Delivery device and method for the nasal cavity and olfactory cortex.

Abstract

This disclosure describes a device for intranasal delivery. The device may have a housing with a dispensing element and a placement element or trigger element connected to the housing, which engages with the columella region of a subject to position the dispensing element in the nasal canal and limit its insertion depth. The device may also include two insertable portions, each intended for insertion into the nasal canal of a subject, and an actuator for delivering the composition from either or both of the insertable portions. The device can transition from a first configuration to a second configuration. The device of this disclosure can provide a convenient and effective method for delivering a composition intranasally to achieve unilateral delivery to a targeted region of the brain.

Description

Technical Field

[0001] Cross-reference This PCT application claims the benefit of U.S. Provisional Application No. 63 / 499,204, filed Apr. 28, 2023; U.S. Provisional Application No. 63 / 516,036, filed Jul. 27, 2023; and U.S. Provisional Application No. 63 / 618,104, filed Jan. 4, 2024, the contents of which are incorporated herein by reference.

Background Art

[0002] Drug delivery into the nasal cavity is an effective route for the administration of certain drugs, such as drugs that act locally in the nasal passages or drugs that are rapidly absorbed from the nasal mucosa into the bloodstream. Among the challenges associated with delivering a composition to the nasal passages of a subject are the difficulties of adapting to the diversity of the nasal passages, targeting the deposition of the therapeutic compound to the correct location within the nasal passages, and providing an apparatus that can reliably and repeatedly deliver the composition to locations within the nasal passages with high precision across a population of subjects.

Summary of the Invention

[0003] The inventors understand that providing reliable and effective nasal delivery devices presents challenges in nasal delivery, including anatomical, cognitive, and dexterity-related issues. For example, the internal nasal valve is a flow-regulating compartment of the nasal passage enclosed medially by the dorsal side of the nasal septum, laterally by the caudal portion of the superior lateral nasal cartilage, and inferiorly by the superior part of the inferior turbinate. Together, these form a physical wall between the nasal vestibule and the rest of the nasal passage, including the respiratory area and olfactory cleft. The internal nasal valve is surrounded by nasal tissue that can expand or occlude the pathway to the nasal passage, and this nasal tissue varies between individuals due to time, environmental factors, and genetics. Devices may need to be inserted at specific angles or depths to target particular compartments, and users may struggle to properly position and operate the devices. Users with motor skill impairments (e.g., Parkinson's disease, arthritis) or cognitive impairments (e.g., Alzheimer's disease) may particularly struggle to properly articulate, position, and operate intranasal delivery devices.

[0004] To address these challenges, this disclosure provides a novel injector for targeted delivery of a composition to a target area in the nasal cavity of a subject, which can be easily operated and positioned by users of various patient populations and can reliably deliver the composition to a target area in the nasal cavity. The exemplary device utilizes a double nasal injector with a columella engagement portion positioned between them to quickly and reliably secure the insertable portion of the device to the target dispensing area in the subject's nasal cavity. The exemplary device disclosed herein can quickly, easily, and reliably position a dispensing element within the nasal passage to enable precise targeted accumulation of the composition in the target area within the nasal cavity. Furthermore, the exemplary device disclosed herein can be quickly, easily, and reliably positioned and enabled for targeted accumulation by users with varying abilities (e.g., untrained bystanders) in high-stress environments (e.g., emergency medical care) and across diverse patient populations (e.g., elderly, cognitively impaired, dexterous, or users with diverse nasal anatomical structures), which would otherwise hinder the proper use of intranasal delivery devices.

[0005] The apparatus of this disclosure may comprise a housing comprising one or a combination of a subject engagement portion, one or more insertable portions, one or more dispensing elements, and a trigger.

[0006] In one embodiment, the present disclosure provides a device for intranasal delivery to a subject, the device comprising a housing having an insertable portion having a distal end and a proximal end, and a subject engagement portion engaging with the columella region of the subject to secure the distal end of the insertable portion within a discharge area of ​​the subject's nasal passage. In some embodiments, the discharge area is located 0 mm to 30 mm above a horizontal line intersecting the anterior surface of the internal nasal valve and 0 mm to 20 mm anterior to an inclined line intersecting the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule. As used herein, the term “distal” generally refers to the direction toward the end of the device configured to dispense fluid, and the term “proximal” generally refers to the direction toward the end of the device furthest from the tip of fluid dispensing. In a non-limiting example, the device may have one or more insertable portions at the distal end and a handle portion at the proximal end. However, these names are merely to describe the relative arrangement of features, and it may be appropriate to use the terms in reverse.

[0007] In some embodiments, the discharge area is further located 0 to 40 mm below a horizontal line parallel to the inferior surface of the olfactory cleft, 0 to 20 mm posterior to the dorsum of the nose, 10 mm and 50 mm above a horizontal line intersecting the inferior surface of the columella, 0 to 30 mm above a horizontal line intersecting the superior surface of the inferior turbinate, 0 to 3 mm from the nasal septum, or any combination thereof.

[0008] In some embodiments, the insertable portion, when inserted into the subject's nasal passage, opens or expands the internal nasal flap by pushing up the superior lateral nasal cartilage and surrounding tissues, separating them from the nasal septum. In some embodiments, the insertable portion, when inserted into the subject's nasal passage, is proximal to the nasal septum. In some embodiments, the subject-engaging portion prevents the distal end from moving within or away from the discharge area when the subject-engaging portion is fixed to the columella region. As used herein, the term “seated” means being positioned in contact with the columella region, such as when the subject-engaging portion is positioned to be in contact with the columella region. The term “seated” does not necessarily mean that the seated component is completely locked in place without any degree of freedom of movement. For example, the device may have some degree of rotational freedom while the subject-engaging portion is seated to the columella region. However, the shape of the intranasal portion and the way in which this shape interacts with the intranasal geometry may significantly limit the degree of freedom of movement of the device while the subject engagement portion is fixed to the columella region, so that the desired orientation is easily maintained. In some embodiments, the dispensing area is aligned with the olfactory cleft, defined by a linear vector between the olfactory cleft and the distal end of the insertable portion. In some embodiments, dispensing the composition from the dispensing area increases the targeted accumulation of the composition in the olfactory cleft. In some embodiments, dispensing the composition from the dispensing area increases the targeted accumulation of the composition on a surface of the respiratory area, such as the middle turbinate. In some embodiments, dispensing the composition from the dispensing area increases the targeted accumulation of the composition on two or more regions or subregions of the nasal passage. In some embodiments, the subject engagement portion is fixed to the columella region when the subject engagement portion is in contact with the lower side of the columella, the left side of the columella, and the right side of the columella simultaneously. In some embodiments, the subject engagement portion limits the insertion depth of the insertable portion into the nasal passage. In some embodiments, the insertable portion incorporates one or more dispensing channels leading to one or more dispensing ports configured to deliver a composition to one or more regions or subregions of the nasal passage of a subject.In some embodiments, the insertable portion comprises a dispensing element for delivering a composition to a region or partial region of the subject's nasal passage. In some embodiments, the housing comprises a trigger, which, when pressure is applied to the trigger, activates the device to dispense a composition from the insertable portion or dispensing element to the subject. In some embodiments, the subject engagement portion comprises a trigger connected to the housing and the subject engagement portion, which, when pressure is applied to the columella region of the subject engagement portion, activates the device to dispense a composition from the insertable portion or dispensing element to the subject. In some embodiments, the subject engagement portion comprises a trigger release portion connected to the housing and the subject engagement portion, which, when pressure is applied to the columella region of the subject engagement portion, allows the device to operate to deliver a composition from the insertable portion or dispensing element to the subject. In some embodiments, the device further comprises a trigger that is activatable when the trigger release portion is engaged. In some embodiments, the housing defines two insertable portions, each intended for insertion into the nasal passage of a subject, and when the first insertable portion is inserted into the nasal passage of the subject, the first insertable portion engages with the tissue within the nasal passage to open or expand the internal nasal valve of the subject, thereby positioning at least one of the insertable portions to deliver a composition to the subject, and the device further comprises an actuator for delivering the composition from either or both of the insertable portions when the device is activated. In some embodiments, the housing defines two insertable portions, each intended for delivery of a composition into the nasal passage of a subject, and the device further comprises an actuator for delivering the composition from either or both of the insertable portions when the device is activated. In some embodiments, the device is transitionable from a first configuration to a second configuration, and the device further comprises one or two dispensing elements connected to the insertable portions, at least one dispensing element emerging from at least one insertable portion when the device transitions from a first configuration to a second configuration.In some embodiments, the device is transitionable from a first configuration to a second configuration when pressure is applied around the longitudinal axis of the device, and at least one dispensing element appears as a linear vector with respect to the longitudinal axis of at least one insertable portion, or the device is configured to transition from the first configuration to the second configuration with only one hand. In some embodiments, the device is activated simultaneously when it transitions from the first configuration to the second configuration. In some embodiments, the distal surface of at least one dispensing element is positioned in the dispensing area when the device is in the second configuration.

[0009] In one embodiment, the Disclosure provides a device for intranasal delivery to a subject, the device comprising a housing having an insertable portion configured to be inserted into the nasal passage of a subject, and a subject engaging portion connected to the housing, which engages with the columella region of the subject, and which, when pressure is applied to the columella region of the subject by the subject engaging portion, enables and / or causes delivery of a composition from the insertable portion to the subject. In some embodiments, the insertable portion incorporates one or more dispensing channels leading to one or more dispensing ports configured to deliver a composition intranasally to one or more regions or sub-regions of the subject's nasal passage. In some embodiments, the insertable portion comprises a dispensing element for delivering a composition to a region or sub-region of the subject's nasal passage. In some embodiments, the housing comprises a trigger which activates the device to deliver a composition to the subject from the insertable portion or dispensing element. In some embodiments, the subject engagement portion includes a trigger connected to the housing and the subject engagement portion, and when pressure from the subject engagement portion is applied to the columella region, the trigger activates the device to dispense a composition to the subject from the insertable portion or dispensing element. In some embodiments, the subject engagement portion includes a trigger release portion connected to the housing and the subject engagement portion, and when pressure from the subject engagement portion is applied to the columella region, the trigger release portion allows the device to operate to deliver a composition to the subject from the insertable portion or dispensing element. In some embodiments, the device further includes a trigger that is activatable when the trigger release portion is engaged. In some embodiments, the subject engagement portion positions the insertable portion within the subject's nasal canal and limits the insertion depth of the insertable portion into the nasal canal. In some embodiments, the housing defines two insertable portions, each intended for insertion into the nasal passage of a subject, and when the first insertable portion is inserted into the nasal passage of the subject, the first insertable portion engages with the tissue within the nasal passage to open or expand the subject's internal nasal valve, thereby positioning at least one of the insertable portions to deliver a composition to the subject, and the device further comprises an actuator that delivers the composition from one or both of the insertable portions when the device is activated.In some embodiments, the housing defines two insertable portions, each intended for delivering a composition into the nasal passages of a subject, and the device further includes an actuator for delivering the composition from one or both insertable portions when the device is activated. In some embodiments, the device is transitionable from a first configuration to a second configuration, and the device further includes a dispensing element connected to the housing, which emerges from the first insertable portion when the device transitions from the first configuration to the second configuration. In some embodiments, the device is activated simultaneously when it transitions from the first configuration to the second configuration. In some embodiments, the device is transitionable from the first configuration to the second configuration when pressure is applied about the longitudinal axis of the device, and the dispensing element emerges as a linear vector with respect to the longitudinal axis of the first insertable portion, or the device is configured to transition from the first configuration to the second configuration with only one hand. In some embodiments, the subject engagement portion engages with the columella region of the subject to fix the distal end of the insertable portion within the nasal cavity discharge area of ​​the subject's discharge area. In some embodiments, the discharge area is located 0 to 30 mm above a horizontal line intersecting the anterior surface of the internal nasal valve, 0 to 20 mm anterior to an inclined line intersecting the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule, 0 to 40 mm below a horizontal line parallel to the inferior surface of the olfactory cleft, 0 to 20 mm posterior to the dorsum of the nose, 10 mm and 50 mm above a horizontal line intersecting the inferior surface of the columella, 0 to 30 mm above a horizontal line intersecting the superior surface of the inferior turbinate, 0 to 3 mm from the nasal septum, or one or more of any combination thereof. In some embodiments, the subject engagement portion prevents the distal end from moving within or away from the discharge area when the subject engagement portion is fixed in the columella region. In some embodiments, the dispensing area is aligned with the olfactory cleft, defined by a linear vector between the olfactory cleft and the distal end of the insertable portion. In some embodiments, dispensing the composition from the dispensing area increases the targeted accumulation of the composition in the olfactory cleft.In some embodiments, the subject engagement portion is fixed to the columella region when it simultaneously contacts the lower side of the columella, the left side of the columella, and the right side of the columella. In some embodiments, dispensing the composition from the discharge area increases the targeted accumulation of the composition on a respiratory surface such as the middle turbinate.

[0010] In one embodiment, the Disclosure provides a device for intranasal delivery to a subject, the device comprising a housing defining first and second insertable portions, each to be inserted into the nasal passage of a subject, wherein when the first insertable portion is inserted into the nasal passage of the subject, at least one insertable portion engages with tissue in the nasal passage to open or expand the subject's internal nasal flap, thereby positioning at least one of the insertable portions to deliver a composition to the subject; and an actuator for delivering the composition from either or both of the insertable portions when the device is activated. In some embodiments, the at least one insertable portion that opens or expands the internal nasal flap does so by moving a superior lateral cartilage defining the internal nasal flap away from the subject's nasal septum. In some embodiments, the at least one insertable portion that opens or expands the internal nasal flap does so by moving the superior lateral cartilage defining the internal nasal flap toward the dorsum of the subject's nose. In some embodiments, the insertable portion incorporates one or more dispensing channels leading to one or more dispensing ports configured to deliver a composition intranasally to one or more regions or sub-regions of the subject's nasal passage. In some embodiments, the insertable portion comprises a dispensing element for delivering a composition to a region or sub-region of the subject's nasal passage. In some embodiments, the device further comprises a trigger connected to the housing, which, when pressure is applied to the trigger, activates the device to dispense a composition from the insertable portion or dispensing element to the subject. In some embodiments, the device further comprises a trigger connected to the housing and a subject engagement portion, which, when pressure is applied to the columella region of the subject engagement portion, activates the device to dispense a composition from the insertable portion or dispensing element to the subject. In some embodiments, the device further comprises a subject engagement portion, the subject engagement portion comprising a trigger release portion connected to the housing, and when pressure from the subject engagement portion is applied to the nasal columella region, the trigger release portion permits the device to operate to deliver a composition to the subject from the insertable portion or dispensing element. In some embodiments, the device further comprises a trigger that is activatable when the trigger release portion is engaged.In some embodiments, the device further comprises a subject engagement portion connected to the housing, which engages with the columella region, and which positions an insertable portion within the subject's nasal canal, limiting the insertion depth of the delivery element into the nasal canal. In some embodiments, the housing defines two insertable portions, each for delivering a composition into the subject's nasal canal, and the device further comprises an actuator for delivering the composition from one or both of the dispensing elements when the device is activated. In some embodiments, the device is transitionable from a first configuration to a second configuration, with the housing defining a first insertable portion, and the device further comprises a dispensing element connected to the housing, which emerges from the first insertable portion when the device transitions from the first configuration to the second configuration. In some embodiments, the device is activated simultaneously when transitioning from the first configuration to the second configuration. In some embodiments, the device is capable of transitioning from a first configuration to a second configuration when pressure is applied around the longitudinal axis of the device, and the dispensing element appears as a linear vector with respect to the longitudinal axis of the first insertable portion, or the device is configured to transition from the first configuration to the second configuration with only one hand. In some embodiments, the subject engagement portion engages with the columella region of the subject to fix the distal end of the insertable portion within the discharge area of ​​the subject's nasal cavity, the discharge area being located 0 to 30 mm above a horizontal line intersecting the anterior surface of the internal nasal valve, 0 to 20 mm anterior to an inclined line intersecting the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule, 0 to 40 mm below a horizontal line parallel to the inferior surface of the olfactory cleft, 0 to 20 mm posterior to the dorsum of the nose, 10 mm and 50 mm above a horizontal line intersecting the inferior surface of the columella, 0 to 30 mm above a horizontal line intersecting the superior surface of the inferior turbinate, 0 to 3 mm from the nasal septum, or any combination of these. In some embodiments, the subject engagement portion prevents the distal end from moving within or away from the discharge area when the subject engagement portion is fixed in the columella region. In some embodiments, the discharge area corresponds to the olfactory cleft, defined by a linear vector between the olfactory cleft and the distal end of the insertable portion.In some embodiments, dispensing the composition from a discharge area increases the targeted accumulation of the composition in the olfactory cleft. In some embodiments, the subject engagement portion is fixed to the columella region when the subject engagement portion is in simultaneous contact with the lower side of the columella, the left side of the columella, and the right side of the columella. In some embodiments, dispensing the composition from a discharge area increases the targeted accumulation of the composition on a respiratory surface such as the middle turbinate.

[0011] In one embodiment, the present disclosure provides a device for intranasal delivery to a subject, the device being transitionable from a first configuration to a second configuration, the device comprising a housing defining a first insertable portion configured to be inserted into the nasal passage of the subject, and a dispensing element connected to the housing, which emerges from the first insertable portion when the device transitions from the first configuration to the second configuration, the device transitions from the first configuration to the second configuration by applying pressure about the longitudinal axis of the device, and the device is activated simultaneously with the transition from the first configuration to the second configuration. In some embodiments, simultaneous activation of the dispensing element refers to the transition from the first configuration to the second configuration, and the activation occurs in a single movement when pressure is applied about the longitudinal axis of the device. In some embodiments, the dispensing element emerges from the first insertable portion in a linear vector parallel to the dorsum of the nose, at a position on the inferior turbinate of the subject. In some embodiments, the device avoids contamination of the dispensing element by bacteria from the lower nasal cavity by housing the dispensing element in the insertable portion before exposing the dispensing element when transitioning from a first configuration to a second configuration. In some embodiments, the device avoids contamination of the dispensing element by covering the dispensing element within the insertable portion before operation. In some embodiments, the insertable portion incorporates one or more dispensing channels leading to one or more dispensing ports configured to deliver a composition into one or more regions or sub-regions of the subject's nasal passage. In some embodiments, the dispensing element appears as a linear vector with respect to the longitudinal axis of the first insertable portion. In some embodiments, the device is configured to transition from a first configuration to a second configuration with only one hand. In some embodiments, the dispensing element emerges from the insertable portion when the device transitions from a first configuration to a second configuration and pressure from a portion of the housing is applied to the columella region of the subject. In some embodiments, the second configuration moves the first portion of the housing toward the second portion of the housing about the longitudinal axis of the device.In some embodiments, the device further includes a subject engagement portion connected to the housing, the subject engagement portion engaging with the columella region, the subject engagement portion positioning an insertable portion within the subject's nasal passage, and limiting the insertion depth of the dispensing element into the nasal passage. In some embodiments, a subject engagement portion that engages with the columella region of the subject fixes the distal end of the dispensing element within the dispensing area of ​​the subject's nasal cavity, the dispensing area being located 0 to 30 mm above a horizontal line intersecting the anterior surface of the internal nasal valve, 0 to 20 mm anterior to an inclined line intersecting the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule, 0 to 40 mm below a horizontal line parallel to the inferior surface of the olfactory cleft, 0 to 20 mm posterior to the dorsum of the nose, 10 mm and 50 mm above a horizontal line intersecting the inferior surface of the columella, 0 to 30 mm above a horizontal line intersecting the superior surface of the inferior turbinate, 0 to 3 mm from the nasal septum, or any combination of these. In some embodiments, the subject engagement portion prevents the distal end of the dispensing element from moving within or away from the dispensing area when the subject engagement portion is fixed to the columella region. In some embodiments, the dispensing area is aligned with the olfactory cleft, defined by a linear vector between the olfactory cleft and the distal end of the insertable portion. In some embodiments, dispensing the composition from the dispensing area increases the targeted accumulation of the composition in the olfactory cleft. In some embodiments, dispensing the composition from the dispensing area increases the targeted accumulation of the composition on a surface of the respiratory area, such as the middle turbinate. In some embodiments, the subject engagement portion is fixed to the columellar region when the subject engagement portion is in contact with the lower side of the columella, the left side of the columella, and the right side of the columella simultaneously. In some embodiments, the device further includes a trigger connected to the housing and the subject engagement portion, where the subject engagement portion engages with the columellar region of the subject, and when pressure from the subject engagement portion is applied to the columellar region, the trigger activates the device to deliver the composition from the dispensing element to the subject.In some embodiments, the housing defines two insertable portions, each intended for insertion into the nasal passage of a subject, and when the first insertable portion is inserted into the nasal passage of a subject, the first insertable portion engages with the tissue within the nasal passage to open or expand the internal nasal valve of the subject, thereby positioning at least one of the insertable portions to deliver a composition to the subject, and the device further includes an actuator for delivering the composition from one or both of the insertable portions when the device is activated. In some embodiments, the housing defines two dispensing elements, each intended for delivering a composition into the nasal passage of a subject, and the device further includes an actuator for delivering the composition from one or both of the dispensing elements when the device is activated. In some embodiments, the device further includes a trigger release unit connected to the housing and the subject engagement portion, and when pressure from the subject engagement portion is applied to the columella region, the trigger release unit allows the device to operate to deliver the composition to the subject from the insertable portion. In some embodiments, the device further includes a trigger that is activatable when the trigger release unit is engaged. In some embodiments, the device avoids contamination of the dispensing element by covering it within the insertable portion before activation. In some embodiments, the composition is dispensed from the distal end of the insertable portion. In some embodiments, the dispensing element is located in the dispensing area when the device is in the second configuration. In some embodiments, the dispensing element is located at the distal end of the dispensing area when the device is in the second configuration. In some embodiments, the device is activated simultaneously when transitioning from the first configuration to the second configuration. In some embodiments, the dispensing element appears on the inferior turbinate of the subject in a straight line vector parallel to the dorsum of the nose from the first insertable portion. In some embodiments, when transitioning from the first configuration to the second configuration, the device avoids contamination of the dispensing element by bacteria from the lower nasal cavity by retracting the dispensing element into the insertable portion before exposing the dispensing element. In some embodiments, at least one insertable portion that opens or expands the internal nasal flap does so by moving the superior lateral nasal cartilage away from the nasal septum of the subject.In some embodiments, at least one insertable portion that opens or expands the internal nasal valve does so by moving the superior lateral nasal cartilage defining the internal nasal valve toward the dorsum of the subject's nose. In some embodiments, a subject engagement portion prevents the distal end of the insertable portion or dispensing element from moving into or away from the dispensing area when the subject engagement portion is fixed to the columella region. In some embodiments, the dispensing area is aligned with the olfactory cleft, defined by a linear vector between the olfactory cleft and the distal end of the insertable portion. In some embodiments, dispensing the composition from the dispensing area increases the targeted accumulation of the composition in the olfactory cleft. In some embodiments, dispensing the composition from the dispensing area increases the targeted accumulation of the composition on a surface of the respiratory area, such as the middle turbinate. In some embodiments, the subject engagement portion is fixed to the columella region when the subject engagement portion is in contact with the lower side of the columella, the left side of the columella, and the right side of the columella simultaneously. In some embodiments, the subject engagement portion limits the insertion depth of the insertable portion into the nasal passage. In some embodiments, the subject engagement portion limits the insertion depth of the dispensing element into the nasal canal. In some embodiments, the first and second insertable portions are configured to dispense the composition simultaneously from the first and second insertable portions. In some embodiments, the first and second insertable portions are configured to dispense the composition sequentially from the first and second insertable portions. In some embodiments, the first and second dispensing elements are configured to dispense the composition simultaneously from the first and second dispensing elements. In some embodiments, the first and second dispensing elements are configured to dispense the composition sequentially from the first and second dispensing elements. In some embodiments, the first insertable portion moves along the nasal septum, moving the superior lateral nasal cartilage away from the nasal septum. In some embodiments, the first and second dispensing elements move along the nasal septum. In some embodiments, the two insertable portions each contact both sides of the nasal septum. In some embodiments, the two dispensing elements each contact both sides of the nasal septum.In some embodiments, two insertable portions each contact both sides of the nasal septum and apply pressure to the superior lateral nasal cartilage away from the nasal septum. In some embodiments, two insertable portions each contact both sides of the nasal septum and apply pressure to the superior lateral nasal cartilage in a direction perpendicular to the lateral axis of the nasal septum. In some embodiments, at least one insertable portion that opens or expands the internal nasal flap does so by moving the superior lateral nasal cartilage defining the internal nasal flap away from the subject's nasal septum. In some embodiments, at least one insertable portion that opens or expands the internal nasal flap does so by moving the superior nasal cartilage defining the internal nasal flap toward the dorsum of the subject's nose. In some embodiments, the insertable portion is configured to fit into the wedge shape of the nasal flap where the nasal septum contacts the superior lateral nasal cartilage. In some embodiments, the anterior surface of the insertable portion is configured to fit into the narrow anterior surface of the internal nasal flap. In some embodiments, the anterior surface of the insertable portion is configured to fit into an opening with an angle of 9 to 15 degrees. In some embodiments, the insertable portion is configured to fit into the narrow anterior surface of the internal nasal valve when fixed around the columella region. In some embodiments, the insertable portion is configured to fit into an opening with an angle of 9 to 15 degrees when fixed around the columella region. In some embodiments, the insertable portion is configured to be inserted into the wedge-shaped internal nasal valve of the subject. In some embodiments, the insertable portion is tapered around its distal end and is configured to be inserted into the wedge-shaped internal nasal valve of the subject. In some embodiments, the insertable portion is tapered with a rounded edge around its distal end and is configured to be inserted into the wedge-shaped internal nasal valve of the subject. In some embodiments, the insertable portion has a tip portion having a width corresponding to the diameter of a circle approximating the average cross-sectional area of ​​the internal nasal valve. In some embodiments, the insertable portion has a flat surface on the side of the insertable portion that contacts the nasal septum. In some embodiments, the insertable portion has a rounded surface on the side of the insertable portion opposite the nasal septum.In some embodiments, the insertable portion has a width of up to 3 mm. In some embodiments, one or both insertable portions have a proximal and distal end, and the dispensing element emerges from the distal end of the insertable portion. In some embodiments, the distal end of the insertable portion is configured to be inserted into the nasal passage of the subject. In some embodiments, the emergence of the dispensing element from the first insertable portion when the device transitions from a first configuration to a second configuration includes the dispensing element extending from the first insertable portion.

