug delivery and intranasal devices.

Background Art

[0003] Various devices for delivering drugs to the nasal cavity are currently available. 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. 2014 / 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 improved intranasal delivery devices.

Summary of the Invention

[0005] In one embodiment, an intranasal drug delivery device is provided having a flexible or pliable, soft tip for precise drug placement and to provide comfort to the user. In this specification, the term “drug” may also be used to refer to other preparations, such as vitamins, fragrances, saline solutions, or unprocessed drugs.

[0006] According to one embodiment, an intranasal drug delivery device is provided having a cocking mechanism and an actuator for filling and dispensing a dosage.

[0007] In one embodiment, an intranasal drug delivery device is provided which has a fluid reservoir that is mechanically pressurized at a non-air interface, enabling drug delivery and filling of the launch chamber regardless of the orientation of placement. In some illustrative embodiments, the reservoir may be folded by external pressure, including atmospheric pressure.

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

[0009] In one embodiment, the intranasal fluid delivery device includes a drug delivery tip connected to a hollow needle, a delivery chamber for transporting fluid, the delivery chamber having a diaphragm at one end and a plunger at the other, and an actuator connected to a push rod movable toward the delivery chamber and having a locking mechanism, wherein pushing the actuator releases the locking mechanism, allowing the push rod to push the plunger, pressurizing the fluid and pushing the needle through the diaphragm into the delivery chamber so that the fluid flows from the needle to the drug delivery tip.

[0010] In one embodiment, a device is provided for delivering fluid to the volume of the nose, the device comprising: a housing having a first end with a dispensing opening and a second end with an operating opening; a dispensing tip coupled to the dispensing opening; a capsule having a tube pre-filled with fluid between a diaphragm and a plunger, located within the housing between the operating opening and the dispensing opening; and an actuator coupled to the operating opening, the actuator comprising a push rod movable toward a contact with a plunger and a spring for propelling the push rod toward the plunger, and being held in place by a locking mechanism.

[0011] According to one embodiment, a method is provided for targeting and delivering fluid into the nasal cavity. The method includes the steps of inserting a flexible dispensing tip into the nasal cavity and discharging the fluid from the flexible dispensing tip to deliver a bolus of laminar flow of liquid to a targeted area in the nasal cavity. The targeted area may be the olfactory region of the nasal cavity. The step of inserting a flexible dispensing tip into the nasal cavity includes inserting the flexible dispensing tip at least into the upper part of the nostril. The step of inserting a flexible dispensing tip into the nasal cavity may include positioning the end of the flexible dispensing tip in an area adjacent to the olfactory region. The flexible dispensing tip may include a cannula. The step of discharging the fluid may include discharging the fluid at a controlled velocity profile to limit shear stress on the fluid.

[0012] In various embodiments, the disclosure provides corresponding systems and devices, and logical structures such as machine-executable instruction sets for carrying out the devices and methods.

[0013] In this regard, before describing in detail at least one embodiment, it should be understood that the embodiment is not limited in its application to the structural details and arrangement of components revealed in the following description or illustrated in the drawings. Furthermore, it should be understood that the expressions and terms used herein are for illustrative purposes only and should not be considered limiting.

[0014] Many further features and combinations relating to the embodiments described herein may be conceived by those skilled in the art after reading this disclosure. [Brief explanation of the drawing]

[0015] explanation [Figure 1] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 2] According to several embodiments, exemplary intranasal drug delivery devices with a lid or cap are shown. [Figure 3] A diagram of the olfactory region is shown. [Figure 4] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 5] According to several embodiments, the dispensing and refilling strokes of an exemplary intranasal drug delivery device are shown. [Figure 6] According to several embodiments, illustrative internal diagrams of the tip and tip mechanism of an intranasal drug delivery device are shown. [Figure 7] According to several embodiments, an exemplary intranasal drug delivery device with a removable reservoir is shown. [Figure 8] According to several embodiments, an exemplary intranasal drug delivery device with its tip inserted into the nasal cavity is shown. [Figure 9] This diagram illustrates an integrated intranasal drug delivery platform. [Figure 10] According to several embodiments, exemplary disposable intranasal drug delivery devices are shown. [Figure 11] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 12] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 13] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 14]An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 15] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 16] An external view of an exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 17] An external view of an exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 18] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 19a] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 19b] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 19c] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 20a] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 20b] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 20c] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 21] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 22] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 23] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 24] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 25] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 26a] An exemplary intranasal drug delivery device is shown in accordance with some embodiments. [Figure 26b] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 27a] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 27b] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 28] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 29a] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 29b] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 29c] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 30a] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 30b] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 30c] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 31] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 32] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 33a] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 33b] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 33c] According to several embodiments, exemplary intranasal drug delivery devices are shown. [Figure 34] According to several embodiments, an exemplary intranasal drug delivery device is shown, which has a drug delivery tip with a bulbous end. [Figure 35]According to several embodiments, an exemplary intranasal drug delivery device is shown, which has a drug delivery tip with an alpha loop. [Figure 36] The images shown are those obtained by scanning the subject while testing the prototype device using a tracer fluid. [Modes for carrying out the invention]

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

[0017] Currently, disposable intranasal drug delivery devices are characterized by low accuracy / uniformity of drug delivery, lack of design for anatomical variability, and insufficient design for human factors—efficacy and safety. These drawbacks are particularly detrimental to applications such as: direct delivery routes to the brain (ingestion into CSF ​​(cerebrospinal fluid) via the olfactory epithelium, acting within the brain), systemically acting drugs (ingestion into the vascular system via the mucous membrane, acting systemically), vaccines (ingestion and action in the mucous membrane), and locally acting drugs (ingestion and action in the mucous membrane).