[0012] In some embodiments, the subject engagement portion engages with both the right and left sides of the columella region. In some embodiments, the subject engagement portion has a concave shape. In some embodiments, the subject engagement portion has a U-shape. In some embodiments, the subject engagement portion has a saddle shape. In some embodiments, the subject engagement portion has a concave elliptical shape. In some embodiments, the subject engagement portion has a trench with a rounded bottom or rounded edge. In some embodiments, the subject engagement portion centers two insertable portions around the subject's columella. In some embodiments, the subject engagement portion is a positioning element that aligns at least one of the insertable portion, dispensing element, or housing with respect to the user's nasal passage. In some embodiments, the device targets the olfactory cleft or a portion thereof, and the subject engagement portion aligns the dispensing element with the subject's olfactory cleft. In some embodiments, the insertable portion has a single dispensing channel leading to a dispensing port located on the distal surface of the insertable portion. In some embodiments, the insertable portion comprises a single dispensing channel leading to a dispensing port arranged along the length of the insertable portion. In some embodiments, the insertable portion comprises two or more dispensing channels leading to two or more dispensing ports arranged on different faces of the insertable portion. In some embodiments, the insertable portion comprises a single dispensing channel leading to a dispensing port arranged to deliver the composition to the olfactory cleft. In some embodiments, the insertable portion comprises a single dispensing channel leading to a dispensing port arranged to deliver the composition to a surface of the respiratory area, such as the middle nasal concha. In some embodiments, the insertable portion comprises two or more dispensing channels leading to two or more dispensing ports arranged to deliver the composition to one or more regions or subregions of the nasal passage, such as the olfactory cleft and / or the middle nasal concha. In some embodiments, the first insertable portion comprises a single dispensing channel leading to a dispensing port located on the distal face of the insertable portion, and the second insertable portion comprises a single dispensing channel leading to dispensing ports arranged along the length of the insertable portion.In some embodiments, the first insertable portion comprises a single dispensing channel leading to a dispensing port located on the distal face of the insertable portion, and the second insertable portion comprises two or more dispensing channels leading to two or more dispensing ports located on various faces of the insertable portion. In some embodiments, the composition is dispensed simultaneously from two insertable portions. In some embodiments, the composition is dispensed sequentially from two insertable portions. In some embodiments, the composition is dispensed simultaneously from two dispensing elements. In some embodiments, the composition is dispensed sequentially from two dispensing elements. In some embodiments, a trigger and / or subject engagement portion activates the device when pressed against the subject's nasal bridge, dispensing the composition from a single cannula. In some embodiments, the dispensing element comprises a fluid-flowing cannula housed within the dispensing element. In some embodiments, the entire cannula is housed within the dispensing element. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion. In some embodiments, the entire dispensing element is housed within the insertable portion. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion when the device is activated. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion when the device is moved from a first position to a second position, or from a first configuration to a second configuration. In some embodiments, the dispensing element does not extend from or appear from the insertable portion when the device is activated. In some embodiments, the trigger is located on the subject engagement portion or the saddle for the columella and is configured to activate the device when pressure is applied to the trigger by the subject's columella. In some embodiments, the dispensing element comprises a cannula. In some embodiments, the trigger and / or subject engagement portion comprises an actuator that dispenses a composition from the storage portion when the housing is moved from a first position to a second position. In some embodiments, the subject engagement portion engages with the subject's columella to limit the insertion depth of the first and second insertable portions into the subject's nasal passages.In some embodiments, the subject engagement portion engages with the subject's columella to limit the insertion depth of the first and second dispensing elements into the subject's nasal passages. In some embodiments, the subject engagement portion is concave and engages with the subject's columella around multiple sides of the columella. In some embodiments, the trigger includes a saddle-shaped portion for receiving the subject's columella. In some embodiments, the saddle-shaped portion positions the first and second insertable portions to align one or more dispensing elements with the olfactory cleft when the device is activated. In some embodiments, the saddle portion, subject engagement portion, or positioning trigger has a shape that conforms to the anatomical structure of the subject's columella and aligns one or more dispensing elements with the subject's olfactory cleft. In some embodiments, one or more dispensing elements are positioned along an unobstructed path to the subject's olfactory cleft when the subject engagement portion is engaged with the subject's columella. In some embodiments, the dispensing element is positioned 0 mm to approximately 40 mm from the lower surface of the subject's olfactory cleft when the subject engagement portion engages with the subject's columella. In some embodiments, the saddle has a recess for the subject's columella. In some embodiments, the subject engagement portion has dimensions of approximately 20 mm × approximately 17 mm. In some embodiments, the saddle-shaped portion engages with the subject's columella around multiple sides of the columella. In some embodiments, the subject engagement portion activates the device by pressing down a trigger connected to the subject engagement portion. In some embodiments, the first and / or second insertable portion limits the sagittal angle or anterior-posterior tilt angle of the device. In some embodiments, the first and / or second insertable portion limits the coronal angle or inward-posterior tilt angle of the device. In some embodiments, the first and / or second insertable portion limits the sagittal angle or anterior-posterior tilt angle of the device. In some embodiments, the first and / or second insertable portion and the subject engagement portion limit the sagittal plane angle, the anterior-posterior tilt angle of the device, the coronal plane angle or inward-posterior tilt angle of the device, the sagittal plane angle or anterior-posterior tilt angle of the device, or any combination thereof.In some embodiments, the subject's internal nasal flap is enclosed medially by the nasal septum, laterally by the caudal portion of the superior lateral nasal cartilage, and inferiorly by the superior portion of the inferior turbinate. In some embodiments, the first and / or second insertable portion moves the superior lateral nasal cartilage, thereby opening or widening at least a portion of the subject's internal nasal flap. In some embodiments, the first and / or second insertable portion has torsional flexibility. In some embodiments, the first and / or second insertable portion has torsional flexibility to adjust to the anterior surface or wedge angle of the internal nasal flap. In some embodiments, the first and / or second insertable portion extends proximal to the user's nasal septum. In some embodiments, one or more dispensing elements extend outward from or emerge from the insertable portion when the device is activated. In some embodiments, two dispensing elements emerge outward from the insertable portion when the device is activated. In some embodiments, the device dispenses a composition from one or more dispensing elements when the device is activated. In some embodiments, the housing further comprises a second insertable portion for insertion into the user's second nasal canal. In some embodiments, the first and / or second insertable portions move tissue within the nasal canal to define a pathway between one or more dispensing elements and a delivery site. In some embodiments, the first and / or second insertable portions move tissue within the nasal canal to open or widen the internal nasal flap of the subject. In some embodiments, the dispensing elements are housed within the insertable portion. In some embodiments, the device further comprises a second dispensing element, the first dispensing element housed within the first insertable portion, and the second dispensing element housed within the second insertable portion. In some embodiments, the first and / or second insertable portions have dimensions of approximately 20 mm × approximately 3.5 mm. In some embodiments, the first and / or second insertable portion is wedge-shaped, paddle-shaped, cylindrical, bulbous, conical, spherical, hemispherical, or any combination thereof.In some embodiments, the transition of the device from a first configuration to a second configuration is actuated by a subject engagement portion, thereby causing the dispensing element to emerge from the first insertable portion. In some embodiments, the transition of the device from a first configuration to a second configuration is actuated by an actuator, thereby causing the dispensing element to emerge from the first insertable portion. In some embodiments, the first or second insertable portion moves the nasal cartilage and / or tissue within the nasal passage when the device is inserted in the first configuration. In some embodiments, the first or second insertable portion fits proximal to the junction of the subject's nasal septum and lateral nasal cartilage when the device is in the second configuration. In some embodiments, the housing is movable from a first position to a second position. In some embodiments, the housing comprises a proximal portion and a distal portion, the distal portion being pushed against the proximal portion when the housing is transitioned from the first configuration to the second configuration to actuate the device. In some embodiments, the distal portion is inserted into the proximal portion when the housing is transitioned from the first configuration to the second configuration. In some embodiments, when transitioning from a first configuration to a second configuration, the distal portion moves relative to the subject, while the proximal portion remains stationary relative to the subject, and either the proximal or distal portion is connected to the dispensing element. In some embodiments, when transitioning from a first configuration to a second configuration, the dispensing element emerges outward from the distal portion. In some embodiments, the columella region includes the subnasal point, subnasion, anterior nasal spine, or any combination thereof. In some embodiments, the insertable portion has flexibility characteristics of inward and outward flexibility along a width perpendicular to the length of the insertable portion, lack of anterior-posterior flexibility around the length of the insertable portion, or vertical flexibility around a rotation axis perpendicular to the length of the insertable portion.

[0013] In some embodiments, the dispensing element is configured to dispense a composition into a single nasal passage of the subject. In some embodiments, the dispensing element fits proximal to the junction of the subject's nasal septum and lateral nasal cartilage. In some embodiments, the dispensing element fits proximal to the subject's nasal septum. In some embodiments, the dispensing element includes a dispensing port. In some embodiments, the dispensing element includes a cannula or catheter. In some embodiments, the dispensing element includes a fluid-flowing cannula housed within the dispensing element. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion. In some embodiments, the entire dispensing element is housed within the insertable portion. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion when the device is activated. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion when the device is moved from a first position to a second position, or from a first configuration to a second configuration. In some embodiments, the dispensing element does not extend from or appear from the insertable portion when the device is activated. In some embodiments, the trigger is located on the subject engagement portion or the nasal saddle and is configured to activate the device when pressure is applied to the trigger by the subject's nasal saddle. In some embodiments, the dispensing element comprises a cannula. In some embodiments, one or more insertable portions comprise multiple dispensing ports. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion. In some embodiments, the entire dispensing element is contained within the insertable portion. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion when the device is activated. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion when the device is moved from a first position to a second position, or from a first configuration to a second configuration. In some embodiments, the dispensing element does not extend from or appear from the insertable portion when the device is activated. In some embodiments, the trigger is located on the subject engagement portion or the nasal saddle and is configured to activate the device when pressure is applied to the trigger by the subject's nasal saddle.In some embodiments, the dispensing element includes a cannula.

[0014] In some embodiments, one or more dispensing elements are provided with a dispensing port. In some embodiments, the dispensing port has one dispensing port at its distal end, one or more dispensing ports along its length, or a combination of both. In some embodiments, the dispensing port is directed to different target compartments within the nasal canal. In some embodiments, the dispensing port is provided with a sprayer. In some embodiments, the dispensing element is provided with a sprayer. In some embodiments, the dispensing port is configured to provide laminar flow. In some embodiments, the dispensing port is configured to provide fluid jet. In some embodiments, one or more dispensing elements are 20 mm to 50 mm in length. In some embodiments, one or more dispensing elements extend from 0 mm to 40 mm from the insertable portion. In some embodiments, one or more dispensing elements are provided with multiple dispensing ports. In some embodiments, one or more dispensing elements are provided with multiple fluid channels. In some embodiments, one or more dispensing elements are provided with a dispensing port. In some embodiments, one of the multiple fluid channels is configured to dispense gas. In some embodiments, one of a plurality of fluid channels is configured to dispense a gas after a composition has been dispensed by another fluid channel. In some embodiments, the device is configured to target the olfactory fissure or a portion thereof. In some embodiments, one or more dispensing elements comprise a first tubular portion surrounding the dispensing element. In some embodiments, the first tubular portion remains within the first insertable portion when the device is operated to a second position. In some embodiments, the insertable portion is flexible. In some embodiments, one or more dispensing elements are flexible. In some embodiments, the device further comprises a storage portion fluidly connected to one or more insertable portions. In some embodiments, the device further comprises a storage portion fluidly connected to one or more dispensing elements. In some embodiments, the compound includes a therapeutic agent. In some embodiments, the compound includes a sampling agent. In some embodiments, the compound includes a liquid, powder, or gas, or a combination thereof. In some embodiments, the target region is one or both of the olfactory fissures or a portion thereof.In some embodiments, the target compartment is one or both respiratory compartments, or a portion thereof. In some embodiments, the actuator is spring-loaded. In some embodiments, the actuator dispenses approximately equal amounts of fluid from each insertable portion. In some embodiments, the actuator dispenses approximately equal amounts of fluid from each dispensing element. In some embodiments, the actuator dispenses fluid from only one insertable portion. In some embodiments, the actuator dispenses fluid from only one dispensing element. In some embodiments, one or more dispensing elements are housed together with auxiliary tubular members. In some embodiments, the storage unit is removable. In some embodiments, the storage unit is contained within a removable cartridge. In some embodiments, the placement trigger activates the device by pressing down a switch located beneath the placement trigger. In some embodiments, the device further comprises a central cylinder fluid-connected to one or more insertable portions, the central cylinder being inserted into the storage unit when the device is activated. In some embodiments, the device further comprises a central cylinder fluid-connected to one or more dispensing elements, the central cylinder being inserted into the storage unit when the device is activated. In some embodiments, the device comprises a central cylinder fluidly connected to two or more insertable portions, the central cylinder being inserted into a storage portion when the device is activated. In some embodiments, the device further comprises a central cylinder fluidly connected to two dispensing elements, the central cylinder being inserted into a storage portion when the device is activated. In some embodiments, the device further comprises one or more bases connected to the bottom of one or more dispensing elements, thereby moving one or more dispensing elements when the device is activated. In some embodiments, the dispensing channel has a diameter of about 0.3 mm to about 3 mm. In some embodiments, the dispensing elements have an inner diameter of about 0.3 mm to about 3 mm. In some embodiments, the dispensing elements are configured to prevent bacteria or microorganisms from entering different areas of the nasal cavity from the subnasal cavity or the external environment.

[0015] In one embodiment, the present disclosure provides a device for intranasal delivery to a subject, the device being transitionable from a first configuration to a second configuration, the device comprising a housing defining two insertable portions each having at least one dispensing element, each insertable portion being for insertion into the nasal passage of a subject, the first insertable portion engaging with tissue within the nasal passage to open or expand the internal nasal valve of the subject, thereby positioning at least one of the dispensing elements for delivery of a composition to the subject; a subject engaging portion connected to the housing and comprising a trigger, the trigger comprising a subject engaging portion engaging with the columella region, the trigger allowing the device to operate to deliver a composition from the dispensing element to the subject when pressure is applied to the subject engaging portion; and a dispensing element, which emerges from the first insertable portion when the device is transitioned from a first configuration to a second configuration.

[0016] In one embodiment, the present disclosure provides a method for intranasal delivery to a subject using a device, the method comprising the step of positioning the insertable portion of the device within the discharge area of ​​the subject's nasal cavity by engaging the columella region of the subject with the subject engagement portion of the device and fixing the insertable portion within the discharge area of ​​the subject's nasal cavity, the discharge area being located 0 mm to 30 mm above a horizontal line intersecting the anterior surface of the internal nasal valve, 0 mm to 20 mm anterior to an inclined line intersecting the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule, 0 mm to 40 mm below a horizontal line parallel to the inferior surface of the olfactory cleft, 0 mm to 20 mm posterior to the dorsum of the nose, 10 mm and 50 mm above a horizontal line intersecting the inferior surface of the columella, 0 mm to 30 mm above a horizontal line intersecting the superior surface of the inferior turbinate, 0 mm to 3 mm from the nasal septum, or any combination of these. In some embodiments, the method further includes the step of activating the device by applying pressure to the columella region of the subject using the subject engagement portion of the device. In some embodiments, the method further includes the step of positioning the insertable portion of the device, which includes positioning two insertable portions within the two nasal passages of the subject to open or widen the opening of the internal nasal valves of the subject. In some embodiments, the method further includes the step of positioning the dispensing element of the device, which includes positioning two dispensing elements within the nasal passages of the subject, with the two dispensing elements emerging from the insertable portion. In some embodiments, the method further includes the step of transitioning the device from a first configuration to a second configuration, wherein the dispensing elements emerge from the insertable portion when the device is transitioned from the first configuration to the second configuration.

[0017] In one embodiment, the present disclosure provides a method for intranasal delivery to a subject using a device, the method comprising the steps of inserting two insertable portions into the nasal passage of the subject, wherein, upon insertion, at least one of the insertable portions engages with the tissue within the nasal passage, thereby opening or widening the opening of the internal nasal valve of the subject, thereby positioning at least one of the insertable portions for delivery of a composition to the subject. In some embodiments, the method further comprises the steps of positioning the insertable portions within the nasal passage of the subject by engaging the columella region of the subject with the subject engagement portion of the device, thereby limiting the insertion depth of the device into the nasal passage of the subject and aligning the insertable portions within the nasal passage of the subject. In some embodiments, the method further comprises the steps of operating the device by applying pressure to the subject engagement portion of the device using the columella region of the subject. In some embodiments, the method further comprises two insertable portions, each comprising at least one dispensing element. In some embodiments, the method further comprises at least one dispensing element that emerges outward from at least one of two insertable portions. In some embodiments, the method further comprises a step of transitioning the device from a first configuration to a second configuration, wherein the dispensing element emerges from the insertable portion when the device is transitioned from the first configuration to the second configuration. In some embodiments, the method further comprises a step of inserting the two insertable portions of step a, which advances the two insertable portions along the dorsum of the nose and / or along either side of the nasal septum until the columella engagement area of ​​the device contacts the columella of the subject, thereby preventing further insertion and establishing a depth reference. In some embodiments, the method further comprises a dispensing port positioned in a targeted or partial region of the nasal cavity. In some embodiments, the method further comprises a step of inserting the two insertable portions of step a, which uses the nasal frontal angle as an angular reference reference to position the insertable portions within the nasal passage.

[0018] In some embodiments, the method further includes a dispensing port positioned in a targeted or partial region of the nasal cavity. In some embodiments, the method further includes inserting the two insertable portions of step a, which involves advancing the two insertable portions along the dorsum of the nose until the columella engagement region of the device contacts the columella of the subject, thereby preventing further insertion and establishing a depth reference. The step of inserting the two insertable portions of step a uses the nasofrontal angle as an angular reference reference to position the insertable portions within the nasal passage, thereby positioning the two insertable portions at known locations within the nasal cavity. In some embodiments, the method further includes inserting the two insertable portions of step a, which includes inserting the two insertable portions beyond the nasal vestibule. In some embodiments, the method further includes inserting the two insertable portions of step a, which includes inserting the two insertable portions along the soft tissue above the nasal cleft, in an orientation parallel to the soft tissue. In some embodiments, the method further includes inserting the two insertable parts of step a., which prevents the device from rotating about an axis parallel to the height of the subject. In some embodiments, the method further includes inserting the two insertable parts of step a., which forms a reference yaw angle on the coronal plane with respect to the y-axis of the device. In some embodiments, the method further includes inserting the two insertable parts of step a., which forms a substantially unobstructed flow channel to the olfactory cleft. In some embodiments, the method further includes inserting the two insertable parts of step a., which forms a substantially unobstructed flow to the nasal turbinates.

[0019] In one embodiment, the present disclosure provides a method for intranasal delivery to a subject using a device, the method comprising the steps of positioning an insertable portion of the device within the subject's nasal passage and transitioning the device from a first configuration to a second configuration by applying pressure about the longitudinal axis of the device, thereby exposing a dispensing element from the first insertable portion and simultaneously activating the device to deliver a composition to the subject. In some embodiments, simultaneous activation refers to the transition from the first configuration to the second configuration, and the activation occurs in a single movement when pressure is applied about the longitudinal axis of the device. In some embodiments, the step of positioning the insertable portion of the device within the subject's nasal passage is achieved by engaging the columella region of the subject with the subject engagement portion of the device. In some embodiments, the method further includes the step of activating the device by applying pressure to the subject engagement portion of the device using the columella region of the subject. In some embodiments, the method further includes the step of positioning the insertable portion of the device within the nasal canal of a subject, which engages with the tissue within the nasal canal to open or dilate the internal nasal flap of the subject, thereby positioning the insertable portion to deliver a composition to the subject. In some embodiments, the insertable portion of the device comprises two insertable portions, each intended for insertion into the nasal canal of a subject, and step a. includes inserting the two insertable portions into the nasal canal of the subject. In some embodiments, the step of inserting the two insertable portions in step a. advances the two insertable portions along the dorsum of the nose and / or along either side of the nasal septum until the columella engagement area of ​​the device contacts the columella of the subject, preventing further insertion and establishing a depth reference. In some embodiments, the method further includes the step of inserting the two insertable portions in step a., which uses the nasal frontal angle as an angular reference reference to position the insertable portion within the nasal canal. In some embodiments, the method further includes a dispensing port positioned in a targeted or partial region of the nasal cavity.In some embodiments, the method further includes inserting the two insertable parts of step a., which advances the two insertable parts along the dorsum of the nose and / or along either side of the nasal septum until the columella engagement area of ​​the device contacts the columella of the subject, thereby preventing further insertion and establishing a depth reference. The step of inserting the two insertable parts of step a. uses the nasal frontal angle as an angular reference reference to position the insertable parts within the nasal canal, thereby positioning the two insertable parts at known positions within the nasal canal. In some embodiments, the method further includes inserting the two insertable parts of step a., which includes inserting the two insertable parts beyond the nasal vestibule. In some embodiments, the method further includes inserting the two insertable parts of step a., which includes inserting the two insertable parts along the soft tissue above the nasal cleft, in an orientation parallel to the soft tissue. In some embodiments, the method further includes inserting the two insertable parts of step a., which prevents rotation of the device about an axis parallel to the subject's height. In some embodiments, the method further includes the step of inserting two insertable portions of step a, which form a reference yaw angle on the coronal plane with respect to the y-axis of the apparatus. In some embodiments, the method further includes the step of inserting two insertable portions of step a, which form a substantially unobstructed flow channel to the olfactory fissure.

[0020] In one embodiment, the present disclosure provides a method for intranasal delivery of a composition to a target region of the nasal cavity of a subject, the method comprising the step of inserting a dispensing element into a dispensing area of ​​the nasal cavity, the dispensing area being located 0 mm to 30 mm above a horizontal line intersecting the anterior surface of the internal nasal valve, 0 mm to 20 mm anterior to an inclined line intersecting the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule, 0 mm to 40 mm below a horizontal line parallel to the inferior surface of the olfactory cleft, or 0 mm to 20 mm posterior to the dorsum of the nose, or 1 mm from a horizontal line intersecting the inferior surface of the columella The steps include: a step of being located at 0 mm and 50 mm above, or 0 mm to 30 mm above a horizontal line intersecting the superior surface of the inferior turbinate, or 0 mm to 3 mm from the nasal septum, or one or more of any combination thereof; and a step of dispensing a composition from a dispensing element to bring the composition into contact with a target area, wherein the step of dispensing a composition from a dispensing area is to a) increase targeted delivery of the composition to the target area, b) decrease off-target delivery of the composition to the nasal cavity, or c) both. In some embodiments, the dispensing area is a trapezium or irregular quadrilateral comprising: (i) a lower lateral line extending posteriorly and horizontally from the anterior surface of the internal nasal valve, 10–25 mm; (ii) an anterior lateral line extending posteriorly and horizontally from the anterior surface of the internal nasal valve, 10–35 mm; (iii) an upper lateral line extending posteriorly and horizontally from a point in the nasal dorsum 0–10 mm below the lower surface of the olfactory cleft, 10–25 mm; and (iv) a posterior line extending 10–35 mm perpendicularly along a plane intersecting the anterior surface of the middle turbinate. In some embodiments, the target region is one or both of the olfactory clefts, or a portion thereof, and dispensing the composition from the anterior end of the dispensing element increases the targeted delivery of the composition to the target region. In some embodiments, the target region is the middle nasal meatus, and target delivery of the composition to the target region is increased by dispensing the composition from the posterior end of the dispensing element. In some embodiments, the dispensing area is further parallel to the subject's middle nasal turbinate and not located within the middle nasal meatus.In some embodiments, the delivery region is aligned with the olfactory cleft defined by a linear vector between the olfactory cleft and the distal end of the insertable portion. In some embodiments, the target region is one or both of the olfactory clefts, or a subcompartment thereof.

[0021] The devices and methods of the present disclosure provide a number of advantages over existing intranasal drug delivery devices. For example, the device is easy to use and provides accurate, consistent, and effective drug delivery. Further, the device can accurately deliver the drug to a target site within the nasal passage, resulting in a number of therapeutic benefits, such as reduced drug loss, improved comfort, increased compliance, improved subject experience, and improved treatment outcome.