[0018] The following offers 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 products present opportunities in terms of their design for marketability in areas with limited access to healthcare (humanitarian impact) and their design for preventing drug misuse.

[0020] Figure 1 shows specific examples of intranasal drug delivery devices (100) according to several embodiments.

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

[0022] Nasal septum deviation can cause a variety of health-related problems. In some embodiments, a flexible, soft tip (102) is aligned with the anterior side of the nasal passage. In some embodiments, the soft tip (102) is deflected to conform to the patient's septum. This allows the tip (110) to be positioned in such a location as to release the medicine targeting the olfactory region in the nasal cavity, adapting to anatomical differences in the nasal cavity.

[0023] In some embodiments, the flexible, soft tip (102) has a kiss-cut valve near the tip (110). The valve suppresses partial release in the pre- and post-operation steps. The tip (110) also reduces or eliminates contamination by contact with air or line-fill remaining in the nozzle during administration. In some embodiments, the orientation of the kiss-cut is offset from the end of the tip (110) to direct the drug toward the olfactory portion of the nasal structure. The tip (102) may be an over-moulded tip in several embodiments. As shown in Figure 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 Figure 35, in some embodiments, the flexible tip utilizes an "alpha loop" (3500) to facilitate positioning of the end of the drug-dosing tip as it exits the occlusion. In interventional cardiology, one strategy for navigating a stenosis or calcified occlusion with a guidewire is to push a flexible-tipped guidewire through the occlusion. The tip naturally bends back on its own, and the wire finds its way through the occlusion via the leading alpha loop. A larger support surface helps guide the wire to the point of least resistance, and it then slides through the stenosis / occlusion. This embodiment may be used in cases of nasal trauma where nasal integrity is lost, and this can be a shape in which 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 dispensing a reproducible dose to reduce human error / variation. In some embodiments, the use of a cocking-dispensing mechanism facilitates stable positioning during delivery and reduces the need for priming the device (100), thereby reducing the possibility of operator error. In some embodiments, the dispensing chamber is emptied by activating a finger-pressure button. This method of activating the device (100) requires little dexterity or superior motor skills, which may be particularly important for patients who may have impaired motor skills, such as patients with Parkinson's disease. Priming may refer to ensuring that there is a sufficient amount of liquid to fill a drug injection / measuring mechanism suitable for drawing liquid, including but not limited to volumetric pumping.

[0025] In some embodiments, the device (100) has an internal reservoir that can be kept under constant pressure to enable dispensing regardless of orientation (e.g., it works whether the user is standing or lying down). The reservoir may be a bag and can be folded by external pressure, including atmospheric pressure. The pressure inside the reservoir may vary depending on the spring used, but it can always be under some pressure.

[0026] In some embodiments, the device (100) does not have an air vent for filling, storing, or operating the device (100). This may be useful for air travel, particularly by aircraft at reduced pressure or higher altitudes, and for oxygen-sensitive pharmaceuticals, and especially where there is no cold chain infrastructure, and for extending the shelf life of certain pharmaceuticals. Furthermore, this makes it difficult to tamper with the device. In some embodiments, there may be an air vent.

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

[0028] In some embodiments, the design of the device (100) is made into a highly ergonomic form, drawing inspiration from both the design of a wider remote controller and the design of a pen that is easier to use.

[0029] Ergonomics and consideration of human factors have transformed the technological landscape for nasal delivery devices. The design minimizes human error by enabling targeted, repeatable, and measured dose delivery. This design accommodates consumable drug reservoirs for short- to long-term use, while making drug reservoirs cost-effective and consumable for a single patient. This provides the ability to fill a variety of drugs at the care site or by the pharmaceutical filling line. The design, as an example, allows for a flexible and soft tip (102) with an extremely soft, matte-finish elastomer shroud.

[0030] The device's flexible, soft tip (102) is placed within the nasal cavity, using the general nasal geometry to bring the tip closer to the olfactory region. The flexible, soft tip (102) remains at a distance from the olfactory region, and the dispensed drug bolus is guided to the olfactory region by the inherent geometry of the nasal structure. The device mechanism supports a pocket-sized form based on compact, low-cost, injection-molded components.

[0031] Figure 2 shows specific examples of intranasal drug delivery devices (100) with a lid (202) or cap according to several embodiments.

[0032] In some embodiments, the lid (202) may be used together with or in place of the cocking mechanism (108) as a portion to be refilled into 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 discharge of the drug delivery device (100). In some embodiments, the lid (202) may provide extra space for gripping with the whole hand when attached to the bottom of the device (100). In some embodiments, the lid (202) is formed to increase the surface area that is not obstructed by the hand during use, so that a machine-readable mark (i.e., a URL code) can be added to the increased surface.

[0033] In some embodiments, the device (100) may include a rechargeable energy storage to supply start-up energy for intermittent operation. The rechargeable energy may include an electrical, chemical, or pressurized fluid storage.

[0034] Figure 3 shows an illustration of the nasal cavity (300), including the olfactory region (306), the upper part of the nostril (308), and the lower part of the nostril (310).

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

[0036] Current formulations for nasal delivery use standard sprays that are not specific to the olfactory region (306), utilize relatively small molecules, and the formulations are primarily water with some alcohol. For the inactive components in formulations for nasal delivery, a variety of functionalities are used, including solvents, mucosal adhesives, absorption enhancers, viscosity modifiers, pH buffers, antioxidants, preservatives, and surfactants.

[0037] Most of the airflow passes through the lower part of the nostril (310). Therefore, it is unlikely that sneezing will expel any liquid remaining in the olfactory region (306). Nasal congestion can primarily affect the lower part of the nostril (310) while the olfactory region (306) remains empty.

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

[0039] In some embodiments, to achieve the current state of the art of local drug delivery by saturating the entire mucous membrane, or systemic drug delivery by targeting the upper part of the nostril (308), the device (100) may be fitted with the addition of a lateral atomizer tip.

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

[0041] Figure 4 shows an exemplary intranasal drug delivery device with a reservoir (402) and a flexible tip (404) according to several embodiments.

[0042] Figure 5 shows specific examples of the release and refill mechanism (500) according to several embodiments. The release and refill mechanism (500) is incorporated into an intranasal drug delivery device, such as device (100).

[0043] The release and refilling mechanism (500) includes a reservoir (502) containing the drug for delivery to the nasal cavity.

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

[0045] In some embodiments, the storage tank may be a bag that can be folded by external pressure, including atmospheric pressure.

[0046] In some embodiments, the reservoir (502) is removable, and the insertion needle (504) is inserted through a silicone stopper at the top of the reservoir (502) to pull the substance into the device (100). The silicone stopper has resealing properties for air-sensitive pharmaceuticals. The insertion needle (504) may be left in the bottle where the drug for the device is 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 refilling mechanism (500) is connected to an actuator (506) for releasing a spring (508).

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

[0049] The discharge and refilling mechanism (500) includes a launch chamber (516), a fluid chamber (518), a discharge valve (520), and a nozzle (522). The nozzle (522) may be in fluid communication with the tip (102) so that the fluid is discharged 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 its tip to reduce and discriminate line / dead volume.

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

[0052] In some embodiments, the flexible, soft tip (102) is designed to emit laminar flow, which may contain an inconspicuous liquid slag at a turbulent boundary, ideally suited to maximizing drug delivery to the horizontal, narrow portion of the nasal cavity leading to the olfactory region. The delivery of the laminar liquid slag assists the capillary action required for maximum drug delivery to the olfactory region. In some embodiments, the laminar flow is generated by a tubular array or hydrodynamic focusing.

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

[0054] In some embodiments, the device (100) is cocked by pushing down or compressing the bottle. This method of activating the device (100) requires little dexterity or superior motor skills. This method of preparing the device for administering medicine may be particularly important for patients who may have impaired motor skills, such as patients with Parkinson's disease. The device can be oriented in any direction, and the refilling and firing functions of the firing chamber are unaffected; that is, 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 device's length profile for shipping, shelf placement, and pocket placement. When not in use, 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 an individual firing counter for each dose session.

[0057] In some embodiments, cocking may trigger an administration delay. In some embodiments, cocking may trigger a timer to remind the patient when to initiate the firing required for the administration session. Delays between firings are adapted to indicators of drug administration, including the timing of maximum drug absorption via olfactory tight junctions and the natural cleansing of mucociliary tissue.

[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 fit onto the lid (202) while cocked), makes it clearly visible and / or feel to the patient or caregiver that the device is ready for dispensing or storage. In some embodiments, the exposed color (112) is made of glow-in-the-dark plastic to improve ease and convenience of nighttime use, for example, for administering pupil-dilating medications, for patients sensitive to light.

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

[0060] In some embodiments, the drug may be delivered by an intranasal drug delivery device (100) not by spray, but by a liquid jet, ejection, or plug delivery. In some embodiments, the design of the flexible and soft tip (102), nozzle (522), and valve in the refilling mechanism (500) may be designed to optimize the laminar flow discharge of the drug.

[0061] The technology for liquid delivery is effective for a wide variety of liquid properties. This technology can be adapted for olfactory, systemic, and local drug delivery via an 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 that the fluid delivered in the target region (i.e., the olfactory region) by capillary bridging remains there for an extended period.

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

[0064] In some embodiments, the intranasal drug delivery device (100) may include a measurement method or accessory 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 overdose. The intranasal drug delivery device (100) may incorporate the use of mobile technology to identify the user and track usage to prevent overdose. The intranasal drug delivery device (100) may incorporate the use of a cocking-release mechanism to stabilize positioning during drug delivery. These additions help patients adhere to their medication.

[0066] In some embodiments, the intranasal drug delivery device (100) may be used for one or more of the following applications: 1) drugs that directly target the brain via the olfactory region; 2) drugs that act systemically (e.g., better systemic bioavailability or less degradation than via the GI tube); 3) vaccines 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) handheld, 2) usable with one hand, 3) designed for ambidextrous use, 4) priming mechanism is simple and intuitive to the user, 5) has a clear indication when the dose is filled, 6) shape facilitates proper positioning in the nasal cavity, 7) designed to require a single user action to deliver the filled dose, 8) designed to prevent the user from administering a partial dose, and 9) usable for multiple doses.

[0068] In some embodiments, the intranasal drug delivery device (100) is intended to be filled by a pharmacist or other healthcare professional. In some embodiments, the intranasal drug delivery device (100) will include means to prevent unintended 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 and soft tip (102) is disposable.

[0070] In some embodiments, the intranasal drug delivery device (100) is designed to have a movable gasket in a disposable or reusable storage tank (502).

[0071] In some embodiments, the drug delivery device (100) may be integrated with a system involving mobile technologies, such as, for example, facial recognition and location tracking, gyroscope position tracking of the device and correlation with facial position, and the use of NFC for tracking the number of shots.

[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 applying an ionic charge to facilitate the translocation of drug molecules. In some embodiments, the drug delivery device (100) may include tips that interlock and extend with each other.