[0022] Incorporation by reference All publications, patents, and patent applications mentioned in this specification are hereby incorporated by reference into this specification to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The novel features of the present disclosure are particularly pointed out in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained from the following detailed description that sets forth illustrative embodiments in which the principles of the present disclosure are utilized, and the accompanying drawings. [Figure 1A] A bottom view of an exemplary embodiment of a subject's nose is shown. [Figure 1B] A side view of an exemplary embodiment of a subject's nose is shown. [Figure 1C] A side view of a side view of a representative subject's nasal passage is shown. [Figure 1D] A side view of an exemplary embodiment of a representative subject's nasal passage from the nasal vestibule to the olfactory cleft based on a posterior direction plane is shown. [Figure 1E] A side view of an exemplary embodiment of a representative subject's nasal passage from the nasal vestibule to the olfactory cleft based on an anterior direction plane is shown. [Figure 1F]A side view of an exemplary embodiment of a representative of a target ejection area according to some embodiments is shown. [Figure 1G] A front view, a bottom view, and a perspective view of an exemplary embodiment of a subject's nose and nasal column area are shown. [Figure 1H] A side view of an exemplary embodiment of a nasal cavity of a representative subject, including anatomical internal features, is shown. [Figure 1I] A side view of an exemplary embodiment of a paranasal sinus of a representative subject according to some embodiments is shown. [Figure 1J] A side view of a subject's nasal cavity is shown. [Figure 2A] An exemplary embodiment of an exemplary device in a second configuration according to some embodiments is shown. [Figure 2B] A top view of an exemplary embodiment of an exemplary device in a second configuration according to some embodiments is shown. [Figure 2C] A side view of an exemplary embodiment of an exemplary device in a second configuration on the trigger button side according to some embodiments is shown. [Figure 2D] A side view of an exemplary embodiment of an exemplary device in a second configuration on the chassis side according to some embodiments is shown. [Figure 2E] A bottom view of an exemplary embodiment of an exemplary device in a second configuration according to some embodiments is shown. [Figure 2F] A perspective view of an exemplary embodiment of an exemplary device in a first configuration according to some embodiments is shown. [Figure 2G] A front view of another exemplary embodiment of an exemplary device in a first configuration according to some embodiments is shown. [Figure 2H] A front view of an exemplary embodiment of an exemplary device in a second configuration according to some embodiments is shown. [Figure 2I] A front view of another exemplary embodiment of an exemplary device in a first configuration according to some embodiments is shown. [Figure 2J] A front view of an exemplary embodiment of an exemplary device in a second configuration according to some embodiments is shown. [Figure 3A] The following are exploded views of exemplary devices without a chassis, according to several embodiments. [Figure 3B] The following are exemplary exploded views of an exemplary apparatus according to several embodiments. [Figure 3C] The diagram shows an exemplary device without a chassis, according to several embodiments. In this diagram, the rear cover has been removed, allowing for the insertion of a syringe or cannula. [Figure 3D] A side view is shown illustrating the internal components of an exemplary device in a second configuration, where a single dispensing element is visible, according to several embodiments. The rear cover of the device has been removed to make the internal components easier to see. [Figure 4A] The images show exemplary embodiments of the exemplary apparatus in a second configuration, in which a single dispensing element is exposed, and a side view of an exemplary embodiment of the nose of a subject. The rear cover of the apparatus has been removed to make the internal components more visible. [Figure 4B] The images show exemplary embodiments of an exemplary device in a second configuration, in which a single dispensing element appears along the pathway, and a side view of an exemplary embodiment of the nasal passage of a representative subject from the nasal vestibule to the olfactory cleft, based on a forward-facing plane. The rear cover of the device has been removed to make the internal components more visible. [Figure 5] Several embodiments of the exemplary apparatus in the first configuration are shown. [Figure 6A] Exemplary embodiments of the reference Cartesian coordinate planes of the front, top, and side views of an exemplary apparatus, according to several embodiments, are shown (from left to right). [Figure 6B] Several embodiments illustrate the planar aspects of the test subject. [Figure 6C] Illustrative embodiments of several embodiments are shown (from left to right) as a front view of the coronal plane, a top view of the cross-sectional plane, and a rear view of the sagittal plane. [Figure 6D]This document illustrates exemplary embodiments of an exemplary apparatus positioned at a sagittal angle to the test subject, according to several embodiments. [Figure 6E] Exemplary embodiments of exemplary devices positioned in the subject at a coronal-internal angle are shown along the coronal front view and along the cross-sectional top view, according to several embodiments. [Figure 6F] Exemplary embodiments of exemplary devices positioned at a certain depth in the test subject are shown along the coronal front view and the sagittal side view, according to several embodiments. [Figure 6G] The following are exemplary embodiments of an exemplary apparatus for delivering to a target region of a subject along a sagittal side view, according to several embodiments. [Figure 6H] Exemplary embodiments of an exemplary device for targeting the respiratory area of ​​a subject are shown along a sagittal side view according to several embodiments. [Figure 7A] The following are perspective views of exemplary embodiments of the insertable portion and the subject engagement portion for the columella in the first configuration, according to several embodiments. [Figure 7B] The following are perspective views of the internal components of exemplary embodiments of the insertable portion and the subject engagement portion for the columella in the first configuration, according to several embodiments. [Figure 7C] The following are perspective views of the internal components of exemplary embodiments of the insertable portion and the subject engagement portion for the columella in the first configuration, according to several embodiments. [Figure 7D] The following are perspective views of the internal components of exemplary embodiments of the insertable portion and the subject engagement portion for the columella in the first configuration, according to several embodiments. [Figure 7E] The following are perspective views of the internal components of exemplary embodiments of the insertable portion and the subject engagement portion for the columella in the second configuration, according to several embodiments. [Figure 8A] The anatomical structure of the nasal cavity of a subject is shown in several embodiments. [Figure 8B] The anatomical structure of the nasal cavity of a subject is shown in several embodiments. [Figure 8C] The anatomical structure of the nasal cavity of a subject and the configuration of exemplary devices are shown according to several embodiments. [Figure 8D] The anatomical structure of the nasal cavity of a subject and the configuration of exemplary devices for opening or expanding exemplary internal nasal valves are shown in several embodiments. [Figure 9A] The following are side views of the target discharge area according to several embodiments. [Figure 9B] The images show lateral views of the target discharge area relative to other nasal cavity anatomical structures according to several embodiments. [Figure 10] The following shows perspective views, front views, and side views of exemplary embodiments of the saddle for the bridge of a nose in a first configuration, according to several embodiments. [Figure 11] The anatomical structure of the nasal cavity of a subject according to several embodiments, as well as exemplary devices for opening or expanding the internal nasal valve, and exemplary side views of exemplary insertable portions and subject engagement portions for the columella in the first configuration are shown. [Figure 12A] The images show exemplary images of a subject's nasal cavity before (top), during (center), and after (bottom) dispensing of a composition from a position where the dispensing element is directly in front of the nasal cavity, using an exemplary apparatus. It demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 12B] The images show exemplary images of a subject's nasal cavity before (top), during (center), and after (bottom) dispensing of a composition from a position where the dispensing element is directly in front of the nasal cavity, using an exemplary apparatus. It demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 12C] The images show exemplary images of a subject's nasal cavity before (top), during (center), and after (bottom) dispensing of a composition from a position where the dispensing element is directly in front of the nasal cavity, using an exemplary apparatus. It demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 12D]The images show exemplary images of a subject's nasal cavity before (top), during (center), and after (bottom) dispensing of a composition from a position where the dispensing element is at an angle of approximately 20 degrees to the front of the nasal cavity, using an exemplary apparatus. It demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target area. [Figure 12E] The images show exemplary images of a subject's nasal cavity before (top), during (center), and after (bottom) dispensing of a composition from a position where the dispensing element is at an angle of approximately 20 degrees to the front of the nasal cavity, using an exemplary apparatus. It demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target area. [Figure 12F] The images show exemplary images of a subject's nasal cavity before (top), during (center), and after (bottom) dispensing of a composition from a position where the dispensing element is at an angle of approximately 20 degrees to the front of the nasal cavity, using an exemplary apparatus. It demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target area. [Figure 13A] The images show exemplary images of the subject's nasal cavity before (top), during (center), and after (bottom) dispensing of a composition from a position where the dispensed fluid targets the anterior portion of the middle turbinate, demonstrating that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 13B] The images show exemplary images of the subject's nasal cavity before (top), during (center), and after (bottom) dispensing of a composition from a position where the dispensed fluid targets the anterior portion of the middle turbinate, demonstrating that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 13C] The images show exemplary images of the subject's nasal cavity before (top), during (center), and after (bottom) dispensing of a composition from a position where the dispensed fluid targets the anterior portion of the middle turbinate, demonstrating that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 13D]The images show exemplary images of the subject's nasal cavity before (top), during (center), and after (bottom) dispensing of the composition from a position where the angle is increased by 10 degrees towards the rear, using an exemplary apparatus, demonstrating that dispensing the composition from this position prevents accumulation of the composition in the target area. [Figure 13E] The images show exemplary images of the subject's nasal cavity before (top), during (center), and after (bottom) dispensing of the composition from a position where the angle is increased by 10 degrees towards the rear, using an exemplary apparatus, demonstrating that dispensing the composition from this position prevents accumulation of the composition in the target area. [Figure 13F] The images show exemplary images of the subject's nasal cavity before (top), during (center), and after (bottom) dispensing of the composition from a position where the angle is increased by 10 degrees towards the rear, using an exemplary apparatus, demonstrating that dispensing the composition from this position prevents accumulation of the composition in the target area. [Figure 13G] The images show exemplary images of the subject's nasal cavity before (top), during (center), and after (bottom) dispensing of the composition from a position where the angle is increased by 20 degrees towards the rear, using an exemplary apparatus. This demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 13H] The images show exemplary images of the subject's nasal cavity before (top), during (center), and after (bottom) dispensing of the composition from a position where the angle is increased by 20 degrees towards the rear, using an exemplary apparatus. This demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 13I] The images show exemplary images of the subject's nasal cavity before (top), during (center), and after (bottom) dispensing of the composition from a position where the angle is increased by 20 degrees towards the rear, using an exemplary apparatus. This demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 14A]The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, positioned at a -10 degree angle toward the center of the nasal cavity, using an exemplary apparatus. This demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 14B] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, positioned at a -10 degree angle toward the center of the nasal cavity, using an exemplary apparatus. This demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 14C] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, positioned at a -10 degree angle toward the center of the nasal cavity, using an exemplary apparatus. This demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 14D] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, with the angle from the center of the nasal cavity being 0 degrees, using an exemplary apparatus. This demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 14E] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, with the angle from the center of the nasal cavity being 0 degrees, using an exemplary apparatus. This demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 14F] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, with the angle from the center of the nasal cavity being 0 degrees, using an exemplary apparatus. This demonstrates that dispensing the composition from outside the dispensing area at this position prevents the accumulation of the composition in the target region. [Figure 14G]The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, using an exemplary apparatus, from a position where the angle from the center of the nasal cavity is increased by 15 degrees. The images demonstrate that dispensing the composition from this position hinders the proper accumulation of the composition in the target area, resulting in partial accumulation failure where the majority of the composition misses the target area. [Figure 14H] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, using an exemplary apparatus, from a position where the angle from the center of the nasal cavity is increased by 15 degrees. The images demonstrate that dispensing the composition from this position hinders the proper accumulation of the composition in the target area, resulting in partial accumulation failure where the majority of the composition misses the target area. [Figure 14I] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, using an exemplary apparatus, from a position where the angle from the center of the nasal cavity is increased by 15 degrees. The images demonstrate that dispensing the composition from this position hinders the proper accumulation of the composition in the target area, resulting in partial accumulation failure where the majority of the composition misses the target area. [Figure 14J] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, using an exemplary apparatus, from a position where the angle from the center of the nasal cavity is magnified by 30 degrees. The images demonstrate that dispensing the composition from this position hinders the proper accumulation of the composition in the target area, resulting in partial accumulation failure where the majority of the composition misses the target area. [Figure 14K] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, using an exemplary apparatus, from a position where the angle from the center of the nasal cavity is magnified by 30 degrees. The images demonstrate that dispensing the composition from this position hinders the proper accumulation of the composition in the target area, resulting in partial accumulation failure where the majority of the composition misses the target area. [Figure 14L]The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various frontal angles, using an exemplary apparatus, from a position where the angle from the center of the nasal cavity is magnified by 30 degrees. The images demonstrate that dispensing the composition from this position hinders the proper accumulation of the composition in the target area, resulting in partial accumulation failure where the majority of the composition misses the target area. [Figure 15] Figures 16A to 16I show the anatomical structure of the nasal vestibule at various ejection angles in a frontal view. [Figure 16A] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various lateral angles from a position where the angle to the reference line is 0 degrees, using an exemplary apparatus, demonstrating that dispensing the composition from this position prevents the accumulation of the composition in the target area. [Figure 16B] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various lateral angles from a position where the angle to the reference line is 0 degrees, using an exemplary apparatus, demonstrating that dispensing the composition from this position prevents the accumulation of the composition in the target area. [Figure 16C] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various lateral angles from a position where the angle to the reference line is 0 degrees, using an exemplary apparatus, demonstrating that dispensing the composition from this position prevents the accumulation of the composition in the target area. [Figure 16D] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various lateral angles from a position at a 10-degree angle to a reference line, demonstrating that dispensing the composition from this position allows for partial accumulation of the composition in the target area. [Figure 16E]The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various lateral angles from a position at a 10-degree angle to a reference line, demonstrating that dispensing the composition from this position allows for partial accumulation of the composition in the target area. [Figure 16F] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various lateral angles from a position at a 10-degree angle to a reference line, demonstrating that dispensing the composition from this position allows for partial accumulation of the composition in the target area. [Figure 16G] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various lateral angles from a position at a 20-degree angle to a reference line, using an exemplary apparatus, demonstrating that dispensing the composition from this position prevents its accumulation in the target area. [Figure 16H] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various lateral angles from a position at a 20-degree angle to a reference line, using an exemplary apparatus, demonstrating that dispensing the composition from this position prevents its accumulation in the target area. [Figure 16I] The images show exemplary images of the nasal cavity of a subject before (left), during (center), and after (right) dispensing of the composition from various lateral angles from a position at a 20-degree angle to a reference line, using an exemplary apparatus, demonstrating that dispensing the composition from this position prevents its accumulation in the target area. [Figure 17A] Images of the nasal cavity of a transparent model are shown, demonstrating the delivery of a colored solution to the olfactory region of the model. [Figure 17B] Images of the nasal cavity of a transparent model are shown, demonstrating the delivery of a colored solution to the olfactory region of the model. [Figure 17C] Images of the nasal cavity of a transparent model are shown, demonstrating the delivery of a colored solution to the olfactory region of the model. [Figure 18A] This shows a frontal, rightward oblique view of the intranasal delivery device. [Figure 18B] A top view of the intranasal delivery device is shown. [Figure 18C] This shows a bottom view of the intranasal delivery device. [Figure 18D] This shows a front elevation view of an intranasal delivery device. [Figure 18E] This shows a rear elevation view of the intranasal delivery device. [Figure 18F] This shows a right-side elevation view of the intranasal delivery device. [Figure 18G] This shows a left-side elevation view of an intranasal delivery device. [Figure 19A] The image shows an anterior upper right perspective view of an exemplary insertable portion and a subject engagement portion for the columella in a first configuration, according to several embodiments. [Figure 19B] The image shows a front view of an exemplary insertable portion and a subject engagement portion for the columella in a first configuration, according to several embodiments. [Figure 19C] The rear view shows an exemplary insertable portion and a subject engagement portion for the columella in a first configuration according to several embodiments. [Figure 19D] The following are side views of exemplary insertable portions and subject engagement portions for the columella in a first configuration according to several embodiments. [Figure 19E] The images show opposite side views of the exemplary insertable portion and the subject engagement portion for the columella in the first configuration, according to several embodiments. [Figure 19F] The image shows a top view of an exemplary insertable portion and a subject engagement portion for the columella in a first configuration, according to several embodiments. [Figure 19G] The following are bottom views of the exemplary insertable portion and the subject engagement portion for the columella in the first configuration, according to several embodiments. [Figure 19H] The image shows an exemplary front right bottom view of the insertable portion and the subject engagement portion for the columella in a first configuration according to several embodiments. [Figure 20A]An anterior upper right perspective view of an exemplary insertable portion and a subject engagement portion for the columella in a second configuration, according to several embodiments, is shown. [Figure 20B] The image shows a front view of an exemplary insertable portion and a subject engagement portion for the columella in a second configuration according to several embodiments. [Figure 20C] The rear view shows an exemplary insertable portion and a subject engagement portion for the columella in a second configuration according to several embodiments. [Figure 20D] The following are side views of the exemplary insertable portion and the subject engagement portion for the columella in a second configuration according to several embodiments. [Figure 20E] The image shows an exemplary opposite side view of the insertable portion and the subject engagement portion for the columella in a second configuration according to several embodiments. [Figure 20F] The image shows a top view of an exemplary insertable portion and a subject engagement portion for the columella in a second configuration according to several embodiments. [Figure 20G] The following are bottom views of the exemplary insertable portion and the subject engagement portion for the columella in a second configuration according to several embodiments. [Figure 20H] An example of an insertable portion and a subject engagement portion for the columella in a second configuration, according to several embodiments, is shown in a front right bottom view. [Figure 21A] The image shows a front view of the subject engagement portion for the insertable portion and the columella in an exemplary configuration according to several embodiments. In this non-limiting example, the two extendable cannulas are slightly fitted into the insertable portion such that the width of the saddle is 9 mm and the width between the two cannulas is 11 mm. The two insertable portions and the two cannulas are all essentially parallel. [Figure 21B] The following are front views of exemplary insertable portions and subject engagement portions for the columella in a first configuration, according to several embodiments. In this non-limiting example, the saddle width is 9 mm, and the two insertable portions are biased inward so that the cannula width is only 6 mm. [Figure 21C]Front views of exemplary insertable portions and subject engagement portions for the columella in the first and second configurations, according to several embodiments, are shown. In this non-limiting example, the saddle width is 9 mm. The two cannulas extend inward toward each other, such that the cannula width is 9 mm in the first configuration, but is reduced to 6 mm in the second configuration. [Figure 22] Figures demonstrating lateralized delivery of targeted drugs in an in vivo model using a cannula are shown, including a custom cannula design [2], animals with physically obstructed right nostrils to prevent delivery to the right hemisphere [3], delivery of an active pharmaceutical ingredient (API) via the cribriform plate [4], and ingestion of an API via the olfactory cortex delivery pathway to demonstrate lateralized delivery from the left nostril [5]. Note that in this example, the right hemisphere is targeted by delivery via the right nostril. [Figure 23A] This diagram illustrates the cannula placement for successful olfactory cortex delivery in group A using a 24GA × 0.75 inch (0.6 × 19 mm) BD InSight IV catheter. The scale bar is set to 4 mm. [Figure 23B] Figure 23A shows an image of the in vivo model based on the diagram. [Figure 24] The figure demonstrates imaging and detection of molecules of interest via time-of-flight mass spectrometry. [Figure 25A] Figures 25A to 25D show standard curves for oxytocin analysis and imaging, and the intensities detected in Figures 25A and 25C are used to create the calibration curves in Figures 25B and 25D, respectively. [Figure 25B] Figures 25A to 25D show standard curves for oxytocin analysis and imaging, and the intensities detected in Figures 25A and 25C are used to create the calibration curves in Figures 25B and 25D, respectively. [Figure 25C] Figures 25A to 25D show standard curves for oxytocin analysis and imaging, and the intensities detected in Figures 25A and 25C are used to create the calibration curves in Figures 25B and 25D, respectively. [Figure 25D] Figures 25A to 25D show standard curves for oxytocin analysis and imaging, and the intensities detected in Figures 25A and 25C are used to create the calibration curves in Figures 25B and 25D, respectively. [Figure 26] The in vivo model animal brain is shown with labeled sections to indicate cross-sections for mass spectrometry imaging (MSI). The section closest to the injection site represents the olfactory bulb (OB). The central section represents the striatum. The section furthest from the injection site represents the cerebrum. The injection site corresponds to the right hemisphere. [Figure 27A] The image shows mass spectrometry imaging (MSI) data from an olfactory bulb section, demonstrating a unilateral bias consistent with the target (right) hemisphere based on the distribution of detected oxytocin. The dashed lines indicate the contours of the brain hemispheres. Note that, depending on the orientation of the brain section, the area to the left of the dashed line corresponds to the right hemisphere of the brain. [Figure 27B] The image shows mass spectrometry (MSI) imaging data from a striatal section, demonstrating a unilateral bias consistent with the target (right) hemisphere based on the distribution of detected oxytocin. The dashed lines indicate the contours of the brain hemispheres. Note that, depending on the orientation of the brain section, the area to the left of the dashed line corresponds to the right hemisphere of the brain. [Figure 27C] The image shows mass spectrometry (MSI) imaging data from a cerebral section, demonstrating a unilateral bias consistent with the target (right) hemisphere based on the distribution of detected oxytocin. The dashed lines indicate the contours of the cerebral hemispheres. Arrows indicate areas where the unilateral bias is particularly pronounced. Note that, depending on the orientation of the brain section, the area to the left of the dashed line corresponds to the right hemisphere of the brain. [Modes for carrying out the invention]

[0024] The nasal cavity consists of the nasopharynx region and two nasal passages separated by the nasal septum, each containing the nasal vestibule, respiratory area, and olfactory cleft. The inventors understand that facilitating intranasal delivery of therapeutic compositions presents numerous challenges, including anatomical, cognitive, and dexterity-related issues for the subject population. For example, the internal nasal valve is a flow-regulating compartment of the nasal passage enclosed medially by the dorsal side of the nasal septum, laterally by the caudal portion of the superior lateral nasal cartilage, and inferiorly by the superior part of the inferior turbinate. Together, these form a physical wall between the nasal vestibule and the rest of the nasal passage, including the respiratory area and olfactory cleft. The internal nasal valve is surrounded by nasal tissue that can expand or occlude the pathway to the nasal passage, and this tissue varies between individuals due to time, environmental factors, and genetics. Devices may need to be inserted at specific angles or depths to target particular compartments, and users may struggle to position and operate the devices correctly. Users with motor skill impairments (e.g., Parkinson's disease, arthritis) or cognitive impairments (e.g., Alzheimer's disease) may have particular difficulty properly articulating, positioning, and operating intranasal delivery devices.

[0025] To address these challenges, this disclosure provides a novel injector for targeted delivery of a composition to a target area in the nasal cavity of a subject, which can be easily operated and positioned by users of various patient populations and can reliably deliver the composition to a target area in the nasal cavity. The exemplary device utilizes a double nasal injector with a columella engagement portion positioned between them to quickly and reliably secure the insertable portion of the device to the target dispensing area in the subject's nasal cavity. The exemplary device disclosed herein can quickly, easily, and reliably position a dispensing element within the nasal passage to enable precise targeted accumulation of the composition in the target area within the nasal cavity. Furthermore, the exemplary device disclosed herein can be quickly, easily, and reliably positioned and enabled for targeted accumulation by users with varying abilities (e.g., untrained bystanders) in high-stress environments (e.g., emergency medical care) and across diverse patient populations (e.g., elderly, cognitively impaired, dexterous, or users with diverse nasal anatomical structures), which would otherwise hinder the proper use of intranasal delivery devices.

[0026] The apparatus of the present disclosure may comprise a subject engagement portion that engages with the columella region of a subject, and one or more insertable portions that open or expand one or both internal nasal valves of the subject, thereby appropriately positioning one or more insertable portions or one or more dispensing elements of the apparatus within the dispensing area for targeted delivery of a composition to one or more specific compartments of the nasal cavity, such as one or both olfactory clefts, one or both middle meatuses, or one or both middle turbinates. The subject engagement portion may engage with the columella region centered on one or both sides of the columella region, and may have a saddle or concave shape, and the columella region may be slidable such that the apparatus uses the columella region as a depth reference and the line of the dorsum of the nose as an angle reference to position the insertable portions and / or dispensing elements at a desired depth and orientation within the dispensing area. Utilizing the columella region as a depth reference and the dorsum of the nose as an angle reference, such subject engagement parts allow for the placement of the device and the dispensing of compositions from there to targeted areas in one or both nasal cavities in a repeatable manner across subject populations. For example, subjects with different anatomical structures, backgrounds, cognitive abilities, and motor skills may be able to position the device in approximately the same location within one or both nasal canals. The columella region and dorsum of the nose lines enable accurate and consistent placement of either one or both insertable parts and / or one or both dispensing elements within one or both nasal canals by positioning the insertion device. Relying on the columella region and dorsum of the nose lines establishes reliable reference points that can be used across different populations and anthropometric differences. This eliminates the need for subject-specific adjustments and measurements, making the process more efficient, accurate, cost-effective, and user-friendly. The subject engagement portion may include, or be connected to, an actuator, trigger, or both, which activates the device or enables its operation and dispenses the composition when pressure is applied to the user's nasal columella region by the subject engagement portion, or when pressure is applied to the subject engagement portion by the user's nasal columella.The apparatus of the present disclosure may further comprise one or more insertable portions which are inserted into one or both nasal passages of a subject and open or dilate one or both internal nasal valves by pushing up the superior lateral nasal cartilage and surrounding tissue away from the nasal septum, thereby defining a pathway through which a composition can be delivered to one or more target compartments of one or both nasal passages of the subject, such as one or both olfactory clefts, nasal passages, such as the middle nasal passage, or one or both middle turbinates.

[0027] One or more insertable portions may advance along the nasal passage and along the nasal dorsum and nasal septum until the subject engagement portion contacts the columella region. One or more insertable portions may use the columella region as the depth reference and the line of the nasal dorsum as the angle reference reference. One or more insertable portions may be aligned with the line of the nasal dorsum. One or more insertable portions may be configured to maintain a constant, repeatable angle in the sagittal plane, following the shape of the nasal dorsum and the lateral surface of the nasal septum. The morphology of one or more insertable portions may be configured to hold the insertable portion in the soft tissue of the nasal dorsum and guide the insertable portion along the soft tissue inside the nasal dorsum to ensure that the insertable portion remains parallel to these tissues. The device may further include one or more dispensing elements that emerge from or are revealed by one or more insertable portions when the device is moved from a first position to a second position (e.g., from a first configuration to a second configuration).

[0028] Such features may help enable the design of a versatile intranasal delivery device that can be used across a wide range of subject populations and anthropometric differences. For example, by using the columellar region and nasal dorsum as reference points for positioning one or more insertable portions within the subject's nasal canal, accurate and consistent placement of the insertable portions and dispensing elements into the nasal cavity can be achieved. Furthermore, if the device is equipped with a trigger coupled to the subject engagement portion, which is activated by applying pressure to the columellar region using the subject engagement portion, then easy administration of a composition into one or more nasal canals becomes possible without the user needing to use their fingers to activate the device or without the user needing to be concerned with the proper alignment or insertion depth of the device within the nasal canal. The ease of administration enabled by the apparatus of this disclosure may allow subjects with limited cognitive abilities (e.g., subjects with dementia), subjects with limited motor skills (e.g., subjects with arthritis), or users in high-stress situations (e.g., paramedics, healthcare workers, or untrained bystanders treating victims of drug overdoses) to reliably, conveniently, and quickly use the targeted intranasal delivery devices disclosed herein to accurately and reliably deliver compositions to targeted areas of the nasal cavity. Similarly, one or more insertable portions may be aligned in close proximity to the nasal septum, thereby preventing one or more dispensing elements extending from or emerging from the insertable portion from snagging or bumping into tissues within the nasal passage, while pushing away hairs in the nasal passage and minimizing the possibility of a sneeze reflex that could adversely affect administration.In some cases, depending on the user's anatomical structure and condition, one or more insertable portions allow for comfortable and precise insertion beyond the internal and internal nasal valves by moving the superior lateral nasal cartilage upward as needed, away from the nasal septum. One or more dispensing elements extending from or represented by one or more insertable portions in the direction of the olfactory cleft, nasal meatus, e.g., the middle meatus, nasal turbinates, or other areas of the nasal anatomy can enable highly targeted delivery to the olfactory cleft, nasal meatus, e.g., the middle meatus, nasal turbinates, or other areas of the nasal anatomy, thereby enabling precise delivery of the composition to the olfactory cleft, nasal meatus, e.g., the middle meatus, nasal turbinates, or other areas of the nasal anatomy, and from there to reach the CNS via various routes.

[0029] Embodiments of the present disclosure include an intranasal drug delivery device comprising a housing having one or a combination of a subject engagement portion, one or more insertable portions, one or more dispensing elements, and a trigger. The subject engagement portion allows the device to be precisely positioned in one or both nasal passages by engaging the subject's columella region with a columella saddle to fix the distal end of the insertable portion within the discharge area of ​​the subject's nasal passage, the discharge area 29 is located 0 to 30 mm above a horizontal line 624 intersecting the anterior surface of the internal nasal valve and 0 to 20 mm anterior to an inclined line intersecting the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule. One or more insertable portions move the superior lateral nasal cartilage upward, away from the nasal septum of the subject's nasal passage, so that when the device is activated, the composition can be precisely delivered from one or more insertable portions to one or more targeted compartments in the nasal passage, such as the olfactory cleft, nasal passage, e.g., the middle nasal passage, or middle turbinate. One or more dispensing elements, either independently or extending from or being manifested by one or more insertable parts, accurately deliver a composition to one or more compartments in the nasal passages, such as the olfactory cleft, nasal passage, or middle nasal passage, or middle turbinate, when the device is activated. The device is activated when the subject applies pressure to the subject engagement part against the columella region, or when the subject applies pressure directly to the trigger button.

[0030] As used herein, a composition may include therapeutic compounds (small and large molecules), pharmaceuticals in liquid, powder, or gaseous form, or combinations thereof, or a sampling fluid. The columella region includes the columella, subnasal point, or anterior nasal spine, or combinations thereof. The dispensing element comprises a cannula or catheter, an insertable portion, a syringe, a fluid chamber, or combinations thereof, or any component acting on a cannula or catheter, syringe, or fluid chamber. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion when the device is fully operational.

[0031] Figure 1A shows a bottom view of an exemplary embodiment of the subject's nose. Figure 1B shows a side view of an exemplary embodiment of the subject's nose. In some embodiments, the nose 1 has a columella region 10 between the entrances to two nasal passages 20. In some embodiments, the nose 1 has an external nasal flap 12 connected to the nasal passages 20. In some embodiments, the nose 1 has an internal nasal flap 13 (INV) connected to the nasal passages 20.

[0032] Figure 1C shows a side view of an exemplary embodiment of the nasal cavity of a subject, showing the inferior turbinate 16, middle turbinate 15, and superior turbinate 14. Figure 1D shows an angled side view of an exemplary embodiment of the nasal passage 20 of a representative subject, from the nasal vestibule 21 to the olfactory cleft 23, based on a posterior plane 17, showing the middle turbinate 15. Figure 1E shows an angled side view of an exemplary embodiment of the nasal passage 20 of a representative subject, from the nasal vestibule to the olfactory cleft, based on an anterior plane 18. Figure 1F shows a side view of an exemplary embodiment of the target discharge compartment 19 of a representative subject. Figure 1G shows a front view, bottom view, and perspective view of an exemplary embodiment of the nose of a representative subject, exposing the columella region 10. The respiratory area includes turbinates that provide a physical obstruction to the upper reach of the nasal passage 20, for example, to the olfactory cleft 23. Each respiratory area includes at least one superior turbinate 14. Each respiratory region includes at least one middle turbinate 15. Each respiratory region includes at least one inferior turbinate 16. Each respiratory region includes at least one posterior pathway 17 that includes at least one middle turbinate 15. Each respiratory region includes at least one anterior pathway 18 that does not include at least one middle turbinate 15.

[0033] In some cases, the middle nasal conchae 15 includes a physical obstruction to the delivery of the composition to the olfactory cleft. In some cases, the middle nasal conchae 15 has an anterior surface substantially aligned with the zygomatic bone. In some embodiments, the middle nasal conchae 15 has an anterior surface not aligned with the zygomatic bone. In some cases, the nasal passage 20 is simple anteriorly and has an angled pathway, and one or more nasal conchae do not cause a physical obstruction to the delivery of the composition 111 to the superior nasal passage including the olfactory cleft 23, or to guide the composition 111 down one or more nasal passages, e.g., the middle nasal passage 30, to the nasopharynx. In some cases, the nasal passage 20 includes a single pathway from the nasal vestibule 21 to the olfactory cleft 23 based on an anterior plane 18 having a target ejection point 19. In some embodiments, the nose includes the nasal septum 24, the superior lateral nasal cartilage 25, and the inferior lateral nasal cartilage 26.

[0034] Figure 1H shows a side view of an exemplary embodiment of the nasal cavity of a representative subject. In some cases, the subject's nasal cavity 11 includes the nasal vestibule 21, inferior turbinate 16, middle turbinate 15, superior turbinate 14, cribriform plate 31, or a combination thereof.

[0035] Figure 1I shows a side view of an exemplary embodiment of the paranasal sinuses of a representative subject. In some cases, the subject's paranasal sinuses include the inferior turbinate 16, middle turbinate 15, superior turbinate 14, cribriform plate 31, middle meatus 30, or a combination thereof.

[0036] Figure 1J shows a side view of an exemplary embodiment of the nasal cavity of a representative subject. In some embodiments, the nasal cavity 11 includes the nasal bone 33, the junction of the nasal septum and lateral nasal cartilage 27, the inferior lateral nasal cartilage 26, the anterior nasal spine 32, or a combination thereof.

[0037] Figure 2A shows an exemplary embodiment of the exemplary device in the second configuration. Figure 2B shows a top view of the exemplary device in the second configuration. Figure 2C shows a side view of the exemplary device in the second configuration, on the trigger button side. Figure 2D shows a side view of the exemplary device in the second configuration, on the chassis side. Figure 2E shows a bottom view of the exemplary device in the second configuration. Figure 2F shows an exemplary embodiment of the exemplary device in the first configuration.

[0038] Referring to Figures 7A to 7E, in some embodiments, the subject engagement portion 106 limits the insertion depth of the insertable portion 107 into the nasal passage 20. In some embodiments, the insertable portion 107 incorporates one or more dispensing channels 125 leading to one or more dispensing ports 126 configured to deliver the composition 111 to one or more regions or sub-regions of the subject's nasal passage 20. In some embodiments, the insertable portion 107 includes a dispensing element 110 for delivering the composition 111 to a region or sub-region of the subject's nasal passage 20. In some embodiments, the housing 101 includes a trigger, and when pressure is applied to the trigger, the trigger activates the device to dispense the composition 111 to the subject from the insertable portion 107 or the dispensing element 110. In some embodiments, the subject engagement portion 106 includes a trigger connected to the housing 101 and the subject engagement portion 106, and when pressure from the subject engagement portion 106 is applied to the columella region 10, the trigger activates the device to dispense the composition 111 to the subject from the insertable portion 107 or the dispensing element 110. In some embodiments, the subject engagement portion 106 includes a trigger release portion 104 connected to the housing 101 and the subject engagement portion 106, and when pressure from the subject engagement portion 106 is applied to the columella region 10, the trigger release portion 104 allows the device to operate to deliver the composition 111 to the subject from the insertable portion 107 or the dispensing element 110. In some embodiments, the device further includes a trigger that is activatable when the trigger release portion 104 is engaged. In some embodiments, the housing 101 defines two insertable portions 107, each intended for insertion into the nasal passage 20 of a subject. When the first insertable portion 107 is inserted into the nasal passage 20 of the subject, it engages with the tissue within the nasal passage 20 to open or expand the subject's internal nasal valve 13, thereby positioning at least one of the insertable portions 107 to deliver the composition 111 into the subject's discharge area. The device may further include an actuator that delivers the composition 111 from either or both of the insertable portions 107 when the device is activated.In some embodiments, the housing 101 defines two insertable portions 107, each intended for delivering composition 111 into the nasal passage 20 of a subject, and the device further comprises actuators for delivering composition 111 from either or both of the insertable portions 107 when the device is activated. In some embodiments, the device is transitionable from a first configuration 100 to a second configuration 200, and the device further comprises one or two dispensing elements 110 connected to the insertable portions 107, at least one dispensing element 110 emerging from at least one insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200.

[0039] In some embodiments, the device is transitionable from a first configuration 100 to a second configuration 200 when pressure is applied around the longitudinal axis 610 of the device, and at least one dispensing element 110 appears as a linear vector with respect to the longitudinal axis 610 of at least one insertable portion 107, or the device is configured to transition from the first configuration 100 to the second configuration 200 with only one hand. In some embodiments, the device is activated simultaneously when it transitions from the first configuration 100 to the second configuration 200. In some embodiments, the distal surface 131 of at least one dispensing element 110 is located within the dispensing area 29 when the device is in the second configuration 200.

[0040] In one embodiment, the present disclosure provides a device for intranasal delivery to a subject, the device comprising a housing 101 having a dispensing element 110, and a subject engagement portion 106 connected to the housing 101, the subject engagement portion 106 engaging with a columella region 10, the subject engagement portion 106 positioning the dispensing element 110 within the subject's nasal passage 20, and limiting the insertion depth of the delivery element 111 into the nasal passage 20. In some embodiments, the subject engagement portion 106 comprises a columella saddle 121, the columella saddle 121 having a “U” or “saddle” shape adapted to engage with the subject's columella region 10. In some embodiments, the device comprises at least one insertable portion 107. In some embodiments, the device comprises two insertable portions 107, each intended for insertion into the subject's nasal passage 20. In some embodiments, the subject engagement portion 106 is concave and engages with the columella region 10 of the subject, centering on multiple sides of the columella region 10. In some embodiments, at least one dispensing element 110 emerges from or is revealed by at least one insertable portion 107 when the device transitions from a first configuration 100 to a second configuration 200. In some embodiments, the housing 101 defines the external shell of the device. In some embodiments, the housing comprises a first portion 102, the first portion 102 defining a portion of the external shell of the device. In some embodiments, the device comprises a trigger button 104. In some embodiments, the trigger button 104 activates a dispensing mechanism, which then delivers composition 111 from the device. In some embodiments, the trigger button 104 engages with an actuation mechanism, which then activates the dispensing mechanism for composition 111. In some embodiments, the trigger button 104 may comprise a safety mechanism or a locking mechanism. In some embodiments, the device is activated by the user applying pressure to the trigger button 104. In some embodiments, the user may activate the device using any finger. In some embodiments, the device comprises at least one dispensing element 110. In some embodiments, the device comprises at least one insertable portion 107. In some embodiments, at least one dispensing element 110 extends from or is represented by at least one insertable portion 107. In some embodiments, at least one insertable portion 107 comprises at least one dispensing element 110. In some embodiments, the cannula is located within the insertable portion 107, or at least one dispensing element 110 has an inner diameter that defines a flow path. In some embodiments, the entire cannula is contained within the dispensing element. In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion. In some embodiments, the entire dispensing element is contained within the insertable portion when the device is operated or when the housing is moved from a first position to a second position (see Figures 2G to 2J). In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion when the device is activated or when the housing is moved from a first position to a second position (see Figures 2G to 2J). In some embodiments, the dispensing element does not extend from or appear from the insertable portion when the device is activated or when the housing is moved from a first position to a second position (see Figures 2G to 2J). In some embodiments, the device may further include a trigger or trigger button 104 connected to the subject engagement portion 106 by a columella saddle, and the device may be activated when pressure is applied to the trigger button 104 by the subject's columella (see Figures 2G to 2H). In some embodiments, the dispensing element comprises a cannula.

[0041] In some embodiments, at least one channel 125 within the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.3 to 3.0 mm. In some embodiments, at least one composition channel 125 within the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.3 to 0.7 mm. In some embodiments, at least one composition channel 125 within the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.5 to 1.0 mm. In some embodiments, at least one dispensing element 110, for example a cannula, may be adapted to deliver a composition 111 having low viscosity, medium viscosity, or high viscosity to the olfactory cleft 23, middle nasal meatus 30, or other compartment of the nasal anatomical structure for entry into the CNS of the subject along the pathway. In some embodiments, at least one dispensing element 110, such as a cannula, may be adapted to deliver a composition 111 having a moderate (e.g., greater than 1 cP) or high viscosity (e.g., greater than 50 cP) to the olfactory cleft 23 of the subject.

[0042] In some embodiments, the first part 102 comprises a semi-elliptical outer shell 114. In some embodiments, the semi-elliptical outer shell 114 includes the outermost portion of the first part 102. In some embodiments, the first part 102 comprises a semi-conical outer shell 115 having at least one step formed thereon, which is positioned horizontally adjacent to the semi-elliptical outer shell 114. In some embodiments, the semi-conical outer shell 115 having at least one step comprises two steps of the semi-conical outer shell, where each step of the semi-conical outer shell is perpendicularly adjacent to one or more other steps of the semi-conical outer shell. In some embodiments, the semi-conical outer shell 115 having at least one step comprises an uppermost step of the semi-conical outer shell that partially accommodates the lowest step of the semi-conical outer shell. In some embodiments, the first part 102 comprises a trigger button 104. In some embodiments, the first part 102 includes a rectangular cutout having dimensions approximately the same length and width as the trigger button 104. In some embodiments, the trigger button 104 is inserted into the housing 101 through the rectangular cutout, which has dimensions approximately the same length and width as the trigger button 104. In some embodiments, the housing includes a second part 103. In some embodiments, the second part 103 includes a chassis 116. In some embodiments, the chassis 116 includes a chassis rectangular region 117, a chassis semiconical region 118, and a chassis final region 119. In some embodiments, the chassis rectangular region 117 includes an elliptical hole 132 that appears vertically along the horizontal center of the rectangular region 117. In some embodiments, the semiconical region 118 is perpendicularly adjacent to the rectangular region 117. In some embodiments, the rectangular region 117 appears along the length of the semiconical region 118 so as to form two adjacent rectangular regions 120. In some embodiments, the terminal region 119 is located perpendicularly adjacent to the semiconical region 118. In some embodiments, the terminal region 119 has a horizontal width shorter than the horizontal width of the semiconical region 118. In some embodiments, the chassis 116 has a shape for insertion into the first portion 102.In some embodiments, the chassis rectangular region 117 is aligned with a semiconical outer shell 115 having at least one step, and such arrangement forms the bottom 124 of the housing. In some embodiments, the chassis end region 119 is aligned with a semiconical outer shell 115 having at least one step, and such arrangement forms the outer shell of the insertable portion 107 of the housing 101.

[0043] In some embodiments, the device is transitionable from a first configuration 100 to a second configuration 200. In some embodiments, a subject engagement portion 106 engages with the user's columella region 10 when the device is inserted into the subject's nasal passage 20, and the subject engagement portion 106 causes the columella saddle 121 to be retracted into the first portion 102 of the housing 101 or into a semiconical outer shell 115 with at least one step formed thereon. In some embodiments, at least one dispensing element 110 emerges from at least one insertable portion 107 when the device is transitioned from the first configuration 100 to the second configuration 200. In some embodiments, the vertical length 122 in the second configuration is longer than the vertical length 123 in the first configuration. In some embodiments, when the device is transitionable from a first configuration 100 to a second configuration 200, the housing 101 defines a first insertable portion 107, and the device further comprises a dispensing element 110 connected to the housing 101, the dispensing element 110 emerging from the first insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200. In some embodiments, the device comprises a bottom 124, and the first portion 102 and the second portion 103 are joined or connected.

[0044] In some embodiments, the device comprises a housing 101 with a subject engagement portion 106 and one or more insertable portions 107 connected to the housing 101. In some embodiments, the subject engagement portion 106 includes a subject engagement portion 106 that engages with the columella region 10, thereby positioning one or more insertable portions 107 within one or both of the subject's nasal canals 20 and limiting the insertion depth of one or both of the one or more insertable portions 107. In some embodiments, the device may further include a trigger button 104 connected to the housing 101 and the subject engagement portion 106, which, when pressure is applied to the columella region 10 by the subject engagement portion 106, activates one or both of one or more dispensing elements simultaneously or sequentially to deliver the composition 111 into one or both of the subject's nasal canals 20. In some embodiments, the trigger button 104 may be located on the columella saddle of the subject engagement portion 106 (see Figure 2G). In some embodiments, the device can be activated when pressure is applied to the trigger button 104 by the nasal bridge.

[0045] In some embodiments, the housing 101 may define a subject engagement portion 106 and one or two insertable portions 107 for insertion into one or both nasal passages 20 of the subject. In some embodiments, once one or both insertable portions 107 are inserted into one or both nasal passages 20 of the subject, one or both insertable portions 107 engage with the tissue within the nasal passages 20 to open or expand one or both internal nasal valves 13, thereby positioning one or both insertable portions 107 to deliver the composition 111 to the subject simultaneously or sequentially from one or more dispensing ports 126. In some embodiments, the device may further include a trigger or trigger button 104 connected to the housing 101 and the subject engagement portion 106, the trigger or trigger button 104, when pressure is applied to the columella region 10 by the subject engagement portion 106, to activate one or both insertable portions 107 simultaneously or sequentially to deliver the composition 111 to one or both nasal passages 20 of the subject. In some embodiments, the housing 101 may define a subject engagement portion 106, one or two insertable portions 107 for insertion into one or both nasal passages 20 of the subject, and one or two dispensing elements 110 extending from or being exposed by one or both insertable portions 107. In some embodiments, the device is in a first configuration, where, once one or both insertable portions 107 are inserted into one or both nasal passages 20 of the subject, one or both insertable portions 107 engage with the tissue within the nasal passages 20 to open or expand one or both internal nasal flap 13. In some embodiments, the device is in a second configuration 200, where one or both dispensing elements 110 extend from or are exposed by one or both insertable portions 107 and are arranged to deliver the composition 111 to the subject simultaneously or sequentially from one or more dispensing ports 126. In some embodiments, the device may further include a trigger or trigger button 104 connected to the housing 101 and the subject engagement portion 106, the trigger or trigger button 104, when pressure is applied to the columella region 10 by the subject engagement portion 106, to activate one or both dispensing elements 110 simultaneously or sequentially to deliver the composition 111 to one or both nasal passages 11 of the subject. In some embodiments, the ends of the dispensing elements have the same spread as the ends of the insertable portion. In some embodiments, the dispensing elements are entirely contained within the insertable portion when the device is activated or when the housing is moved from a first position to a second position (see Figures 2G to 2J). In some embodiments, the ends of the dispensing elements have the same spread as the ends of the insertable portion when the device is activated or when the housing is moved from a first position to a second position (see Figures 2G to 2J). In some embodiments, the dispensing element does not extend from or appear from the insertable portion when the device is operated or when the housing is moved from a first position to a second position (see Figures 2G to 2J).In some embodiments, the device may further include a trigger or trigger button 104 connected to the subject engagement portion 106 by a nasal columella saddle, and the device may be activated when pressure is applied to the trigger button 104 by the subject's nasal columella (see Figures 2G to 2H). In some embodiments, the dispensing element includes a cannula.

[0046] In some embodiments, the housing 101 includes a dispensing element in the first configuration 100. In some embodiments, at least one dispensing element 110 has a cylindrical shape. In some embodiments, at least one composition channel 125 in the insertable portion 107 or at least one dispensing element 110 has an inner diameter. In some embodiments, at least one composition channel 125 in the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.3 to 3.0 mm. In some embodiments, at least one composition channel in the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.3 to 0.7 mm. In some embodiments, at least one composition channel 125 in the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.5 to 1.0 mm. In some embodiments, the dispensing element 110 is configured to dispense a composition 111 having low viscosity, medium viscosity, or high viscosity into a single nasal passage 20 of the subject. In some embodiments, the dispensing element 110 is configured to dispense a composition 111 having low viscosity, medium viscosity, or high viscosity into both nasal passages 20 of the subject.

[0047] In some embodiments, the insertable portion 107 can limit ecosystem contamination from different subregions of the nasal passage 20 and / or stabilize the dispensing element 110. The insertable portion 107 can enable a shorter dispensing element 110 that is more stable and less prone to bending or distortion.

[0048] The device may include an insertable portion 107 designed to fit snugly into the angle at which the anterior part of the internal nasal flap 13 narrows, where the nasal septum 24 contacts the superior lateral nasal cartilage 25. The device may include an insertable portion 107 having a shape 130, including wing-shaped, slender, wedge-shaped, elliptical or oblong, or even rounded forms. The device may include one insertable portion 107, which includes one or more channels 125 connected to one or more dispensing ports 126.

[0049] The device may further comprise one insertable portion 107, and one or more dispensing elements 110 are fixed to the insertable portion 107 connected to one or more dispensing ports 126. The device may further comprise one insertable portion 107, and one or more dispensing elements 110 are movable to the insertable portion 107 having one or more dispensing ports 126. The device may further comprise one insertable portion 107, and the composition 111 can be delivered to any partial region of the nasal passage 20, for example, the olfactory cleft or the nasal concha. The device may further comprise one insertable portion 107 and a user engagement element 106 that engages with the columella region 10. The device may further comprise one insertable portion 107, a user engagement element 106 that engages with the columella region 10, and a trigger or trigger button 104, the trigger or trigger button 104 which activates the device when pressure is applied to the columella 10 by the user engagement element 106.

[0050] Figure 3A shows an exploded view of exemplary internal components of an exemplary device without a chassis. Figure 3B shows a partial exploded view of exemplary internal components of an exemplary device. Figure 3C shows an assembled view of the internal components of an exemplary device without a chassis.

[0051] In some embodiments, the device includes an adjustable or reconfigurable spring 301. In some embodiments, the device includes a sub-shaft 302. In some embodiments, the device includes a spring core guide 306. In some embodiments, the device includes a columella slider 307. In some embodiments, the device includes a columella saddle 121. In some embodiments, the device includes a guide dowel 309. In some embodiments, the device includes a spring support 310. In some embodiments, the device includes a movement limiter 311. In some embodiments, the device includes a trigger button 104. In some embodiments, the device includes a turcite damper 312. In some embodiments, the device includes a bush support 314. In some embodiments, the device includes a turcite preload ring 313. In some embodiments, the device includes a syringe 315 containing a therapeutic composition. In some embodiments, the syringe 315 has a syringe volume. In some embodiments, the syringe volume is 1cc to 5cc. In some embodiments, the syringe volume is a maximum of 10 cc. In some embodiments, the syringe volume is at least 1 cc. In some embodiments, the syringe volume is at least 1 cc, 2 cc, 3 cc, 4 cc, 5 cc, 6 cc, 7 cc, 8 cc, 9 cc, or 10 cc. In some embodiments, the syringe volume is a maximum of 1 cc, 2 cc, 3 cc, 4 cc, 5 cc, 6 cc, 7 cc, 8 cc, 9 cc, or 10 cc.

[0052] In some embodiments, the columella saddle 121 includes a "U-shaped" saddle that intersects the columella slider insertion portion 320 at a right angle. In some embodiments, the columella slider insertion portion 320 comprises a columella saddle concave region 321 and a columella saddle semiconical region 322. In some embodiments, the columella slider insertion portion 320 is designed to be inserted into the columella slider 307. In some embodiments, the columella slider 307 is designed to be inserted into the columella slider insertion portion 320. In some embodiments, the columella slider 307 comprises a cylinder having a notched columella slider semiconical region 323, the notched columella slider semiconical region 323 having a radius larger than the radius of the columella saddle semiconical region 322. In some embodiments, the columella slider 307 includes a concave notch region, the rectangular concave notch being substantially the same size as the columella saddle concave region 321. In some embodiments, the syringe 315 includes a dispensing element 110, a syringe cylindrical barrel 324, a syringe funnel-shaped region 325, a syringe arm region 333, and a syringe operating region 327. In some embodiments, the syringe operating region 327 includes two circular stops, at least one of which is configured to apply pressure to the syringe cylindrical barrel 324. In some embodiments, the syringe operating region 327 includes two circular stops, at least one of which is configured to stop the movement of the syringe 315. In some embodiments, the syringe 315 is inserted into the notched columella slider 323 and the columella saddle semiconical region 322. In some embodiments, the syringe push arm 326 includes a circular notch for inserting the area of ​​the syringe operating region 327. In some embodiments, the first portion 102 includes a first portion back 328 into which the chassis 116 is inserted. In some embodiments, the back 328 includes a semi-cylindrical notched region for inserting the syringe cylindrical barrel 324. In some embodiments, the first portion back 328 includes a first portion back notched concave rectangular region 330.In some embodiments, the notched concave rectangular region 330 includes a storage region that houses the region of the syringe operating region 327 and the region of the syringe push arm 326. In some embodiments, the first partial rear 328 includes a first partial rear rectangular region 331 and a first partial rear concave rectangular region 332. In some embodiments, the first partial rear rectangular region 331 includes an interface between the rectangular region and the concave rectangular region by at least one arm stop 334. In some embodiments, at least one arm stop 334 is coplanar with the syringe arm 333. In some embodiments, the rectangular region 331 includes two first partial rear concave notched rectangular regions 335. In some embodiments, the chassis 116 includes two chassis rectangular regions 345, and the two concave notched rectangular regions 335 are inserted into the two rectangular regions 345. In some embodiments, the syringe push arm 326 includes at least one syringe push arm cylindrical notch region 336 for inserting the sub-shaft 302. In some embodiments, the sub-shaft 302 includes at least one threaded hole extending along the horizontal length of the sub-shaft 302, the threaded hole located at the second end 338 of the sub-shaft 302. In some embodiments, the second end 338 is connected via a thread to at least one cylindrical notch region 336. In some embodiments, the sub-shaft 302 extends from the bottom 124 of the device toward the trigger button 104. In some embodiments, the turkite preload ring 313 has a larger circumference than the turkite bush 312. In some embodiments, the turkite preload ring 313 is wrapped around the sub-shaft 302 such that the turkite preload ring 313 extends along a portion of the vertical length of the sub-shaft 302. In some embodiments, the turkite preload ring 313 has an inner surface such that the inner surface of the turkite preload ring 313 contacts the outer surface of the sub-shaft 302. In some embodiments, the turkite bush 312 is wrapped around the turkite preload ring 313 such that the turkite bush 312 extends along approximately the same portion of the vertical length of the turkite preload ring 313 and the sub-shaft 302.In some embodiments, the spring support 310 is located along the vertical length of the shaft 302. In some embodiments, the sub-shaft 302 has at least one screw hole into which at least one screw is inserted to secure the spring support 310 to the sub-shaft 302. In some embodiments, the sub-shaft 302 has at least one screw hole extending along the horizontal length of the sub-shaft 302, the screw hole located at the first end 337 of the sub-shaft 302. In some embodiments, the first end 337 is connected to the trigger button 104 via a screw. In some embodiments, the trigger button 104 has a pin hole for inserting a stainless steel dowel pin 339. In some embodiments, the spring 301 extends vertically along the 302. In some embodiments, the spring 301 has a first end 340 and a second end 341. In some embodiments, the first end 340 is wrapped around the turkey bush 312. In some embodiments, the second end 341 is wrapped around a stainless steel dowel pin 339. In some embodiments, the columella slider 307 includes a guide dowel hole 342. In some embodiments, the guide dowel 309 includes a first end 343 and a second end 344. In some embodiments, the first end 343 of the guide dowel is in contact with a concave region 321 of the columella saddle. In some embodiments, the guide dowel extends along the vertical length of the device such that the second end 344 of the guide dowel is positioned parallel to the spring 301. In some embodiments, the trigger button 104 has a concave semi-cylindrical region, and the actuation of the trigger button 104 presses the trigger button 104 against the guide dowel 309. In some embodiments, the device is activated when pressure is applied to the trigger button 104 by the user. In some embodiments, the device is activated when the user applies pressure to the trigger button 104 after the trigger is released by pressure being applied to the subject engagement portion 106 using the user's nasal region 10. In some embodiments, the user may activate the device using any of their fingers.