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

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

[0075] In some embodiments, the intranasal drug delivery device (100) has a piston that moves to the top of the reservoir with each operation, marking a record on the chamber wall. This renders the device unusable after a single use.

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

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

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

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

[0080] The flexible, soft tip (102) of the device enters the space within the nasal cavity and utilizes the general intranasal geometry to self-guide the flexible, soft tip (102) to the olfactory region. The flexible, soft tip (102) is held in place by lateral displacement and lateral nasal wall via the adjacent medial septum.

[0081] In some embodiments, when the device (100) is activated, the internal measuring chamber dispenses a repeatable and measured dose into the upper / rear side of the olfactory region. A laminar flow is generated, rather than a conventional spray or mist, to ensure that the dispensed dose is delivered to the target area rather than spreading throughout the entire space of the nasal cavity. Due to the Coanda effect, the dispensed excipient adheres to the inner, lateral, and upper sides of the olfactory passages, but remains in motion.

[0082] When the kinetic energy of the discharged liquid dissipates, capillary motion in the opposing wall allows the excipient to coat the entire olfactory cortex. This is due to a combination of the excipient's surface tension (due to aggregation within the excipient) and the mucosal adhesion properties between the excipient and the olfactory mucosal wall.

[0083] To achieve residence time and as a result of capillary action, the excipient is retained in the olfactory passages by a capillary bridge effect caused by the opposing walls of the inner, outer, and upper sides of the olfactory passages. This prevents the excipient from flowing out to the lower sides of the nasal fornix. The appropriate viscosity or thixotropic properties of the excipient help to extend the residence time.

[0084] In one embodiment, a proposed method for targeted drug administration using device (100) is as follows: 1) the flexible tip is applied to the anterior side of the olfactory passage; 2) the excipient is discharged from the tip in a "moderately" laminar jet toward the posterior side of the olfactory passage; 3) due to the Coanda effect, the discharge of the jet causes the excipient to adhere to the inner, lateral, and upper sides of the olfactory passage, but it is still in motion; 4) when the kinetic energy of the discharged liquid dissipates, the excipient covers the entire olfactory cortex by capillary action of the opposing walls. This is due to a combination of the surface tension of the excipient (due to aggregation in the excipient) and the mucosal adhesion properties between the excipient and the olfactory mucosal wall; 5) in order to achieve residence time and as a result of capillary action, the excipient is retained in the olfactory passage by a capillary bridge effect caused by the opposing walls on the inner, outer, and upper sides of the olfactory passage. Therefore, this prevents the excipient from flowing out to the lower sides of the nasal fornix. The moderate viscosity or thixotropic properties of the excipient help to extend the residence time.

[0085] Figure 9 shows 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) which may be shared with stakeholders (912).

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

[0087] In some embodiments, to constitute an integrated hardware and software intranasal drug delivery platform (900), a software application will be available in cooperation with a device (100). This will include a database for storing data generated from the device (100), which will serve as a foundation for extension to a consent-based personal data ecosystem platform.

[0088] In some embodiments, the software application may be extended to become a platform for broader data aggregation and consent-based sharing. Patient personal data is collected and exchanged with consent from / to all parties with the role and responsibility to perform (permitted and applied) intranasal procedures. The data exchange portal will provide consistent, continuously impactful, and action-oriented patient awareness. The extension facilitates the sharing of various types of personal data via smartphones to a variety of stakeholders, including other patients, guardians, doctors, clinics, clinical trial research, 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 the management of personal data are important. Users may wish to share data in certain circumstances based on incentives or goodwill.

[0089] In some embodiments, the integrated intranasal drug delivery platform (900) may include: an intranasal drug delivery device (902) that inevitably links a designated drug to an individual patient through device and patient verification; an intranasal drug delivery system (902) that provides machine-readable signals (origin markers) at the points of time of scrip creation, scrip filling, patient administration, patient retention, and device retrieval (i.e., patient lifecycle events); continuous data acquisition, transfer, storage, and retrieval capabilities; aggregation and anonymization of personal data to make it a retrievable and user-friendly dataset for, for example, reporting, analysis, gamification, rewards, etc.; and personal data for a consent-based sharing system for optimizing the patient's immediate and ongoing healthcare.

[0090] Categories of data that the Integrated Intranasal Drug Delivery Platform (900) may utilize include patient profiles; stakeholder profiles for managing data shared with stakeholders; non-medical passive personal data (which may be in the process of being collected); medical / biometric personal data (which may be in the process of being collected); event-driven personal data at points in time such as scrap creation, scrap filling, patient administration, patient retention, and device retrieval (i.e., the patient lifecycle); and event-driven prompting to influence current actions.

[0091] As an example of an integrated intranasal drug delivery platform (900) for a user prescribed medication to be administered using an intranasal drug delivery system (902), 1) the user receives an alert on their mobile device (904) indicating that it is time to administer the scheduled medication; 2) the user unlocks the mobile device (904) using conventional 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 by another form of recognition; 4) the user uses the mobile device (902) for facial recognition authentication; 5) the intranasal device software application (906) uses pre-activation indicators / biometric indicators (relevant metrics may be determined by the clinician, e.g., cognitive surveys, HR measurement, emotional state / disorder, etc.) to determine short video captures (video 6) The user is prompted to input for measurements such as capture, 7) the intranasal device software application (906) determines that the intranasal drug delivery system (902) is activated (its operation may be timestamped and recorded, and methods of confirming activation include Bluetooth® connection and visual images, sounds, color changes, artificial intelligence that recognizes activation), 8) the intranasal device software application (906) is prompted to input for measurements of post-activation biometrics (relevant indicators may be determined by a clinician), 9) the user is taken back to a dashboard, which is part of the interface controlled by the software application (906), where the user can track various indicators and manage permissions (who can see which data).

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

[0093] In some embodiments, the device may include an olfactory marker that is contained in the excipient / drug and provides biofeedback to the user. This may 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 may include, but is not limited to, feedback on drug / excipients that have missed their target, not deployed, deployed, or been over-deployed. The marker may be included in the drug / excipient formulation or, in some embodiments, added during the release step. In some embodiments, to provide feedback to the user, the marker may be included without the active drug, and application and administration (without the drug) has been successful in eliciting a psychological response.

[0094] Figure 11 shows an exemplary intranasal drug delivery device (1100) according to several embodiments. The device (1100) includes an outer chassis (1108) having a drug delivery opening at a first end and an actuator opening at a second end. A drug delivery tip is coupled to the drug delivery opening, and an actuator (1130) is coupled to the actuator opening. Fluid can be delivered through the drug delivery tip to the nasal volume by pressing the actuator (1130), as described below.

[0095] In some embodiments, the device (1100) is configured to house a carpule (1120) (including a diaphragm (1110), a tube (1112), a launch chamber (1114), and a plunger (1116) as described, and is pre-filled with a fluid, such as a pharmaceutical fluid. In the specific example shown in Figure 11, the device (1100) includes an enclosure (1122) slidably housed within an outer chassis (1108) and formed to receive the carpule (1120).

[0096] The carple (1120) includes a tube (1112) with an internal discharge chamber (1114) containing a fluid. In some embodiments, the discharge chamber (1114) may carry an anesthetic compound such as ketamine for delivery to the patient's nasal cavity or olfactory region. The discharge 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 such that when the user operates an actuator (1130), the fluid in the discharge chamber (1114) is delivered through the delivery tip with predetermined flow characteristics. In the specific example illustrated in Figure 11, as previously described, the delivery tip includes a flexible cannula, or tip (102), configured to deliver a slug of laminar flow liquid.

[0097] In some embodiments, the plunger (1116) may be engaged by a push rod (1124). In the specific example shown in Figure 11, the push rod (1124) is located at the bottom of the enclosure (1112), and a spring (1134) is compressed between the push rod (1124) and the push button (1132). A locking mechanism (1128) holds the push rod (1124) and prevents it from engaging with the plunger (1116) until the push button (1132) is pressed. In the illustrated specific example, the locking mechanism (1128) includes a pair of swivelable tabs having an inner end that engages the push rod and an outer end that extends past the outer edge of the enclosure (1122), and the tabs swivel to release the push rod (1124) when the enclosure (1122) is pushed into the chassis (1108) by pressing the push button (1132). In other embodiments, the locking mechanism may include one or more tabs of locking material that can be broken by pressing a push button (1132).

[0098] The diaphragm (1110) is perforated by a needle (1106). At a flexible tip (102) inserted into the nasal cavity for fluid delivery as described above, the needle (1106) is connected to a channel (1104). When activated, the fluid in the launch chamber (1114) is pushed into the nasal cavity through the needle (1106) and channel (1104). An arm (1126) may assist the user in grasping the device (1100) and engaging the push button (1132).

[0099] In some embodiments, the kapple (1120) may be inserted into a kapple enclosure (1122) to assemble the device (1100). The kapple enclosure (1122) may then be inserted into an outer chassis (1108). In the illustrated specific example, the chassis (1108) includes a resilient lip (1109), and the actuator opening is slightly deformed to accommodate the kapple enclosure (1122) and the kapple (1120), and then holds them within the chassis (1108). In other embodiments, seals may be added to aid in tamper detection.

[0100] Carples are commonly used containers for manufactured drugs, and because they are made of materials that are non-reactance to drugs, such as glass, the use of carples can be advantageous in certain situations.

[0101] Figure 12 shows an exemplary intranasal drug delivery device (1100) according to several embodiments, where the carple (1120) is inserted into the carple enclosure (1122), and the carple enclosure (1122) is inserted into the outer chassis (1108), but the actuator (1130) is not engaged by the user, and a locking mechanism (1128) holds the push rod (1124) so ​​that the plunger (1116) is not engaged, and the fluid in the launch 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 launch chamber (1114) unpressurized. The flexible tip (102) may be placed in the patient's nasal cavity before the actuator (1130) is engaged by the user.

[0102] Figure 13 shows an exemplary intranasal drug delivery device (1100) according to several embodiments, in which the user engages a push button (1132) by pressing it, for example, with their thumb. The user may hold the device (1100) in their hand using an arm (1126) which is positioned to open outwards. 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 are folded off to release the push rod (1124), making the device (1100) usable only once. In other embodiments, the locking mechanism may include one or more foldable tabs or cantilevers that are detached 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 the push rod (1124) presses against the plunger (1116), it pressurizes the fluid in the firing chamber (1114) and moves the curl (1120) toward the needle. In some embodiments, a spring (1134) is included to ensure that the push rod (1124) applies even pressure to the plunger (1116), and once the locking mechanism (1128) is released, the spring (1134) may move the curl (1120) further into the outer chassis (1108) toward the needle (1106) until the needle (1106) pierces the diaphragm (1110). In some embodiments, the user continues to press the push button (1132) to move the curl (1120) further into the outer chassis (1108) until the needle (1106) pierces the diaphragm (1110).

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

[0105] In some embodiments, the device (1100) may be designed for single use only, with a locking mechanism (1128) that includes a breakable tab or other sacrificial fastener or structure, and as a result, the karple enclosure (1122) cannot be removed from the outer chassis (1118) to replace a used karple (1120) with a new karple (1120) without damaging the device (1100).