[0053] Figure 3D shows a front view illustrating the internal components of an exemplary device in a second configuration, with one dispensing element exposed. In some embodiments, the device is transitionable from a first configuration 100 to a second configuration 200. In some embodiments, the subject engagement portion 106 engages, and when the placement element 106 engages, it causes the nasal saddle 121 to retract into the first portion 102. In some embodiments, at least one dispensing element 110 emerges from at least one insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200. In some embodiments, the vertical length 122 in the second configuration is longer than the vertical length 123 in the first configuration. In some embodiments, when the device is transitionable from a first configuration 100 to a second configuration 200, the housing 101 defines a first insertable portion 107, and the device further comprises a dispensing element 110 connected to the housing, the dispensing element 110 emerging from the first insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200.

[0054] Figure 4A shows an exemplary embodiment of an exemplary device in a second configuration, where the insertable portion is located within the nasal canal and one dispensing element is exposed. Figure 4B shows an exemplary embodiment of an exemplary device in a second configuration, where one dispensing element is exposed.

[0055] In one embodiment, the Disclosure provides a device for intranasal delivery to a subject, the device comprising a housing 101 having an insertable portion 107 configured to be inserted into the subject's nasal passage 20, and a subject engaging portion 106 connected to the housing 101, which engages with the subject's columella region 10, and which, when pressure is applied to the subject's columella region 10 by the subject engaging portion 106, enables and / or causes delivery of a composition 111 from the insertable portion 107 to the subject. In some embodiments, the insertable portion 107 incorporates one or more dispensing channels 125 leading to one or more dispensing ports 126 configured for intranasal delivery of the composition 111 to one or more regions or partial regions of the subject's nasal passage 20.

[0056] In some embodiments, the insertable portion 107 includes a dispensing element 110 for delivering the composition 111 to a region or portion of the subject's nasal passage 20. In some embodiments, the housing 101 includes a trigger which activates the device to deliver the composition 111 to the subject from the insertable portion 107 or the dispensing element 110. In some embodiments, the subject engagement portion 106 includes a trigger connected to the housing 101 and the subject engagement portion 106, and when pressure from the subject engagement portion 106 is applied to the columella region 10, the trigger activates the device to dispense the composition 111 to the subject from the insertable portion 107 or the dispensing element 110.

[0057] In some embodiments, the subject engagement portion 106 includes a trigger release portion 104 connected to the housing 101 and the subject engagement portion 106, and when pressure from the subject engagement portion 106 is applied to the columella region 10, the trigger release portion 104 allows the device to operate to deliver the composition 111 to the subject from the insertable portion 107 or the dispensing element 110. In some embodiments, the device further includes a trigger that is activatable when the trigger release portion 104 is engaged.

[0058] In some embodiments, the subject engagement portion 106 positions the insertable portion 107 and / or dispensing element 110 within the subject's nasal passage 20, limiting the insertion depth of the insertable portion 107 and / or dispensing element 110 into the nasal passage 20. In some embodiments, once the first insertable portion 107 is inserted into the subject's nasal passage 20, the first insertable portion 107 opens or expands the internal nasal flap 13 by pushing up the superior lateral nasal cartilage 25 and surrounding tissue away from the subject's nasal septum 24, thereby positioning at least one of the insertable portions 107 to deliver the composition 111 to the subject. In some embodiments, the internal nasal flap 13 is located approximately 1.3 cm from the entrance to the nasal vestibule 21. In some embodiments, the internal nasal flap 13 comprises the narrowest portion of the nasal passage 20. The internal nasal flap 13 has an average angle ranging from 9° to 15° in Caucasians. In some embodiments, the device is activated by the user applying pressure to the trigger button 104. In some embodiments, the user may activate the device using any finger.

[0059] In some embodiments, the saddle-shaped subject engagement portion 121 for the columella is equipped with a trigger, and the saddle-shaped subject engagement portion 121 for the columella is equipped with a trigger, and the saddle-shaped subject engagement portion 121 for the columella is equipped with a trigger, and the saddle-shaped subject engagement portion for the columella is equipped with a placement trigger 106, which, when pressed against the subject's columella 10, activates the device and dispenses the composition 111 in parallel from at least two insertable portions 107 and / or dispensing elements 110. In some embodiments, the device is equipped with a placement trigger 106, which, when pressed against the subject's columella 10, activates the device and dispenses the composition 111 sequentially from at least two insertable portions 107 and / or dispensing elements 110. In some embodiments, the placement trigger 106, when pressed against the subject's columella 10, unlocks the trigger 104 so that when a button is pressed, composition 111 is dispensed from at least one insertable portion 107 and / or dispensing element 110. In some embodiments, the placement trigger 106, when pressed against the subject's columella 10, activates the device and dispenses composition 111 from at least one insertable portion and / or dispensing element 110. In some embodiments, the placement trigger 106 includes an actuator that dispenses composition 111 from syringe 315 when the housing 101 is moved from a first position 100 to a second position 200. In some embodiments, syringe 315 includes a cylindrical barrel 324. In some embodiments, the device further includes syringe 315 fluidly connected to at least one insertable portion and / or dispensing element 110. In some embodiments, the columella saddle 121 includes a trigger for receiving the subject's columella 10. In some embodiments, the placement trigger 106 activates the device by pressing down a switch below the placement trigger 106, or by releasing a safety or lock in the trigger mechanism. In some embodiments, the switch comprises a columella saddle 121, a columella saddle slider 307, and a syringe 315.In some embodiments, the subject engagement portion 106, including the columella saddle 121, may be equipped with a trigger such that the trigger activates the mechanism of the device when the subject engagement portion 106 is pressed against the columella 10.

[0060] In some embodiments, the columella saddle 121 positions the first insertable portion 107 and the second insertable portion 107 such that at least one insertable portion 107 and / or dispensing element 110 is aligned with the olfactory cleft 23 when the device is activated. In some embodiments, the saddle-shaped portion 121 positions the first insertable portion 107 and the second insertable portion 107 such that at least one insertable portion 107 and / or dispensing element 110 is aligned along the path 17 of the olfactory cleft when the device is activated. In some embodiments, the columella saddle 121 has a shape 130 that conforms to the anatomical structure of the subject's columella 10, and aligns one or more insertable portions 107 and / or dispensing elements 110 with the subject's olfactory cleft 23. In some embodiments, the device includes an insertable portion 107 and / or dispensing element 110 positioned proximal to the subject's olfactory cleft 23 when the columella saddle 121 is engaged with the subject's columella 10. In some embodiments, the columella saddle 121 includes a recess for the subject's columella 10.

[0061] In some embodiments, the columella saddle 121 positions the first insertable portion 107 and the second insertable portion 107 such that at least one insertable portion 107 and / or dispensing element 110 is aligned with the middle nasal meatus 30 when the device is activated. In some embodiments, the saddle-shaped portion 121 positions the first insertable portion 107 and the second insertable portion 107 such that at least one insertable portion 107 and / or dispensing element 110 is aligned along the path of the middle nasal meatus 30 when the device is activated. In some embodiments, the columella saddle 121 has a shape 130 that conforms to the anatomical structure of the subject's columella 10 and aligns one or more insertable portions 107 and / or dispensing elements 110 with the subject's middle nasal meatus 30. In some embodiments, the device includes an insertable portion 107 and / or dispensing element 110 positioned proximal to the middle nasal meatus 30 of the subject when the columella saddle 121 is engaged with the columella 10 of the subject.

[0062] In some embodiments, the first and / or second insertable portion 107 opens or expands the internal nasal flap 13 by pushing up the superior lateral nasal cartilage 25 and surrounding tissue away from the nasal septum 24 625, thereby removing an obstruction to the pathway for dispensing the compound 111. In some embodiments, pressure is applied to the subject engagement portion 106 by the columella region 10. In some embodiments, at least one insertable portion 107 and / or dispensing element 110 emerges from the insertable portion 107 toward a target region, such as the olfactory cleft 23, the middle nasal meatus 30, or other nasal anatomical structure, based on the anterior plane 18, for dispensing the composition 111.

[0063] In some embodiments, the subject engagement portion 106 may be configured for delivering a sampling fluid, guiding an endoscope, or a combination thereof. In some embodiments, the device is configured to target the olfactory cleft 23 or a portion thereof. In some embodiments, the target region 19 is one or both of the olfactory clefts or a portion thereof. In some embodiments, the target region is one or both of the respiratory compartments or a portion thereof. In some embodiments, the target region 19 is the middle nasal meatus 30, and the targeted delivery of the composition 111 to the target region 19 is increased by dispensing the composition 111 from the posterior end 110 of the dispensing element. In some embodiments, the discharge region 19 is further parallel to the subject's middle nasal turbinate 15 and not located within the middle nasal meatus 30. In some embodiments, the discharge region 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end 128 of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23 or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and composition 111 is dispensed into both regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the anatomical structure of the nose. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the anatomical structure of the nose, and composition 111 is dispensed into all regions simultaneously.

[0064] The device may comprise two insertable portions 107, one of which has one or more channels 125 connected to one or more dispensing ports 126. The device may comprise two insertable portions 107, both of which have one or more channels 125 connected to one or more dispensing ports 126. The device may comprise two insertable portions 107, both of which have one or more channels 125 connected to one or more dispensing ports 126, and the composition 111 can be delivered simultaneously or sequentially from each insertable portion 107 or dispensing element 110. The device may comprise two insertable portions 107, one of which includes one or more dispensing elements 110 fixed to the insertable portion 107 connected to one or more dispensing ports 126. The device may comprise two insertable sections 107, each containing one or more dispensing elements 110 fixed to the insertable section 107 connected to one or more dispensing ports 126. The device may comprise two insertable sections 107, each containing one or more dispensing elements 110 fixed to the insertable section 107 connected to one or more dispensing ports 126, and the compound 111 can be delivered simultaneously or sequentially from each insertable section 107 or dispensing element 110. The device may comprise two insertable sections 107, each containing one or more dispensing elements 110 movable to the insertable section 107 having one or more dispensing ports 126. The device may comprise two insertable sections 107, each containing one or more dispensing elements 110 movable to the insertable section 107 having one or more dispensing ports 126. The device may comprise two insertable portions 107, each containing one or more dispensing elements movable relative to the insertable portion 107 having one or more dispensing ports 126, and the composition 111 can be delivered simultaneously or sequentially from each insertable portion 107 or dispensing element 110. The device may further comprise two insertable portions 107, and the composition 111 can be delivered to any partial region of the nasal passage 20, for example, the olfactory cleft 23 or the nasal concha.

[0065] The device may further comprise two insertable portions 107 and a user engagement element 106 that engages with the columella 10. The device may further comprise two insertable portions 107, a user engagement element that engages with the columella 10, and a trigger that activates the device when pressure is applied to the columella 10 by the user engagement element 106.

[0066] In some embodiments, one or more cannulas 110 are housed within a secondary tubular member. In some embodiments, the trigger 104 includes a button which is pressed to activate the device. In some embodiments, the device cannot be activated until it is in a second configuration 200. In some embodiments, the device cannot be activated until it is no longer in a first configuration 100. In some embodiments, the device is in the first configuration 100 and the trigger 104 cannot activate the device. In some embodiments, the device is in a second configuration 200 and the trigger 104 can activate the device. In some embodiments, the trigger button 104 can be activated with the thumb. In some embodiments, the trigger button 104 can be activated with the index and middle fingers.

[0067] Figure 5 shows exemplary embodiments of an exemplary apparatus in a first configuration. In one embodiment, the Disclosure provides an apparatus comprising at least one insertable portion 107. In one embodiment, the Disclosure provides an apparatus comprising at least one dispensing element 110 in a first configuration 100. In one embodiment, the Disclosure provides an apparatus for intranasal delivery to a subject, the apparatus comprising a housing 101 comprising the dispensing element 110, and a subject engagement portion 106 connected to the housing, the subject engagement portion 106 including a subject engagement portion 106 that engages with the columella region 10, the subject engagement portion 106 that positions the dispensing element 110 in the subject's nasal passage 20 and limits the insertion depth of the insertable portion into the nasal passage 20. In some embodiments, the subject engagement portion 106 is concave and engages with the subject's columella 10 around multiple sides of the columella 10. In some embodiments, the housing 101 defines the entire outer shell of the device. In some embodiments, the housing 101 comprises a first portion 1020 defining a cylindrical portion 1030 and a rounded bottom portion 1040. In some embodiments, the housing 101 comprises a second portion 1050 located perpendicularly adjacent to the first portion 1020, and the first portion 1020 may have a larger diameter than the second portion 1050 to accommodate the insertion of the second portion 1050 into the first portion 1020. In some embodiments, the second portion 1050 comprises a subject engagement portion 106, which comprises a "U-shaped" or "saddle" shaped element 121. In some embodiments, the subject engagement portion 106 engages with the nasal columella region of the subject 10. In some embodiments, the second portion 1050 comprises at least one insertable portion 107. In some embodiments, the second portion 1050 comprises two insertable portions 107, each intended for insertion into the nasal passage 20 of the subject.

[0068] In some embodiments, a second portion 1050 of the housing 101 comprises a subject engagement portion 106. In some embodiments, the subject engagement portion 106 comprises a concave upper portion. In some embodiments, the concave upper portion comprises a "U-shaped" or "saddle" shaped element 121. In some embodiments, the "U-shaped" or "saddle" shaped element 121 comprises the center of the concave upper portion. In some embodiments, the cylindrical intermediate portion 112 is positioned perpendicularly adjacent to the "U-shaped" or "saddle" shaped element 121 such that the center of the concave upper portion 106 lies coplanar with the upper surface of the cylindrical intermediate portion 112, and they thus form a unilateral plane 1170. In some embodiments, the device comprises a first configuration 100 in which a first reference marker 1080 is fully visible. In some embodiments, the device in the first configuration 100 comprises a vertical length 123 in the first configuration. In some embodiments, the apparatus includes a second cylindrical reference marker 1090, which partially emerges from a cylindrical portion 1030 of a first portion 1020 of the housing 101. In some embodiments, the cylindrical intermediate portion 112 has a bottom surface substantially coplanar with the top surface of the second reference marker 1090 so as to form a one-sided plane 1160. In some embodiments, the housing 101 includes a dispensing element 110 in the first configuration 100. In some embodiments, at least one cannula has a cylindrical shape. In some embodiments, the dispensing element 110 is configured to dispense the composition 110 into a single nasal passage 20 of the subject.

[0069] In some embodiments, the design of the trigger button 104 for the columella is configured to enable triggering only when properly inserted and to restrict movement once triggered.

[0070] In some embodiments, the saddle 121 for the columella includes an anchor or reference 617 to establish the insertion depth as a self-supporting attribute.

[0071] In some embodiments, the columella trigger button 104 is equipped with a handgrip that allows the hand to simply grasp the device without involving the fingers in the act of activation. In some embodiments, the device is equipped with a gripping configuration that allows the subject to grasp the device with the intention of lifting it towards their face (i.e., the intention to grasp), and does not require any adjustment of the grip to activate it. In some embodiments, the device is equipped with a columella trigger 104 that does not require any judgment about when to activate, thus facilitating a low / none cognitive action, thereby allowing the subject to concentrate solely on insertion.

[0072] In some embodiments, the insertable portion 107 has an insertion angle configured to open a pathway between the nasal septum 24 and the nasal valve 13, reducing the insertion depth aspect of the cannula. In some embodiments, a columellar saddle 121 reduces concerns about the insertion angle. In some embodiments, proper insertion is required for complete insertion. In some embodiments, the width 1103 of the insertable portion 107 fills the lower surface of the nasal passage 20 and pushes aside hairs, minimizing the possibility of sneezing reflex compared to when a smaller diameter catheter is pushed up through the “ear portion” 107. In some embodiments, the device has two flat ear portions 107, which help to embrace the sides of the nasal septum 24 of each nasal passage 20, minimizing the possibility of reaching the nasal valve 13. In some embodiments, the device comprises at least one flat insertable portion 107, which, when partially or fully inserted, causes discomfort or awkwardness when twisted laterally so as not to adversely affect proper insertion while the subject is holding the device. In some embodiments, the device comprises a wedge shape 130 on its anterior edge, which gives the anterior surface of the insertable portion 107 a straighter view to the olfactory cleft 23 or a portion thereof, the middle meatus 30, or back to the nasal concha of the nasal meatus 20 by pushing up the compressible and adaptable nasal cartilage of the nasal flap 13 away from the nasal septum 24 625. In some embodiments, the device comprises a flat shape of the insertable portion 107, which provides a preferential bend to adapt to the irregular surface along the nasal septum 24. In some embodiments, the device comprises a flat insertable portion 107, which provides preferential rigidity in cases of irregular intervention of the inferior nasal cartilage, for example, and minimizes deflection back into the nasal passage 20. In some embodiments, the device comprises an insertable portion 107, which is configured to adapt to columella flaring at various angles. In some embodiments, columella flaring at various angles includes being wider, closer to the face, or further from the tip of the nose.In some embodiments, the device includes a lower surface of the insertable portion 107 that connects to a columella saddle 121 in a manner that allows the fully inserted insertable portion 107 to bend comfortably with respect to the columella shape 10 of the subject without affecting the overall arrangement of the inserted insertable portion 107. In some embodiments, two insertable portions 107 can cradle the nasal septum 24 and remain comfortably in place without being held by hand when fully inserted. In some embodiments, to facilitate the static insertion of the cannula, it may be possible to allow the accumulation and retrieval of a liquid bolus, such as a liquid swab, for collecting a biological sample from the subject's nasal cavity. In some embodiments, a double insertable portion can cradle the nasal septum 24 and remain comfortably in place without being held by hand, thereby allowing the subject's passive involvement for independently time-coordinated action. In some embodiments, in a sleeping or sedated subject, a drug or liquid swab may be dispensed in a time-coordinated manner concurrent with electroencephalogram-slowed sleep. In some embodiments, simultaneous administration to both nasal passages 20 eliminates concerns about nasal circulation during delivery to, for example, the subnasal region 35 (in some embodiments, reference numeral 35 corresponds to an discharge site, e.g., an discharge site within the discharge area). In some embodiments, averaging through both nasal cavities 11 should minimize dose variability associated with administration to a single nasal passage 20, which may open or become blocked depending on the stage of its circulation.

[0073] In some embodiments, at least one cannula is configured to administer a large dose of drug at once, minimizing time and complexity in life-saving situations, for example, reducing multiple doses for opioid reversal. In some embodiments, the cannula tip is bulbous to facilitate insertion without the risk of removal (e.g., snagging on tissue in the nasal passage). In some embodiments, the anterior lumen of the cannula can be made of a drug-compatible material coated with a different material that is biocompatible with the mucosa but not necessarily compatible with the drug. In some embodiments, the anterior lumen of the cannula can be made of a drug-compatible material coated with a different material that is biocompatible with the mucosa but not necessarily compatible with the drug, which allows for reduced manufacturing costs and complexity. In some embodiments, the lumen can be extruded to a constant inner diameter. In some embodiments, the outer surface of the cannula can be manufactured by molding, printing, etc., without concern for tighter tolerances in the inner diameter. In some embodiments, the lumen can be made from stock material, e.g., cannulas for drug delivery via different administration routes, e.g., manual indwelling needles. In some embodiments, the lumen of the nasal covering cannula can provide structural strength to the outer sheath, thereby allowing the outer sheath to be made of a more flexible material that is more comfortable and safer against the mucous membrane. In some embodiments, the device has a lumen, which is configured to adapt to different drugs and formulations, such as different inner diameters, while still using the same outer sheath. In some embodiments, the device includes minimizing SKUs and simplifying the filling line, such as converting the filling line from one formulation to another. In some embodiments, the cannula has a sheath through which gas (air) or liquid can be simultaneously discharged along an intentional channel in the ring between the lumen and the sheath.In some embodiments, the cannula has an annular portion at the tip of the cannula 131 that facilitates the discharge of gas, for example, to assist a liquid jet or spray pattern, or facilitates its combination with the reactive components of a drug formulation when discharged into the subject's body. In some embodiments, the device has a smaller diameter cannula, which is configured to be inserted over the hairs of the nasal passage 20 (to avoid the sneeze reflex) and over the external nasal passage (to avoid cross-contamination with bacteria known to occupy the ecosystem of this face of the anatomical structure) so as not to get caught in the nasal valve 13 or flow into the inferior nasal passage 35. In some embodiments, the device has a smaller diameter cannula, which has a vantage point 34 that allows access to a narrower space behind the nasal bone and provides a more direct view to the olfactory cleft 23, the middle nasal passage 30, or other nasal turbinates. In some embodiments, the device includes not revealing the smaller diameter cannula until after it has been inserted and is outside the field of view, thereby reducing the fear associated with the perception of "shoving a sharp, thin object into the nasal passage," such as fainting.

[0074] In some embodiments, the dispensing element 110 is positioned approximately 0.1 mm to 30 mm from the olfactory region 23 or the anterior entrance to the olfactory region 23, the middle nasal meatus 30, or other nasal anatomical structures. In some embodiments, the tip 131 is positioned approximately 0.1 mm to 25 mm from the olfactory region 23 or the anterior entrance to the olfactory region 23, the middle nasal meatus 30, or other nasal anatomical structures. In some embodiments, the tip 131 is positioned approximately 0.1 mm to 3 mm, approximately 0.1 mm to 5 mm, approximately 0.1 mm to 9 mm, approximately 0.1 mm to 12 mm, approximately 0.1 mm to 18 mm, approximately 0.1 mm to 20 mm, approximately 0.1 mm to 25 mm, approximately 3 mm to 5 mm, approximately 3 mm to 9 mm, approximately 3 mm to 12 mm, approximately 3 mm to 18 mm, approximately 3 mm to 20 mm, approximately 3 mm to 25 mm, and approximately 5 mm to 9 mm. The tip is positioned at approximately 5mm to 12mm, 5mm to 18mm, 5mm to 20mm, 5mm to 25mm, 9mm to 12mm, 9mm to 18mm, 9mm to 20mm, 9mm to 25mm, 12mm to 18mm, 12mm to 20mm, 12mm to 25mm, 18mm to 20mm, 18mm to 25mm, or 20mm to 25mm (including increments therein). In some embodiments, the tip is positioned at approximately 0.1mm, 3mm, 5mm, 9mm, 12mm, 18mm, 20mm, or 25mm from the olfactory region 23 or the anterior entrance to the olfactory region 23, the middle nasal meatus 30, or other nasal anatomical structures. In some embodiments, the tip is positioned at least about 0.1 mm, about 3 mm, about 5 mm, about 9 mm, about 12 mm, about 18 mm, or about 20 mm from the olfactory region 23 or the anterior entrance to the olfactory region 23, the middle nasal meatus 30, or other nasal anatomical structures. In some embodiments, the dispensing element is positioned at a maximum of about 3 mm, about 5 mm, about 9 mm, about 12 mm, about 18 mm, about 20 mm, or about 25 mm from the olfactory region 23 or the anterior entrance to the olfactory region 23, the middle nasal meatus 30, or other nasal anatomical structures.

[0075] Figure 7A shows a perspective view of an exemplary embodiment of a columella saddle in the first configuration. In some embodiments, the device comprises a subject engagement portion 106, a columella saddle 121, and two insertable portions 107.

[0076] In some embodiments, the device comprises at least one insertable portion 107. In some embodiments, the device comprises two insertable portions 107. In some embodiments, at least one insertable portion 107 comprises a shape 130 including wing-shaped, flaky, wedge-shaped, elliptical or oblong, or even rounded forms. In some embodiments, the distal surface 128 of the insertable portion 107 comprises a rounded shape 130. In some embodiments, at least one insertable portion 107 comprises a shape 130, thereby allowing a surface of at least one insertable portion 107 to fit snugly onto the narrowed, "slit-like" anterior surface of the internal nasal flap 13 where the nasal septum 24 contacts the superior lateral nasal cartilage 25. In some embodiments, at least one insertable portion 107 has a height of about 10 mm to about 30 mm, a depth of about 3 mm to about 15 mm, and a width of about 1 mm to 5 mm.

[0077] In some embodiments, the columella saddle 121 has a "U-shape" or "saddle" shape adapted to engage with the columella region 10 of the subject. In some embodiments, the subject engagement portion 106 is concave and engages with the columella region 10 of the subject, centering on multiple sides of the columella region 10.

[0078] Figure 7B shows a perspective view of the internal components of an exemplary embodiment of a columella saddle in a first configuration. In some embodiments, the device comprises a subject engagement portion 106, which may function as a placement element, and may include a columella saddle 121, two insertable portions 107, and two dispensing elements or dispensing channels 125, the distal surface 131 of the dispensing element 125 having a dispensing port 126 positioned to deliver a composition 111 to a targeted compartment of the nasal passage 20, such as the olfactory cleft 23, the middle nasal meatus 30, or the nasal concha. In some embodiments, the composition 111 is delivered simultaneously from both dispensing ports 126. In some embodiments, the composition 111 is delivered sequentially from both dispensing ports 126. In some embodiments, the dispensing channel 125 may be a dispensing element 110. In some embodiments, the dispensing element 110 may be a cannula.

[0079] In some embodiments, the device comprises at least one dispensing element / dispensing channel 125 (e.g., a cannula) and at least one dispensing port 126. In some embodiments, the device comprises two dispensing channels 125 and two dispensing ports 126. In some embodiments, at least one dispensing channel 125 is unlined. In some embodiments, at least one dispensing channel 125 is lined with a material different from the material of one or more insertable portions 107. In some embodiments, at least one dispensing channel 125 comprises at least one dispensing element 110, e.g., a cannula, fixed to at least one insertable portion 107. In some embodiments, at least one dispensing channel 125 has an inner diameter 129 of 0.5 mm to 3 mm. In some embodiments, at least one dispensing channel 125 has a round cylindrical shape. In some embodiments, at least one dispensing channel 125 has an elliptical cylindrical shape. In some embodiments, the first and / or second insertable portion has a cross-sectional shape including an elongated ellipse with a constant width and symmetrically rounded ends. In some embodiments, the first and / or second insertable portion has a cross-sectional shape including an elongated rounded rectangle with semicircular ends. Exemplary cross-sectional shapes of the insertable portion are shown in Figure 19F.

[0080] In some embodiments, at least one dispensing port 126 delivers the composition 111 to a target compartment of the nasal passage 20, such as the olfactory cleft 23, the middle nasal meatus 30, or the nasal concha. In some embodiments, at least one dispensing port 126 is equipped with a sprayer. In some embodiments, at least one dispensing port 126 is not equipped with a sprayer.

[0081] Figure 7C shows a perspective view of the internal components of an exemplary embodiment of an exemplary columella saddle in a first configuration. In some embodiments, the device comprises a placement element comprising a subject engagement portion 106, a columella saddle 121, two insertable portions 107, and two dispensing channels 125, the dispensing ports 126 positioned along the edge of the insertable portion 107 to deliver the composition 111 from the device to a targeted compartment of the nasal passage 20, such as the middle turbinate 15, middle meatus 30, or olfactory cleft 23.

[0082] In some cases, the middle nasal concha 15 includes a physical obstruction to the delivery of the composition 111 to the olfactory cleft 23, the middle nasal meatus 30, or the nasal concha. In some cases, the middle nasal concha 15 has an anterior surface substantially aligned with the zygomatic bone. In some embodiments, the middle nasal concha 15 has an anterior surface not aligned with the zygomatic bone. In some embodiments, the nasal meatus 20 is simple anteriorly and has an angled pathway, so that one or more nasal conchas do not cause a physical obstruction to the delivery of the composition 111 to the superior nasal meatus 20 including the olfactory cleft 23, or to guide the composition down one or more nasal meatus to the nasopharynx.

[0083] In some embodiments, the nasal passage 20 includes a single pathway from the nasal vestibule 21 to the olfactory cleft 23 based on an anterior plane 18 having a target discharge point 19. In some embodiments, the device is adapted to target the delivery of composition 111 to the olfactory cleft 23 or a portion thereof, and the placement elements may align at least one insertable portion 107 or one dispensing element 110 with the olfactory cleft 23 of the subject. In some embodiments, at least one composition channel 125 within the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.3 to 3.0 mm. In some embodiments, at least one composition channel 125 within the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.3 to 0.7 mm. In some embodiments, at least one composition channel 125 within the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.5 to 1.0 mm. In some embodiments, a wider inner diameter 129 may be used to deliver high-viscosity compositions. In some embodiments, the composition channel 125 within the insertable portion 107, or the dispensing element 110, may be adapted to deliver compositions 111 having low, medium, or high viscosity.

[0084] In some embodiments, at least one dispensing channel 125 is divided into multiple dispensing channels 125 leading to multiple dispensing ports 126 located at multiple positions on at least one insertable portion 107 in order to deliver a composition to multiple targeted compartments 19 of one or both nasal passages 20, such as the olfactory cleft 23, the middle nasal passage 30, and the middle turbinate 15.

[0085] Figure 7D shows a perspective view of the internal components of an exemplary embodiment of a columella saddle in a first configuration. In some embodiments, the device comprises, in the first configuration 100, a subject engagement portion 106, a columella saddle 121, two insertable portions 107, and two dispensing elements 110.

[0086] In some embodiments, the device comprises at least one dispensing element 110. In some embodiments, the device comprises two dispensing elements 110. In some embodiments, at least one dispensing element 110 comprises a cannula or catheter. In some embodiments, at least one dispensing element 110 has an inner diameter 129 of 0.5 mm to 3 mm. In some embodiments, at least one dispensing element 110 has a round cylindrical shape. In some embodiments, at least one dispensing element 110 has an elliptical cylindrical shape.

[0087] Figure 7E shows a perspective view of the internal components of an exemplary embodiment of a columella saddle in a second configuration. In some embodiments, the device in the second configuration 200 comprises a placement element having a subject engagement portion 106, a columella saddle 121, two insertable portions 107, and two dispensing elements 110.

[0088] In some embodiments, the device comprises at least one dispensing element 110. In some embodiments, the device comprises two dispensing elements 110. In some embodiments, at least one dispensing element emerges from at least one insertable portion 107 or is revealed from the distal surface 131 of the insertable portion 107 by at least one or more insertable portions 107 when the device transitions from a first configuration 100 to a second configuration 200. In some embodiments, at least one dispensing element 110 emerges from at least one insertable portion 107, such as along the edge of at least one insertable portion 107, or is revealed from another surface of the insertable portion 107 by at least one insertable portion 107. In some embodiments, at least one dispensing element 110 is arranged to deliver the composition 111 to a target compartment in one or both nasal passages 20, such as one or both olfactory clefts 23, the middle nasal meatus 30, or the nasal conchae. In some embodiments, the length of the portion of at least one dispensing element 110 extending from or being represented by at least one insertable portion 107 is approximately 5 mm to approximately 40 mm. In some embodiments, the distance from the distal surface 131 of at least one dispensing element 110 to the anterior surface of the cribriform plate 31 is approximately 5 mm to approximately 40 mm. In some embodiments, the distance from the distal surface 131 of at least one dispensing element 110 to the anterior superior surface of one or both olfactory fissures 23 is approximately 5 mm to approximately 40 mm. In some embodiments, the composition 111 is delivered simultaneously from both dispensing elements 110. In some embodiments, the composition 111 is delivered sequentially from both dispensing elements 110.

[0089] In some embodiments, the device is adapted to target the delivery of composition 111 to the olfactory cleft 23 or a portion thereof, and the placement element 106 may align at least one insertable portion 107 or one dispensing element 110 with the subject's olfactory cleft 23. In some embodiments, the device is adapted to target the delivery of composition 111 to the middle nasal meatus 30 or a portion thereof, and the placement element 106 may align at least one insertable portion 107 or one dispensing element 110 with the subject's middle nasal meatus 30. In some embodiments, at least one composition channel 125 within the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.3 to 3.0 mm. In some embodiments, at least one composition channel 125 within the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.3 to 0.7 mm. In some embodiments, at least one composition channel 125 within the insertable portion 107 or at least one dispensing element 110 has an inner diameter 129 of 0.5 to 1.0 mm. In some embodiments, a wider inner diameter 129 may be used to deliver high-viscosity compositions. In some embodiments, the composition channel 125 within the insertable portion 107 or the dispensing element 110 may be adapted to deliver compositions 111 having low viscosity, medium viscosity, or high viscosity.

[0090] In some embodiments, the subject engagement portion 106 positions an insertable portion 107 within the subject's nasal passage 20 and limits the insertion depth of the insertable portion 107 into the nasal passage 20. In some embodiments, the housing 101 defines two insertable portions 107, each intended for insertion into the subject's nasal passage 20, and once the first insertable portion 107 is inserted into the subject's nasal passage 20, the first insertable portion 107 engages with the tissue within the nasal passage 20 to open or expand the subject's internal nasal valve 13, thereby positioning at least one of the insertable portions 107 to deliver the composition 111 to the subject, and the device further comprises an actuator that delivers the composition 111 from either or both of the insertable portions 107 when the device is activated.

[0091] In some embodiments, the housing 101 defines two insertable portions 107, each for delivering composition 111 into the nasal passage 20 of a subject, and the device further includes an actuator for delivering composition 111 from one or both of the insertable portions 107 when the device is activated. In some embodiments, the device is transitionable from a first configuration 100 to a second configuration 200, and the device further includes a dispensing element 110 connected to the housing 101, the dispensing element 110 emerging from the first insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200. In some embodiments, the device is activated simultaneously when transitioning from the first configuration 100 to the second configuration 200. In some embodiments, the device is transitionable from a first configuration 100 to a second configuration 200 when pressure is applied around the longitudinal axis 610 of the device, and the dispensing element 110 appears as a linear vector with respect to the longitudinal axis 610 of the first insertable portion 107, or the device is configured to transition from the first configuration 100 to the second configuration 200 with only one hand. In some embodiments, the subject engagement portion 106 engages with the columella region 10 of the subject to fix the distal end 128 of the insertable portion 107 within the discharge area 19 of the subject's nasal cavity 11.

[0092] Figure 11 shows the anatomical structure of the nasal cavity, as well as components of an exemplary device for opening or expanding an exemplary internal nasal valve, and a side perspective view of an exemplary embodiment of a saddle for the columella.

[0093] In one embodiment, the Disclosure provides a device for intranasal delivery to a subject, the device comprising a housing 101 defining first and second insertable portions 107, each to be inserted into the nasal passage 20 of the subject, wherein when the first insertable portion 107 is inserted into the nasal passage 20 of the subject, at least one insertable portion 107 engages with tissue in the nasal passage 20 to open or expand the internal nasal valve 13 of the subject, thereby positioning at least one of the insertable portions 107 to deliver a composition 111 to the subject; and an actuator for delivering the composition 111 from either or both of the insertable portions 107 when the device is activated.

[0094] In some embodiments, at least one insertable portion 107 that opens or expands the internal nasal flap 13 does so by moving the superior lateral nasal cartilage 25 defining the internal nasal flap 13 away from the subject's nasal septum 24 625. In some embodiments, at least one insertable portion 107 that opens or expands the internal nasal flap 13 does so by moving the superior lateral nasal cartilage 25 defining the internal nasal flap 13 toward the subject's nasal dorsum 622. In some embodiments, the insertable portion 107 incorporates one or more dispensing channels 125 leading to one or more dispensing ports 126 configured to deliver the composition 111 intranasally to one or more regions or partial regions of the subject's nasal passage 20. In some embodiments, the insertable portion 107 comprises a dispensing element 110 for delivering the composition 111 to a region or partial region of the subject's nasal passage 20.

[0095] In some embodiments, the device further includes a trigger connected to the housing 101, which, when pressure is applied to the trigger, activates the device to dispense the composition 111 to the subject from the insertable portion 107 or the dispensing element 110. In some embodiments, the device further includes a trigger connected to the housing 101 and the subject engagement portion 106, which, when pressure is applied to the columella region 10 by the subject engagement portion 106, activates the device to dispense the composition 111 to the subject from the insertable portion 107 or the dispensing element 110. In some embodiments, the device further includes a subject engagement portion 106, which includes a trigger release unit connected to the housing 101, which, when pressure is applied to the columella region 10 by the subject engagement portion 106, allows the device to operate to deliver the composition 11 to the subject from the insertable portion 107 or the dispensing element 110.

[0096] In some embodiments, the device further includes a trigger that is activatable when a trigger release unit 104 is engaged. In some embodiments, the device further includes a subject engagement portion 106 connected to the housing 101, the subject engagement portion 106 engaging with the columella region 10, the subject engagement portion 106 positioning an insertable portion 107 into the subject's nasal passage 20, and limiting the insertion depth of the delivery element 111 into the nasal passage 20. In some embodiments, the housing 101 defines two insertable portions 107, each for delivering the composition 111 into the subject's nasal passage 20, and the device further includes an actuator for delivering the composition from one or both of the dispensing elements 110 when the device is activated. In some embodiments, the device is transitionable from a first configuration 100 to a second configuration 200, the housing 101 defines a first insertable portion 107, and the device further includes a dispensing element 110 connected to the housing 101, the dispensing element 110 emerging from the first insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200. In some embodiments, the device is activated simultaneously when it transitions from the first configuration 100 to the second configuration 200. In some embodiments, the device is transitionable from the first configuration 100 to the second configuration 200 when pressure is applied around the longitudinal axis 610 of the device, the dispensing element 110 emerging as a linear vector with respect to the longitudinal axis 610 of the first insertable portion 107, or the device is configured to transition from the first configuration 100 to the second configuration 200 with only one hand.

[0097] In some embodiments, the discharge area 29 is located 0 to 30 mm above a horizontal line 627 that intersects the anterior surface of the internal nasal valve 13, and 0 to 20 mm anterior to an inclined line 610 that intersects the anterior surface of the middle turbinate 15 and the posterior surface of the nasal vestibule 21.

[0098] In some embodiments, the subject engagement portion 106 engages with the columella region 10 of the subject to fix the distal end 128 of the insertable portion 107 into the discharge area 29 of the subject's nasal cavity 11, the discharge area 29 is located 0mm to 30mm above a horizontal line 627 intersecting the anterior surface of the internal nasal valve 13, and 0mm to 20mm anterior to an inclined line 610 intersecting the anterior surface of the middle turbinate 15 and the posterior surface of the nasal vestibule 21, and the olfactory cleft 2 It is located 0mm to 40mm below the horizontal line 621 parallel to the lower surface of 3, 0mm to 20mm posterior to the dorsal surface of the nose 622, 10mm and 50mm above the horizontal line 623 intersecting the lower surface of the columella 10, 0mm to 30mm above the horizontal line 624 intersecting the upper surface of the inferior turbinate 16, 0mm to 3mm from the nasal septum 24, or one or more of any combination thereof.

[0099] In some embodiments, the subject engagement portion 106 prevents the distal end 128 from moving within or away from the discharge area 29 when the subject engagement portion 106 is fixed to the columella region 10. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end 128 of the insertable portion 107. In some embodiments, dispensing the composition 111 from the discharge area 29 increases the targeted accumulation of the composition 111 in the olfactory cleft 23. In some embodiments, the subject engagement portion 106 is fixed to the columella region 10 when the subject engagement portion 106 is in contact with the lower side of the columella, the left side of the columella, and the right side of the columella simultaneously. In some embodiments, dispensing the composition 111 from the discharge area 29 increases the targeted accumulation of the composition on a surface of the respiratory area, such as the middle turbinate 15. In some embodiments, the target region 19 is the middle nasal meatus 30, and the targeted delivery of the composition 111 to the target region 19 is increased by dispensing the composition 111 from the posterior end 110 of the dispensing element. In some embodiments, the discharge area 29 is further parallel to the subject's middle nasal turbinate 15 and not located within the middle nasal meatus 30. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and the composition is dispensed into both regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the anatomical structure of the nose. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure, and the composition is dispensed to all regions simultaneously.

[0100] In one embodiment, the present disclosure provides a device for intranasal delivery to a subject, the device being transitionable from a first configuration 100 to a second configuration 200, the device comprising a housing 101 defining a first insertable portion 100 configured to be inserted into the nasal passage 20 of the subject, and a dispensing element 110 connected to the housing 101, the dispensing element 110 emerging from the first insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200, the device transitioning from the first configuration 100 to the second configuration 200 by pressure being applied about the longitudinal axis 610 of the device, and the device operating simultaneously with the transition from the first configuration 100 to the second configuration 200. In some embodiments, simultaneous operation refers to the transition from the first configuration 100 to the second configuration 200, and the operation occurs in a single movement when pressure is applied about the longitudinal axis 610 of the device.

[0101] In some embodiments, the dispensing element 110 appears at a position on the inferior turbinate 16 of the subject in a linear vector parallel to the dorsal nasal cavity 622 from the first insertable portion 100. In some embodiments, when transitioning from the first configuration 100 to the second configuration 200, the device avoids contamination of the dispensing element by bacteria from the lower nasal cavity by housing the dispensing element in the insertable portion 107 before exposing the dispensing element 110. In some embodiments, the device avoids contamination of the dispensing element 110 by covering the dispensing element 110 within the insertable portion 107 before operation. In some embodiments, the insertable portion 107 incorporates one or more dispensing channels 125 leading to one or more dispensing ports 126 configured to deliver the composition 111 intranasally to one or more regions or partial regions of the subject's nasal passage 20. In some embodiments, the dispensing element appears in a linear vector relative to the longitudinal axis 610 of the first insertable portion 107. In some embodiments, the device is configured to allow transition from the first configuration 100 to the second configuration 200 with only one hand. In some embodiments, the dispensing element 110 emerges from the insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200. In some embodiments, the dispensing element emerges from the insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200 and pressure from a portion of the housing 101 is applied to the nasal columella region 10 of the subject. In some embodiments, the second configuration 200 moves the first portion 1020 of the housing toward the second portion 1050 of the housing around the longitudinal axis 610 of the device. In some embodiments, the device further includes a subject engagement portion 106 connected to the housing 101, the subject engagement portion 106 engaging with the columella region 10, and the subject engagement portion 106 positioning an insertable portion 107 into the subject's nasal passage 20, thereby limiting the insertion depth of the dispensing element 110 into the nasal passage 20.In some embodiments, the subject engagement portion 106, which engages with the columella region 10 of the subject, fixes the distal end of the dispensing element 110 within the dispensing area 19 of the subject's nasal cavity 11, and the dispensing area 29 is located 0mm to 30mm above a horizontal line 627 intersecting the anterior surface of the internal nasal valve 13, and 0mm to 20mm anterior to an inclined line 610 intersecting the anterior surface of the middle turbinate 15 and the posterior surface of the nasal vestibule 21, and is either 0mm to 40mm below a horizontal line 621 parallel to the inferior surface of the olfactory cleft 21, or 0mm to 20mm posterior to the dorsal surface of the nasal dorsum 622, or 10mm and 50mm above a horizontal line 623 intersecting the inferior surface of the columella, or 0mm to 30mm above a horizontal line 624 intersecting the superior surface of the inferior turbinate 16, or 0mm to 3mm from the nasal septum 24, or any combination of these. In some embodiments, the target region 19 is the middle nasal meatus 30, and the targeted delivery of the composition 111 to the target region 19 is increased by dispensing the composition 111 from the posterior end 110 of the dispensing element. In some embodiments, the discharge area 19 is further parallel to the subject's middle nasal turbinate 15 and not located within the middle nasal meatus 30. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and the composition is dispensed into both regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the anatomical structure of the nose. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure, and the composition is dispensed to all regions simultaneously.

[0102] In some embodiments, the subject engagement portion 106 prevents the distal end 128 of the dispensing element 110 from moving within or away from the dispensing area 29 when the subject engagement portion 106 is fixed to the columella region 10. In some embodiments, the dispensing area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end 126 of the insertable portion 107. In some embodiments, dispensing the composition 111 from the dispensing area 29 increases the targeted accumulation of the composition 111 on the olfactory cleft 23. In some embodiments, dispensing the composition 111 from the dispensing area 29 increases the targeted accumulation of the composition 111 on a surface of the respiratory area, such as the middle turbinate 15. In some embodiments, the subject engagement portion 106 is fixed to the columella region 10 when the subject engagement portion is in contact with the lower side surface of the columella 10, the left side surface of the columella 10, and the right side surface of the columella 10 simultaneously. In some embodiments, the device further includes a trigger connected to the housing 101 and a subject engagement portion 106, the subject engagement portion 106 engaging with the columella region 10 of the subject, and when pressure from the subject engagement portion 106 is applied to the columella region 10, the trigger activates the device to deliver the composition 111 from the dispensing element 110 to the subject.

[0103] In some embodiments, the housing 101 defines two insertable portions 107, each intended for insertion into the nasal passage 20 of a subject, and when the first insertable portion 107 is inserted into the nasal passage 20 of the subject, the first insertable portion 107 engages with the tissue within the nasal passage 20 to open or expand the internal nasal flap 13 of the subject, thereby positioning at least one of the insertable portions 107 to deliver the composition 111 to the subject, and the device further comprises an actuator for delivering the composition 111 from either or both of the insertable portions 107 when the device is activated. In some embodiments, the housing 101 defines two dispensing elements 110, each intended for delivery of the composition 111 into the nasal passage 20 of a subject, and the device further comprises an actuator for delivering the composition 111 from either or both of the dispensing elements 110 when the device is activated. In some embodiments, the device further includes a trigger release unit 104 connected to the housing 101 and the subject engagement portion 106, and when pressure from the subject engagement portion is applied to the columella region 10, the trigger release unit 104 allows the device to operate to deliver the composition 111 to the subject from the insertable portion 107. In some embodiments, the device further includes a trigger that is activatable when the trigger release unit 104 is engaged.

[0104] In some embodiments, the device avoids contamination of the dispensing element 110 by covering it within the insertable portion 107 before operation. In some embodiments, the composition 111 is dispensed from the distal end 126 of the insertable portion 107. In some embodiments, the dispensing element 110 is located in the dispensing area 29 when the device is in the second configuration 200. In some embodiments, the dispensing element 110 is located at the distal end 126 of the dispensing area 29 when the device is in the second configuration 200. In some embodiments, the device is activated simultaneously when transitioning from the first configuration 100 to the second configuration 200. In some embodiments, the dispensing element 110 appears on the inferior turbinate 16 of the subject in a straight line vector parallel to the dorsum of the nose 622 from the first insertable portion 107. In some embodiments, when transitioning from the first configuration 100 to the second configuration 200, the device avoids contamination of the dispensing element 110 by bacteria from the lower nasal cavity by housing the dispensing element 110 in the insertable portion 107 before exposing the dispensing element 110.

[0105] In some embodiments, at least one insertable portion 107 that opens or expands the internal nasal flap 13 does so by moving the superior lateral nasal cartilage 25 away from the subject's nasal septum 24. In some embodiments, at least one insertable portion 107 that opens or expands the internal nasal flap 13 does so by moving the superior lateral nasal cartilage 25 that defines the internal nasal flap 13 toward the subject's nasal dorsum 622. In some embodiments, a subject engagement portion 106 prevents the distal end 126 of the insertable portion 107 or dispensing element 110 from moving into or away from the dispensing area 29 when the subject engagement portion 106 is fixed in the columella region 10. In some embodiments, the dispensing area 29 is aligned with the olfactory cleft 23, which is defined by a linear vector between the olfactory cleft 23 and the distal end 128 of the insertable portion 107. In some embodiments, dispensing composition 111 from the discharge area 29 increases the targeted accumulation of composition 111 on the olfactory cleft 23. In some embodiments, dispensing composition 111 from the discharge area 29 increases the targeted accumulation of composition 111 on a surface of the respiratory area, such as the middle turbinate 15. In some embodiments, the subject engagement portion 106 is fixed to the columella region 10 when the subject engagement portion 106 is in contact with the lower side of the columella, the left side of the columella, and the right side of the columella simultaneously.

[0106] In some embodiments, the subject engagement portion 106 limits the insertion depth of the insertable portion 107 into the nasal passage 20. In some embodiments, the subject engagement portion 106 limits the insertion depth of the dispensing element 110 into the nasal passage 20. In some embodiments, the first and second insertable portions 107 are configured to simultaneously dispense the composition 111 from the first and second insertable portions 107. In some embodiments, the first and second insertable portions 107 are configured to sequentially dispense the composition 111 from the first and second insertable portions 107. In some embodiments, the first and second dispensing elements 110 are configured to simultaneously dispense the composition 111 from the first and second dispensing elements 110. In some embodiments, the first and second dispensing elements 110 are configured to sequentially dispense the composition 111 from the first and second dispensing elements 110. In some embodiments, the first insertable portion 107 moves along the nasal septum 24, moving the superior lateral nasal cartilage 25 away from the nasal septum 24. In some embodiments, the first and second dispensing elements 110 move along the nasal septum 24. In some embodiments, the two insertable portions 107 each contact both sides of the nasal septum 24. In some embodiments, the two dispensing elements 110 each contact both sides of the nasal septum 24. In some embodiments, the two insertable portions 107 each contact both sides of the nasal septum 24, applying pressure to the superior lateral nasal cartilage 25 in a direction away from the nasal septum 24. In some embodiments, the two insertable portions 107 each contact both sides of the nasal septum 24, applying pressure to the superior lateral nasal cartilage 25 in a direction perpendicular to the lateral axis of the nasal septum 24. In some embodiments, at least one insertable portion 107 that opens or expands the internal nasal flap 13 does so by moving the superior lateral nasal cartilage 25 that defines the internal nasal flap 13 away from the subject's nasal septum 24. In some embodiments, at least one insertable portion 107 that opens or expands the internal nasal flap 13 does so by moving the superior nasal cartilage 25 that defines the internal nasal flap 13 toward the subject's nasal dorsum 622.

[0107] Figure 6A shows exemplary embodiments of the reference Cartesian coordinate plane of the exemplary apparatus (from left to right) in front, top, and side views. Figure 6B shows exemplary embodiments of the plane of the subject. Figure 6C shows exemplary embodiments of the angular reference plane of the exemplary apparatus (from left to right) in front of the coronal plane, top of the cross-sectional plane, and rear of the sagittal plane. In some embodiments, the apparatus is configured for a subject having a coronal or front view 601, a horizontal or axial or cross-sectional plane 602, a sagittal or longitudinal section 603, a median plane 604, or a parasagittal plane 605, or a combination thereof. In some embodiments, the apparatus comprises a relative angular coordinate system of a roll 606 on the Y axis of the apparatus, a pitch 607 on the sagittal plane of the subject, and a yaw 608 on the coronal plane of the subject. In some embodiments, the apparatus is configured for a subject having a linear coordinate system x609 of the subject with respect to the inside / outside of the subject, a linear coordinate system y610 of the subject with respect to the top / bottom of the subject, and a linear coordinate system z611 of the subject with respect to the front / rear of the subject.