[0106] Figure 14 shows an exemplary intranasal drug delivery device (1100) according to several embodiments, in which an actuator (1130) is pressed by a user, resulting in a needle (1106) being pierced by a diaphragm (1110) and the tip of the needle (1106) being in contact with the fluid in a launch chamber (1114). The fluid in the launch chamber (1114) is pressurized from the plunger (1106) and may enter the needle (1106) and flow through a channel (1104) in the tip (102). The fluid may flow through a channel (1104) placed in the patient's nasal cavity or olfactory region.

[0107] Figure 15 shows an exemplary intranasal drug delivery device (1100) according to several embodiments, in which an actuator (1130) is pressed by the user, resulting in a push rod (1124) pushing a plunger (1116) to a diaphragm (1110), and the fluid discharge ends.

[0108] Figure 16 shows the appearance of an exemplary intranasal drug delivery device 1100 according to several embodiments, where the arm (1126) is hinged by a hinge (1602) and may fold toward an outer chassis (1108) for storage, packing, and transport. For example, the hinge (1602) may be a living hinge made of thin material.

[0109] Figure 17 shows the appearance of an exemplary intranasal drug delivery device (1100) according to several embodiments, in which an arm (1126) is extended outward from the outer chassis (1108) to provide a grip to the user when using the device (1100). In its extended state, the arm (1126) may provide a grip to a user wearing gloves or a user with impaired dexterity.

[0110] Figure 18 shows an exemplary intranasal drug delivery device (1100) according to several embodiments, in which the drug delivery tip includes an atomizer (1103) designed to deliver a fluid spray, rather than a laminar flow liquid slag, into the nasal cavity.

[0111] Figures 19a to 19c illustrate exemplary intranasal drug delivery devices (1900) according to several embodiments, in which a two-stage trigger mechanism is performed with a single button press.

[0112] When the actuator (1902) is first pressed by the user, the curl (1904) is pressed into the needle (1906). The needle (1906) penetrates the diaphragm (1908) (i.e., the curl septum), opening a fluid path through the channel (1910) (cannula), as shown in Figure 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 then presses down the plunger (1914), discharging fluid through the channel (1910), as shown in Figure 19c.

[0113] As shown in Figures 19b and 19c, the spring (1912) may be released by breaking the shear pin (1916) into fragments (1918) and (1920). In other embodiments, the spring (1912) may be released when the injection-molded breakoff point or fin of the plunger (1914) is broken off. In other embodiments, the spring (1912) may be released by a ball detent mechanism, a molded snap-fit ​​component that is activated when a preset force is reached, or other mechanism. In yet another embodiment, the spring (1912) may be released by a pressing force that separates the magnet in the plunger from the magnet in the main part of the system.

[0114] The movement of the plunger (1914) is restricted by a stopping mechanism (1904) to set the total dose. The stopping mechanism may include an actuator projection (1922) that engages with the base (1924) of the curl.

[0115] Figures 20a to 20c show exemplary intranasal drug delivery devices (1900A) according to several embodiments, where a two-stage trigger mechanism is performed in a single pushing motion. In this embodiment, an actuator (1902A) is connected to a spring (1912A) connected to a plunger (1914A). After the actuator (1902A) is pressed by the user, the curl (1904A) is pressed into the needle (1906A), and as shown in Figure 20b, the needle (1906A) penetrates the diaphragm (1908A) to open a fluid path through the channel (1910A) (cannula), and further pressing on the actuator (1902A) accumulates spring force in the user's hand (or other means used to press the button). When sufficient spring force is achieved, the actuator (1902A) is released. As described above, the actuator (1902A) may be released in several different ways. The spring force accumulated behind the actuator (1902A) then rapidly compresses the spring (1912A) located between the actuator (1902A) and the plunger (1914A). The spring (1912A) then dispenses fluid from the channel (1910A).

[0116] In some embodiments, the device includes a dampening mechanism, specific examples of which are further described below with respect to Figures 21 to 33. Elements such as the drug delivery tip, the needle penetrating the diaphragm, and the outer body are not shown in all figures but may be included in some embodiments. In each of these exemplary embodiments, the device (2100) / (2200) / (2300) / (2400) / (2500) / (2600) / (2700) / (2800) / (2900) / (3000) / (3100) / (3200) / (3300) is configured to discharge a jet of fluid through a channel at a controlled velocity profile. The delivered drug may be somewhat damaged by shear, but this helps to suppress shear on the delivered drug. For example, in one embodiment, the device is configured to start by discharging a fluid jet at a high initial velocity, but to decelerate linearly to near zero velocity at the end of the jet delivery.

[0117] Figure 21 shows an exemplary intranasal drug delivery device (2100) according to several embodiments, in which a plunger (2102) is pushed by a spring (2104). In the embodiment of Figure 21, the speed of the plunger (2102) is controlled by an eddy current brake connected to the moving end of the spring (2104). In the embodiment of Figure 21, the damping mechanism includes a magnet (2106) connected to the plunger (2102) moving through a conductive jacket (2108) to generate eddy currents and limit the maximum speed of the plunger. In another embodiment, the speed of the plunger (2102) may be controlled by having a magnet (2106) rotated by a helical wire on a shaft connected to the moving end of the spring (not shown).

[0118] Figure 22 shows an exemplary intranasal drug delivery device (2200) according to several embodiments, where the travel speed of the plunger (2202) is controlled by a damping mechanism necessarily formed from the structure and selected materials of the device (2200). For example, in some embodiments, part tolerances and material variations are controlled to provide friction to the plunger (2202) and a K value to the spring (2204), configured to ensure a desirable jet velocity profile.