[0108] Figure 6D shows an exemplary embodiment of the apparatus positioned at a sagittal angle to the subject. In some embodiments, the insertable portion 107 is positioned along its y-axis relative to other anatomical structures, forming a predictable / repeatable relationship 618 with respect to the pitch angle 607 of the apparatus on the sagittal plane 603 of the subject. In some embodiments, from the predictable / repeatable relationship 618 of the apparatus relative to other anatomical structures, the pitch angle 607 can be associated with known anthropometric data. In some embodiments, the insertable portion 107 is configured to maintain a constant, repeatable angle on the sagittal plane 603, following the shape of the olfactory cleft 612 inside the dorsum of the nose and the outer surface of the nasal septum 24 in the nasal cavity 11, and this positioning is achieved when the insertable portion 107 is inserted into the nasal cavity 11 beyond the nasal vestibule 21. In some embodiments, the insertable portion 107 is configured to hold the insertable portion 107 up to the soft tissue of the upper nasal cleft 28 and guide along the soft tissue of the upper nasal cleft 28 to ensure that the insertable portion 107 remains parallel to these soft tissues. In some embodiments, the tissue of the upper nasal cleft 28 is parallel to a known anthropometric axis 613 drawn from the nasal root 619 toward the tip 127 and is used for both the nasofacial angle and the nasofacial frontal angle 614, and the anthropometric range of the known angle can be determined with respect to the position of the Y-axis 610 of the inserter on the sagittal plane 603 relative to the anatomical structure of the subject.

[0109] Figure 6E shows exemplary embodiments of the exemplary device positioned in the subject at a coronal-medial angle along a front view of the coronal plane and a top view of the cross-section, according to several embodiments. In some embodiments, the insertable portion 107 is designed to work in conjunction with the nasal cavity 11. In some embodiments, the insertable portion 107 is configured to be fixed medially to the lateral surface of the nasal septum cartilage and on both sides of the greater alar cartilage and lateral nasal cartilage, including the connective tissue of these structures. In some embodiments, the insertable portion 107 is engaged in y-axis rotation 616 along the device and engaged medially / laterally 604.

[0110] Figure 6F shows exemplary embodiments of the exemplary device positioned at a certain depth in the subject, along a coronal front view and a sagittal side view. In some embodiments, the insertable portion 107 is positioned and interlocked within the nasal cavity 11 to form a predictable / repeatable depth reference 618. In some embodiments, the insertable portion 107 is designed to be fixed to the columella 10, its supporting structures, e.g., the nasal spine and nasal septum cartilage, to provide a hard stop. In some embodiments, the columella 10 provides a depth reference 617 along the y-axis of the device so that the outlet 126 of the insertable portion 107, e.g., along the cannula, is positioned at a desired known distance 618 from the target anatomical structure 19.

[0111] Figure 6G shows an exemplary embodiment of an exemplary apparatus for delivery to a target region 19 of a subject, along a sagittal side view. In some embodiments, to form a desired trajectory of administration, the insertable portion 107 into the anatomical structure of the subject, the known depth 618 of the outlet, e.g., the dispensing port 126 along one or more cannulas 110, the orthogonal coordinates, and the angular reference reference may be positioned in the desired location, and relative fluid profiles and velocities may be selected to repeatedly and accurately deliver the composition 111 to the desired location, e.g., the target discharge point 19. In some embodiments, a coherent jet may be selected along the y-axis 610 of the apparatus to form a substantially unhindered flow to the target discharge point 19, e.g., the olfactory cleft 23, the middle nasal meatus 30, or other nasal anatomical structure, or any combination thereof. In some embodiments, a cohesive spray may be selected along the z-axis 611 of the apparatus to form a substantially unhindered flow to the nasal turbinates, for example, the superior nasal turbinate 14, the middle nasal turbinate 15, or the inferior nasal turbinate 16, or a combination thereof.

[0112] In some embodiments, the target region 19 is the middle nasal meatus 30, and the targeted delivery of the composition 111 to the target region 19 is increased by dispensing the composition 111 from the posterior end 110 of the dispensing element 110. In some embodiments, the discharge area 29 is further parallel to the subject's middle nasal turbinate 15 and not located within the middle nasal meatus 30. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end 128 of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and the composition 111 is dispensed into both regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the anatomical structure of the nose. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the anatomical structure of the nose, and the composition 111 is dispensed into all regions simultaneously.

[0113] Figure 6H shows an exemplary embodiment of an exemplary device for targeting the respiratory area of ​​a subject, along a sagittal side view. In some embodiments, to form a desired trajectory of administration, the insertable portion 107 into the anatomical structure of the subject, the known depth 118 of the dispensing port 126 along the outlet, e.g., one or more cannulas 110, the Cartesian coordinates, and the angular reference reference may be positioned in the desired location, and relative fluid profiles and velocities may be selected to repeatedly and accurately deliver the composition 111 to a desired location, e.g., a target discharge point 19. In some embodiments, along the y-axis 610 of the device, a cohesive spray as a whole may be selected to form a substantially unhindered flow to the target discharge point 19, e.g., delivery to the olfactory cleft 23, the middle nasal meatus 30, or the nasal turbinates. In some embodiments, along the z-axis 611 of the device, a cohesive spray as a whole may be selected to form a substantially unhindered flow to the nasal turbinates, e.g., the superior nasal turbinate 14, the middle nasal turbinate 15, or the inferior nasal turbinate 16, or a combination thereof.

[0114] In one embodiment, the present disclosure provides a device for intranasal delivery to a subject, the device comprising a housing 101 having an insertable portion 107 having a distal end 128 and a proximal end 127, and a subject engagement portion 106 that engages with the columella region 10 of the subject to fix the distal end 128 of the insertable portion 107 within a discharge area 29 of the subject's nasal passage 20. In some embodiments, the discharge area 29 is located 0 mm to 30 mm above a horizontal line 627 intersecting the anterior surface of the internal nasal valve 13, and 0 mm to 20 mm anterior to an inclined line 610 intersecting the anterior surface of the middle turbinate 15 and the posterior surface of the nasal vestibule 21.

[0115] In some embodiments, the discharge area 29 is further located 0 to 40 mm below a horizontal line 621 parallel to the inferior surface of the olfactory cleft 23, 0 to 20 mm posterior to the dorsal nasal area 622, 10 mm and 50 mm above a horizontal line 617 intersecting the inferior surface of the columella 10, 0 to 30 mm above a horizontal line 624 intersecting the superior surface of the inferior turbinate 16, 0 to 3 mm from the nasal septum 24, or any combination thereof.

[0116] In some embodiments, the dispensing area 29 is an irregular quadrilateral or irregular quadrilateral comprising (i) a lower side surface 29A which is a 10-25 mm line extending posteriorly and horizontally from the anterior surface of the internal nasal valve 13, (ii) an anterior side surface 29B which is a 10-35 mm line extending upward from the anterior surface of the internal nasal valve 13 and parallel to the dorsal nasal cavity 622, (iii) an upper side surface 29C which is a 10-25 mm line extending posteriorly and horizontally from a point in the dorsal nasal cavity 622 located 0-10 mm below the lower surface of the olfactory cleft 23, and (iv) a posterior line 29D which is a 10-35 mm line extending vertically along a plane intersecting the anterior surface of the middle turbinate 15. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof, and the targeted delivery of the composition 111 to the target region is increased by dispensing the composition 111 from the anterior end 110 of the dispensing element 110. In some embodiments, the target region 19 is the middle nasal meatus 30, and dispensing the composition 111 from the posterior end 110 of the dispensing element increases the targeted delivery of the composition 111 to the target region 19. In some embodiments, the discharge area 29 is further parallel to the subject's middle nasal turbinate 15 and not located within the middle nasal meatus 30. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the middle nasal meatus 30, and dispensing the composition 111 from the posterior end 110 of the dispensing element increases the targeted delivery of the composition 111 to the target region 19. In some embodiments, the discharge area 29 is further parallel to the subject's middle nasal turbinate 15 and not located within the middle nasal meatus 30. In some embodiments, the dispensing area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the middle nasal meatus 30, and dispensing the composition 111 from the posterior end 110 of the dispensing element 110 increases the targeted delivery of the composition 111 to the target region 19.In some embodiments, the dispensing area 29 is further parallel to the subject's middle turbinate 15 and not within the middle meatus 30. In some embodiments, the dispensing area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle meatus 30. In some embodiments, the target region 19 is the olfactory region 23 and the middle meatus 30, and the composition 111 is dispensed into both regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle meatus 30, as well as other regions of the nasal anatomical structure. In some embodiments, the target region 19 is the olfactory region 23 and the middle meatus 30, as well as other regions of the nasal anatomical structure, and the composition 111 is dispensed into all regions simultaneously.

[0117] In some embodiments, the device further includes an actuator for delivering composition 111 from one or both insertable portions 107 when the device is activated. In some embodiments, the housing 101 defines two dispensing elements 110, each for delivering composition into the subject's nasal passage 20, and the device further includes an actuator for delivering composition 111 from either or both insertable portions 107 when the device is activated. In some embodiments, the dispensing elements 110 are configured to dispense composition 111 into a single nasal passage 20 of the subject. In some embodiments, at least one insertable portion 107 fits proximal to the junction 27 of the subject's nasal septum and lateral nasal cartilage. In some embodiments, the dispensing elements 110 fit proximal to the subject's nasal septum 24. In some embodiments, the dispensing elements 110 comprise one or more cannulas. In some embodiments, the dispensing elements 110 comprise one or more cannulas fixed to the insertable portion 107. In some embodiments, the dispensing element 110 comprises one or more cannulas that emerge from the insertable portion 107 when the device is moved from a first position 100 to a second position 200. In some embodiments, the insertable portion 107 comprises the dispensing element 110. In some embodiments, the insertable portion 107 is the dispensing element 110. In some embodiments, one or more dispensing elements 110 comprises one or more cannulas, and one or more cannulas comprises one or more dispensing ports 126. In some embodiments, the dispensing port 126 comprises one discharge port at its distal end. In some embodiments, the dispensing port 126 comprises one or more discharge ports 126 along its length. In some embodiments, the dispensing port 126 comprises one discharge port at its distal end, one or more discharge ports along its length, or a combination of both.

[0118] In some embodiments, the dispensing port 126 is directed towards different target compartments within the nasal passage 20. In some embodiments, the device discharges fluid from above the internal nasal valve 13. In some embodiments, the device discharges fluid from at least approximately 15–20 mm above the columella 10. In some embodiments, the device discharges fluid from above the compartment of the primary high-speed / low-pressure airflow. In some embodiments, the device discharges fluid from at least 25–30 mm above the columella region 10. In some embodiments, the dispensing port 126 is equipped with a sprayer. In some embodiments, one or more dispensing elements are approximately 5–40 mm in length. In some embodiments, one or more dispensing elements 110 protrude approximately 5–40 mm from the housing. In some embodiments, at least one dispensing element 110 is at least partially housed within the housing 101. In some embodiments, at least one dispensing element 110 protrudes outward from the housing 101 when in the second position 200. In some embodiments, one or more dispensing elements 110 include a plurality of outlets 126. In some embodiments, one or more dispensing elements 110 include a plurality of fluid channels 125. In some embodiments, one of the plurality of fluid channels 125 is configured to dispense a gas 111. In some embodiments, one of the plurality of fluid channels 125 is configured to dispense a gas 111 after the composition 111 has been dispensed by another fluid channel 125.

[0119] In some embodiments, the first and / or second insertable portion 107 limits the sagittal angle or anterior-posterior inclination angle 611 of the device. In some embodiments, the first and / or second insertable portion 107 limits the coronal angle or medial-outward inclination angle 604 of the device. In some embodiments, the first and / or second insertable portion 107 limits the coronal angle or medial-outward inclination angle 604 of the device. In some embodiments, the insertable portion 107 is flexible. In some embodiments, one or more dispensing elements 110 are flexible. In some embodiments, the first and / or second insertable portion 107 is torsionally flexible. In some embodiments, the first and / or second insertable portion 107 is torsionally flexible to adjust to the angle of the anterior surface of the internal nasal flap 13. In some embodiments, the first and / or second insertable portion 107 extends proximal to the user's nasal septum 24. In some embodiments, at least one insertable portion 107 has flexibility characteristics of inward-outward flexibility 1103 along a width 1103 perpendicular to the length 1100 of the insertable portion, lack of front-rear flexibility 1109 around the length 1100 of the insertable portion 107, vertical flexibility 1110 around a rotation axis perpendicular to the length 1100 of the insertable portion 107, or a combination thereof. In some embodiments, at least one dispensing element 110 has flexibility characteristics of inward-outward flexibility 1108 along a width 1103 perpendicular to the length 1100 of the insertable portion 107, lack of front-rear flexibility 1109 around the length 1100 of the insertable portion 107, or vertical flexibility 1110 around a rotation axis perpendicular to the length 1100 of the insertable portion 107.

[0120] In some embodiments, the middle turbinate 15 is at risk of being misdirected and descended into the nasal passage. In some embodiments, the device dispenses the composition 111 to the anterior of the middle turbinate 15, and the pathway to the olfactory cleft up to the anterior 18 of the middle turbinate 15 is unobstructed and more linear. In some embodiments, the device further includes an actuation mechanism that moves the housing 101 from a second position 200 to a first position 100, retracting at least one dispensing element 110 following the operation of the device. In some embodiments, one or more cannulas 110 include a first tubular portion surrounding the cannula. In some embodiments, the first tubular portion remains within the first insertable portion 107 when the device is actuated to the second position 200.

[0121] Figures 8A and 8B show exemplary embodiments of the anatomical structure of the subject's nasal cavity 11. In some embodiments, the anatomical structure of the subject's nasal cavity 11 includes an olfactory cleft 23. In some embodiments, the anatomical structure of the subject's nasal cavity 11 includes a subnasal region 35. In some embodiments, the anatomical structure of the subject's nasal cavity 11 includes an internal nasal flap 13. In some embodiments, the anatomical structure of the subject's nasal cavity 11 includes a scenic point 34.

[0122] Figure 8C shows the anatomical structure of the nasal cavity 11 and the configuration of an exemplary device. Figure 8D shows the anatomical structure of the nasal cavity and the configuration of an exemplary device for opening or dilating an exemplary internal nasal flap. In some embodiments, the device positions a drug dispensing tip 127 in a less conspicuous channel formed by the nasal bone 33, where odorants or pheromones safely travel to the olfactory cortex 23. In some embodiments, the dispensing tip 127 avoids thicker, softer tissues that are less predictable and more sensitive. In some embodiments, the insertable portion 107, when inserted into the subject's nasal passage 20, opens or dilates the internal nasal flap 13 by pushing up the superior lateral nasal cartilage and surrounding tissues, separating them from the nasal septum 24 625. In some embodiments, the insertable portion 107, when inserted into the subject's nasal passage 20, is proximal to the nasal septum 24. In some embodiments, the subject engagement portion 106 prevents the distal end 131 from moving within or away from the discharge area 29 when the subject engagement portion 106 is fixed to the columella region 10. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end 128 of the insertable portion 107.

[0123] In some embodiments, dispensing composition 111 from the discharge area 29 increases the targeted accumulation of composition 111 in the olfactory cleft 23. In some embodiments, dispensing composition 111 from the discharge area 29 increases the targeted accumulation of composition 111 on a surface of the respiratory area, such as the middle turbinate 15.

[0124] In some embodiments, dispensing the composition 111 from the dispensing area 29 increases the targeted accumulation of the composition in two or more regions or sub-regions of the nasal passage 20. In some embodiments, the subject engagement portion 106 is fixed to the columella region 10 when the subject engagement portion 106 is in contact with the lower side of the columella 10, the left side of the columella 10, and the right side of the columella 10 simultaneously.

[0125] Figure 10 shows perspective, front, and side views of exemplary embodiments of an exemplary nasal saddle in a first configuration, according to several embodiments. In some embodiments, the device comprises an ear portion 107 with a length 1100 from the base 127 of the "U-shaped" saddle 121 to the distal surface 128 of the ear portion 107. In some embodiments, the length 1100 of the ear portion 107 from the base 127 of the "U-shaped" saddle 121 to the distal surface 128 of the ear portion 107 is about 20 mm. In some embodiments, the length 1100 of the ear portion 107 from the base 127 of the "U-shaped" saddle 121 to the distal surface 128 of the ear portion 107 is about 1 mm to about 20 mm. In some embodiments, the length 1100 of the ear portion 107 from the base 127 of the "U-shaped" saddle 121 to the distal surface 128 of the ear portion 107 is about 1 mm to about 25 mm. In some embodiments, the device has a depth 1101 of the distal surface 128 of the ear portion 107 from the base 127 of the "U" shaped saddle 121. In some embodiments, the device has a base depth 1101 of the "U" shaped saddle 121, which is about 17 mm. In some embodiments, the device has a base depth 1101 of the "U" shaped saddle 121 of about 1 to about 17 mm. In some embodiments, the device has a base depth 1101 of the "U" shaped saddle 121 of about 1 to about 22 mm. In some embodiments, the device has a radius 1102 of the "U" shaped saddle 121. In some embodiments, the radius 1102 of the "U" shaped saddle 121 is about 5 mm. In some embodiments, the radius 1102 of the "U" shaped saddle 121 is about 1 mm to about 5 mm. In some embodiments, the radius 1102 of the "U-shaped" saddle 121 is approximately 1 mm to approximately 10 mm. In some embodiments, the device has a width 1103 of the ear portion 107 at the vertical midpoint. In some embodiments, the width 1103 of the ear portion 107 at the vertical midpoint is approximately 3.5 mm. In some embodiments, the width 1103 of the ear portion 107 at the vertical midpoint is approximately 1 mm to approximately 3.5 mm. In some embodiments, the width 1103 of the ear portion 107 at the vertical midpoint is approximately 1 mm to approximately 7 mm. In some embodiments, the device has a depth 1100 of the ear portion 107 at the vertical midpoint.In some embodiments, the depth 1100 of the ear portion 107 at the vertical midpoint is approximately 11 mm. In some embodiments, the depth 1100 of the ear portion 107 at the vertical midpoint is approximately 1 mm to approximately 11 mm. In some embodiments, the depth 1100 of the ear portion 107 at the vertical midpoint is approximately 1 mm to approximately 16 mm. In some embodiments, the device has a width 1104 of the ear portion 107 at the vertical midpoint. In some embodiments, the width 1104 of the ear portion 107 at the vertical midpoint is approximately 11 mm. In some embodiments, the width 1104 of the ear portion 107 at the vertical midpoint is approximately 1 mm to approximately 11 mm. In some embodiments, the width 1104 of the ear portion 107 at the vertical midpoint is approximately 1 mm to approximately 16 mm. In some embodiments, the device has a radius 1105 of the distal surface 128 of the ear portion 107 (along the depth). In some embodiments, the radius 1105 of the distal surface of the ear portion 107 (along the depth) is approximately 5.5 mm. In some embodiments, the radius 1105 of the distal surface of the ear portion 107 (along the depth) is approximately 1 mm to approximately 5.5 mm. In some embodiments, the radius 1105 of the distal surface of the ear portion 107 (along the depth) is approximately 1 mm to approximately 10 mm. In some embodiments, the device has a radius 1106 of the distal edge of the ear portion 107 (along the width). In some embodiments, the device has a radius 1106 of the distal edge of the ear portion 107 (along the width), which is approximately 8.5 mm. In some embodiments, the device has a radius 1106 of the distal edge of the ear portion 107 (along the width), which is approximately 1 mm to 8.5 mm. In some embodiments, the device has a radius 1106 of the distal edge of the ear portion 107 (along the width), which is approximately 1 mm to 13.5 mm. In some embodiments, the device has a width 1107 between the ear portions 107 at the vertical midpoint. In some embodiments, the width 1107 between the ear portions 107 at the vertical midpoint is about 10 mm. In some embodiments, the width 1107 between the ear portions 107 at the vertical midpoint is about 1 mm to about 10 mm. In some embodiments, the width 1107 between the ear portions 107 at the vertical midpoint is about 1 mm to about 15 mm.

[0126] In some embodiments, the insertable portion 107 is configured to fit wedge-shaped into the nasal flap 13 where the nasal septum 24 contacts the superior lateral nasal cartilage 25. In some embodiments, the anterior surface of the insertable portion 107 is configured to fit into the narrow anterior surface of the internal nasal flap 13. In some embodiments, the anterior surface of the insertable portion 107 is configured to fit into an opening with an angle of 9 to 15 degrees. In some embodiments, the angle of the insertable portion may be determined with respect to the axis of the nasal dorsum, with a fulcrum at the midpoint where the subject engagement portion touches the columella. Rotation of the device around this fulcrum, such that the tip of the insertable portion moves away from the axis of the nasal dorsum, may increase this angle, which may be necessary to target intranasal regions or subregions such as the olfactory cleft with high precision. In some embodiments, this angle between the axis of the device and the axis of the nasal dorsum is about 9 to 15 degrees. In some embodiments, the angle between the axis of the device and the axis of the nasal dorsum is about 7 to 17 degrees. In some embodiments, the angle between the axis of the device and the axis of the nasal dorsum is approximately 0 to 45 degrees. In some embodiments, the insertable portion 107 is configured to fit into the narrow anterior surface of the internal nasal valve 13 when fixed around the columella region 10. In some embodiments, the insertable portion 107 is configured to fit into an opening with an angle of 9 to 15 degrees when fixed around the columella region 10. In some embodiments, the insertable portion 107 is configured to be inserted into the wedge-shaped internal nasal valve 13 of the subject. In some embodiments, the insertable portion 107 is tapered around the distal end of the insertable portion 128 and is configured to be inserted into the wedge-shaped internal nasal valve 13 of the subject. In some embodiments, the insertable portion 107 has a rounded tapered edge 130 around the distal end 128 of the insertable portion 128 and is configured to be inserted into the wedge-shaped internal nasal valve 13 of the subject. In some embodiments, the insertable portion 107 includes a tip portion having a width 1104 corresponding to the average diameter of the internal nasal valve 13. In some embodiments, the insertable portion 107 includes a flat surface on the side of the insertable portion 107 that contacts the nasal septum 24.In some embodiments, the insertable portion 107 has a rounded surface on the side of the insertable portion opposite the nasal septum 24. In some embodiments, the insertable portion 107 has a width 1103 of up to 3 mm. In some embodiments, the insertable portion 107 has a width 1103 of up to 3.5 mm. In some embodiments, the insertable portion 107 has a width 1103 of up to 5 mm. In some embodiments, one or both insertable portions 107 have a distal end 128, and the dispensing element 110 emerges from the distal end 128 of the insertable portion 107. In some embodiments, the distal end 128 of the insertable portion 107 is configured to be inserted into the nasal passage 20 of the subject. In some embodiments, the emergence of the dispensing element 110 from the first insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200 includes the dispensing element 110 extending from the first insertable portion 107. In some embodiments, the subject engagement portion 106 engages with both the right and left sides of the columella region 10. In some embodiments, the subject engagement portion 106 has a concave shape. In some embodiments, the subject engagement portion 106 has a U-shape. In some embodiments, the subject engagement portion 106 has a saddle shape. In some embodiments, the subject engagement portion 106 has a concave elliptical shape. In some embodiments, the subject engagement portion 106 has a trench with a rounded bottom or rounded edge. In some embodiments, the subject engagement portion 106 centers two insertable portions 107 around the subject's columella 10. In some embodiments, the subject engagement portion 106 is a positioning element that aligns at least one of the insertable portions 107, the dispensing element 110, or the housing 101 with respect to the user's nasal passage 20. In some embodiments, the device targets the olfactory cleft 23 or a portion thereof, and the subject engagement portion 106 aligns the dispensing element 110 with the subject's olfactory cleft 23. In some embodiments, the insertable portion 107 includes a single dispensing channel 125 leading to a dispensing port 126 located on the distal surface 128 of the insertable portion. In some embodiments, the insertable portion 107 includes a single dispensing channel 125 leading to a dispensing port 126 located along the length 1100 of the insertable portion 107.

[0127] In some embodiments, the insertable portion 107 comprises two or more dispensing channels 125 leading to two or more dispensing ports 126 arranged on various surfaces of the insertable portion 107. In some embodiments, the insertable portion 107 comprises a single dispensing channel 125 leading to a dispensing port 126 arranged to deliver the composition 111 to the olfactory cleft 23. In some embodiments, the insertable portion 107 comprises a single dispensing channel 125 leading to a dispensing port 126 arranged to deliver the composition 111 to a surface of the respiratory area, such as the middle nasal concha 15. In some embodiments, the insertable portion 107 comprises two or more dispensing channels 125 leading to two or more dispensing ports 126 arranged to deliver the composition 111 to one or more regions or subregions of the nasal passage 20, such as the olfactory cleft 23 and / or the middle nasal concha 15. In some embodiments, the first insertable portion 107 has a single dispensing channel 125 leading to a dispensing port 126 located on the distal surface 128 of the insertable portion 107, and the second insertable portion 107 has a single dispensing channel 125 leading to a dispensing port 126 located along the length 1100 of the insertable portion 107. In some embodiments, the first insertable portion 107 has a single dispensing channel 125 leading to a dispensing port 126 located on the distal surface 128 of the insertable portion 107, and the second insertable portion 107 has two or more dispensing channels 125 leading to two or more dispensing ports 126 located on various surfaces of the insertable portion 107. In some embodiments, the composition 111 is dispensed simultaneously from two insertable portions 107.

[0128] In some embodiments, composition 111 is dispensed sequentially from two insertable portions 107. In some embodiments, composition 111 is dispensed simultaneously from two dispensing elements 110. In some embodiments, composition 111 is dispensed sequentially from two dispensing elements 110. In some embodiments, a trigger and / or subject engagement portion 106 activates the device when pressed against the subject's columella 110, dispensing composition 111 from one cannula 110. In some embodiments, the trigger and / or subject engagement portion 106 includes an actuator that dispenses composition 111 from the storage portion when the housing 101 is moved from a first position 100 to a second position 200. In some embodiments, the subject engagement portion 106 engages with the subject's columella 10 to limit the insertion depth of the first insertable portion 107 and the second insertable portion 107 into the subject's nasal passage 20. In some embodiments, the subject engagement portion 106 engages with the subject's columella 10 to limit the insertion depth of the first and second dispensing elements 110 into the subject's nasal passage 20. In some embodiments, the subject engagement portion 106 is concave and engages with the subject's columella 10 around multiple sides of the columella 10.