[0119] Figure 23 shows an exemplary intranasal drug delivery device (2300) according to several embodiments, in which the speed of a plunger (2302) is controlled by a damping mechanism including a viscous dampener (2304) connected to the moving end of a spring (2306). The dampener (2304) is filled with air or a highly viscous fluid (e.g., oil). The dampener (2304) controls the speed of the moving end of the spring (2306). The maximum speed is limited by the dampener (2304), and its driving force decreases as the spring (2306) extends. This results in a speed that is fast at the beginning and slows down later over the entire dose.

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

[0121] Figure 25 shows an exemplary device (2500) according to several embodiments, where the damping mechanism includes a spring (2502) used to compress a mass of air into a sealed chamber (2504) (e.g., by pushing a bellow, a diaphragm, or a piston). The compressed air flows through a flow limiter (2506) that controls the airflow velocity 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 the back side (2508) of the piston (2510), pushing the drug out of the channel (2512). The speed of movement of the piston (2510) is controlled because the airflow velocity is controlled by the flow limiter (2506). The flow limiting section (2506) may be as simple as an orifice plate, a narrow tube, or a narrow drilled hole, or it may be an air device such as a pressure relief valve or a flow control valve.

[0122] Figures 26a and 26b show exemplary intranasal drug delivery devices (2600) according to several embodiments, where control over the velocity of a plunger (2602) is achieved by a damping mechanism including a compressed gas container (2604) (e.g., a sealed canister containing CO2, air, N2, etc.). The compressed gas container (2604) is connected to a flow limiter (2606) by penetrating a membrane (2608) or septum, or by connecting to a valve. A leak point may be added to the chamber so that the pressure applied to the device (2600) dissipates over time. This gives the fluid jet a reduced velocity profile. The compressed gas container may be connected to the chamber of the device (2600) by penetrating a membrane on a canister, by a valve, or by a similar mechanism.

[0123] Figures 27a and 27b show an exemplary intranasal drug delivery device (2700) according to several embodiments, where the damping 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 instantaneously supplied by 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), the pin (2708) is pushed by the piston (2702) and opens the ball valve (2710) to release the pressure into the discharge chamber (2712).

[0124] Figure 28 shows an exemplary intranasal drug delivery device (2800) according to several embodiments, in which a plunger (2802) is pushed by an electric motor (2804) (e.g., a stepping motor, DC motor, brushless motor, etc.) which provides both the function of acting force and damping mechanism. A circuit mounted on the electric motor (2804) controls the speed of the plunger (2802) to set a desired discharge flow rate profile. The 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] Figures 29a to 29c show exemplary intranasal drug delivery devices (2900) according to several embodiments, where a controlled jet velocity is provided by a damping mechanism including an elastomer chamber (2902). This occurs in two steps. First, as shown in Figure 29b, a plunger (2904) is pushed down to fill the elastomer chamber (2902). Second, a fluid path to a channel (2906) is opened, where the spring force accumulated in the stretched elastomer chamber (2902) pushes the fluid out of the channel (2906), as shown in Figure 29c.

[0126] To provide a controlled jet velocity profile, the fluid resistance in the fluid path from the elastomer chamber (2902) is balanced by the stiffness of the elastomer chamber (2902). As the elastomer chamber (2902) relaxes, the pressure on the fluid decreases, and this therefore provides a jet velocity that is fast at the beginning and then slows down.

[0127] Figures 30a to 30c show exemplary intranasal drug delivery devices (3000) according to several embodiments, in which a curl (3002) is pushed down to fill an elastomer chamber (3004), and a fluid path to a channel (3006) is opened in one movement. In this embodiment, as shown in Figure 30a, the needle (3008) is partially embedded in a septum (3010) to seal the end of the needle (3008). Firstly, as the plunger (3016) moves, the diaphragm (3012) is penetrated. As the plunger (3016) continues to move as shown in Figure 30b, the elastomer chamber (3004) is filled with fluid. The spring (3014) prevents the movement of the curl (3003) until the plunger (3016) is pushed down sufficiently. Thirdly, the plunger (3016) finishes moving, the spring (3014) is compressed, and the bulkhead (3010) is penetrated by the needle (3008) as shown in Figure 30c. Fourthly, the elastomer chamber (3004) pushes the fluid out through the channel (3006). As the pressure in the elastic elastomer chamber (3004) decreases, the velocity profile decreases. The geometric shape of the chamber can be modified to make a linear or nonlinear decreasing velocity profile.

[0128] Figure 31 shows an exemplary intranasal drug delivery device (3100) according to several embodiments, in which a large spring (3102) with limited initial movement is used, overcoming static friction in the piston (3106), and a second spring (3104) provides power to fully administer the drug. The large spring (3102) is a stronger power spring than the second spring (3104). The fluid path from the channel (3108) is long enough so that the fluid does not leave the channel (3108) due to the high-speed movement by the large spring (3102).

[0129] Figure 32 shows an exemplary intranasal drug delivery device (3200) according to several embodiments, where the flow velocity of the jet is controlled by a flow limiting device (3202) between a curl (3204) and a channel (3206). The flow limiting 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). The flow limiting device (3202) may also be more compact but generate turbulence. This would make a more compact device suitable for delivering larger volumes of drug. The flow limiting device (3202) can also be replaced with an active element such as an isokinetic flow control valve, a pressure relief valve, or a pressure control valve.

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

[0131] The air is either exhausted to the outside from the device, or, to avoid the need for external exhaust, it may be exhausted into a secondary chamber.

[0132] A prototype device, including a cannula and a damping mechanism, was tested to demonstrate targeted fluid bolus delivery. The test involved inserting the cannula into the upper part of the patient's nostril and discharging a laminar flow of fluid through the cannula. Technicium 99 was used as the tracer fluid in the test. As shown in Figure 36, a scan of the patient performed after the discharge of the laminar flow of fluid shows that the fluid was placed 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 previous discussion provides many exemplary embodiments of inventive features that demonstrate an inventive step. While each embodiment represents a single combination of the inventive elements, the inventive features are considered to encompass all possible combinations of the disclosed elements. Therefore, if one embodiment includes elements A, B, and C, and a second embodiment includes elements B and D, the inventive features are considered to encompass other remaining combinations of A, B, C, or D, even if not explicitly disclosed.

[0134] Embodiments of devices, systems, and methods described herein may be implemented in combination of both hardware and software. These embodiments may be implemented on a programmable computer, each comprising at least one processor, a data storage system (including volatile memory or non-volatile memory, or other data storage elements or combinations thereof), and at least one communication interface.

[0135] 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 one for inter-process communication. In yet another embodiment, there may be a combination of communication interfaces implemented as hardware, software, and a combination thereof.

[0136] Throughout the preceding discussion, numerous references are made to servers, services, interfaces, portals, platforms, or other systems formed from computing devices. It should be recognized that the use of such terms is considered to represent one or more computing devices having at least one processor configured to execute software instructions stored on computer-readable, tactile, non-temporary media. For example, a server may include one or more computers operating as a web server, a 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-temporary storage medium, which may be read-only memory using a compact disc (CD-ROM), a USB flash disk, or a removable hard disk. The software product includes many instructions that enable a computer 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, display devices, 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 modifications can be made herein.

[0140] Furthermore, the scope of this application is intended to be limited to specific embodiments of the processes, machines, products, compounds, means, methods, and steps described herein.

[0141] To ensure that this is understood, the specific examples and illustrations described above are intended to be illustrative only.

Claims

1. A fluid delivery device for delivering a fluid to the nasal cavity of a subject, comprising a tip for dispensing the fluid, the tip being contained within a flexible and pliable soft tip configured to self-guide through the nasal geometry of the subject to a region adjacent to the olfactory region within the subject's nasal cavity, and configured to dispense the fluid from there as a liquid jet, wherein the liquid jet exits the tip as a laminar flow.

2. The fluid delivery device according to claim 1, characterized in that the tip is coupled to a chamber containing the fluid to be delivered.

3. The fluid delivery device according to claim 2, characterized in that the chamber is a firing chamber.

4. The fluid delivery device according to claim 3, further comprising an actuator operably coupled to the chamber such that the fluid flows from the chamber to the tip when the actuator is operated.

5. (a) The tip is connected to a needle, (b) The firing chamber is equipped with a diaphragm at a first end and a plunger at a second end, (c) The fluid delivery device according to claim 4, wherein the actuator is connected to a push rod that is movable toward the second end of the launch chamber, the push rod enabling the push rod to push the plunger, pressurizing the fluid in the launch chamber, and pushing the needle into the launch chamber through the diaphragm so that the fluid flows from the needle to the tip.

6. The actuator is equipped with a locking mechanism, and pressing the actuator releases the locking mechanism, allowing the push rod to press the plunger, and furthermore, the locking mechanism (a) One or more tabs made of a locking material, wherein the locking mechanism is released by the user breaking the locking material, and / or (b) One or more swivelable tabs, wherein the locking mechanism is released by swiveling the swivelable tabs. A fluid delivery device according to claim 5, characterized by including the following:

7. The fluid delivery device according to claim 6, further comprising a push button and a spring compressed between the push rod and the push button, wherein the locking mechanism is configured to maintain the spring in a pressurized state, and releasing the locking mechanism releases the spring from the pressurized state, causing the push rod to push the plunger.

8. The fluid delivery device according to claim 1, further comprising a damping mechanism configured to produce a controlled velocity profile of the fluid delivered from the tip, wherein the damping mechanism comprises at least one of a magnet, a spring, a viscous dampener, a sealed chamber having a flow limiter, a compressed gas container, a valve, a motor, an elastomer chamber, and a flow limiter device.

9. The fluid delivery device according to claim 1, further comprising a nostrill stop configured to (i) limit the depth of insertion of the tip into the nasal cavity of the subject, and (ii) provide feedback to the subject when the tip reaches an area adjacent to the olfactory region in the nasal cavity of the subject.

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

11. The fluid delivery device according to claim 1, characterized in that it is configured to deliver multiple doses.

12. The fluid delivery device according to claim 1, characterized in that the liquid jet exiting the tip as a laminar flow contains liquid slug.

13. The fluid delivery device according to claim 12, characterized in that the liquid slug is configured to maximize drug delivery to the horizontal, narrow portion of the nasal cavity extending to the olfactory region.

14. The fluid delivery device according to claim 1, further comprising a housing that defines the outer body of the fluid delivery device.

15. The fluid delivery device according to claim 14, characterized in that the housing includes a drug dispensing opening.

16. The fluid delivery device according to claim 1, characterized in that the tip is deflected to conform to the septum of the subject.

17. The fluid delivery device according to claim 16, characterized in that the tip coincides with the anterior side surface of the nasal passage.

18. The fluid delivery device according to claim 1, further comprising a removable storage tank containing the fluid, wherein the storage tank is in fluid communication with the tip.

19. The fluid delivery device according to claim 18, characterized in that the storage tank includes a disposable storage tank.

20. The fluid delivery device according to claim 18, characterized in that the storage tank includes a refillable storage tank.

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