[0129] In some embodiments, the trigger includes a saddle-shaped portion 121 for receiving the subject's columella 10. In some embodiments, the saddle-shaped portion 121 positions a first insertable portion 107 and a second insertable portion 107 to align one or more dispensing elements 110 with a target area, e.g., the olfactory cleft 23, the middle nasal meatus 30, or other nasal anatomical structure when the device is activated. In some embodiments, the saddle portion 121, the subject engagement portion 106, or the positioning trigger has a shape that conforms to the anatomical structure of the subject's columella 10 and aligns one or more dispensing elements 110 with the subject's olfactory cleft 23. In some embodiments, one or more dispensing elements 110 are positioned along an unobstructed path to the subject's olfactory cleft 23 when the subject engagement portion 106 is engaged with the subject's columella 10. In some embodiments, one or more dispensing elements 110 are positioned along an unobstructed path to the subject's middle nasal meatus 30 when the subject engagement portion 106 is engaged with the subject's columella 10. In some embodiments, one or more dispensing elements 110 are positioned along an unobstructed path to the subject's middle turbinate 15 when the subject engagement portion 106 is engaged with the subject's columella 10.

[0130] In some embodiments, the dispensing element 110 is positioned 0 mm to about 40 mm from the lower surface of the subject's olfactory cleft 23 when the subject engagement portion 106 is engaged with the subject's columella 10. In some embodiments, the dispensing element 110 is positioned 0 mm to about 40 mm from the subject's middle nasal meatus 30 when the subject engagement portion 106 is engaged with the subject's columella 10. In some embodiments, the dispensing element 110 is positioned 0 mm to about 40 mm from the subject's middle turbinate 15 when the subject engagement portion 106 is engaged with the subject's columella 10. In some embodiments, the saddle 121 has a recess for the subject's columella 10.

[0131] In some embodiments, the target region 19 is the middle nasal meatus 30, and the targeted delivery of the composition 111 to the target region 19 is increased by dispensing the composition 111 from the posterior end 110 of the dispensing element 110. In some embodiments, the discharge area 29 is further parallel to the subject's middle nasal turbinate 15 and not located within the middle nasal meatus 30. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end 128 of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and the composition is dispensed into both regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and the composition 111 is dispensed into both regions sequentially. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure, and the composition is dispensed to all regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure, and the composition 111 is dispensed to all regions sequentially.

[0132] In some embodiments, the subject engagement portion 106 has dimensions of approximately 20 mm x approximately 17 mm.

[0133] In some embodiments, the saddle-shaped portion 121 engages with the columella 10 of the subject, centering on multiple sides of the columella 10. In some embodiments, the subject engagement portion 106 activates the device by pressing down a trigger 104 connected to the subject engagement portion 106. In some embodiments, the first and / or second insertable portion 107 restricts the sagittal angle 607 or the anterior-posterior tilt angle 611 of the device. In some embodiments, the first and / or second insertable portion 107 restricts the coronal angle 608 or the in-and-outward tilt angle 604 of the device. In some embodiments, the first and / or second insertable portion 107 restricts the sagittal angle 607 or the anterior-posterior tilt angle 611 of the device. In some embodiments, the first and / or second insertable portion 107 and the subject engagement portion 106 limit the sagittal plane angle 607, the anterior-posterior tilt angle 611 of the apparatus, the coronal plane angle 608 or in-exterior tilt angle 604 of the apparatus, the sagittal plane angle 607 or the anterior-posterior tilt angle 611 of the apparatus, or any combination thereof.

[0134] In some embodiments, the internal nasal flap 13 of the subject is enclosed medially by the nasal septum 24, laterally by the caudal portion of the superior lateral nasal cartilage 25, and inferiorly by the upper part of the inferior turbinate 16. In some embodiments, the first and / or second insertable portion 107 moves the superior lateral nasal cartilage 25, thereby opening or widening at least a portion of the internal nasal flap 13 of the subject. In some embodiments, the first and / or second insertable portion 107 has torsional flexibility. In some embodiments, the first and / or second insertable portion 107 has torsional flexibility to adjust to the anterior surface or wedge angle of the internal nasal valve 13. In some embodiments, the first and / or second insertable portion 107 extends proximal to the user's nasal septum 24. In some embodiments, one or more dispensing elements 110 extend outward from or appear from the insertable portion 107 when the device is activated. In some embodiments, two dispensing elements 110 appear outward from the insertable portion 107 when the device is activated. In some embodiments, the device dispenses composition 111 from one or more dispensing elements 110 when the device is activated. In some embodiments, the housing 101 further comprises a second insertable portion 107 for insertion into the user's second nasal passage 20. In some embodiments, the first and / or second insertable portion 107 moves tissue within the nasal passage 20 to define a pathway between one or more dispensing elements 110 and the delivery site. In some embodiments, the first and / or second insertable portion 107 moves tissue within the nasal passage 20 to open or widen the internal nasal flap 13 of the subject. In some embodiments, the dispensing elements 110 are housed within the insertable portion 107. In some embodiments, the device further comprises a second dispensing element 110, the first dispensing element 110 being housed within the first insertable portion 107, and the second dispensing element 110 being housed within the second insertable portion 107. In some embodiments, the ends of the dispensing elements have the same spread as the ends of the insertable portion. In some embodiments, the dispensing element is entirely contained within the insertable portion when the device is activated or when the housing is moved from a first position to a second position (see Figures 2G to 2J). In some embodiments, the end of the dispensing element has the same spread as the end of the insertable portion when the device is activated or when the housing is moved from a first position to a second position (see Figures 2G to 2J).In some embodiments, the dispensing element does not extend or appear from the insertable portion when the device is activated or when the housing is moved from a first position to a second position (see Figures 2G to 2J). In some embodiments, the device may further include a trigger or trigger button 104 connected to the subject engagement portion 106 by a columella saddle, and the device may be activated when pressure is applied to the trigger button 104 by the subject's columella (see Figures 2G to 2H). In some embodiments, the dispensing element comprises a cannula.

[0135] In some embodiments, at least one insertable portion 107 limits the sagittal plane angle 607 or the anterior-posterior tilt angle of the device. In some embodiments, at least one insertable portion 107 limits the coronal plane angle or the medial-outward tilt angle 604 of the device. In some embodiments, at least one insertable portion 107 limits the coronal plane angle or the medial-outward tilt angle 604 of the device. In some embodiments, at least one insertable portion 107 is flexible. In some embodiments, at least one insertable portion 107 is torsionally flexible. In some embodiments, at least one insertable portion 107 is torsionally flexible to adjust to the angle of the anterior surface of the internal nasal flap 13. In some embodiments, at least one insertable portion 107 extends proximal to the user's nasal septum 24. In some embodiments, at least one insertable portion 107 has flexibility characteristics of inward-outward flexibility 1108 along a width 1103 perpendicular to the length 1100 of the insertable portion, lack of front-rear flexibility 1109 around the length 1100 of the insertable portion 107, vertical flexibility 1110 around a rotation axis perpendicular to the length 1100 of the insertable portion, or a combination thereof.

[0136] In some embodiments, the first and / or second insertable portion 107 has dimensions of approximately 20 mm × approximately 3.5 mm.

[0137] In some embodiments, the first and / or second insertable portion 107 is a shape 130 including a wedge shape, a paddle shape, a cylindrical shape, a bulbous shape, a conical shape, a spherical shape, a hemispherical shape, or any combination thereof. In some embodiments, the transition of the device from the first configuration 100 to the second configuration 200 is actuated by a subject engagement portion 106, thereby causing the dispensing element 110 to emerge from the first insertable portion 107. In some embodiments, the transition of the device from the first configuration 100 to the second configuration 200 is actuated by an actuator, thereby causing the dispensing element 110 to emerge from the first insertable portion 107. In some embodiments, the first or second insertable portion 107 moves the nasal cartilage and / or tissue within the nasal passage 20 when the device is inserted in the first configuration 100. In some embodiments, the first or second insertable portion 107 fits proximal to the junction 27 of the nasal septum and lateral nasal cartilage of the subject when the device is in the second configuration 200.

[0138] In some embodiments, the housing 101 is movable from a first position 100 to a second position 200. In some embodiments, the housing 101 comprises a proximal portion 1020 and a distal portion 1050, the distal portion 1050 being pushed against the proximal portion 1020 when the housing 101 is moved from the first configuration 100 to the second configuration 200 to activate the device. In some embodiments, the proximal portion 1020 is inserted into the distal portion 1050 when the housing 101 is moved from the first configuration 100 to the second configuration 200. In some embodiments, when moving from the first configuration 100 to the second configuration 200, the distal portion 103 moves relative to the subject, while the proximal portion 1020 remains stationary relative to the subject, and the proximal portion 1020 is connected to the dispensing element 110. In some embodiments, when transitioning from the first configuration 100 to the second configuration 1020, the dispensing element 110 appears outward from the proximal portion 1020.

[0139] In some embodiments, the columella region 10 includes the subnasal point, subnasion, anterior nasal spine 32, or any combination thereof. In some embodiments, the insertable portion 107 has flexibility characteristics of inward-outward flexibility 1108 along a width 1103 perpendicular to the length 1100 of the insertable portion 107, lack of anterior-posterior flexibility 1109 around the length 1100 of the insertable portion, or vertical flexibility 1110 around a rotation axis perpendicular to the length 1100 of the insertable portion 107. In some embodiments, the dispensing element 110 is configured to dispense the composition 111 into a single nasal passage 20 of the subject. In some embodiments, the dispensing element 110 fits proximal to the junction 27 of the nasal septum and lateral nasal cartilage of the subject. In some embodiments, the dispensing element 110 fits proximal to the nasal septum 24 of the subject. In some embodiments, the dispensing element 110 comprises a dispensing port 126. In some embodiments, the dispensing element 110 includes a cannula or catheter.

[0140] In some embodiments, one or more insertable portions 107 are provided with a plurality of dispensing ports 126. In some embodiments, one or more dispensing elements 110 are provided with dispensing ports 126. In some embodiments, a dispensing port 126 has one dispensing port 126 at its distal end 131, or has one or more dispensing ports 126 along its length, or a combination of both. In some embodiments, the dispensing ports 126 are directed to different target compartments within the nasal passage 20. In some embodiments, a dispensing port 126 is provided with a sprayer. In some embodiments, a dispensing element 110 is provided with a sprayer. In some embodiments, one or more dispensing elements 110 are 20 mm to 50 mm in length. In some embodiments, one or more dispensing elements 110 appear from 0 mm to 40 mm from the insertable portion 107. In some embodiments, one or more dispensing elements 110 are provided with a plurality of dispensing ports 126. In some embodiments, one or more dispensing elements 110 are provided with a plurality of fluid channels 125. In some embodiments, one or more dispensing elements 110 are provided with a dispensing port 126. In some embodiments, one of a plurality of fluid channels 125 is configured to dispense gas. In some embodiments, one of a plurality of fluid channels 125 is configured to dispense gas after the composition 111 has been dispensed by another fluid channel 125. In some embodiments, the device is configured to target a target region 19, for example, the olfactory cleft 23 or a portion thereof. In some embodiments, the target region 19 is the middle nasal meatus 30, and dispensing the composition 111 from the posterior end 110 of the dispensing element increases the targeted delivery of the composition 111 to the target region 19. In some embodiments, the discharge area 29 is further parallel to the subject's middle nasal conchae 15 and not located within the middle nasal meatus 30. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30.In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and the composition is dispensed into both regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure, and the composition is dispensed into all regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure, and the composition is dispensed into all regions sequentially.

[0141] In some embodiments, one or more dispensing elements 110 include a first tubular portion surrounding the dispensing elements 110. In some embodiments, the first tubular portion remains within the first insertable portion 107 when the device is operated to a second position 200. In some embodiments, the insertable portion 107 is flexible. In some embodiments, one or more dispensing elements 110 are flexible. In some embodiments, the device further includes a storage unit fluidly connected to one or more insertable portions 107. In some embodiments, the device further includes a storage unit fluidly connected to one or more dispensing elements 110.

[0142] In some embodiments, compound 111 comprises a therapeutic agent. In some embodiments, compound 111 comprises a sampling agent. In some embodiments, compound 111 comprises a liquid, powder, or gas, or a combination thereof. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target compartment 19 is one or both of the respiratory compartments, or a portion thereof. In some embodiments, the target region 19 is the middle nasal meatus 30, and dispensing the composition 111 from the posterior end 110 of the dispensing element increases the targeted delivery of the composition 111 to the target region 19. In some embodiments, the discharge region 29 is further parallel to the subject's middle nasal turbinate 15 and not located within the middle nasal meatus 30. In some embodiments, the discharge region 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end 128 of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and the composition 111 is dispensed into both regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the anatomical structure of the nose. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the anatomical structure of the nose, and the composition is dispensed into all regions simultaneously.

[0143] In some embodiments, the actuator is spring-loaded. In some embodiments, the actuator dispenses approximately equal amounts of fluid 111 from each insertable portion 107. In some embodiments, the actuator dispenses approximately equal amounts of fluid from each dispensing element 110. In some embodiments, the actuator dispenses fluid from only one insertable portion 107. In some embodiments, the actuator dispenses fluid from only one dispensing element 110. In some embodiments, one or more dispensing elements 110 are housed together with sub-tubular members 324. In some embodiments, the storage unit is removable. In some embodiments, the storage unit is contained within a removable cartridge. In some embodiments, the placement trigger activates the device by pressing down a switch 104 located beneath the placement trigger.

[0144] In some embodiments, the device comprises a central cylinder fluidly connected to one or more insertable portions 107, the central cylinder being inserted into a storage section when the device is activated. In some embodiments, the device further comprises a central cylinder fluidly connected to one or more dispensing elements 110, the central cylinder being inserted into a storage section when the device is activated. In some embodiments, the device comprises a central cylinder fluidly connected to two or more insertable portions 107, the central cylinder being inserted into a storage section when the device is activated. In some embodiments, the device comprises a central cylinder fluidly connected to two or more dispensing elements 110, the central cylinder being inserted into a storage section when the device is activated. In some embodiments, the device further comprises one or more bases connected to the bottom of one or more dispensing elements 110, thereby moving one or more dispensing elements 110 when the device is activated. In some embodiments, the dispensing channel 125 has a diameter of approximately 0.3 mm to approximately 3 mm. In some embodiments, the dispensing element 110 has an inner diameter 129 of about 0.3 mm to about 3 mm. In some embodiments, the dispensing element 110 is configured to prevent bacteria or microorganisms from entering the lower nasal cavity 11 or the external environment into different areas of the nasal cavity 11.

[0145] In one embodiment, the present disclosure provides a device for intranasal delivery to a subject, the device being transitionable from a first configuration 100 to a second configuration 200, the device comprising a housing 101 defining two insertable portions 107 each having at least one dispensing element 110, each insertable portion being for insertion into the subject's nasal passage 20, and when the first insertable portion 107 is inserted into the subject's nasal passage 20, the first insertable portion 107 engages with the tissue within the nasal passage 20 to open or expand the subject's internal nasal valve 13, thereby delivering the composition 111 to the subject. The device comprises a housing 101 in which at least one of the dispensing elements 110 is positioned; a subject engagement portion 106 connected to the housing 101 and having a trigger, the subject engagement portion 106 having a trigger that engages with the columella region 10, and when pressure is applied to the subject engagement portion 106, the trigger allows the device to operate to deliver the composition 111 from the dispensing element 110 to the subject; and a dispensing element 110 which emerges from the first insertable portion 107 when the device transitions from the first configuration 100 to the second configuration 200.

[0146] In one embodiment, the present disclosure provides a device for intranasal delivery to a subject, the device being transitionable from a first configuration 100 to a second configuration 200, the device comprising a housing 101 defining two insertable portions 107, each insertable portion 107 being for insertion into the subject's nasal passage 20 to deliver a composition 111 into the subject's nasal passage 20, the first insertable portion 107 engaging with the tissue within the nasal passage 20 to open the subject's internal nasal valve 13 The apparatus comprises a housing 101 which expands or contracts to position at least one of the insertable portions 107 for delivering composition 111 to a subject, and a subject engagement portion 106 connected to the housing, the subject engagement portion 106 having a trigger which engages with the columella region 10, and when pressure is applied to the subject engagement portion 106, the trigger allows the apparatus to operate to deliver composition 111 to the subject from at least one of the insertable portions 107.

[0147] Figure 6A shows exemplary embodiments of the reference Cartesian coordinate plane of the exemplary apparatus (from left to right) in front, top, and side views. Figure 6B shows exemplary embodiments of the plane of the subject. Figure 6C shows exemplary embodiments of the angular reference plane of the exemplary apparatus (from left to right) in front view of the coronal plane, top view of the cross-sectional plane, and side view of the sagittal plane. In some embodiments, the apparatus is configured for a subject having a coronal or front view 601, a horizontal or axial or cross-sectional plane 602, a sagittal or longitudinal section 603, a median plane 604, or a parasagittal plane 605, or a combination thereof. In some embodiments, the apparatus comprises a relative angular coordinate system of a roll 606 on the Y axis of the apparatus, a pitch 607 on the sagittal plane of the subject, and a yaw 608 on the coronal plane of the subject. In some embodiments, the apparatus is configured for a subject having a linear coordinate system x609 relative to the inside / outside of the subject, a linear coordinate system y610 relative to the top / bottom of the subject, and a linear coordinate system z611 relative to the front / rear of the subject. Figure 6D shows an exemplary embodiment of the exemplary apparatus positioned at a sagittal plane angle to the subject.

[0148] method In one embodiment, the present disclosure provides a method for intranasal delivery to a subject using a device, the method comprising the step of positioning the insertable portion 107 of the device within the discharge area 29 of the subject's nasal cavity 11 by engaging the subject engagement portion 106 of the device with the columella region 10 of the subject's nasal cavity 11, thereby fixing the insertable portion 107 within the discharge area 29 of the subject's nasal cavity 11, the discharge area 29 being located 0 mm to 30 mm above a horizontal line 627 intersecting the anterior surface of the internal nasal valve 13, and extending from the anterior surface of the middle turbinate 15 and the front of the nose. It is located 0mm to 20mm anterior to the inclined line 610 that intersects the posterior surface of the garden 21, 0mm to 40mm inferior to the horizontal line 621 parallel to the inferior surface of the olfactory cleft 23, 0mm to 20mm posterior to the dorsal surface of the nose 622, 10mm and 50mm superior to the horizontal line 623 that intersects the inferior surface of the columella 10, 0mm to 30mm superior to the horizontal line that intersects the superior surface of the inferior turbinate 16, 0mm to 3mm from the nasal septum 24, or one or more of any combination thereof.

[0149] In some embodiments, the method further includes the step of activating the device by applying pressure to the columella region 10 of the subject using the subject engagement portion 106 of the device. In some embodiments, the step of positioning the insertable portion 107 of the device includes positioning two insertable portions 107 within the two nasal passages 20 of the subject, thereby opening or widening the opening of the internal nasal valves 13 of the subject. In some embodiments, the step of positioning the dispensing element 110 of the device includes positioning two dispensing elements 110 of the device within the nasal passages 20 of the subject, the two dispensing elements 110 emerging from the insertable portion 107. In some embodiments, the method further includes the step of transitioning the device from a first configuration 100 to a second configuration 200, wherein when the device is transitioned from the first configuration 100 to the second configuration 200, the dispensing elements 110 emerge from the insertable portion 107.

[0150] In one embodiment, the present disclosure provides a method for intranasal delivery to a subject using a device, the method comprising the steps of inserting two insertable portions 107 into the subject's nasal passage 20, wherein, upon insertion, at least one of the insertable portions engages with the tissue within the nasal passage 20, thereby opening or widening the opening of the subject's internal nasal valve 13, thereby positioning at least one of the insertable portions 107 for delivery of the composition 111 to the subject. In some embodiments, the method further comprises the steps of positioning the insertable portions 107 into the subject's nasal passage 20 by engaging the subject's columella region 10 with a subject engagement portion 106 of the device, thereby limiting the insertion depth of the device into the subject's nasal passage 20 and aligning the insertable portions 107 within the subject's nasal passage 20. In some embodiments, the method further includes the step of activating the device by applying pressure to the subject engagement portion 106 of the device using the columella region 10 of the subject. In some embodiments, the two insertable portions 107 each comprise at least one dispensing element 110. In some embodiments, at least one dispensing element 110 emerges outward from at least one of the two insertable portions 107. In some embodiments, the method further includes the step of transitioning the device from a first configuration 100 to a second configuration 200, wherein when the device is transitioned from the first configuration 100 to the second configuration 200, the dispensing element 110 emerges from the insertable portion 107. In some embodiments, the step of inserting the two insertable portions 107 in step a. advances the two insertable portions 107 along the dorsal nasal cavity 622 and / or along either side of the nasal septum 24 until the columella 10 engagement area of ​​the device contacts the columella 10 of the subject, preventing further insertion and establishing a depth reference 617. In some embodiments, the dispensing port 126 is positioned in a targeted area or partial area of ​​the nasal cavity 11. In some embodiments, the targeted area is the olfactory cleft, middle turbinate, inferior turbinate, superior turbinate, superior, middle, or inferior nasal meatus, or a combination thereof.

[0151] In some embodiments, the step of inserting the two insertable portions 107 in step a. uses the nasal-frontal angle 614 as an angular reference to position the insertable portions 107 within the nasal passage 20. In some embodiments, the dispensing port 126 is positioned in a targeted area or sub-area of ​​the nasal cavity 20. In some embodiments, the step of inserting the two insertable portions 107 in step a. advances the two insertable portions 107 along the dorsal nasal cavity 622 until the columella engagement area 106 of the device contacts the columella 10 of the subject, preventing further insertion and establishing a depth reference 617, and the step of inserting the two insertable portions 107 in step a. uses the nasal-frontal angle 614 as an angular reference to position the insertable portions 107 within the nasal passage 20, thereby positioning the two insertable portions at known locations within the nasal cavity 20. In some embodiments, the step of inserting the two insertable portions 107 in step a. includes inserting the two insertable portions 107 beyond the nasal vestibule 21. In some embodiments, the step of inserting the two insertable portions 107 in step a. includes inserting the two insertable portions 107 along the soft tissue of the upper nasal cleft 28, in an orientation parallel to the soft tissue. In some embodiments, the step of inserting the two insertable portions 107 in step a. prevents rotation of the device about an axis parallel to the subject's height 601. In some embodiments, the step of inserting the two insertable portions 107 in step a. forms a reference yaw angle 608 on the coronal plane 601 with respect to the y-axis of the device. In some embodiments, the step of inserting the two insertable portions 107 in step a. forms a substantially unobstructed flow channel to a target region 19, e.g., the olfactory cleft 23. In some embodiments, the step of inserting the two insertable portions 107 in step a. forms a substantially unobstructed flow to the nasal turbinates. In some embodiments, the target region 19 is the middle nasal meatus 30, and the targeted delivery of the composition 111 to the target region 19 is increased by dispensing the composition 111 from the posterior end 110 of the dispensing element. In some embodiments, the discharge area 19 is further parallel to the subject's middle nasal turbinate 15 and not located within the middle nasal meatus 30. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and the composition is dispensed into both regions simultaneously. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the anatomical structure of the nose. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure, and the composition is dispensed to all regions simultaneously. In one embodiment, the present disclosure provides a method for intranasal delivery to a subject using an apparatus, the method comprising the steps of positioning an insertable portion 107 of the apparatus within the subject's nasal passage 20, and transitioning the apparatus from a first configuration 100 to a second configuration 200 by applying pressure about the longitudinal axis 610 of the apparatus, thereby exposing a dispensing element 110 from the first insertable portion 107 and simultaneously operating the apparatus to deliver a composition 111 to the subject. In some embodiments, simultaneous operation refers to the transition from the first configuration 100 to the second configuration 200, and the operation occurs in a single movement when pressure is applied about the longitudinal axis 610 of the apparatus. In some embodiments, the step of positioning the insertable portion 107 of the apparatus within the subject's nasal passage 20 is achieved by engaging the columella region 10 of the subject with the subject engagement portion 106 of the apparatus. In some embodiments, the method further includes the step of activating the device by applying pressure to the subject engagement portion 106 of the device using the columella region 10 of the subject. In some embodiments, the step of positioning the insertable portion 107 of the device within the subject's nasal passage 20 involves engaging with the tissue within the nasal passage 20 to open or expand the subject's internal nasal flap 13, thereby positioning the insertable portion 107 to deliver the composition 111 to the subject. In some embodiments, the insertable portion 107 of the device comprises two insertable portions 107, each intended for insertion into the subject's nasal passage 20, and step a. includes inserting the two insertable portions 107 into the subject's nasal passage 20. In some embodiments, the step of inserting the two insertable portions 107 in step a. advances the two insertable portions 107 along the dorsal nasal cavity 622 and / or along either side of the nasal septum 24 until the columella engagement area 106 of the device contacts the columella 10 of the subject, preventing further insertion and establishing a depth reference 617. In some embodiments, the step of inserting the two insertable portions 107 in step a. uses the nasal frontal angle 614 as an angular reference reference to position the insertable portions 107 within the nasal passage 20. In some embodiments, the dispensing port 126 is positioned in a targeted area or partial area of ​​the nasal cavity 11.In some embodiments, the step of inserting the two insertable portions 107 in step a. involves advancing the two insertable portions 107 along the dorsal nasal cavity 622 and / or along either side of the nasal septum 24 until the columella engagement area 106 of the device contacts the columella 10 of the subject, thereby preventing further insertion and establishing a depth reference 617. The step of inserting the two insertable portions 107 in step a. uses the nasal frontal angle 614 as an angular reference reference to position the insertable portions 107 within the nasal passage 20, thereby positioning the two insertable portions at known locations within the nasal cavity 20. In some embodiments, the step of inserting the two insertable portions 107 in step a. includes inserting the two insertable portions 107 beyond the nasal vestibule 2121. In some embodiments, the step of inserting the two insertable portions 107 in step a. includes inserting the two insertable portions 107 along the soft tissue above the nasal cleft 28, in an orientation parallel to the soft tissue. In some embodiments, the step of inserting the two insertable portions 107 in step a. prevents rotation of the device about an axis parallel to the subject's height 601. In some embodiments, the step of inserting the two insertable portions 107 in step a. forms a reference yaw angle 608 on the coronal plane 601 with respect to the y-axis of the device. In some embodiments, the step of inserting the two insertable portions 107 in step a. forms a substantially unobstructed flow channel to a target region 19, for example, the olfactory cleft 23. In some embodiments, the target region 19 is the middle nasal meatus 30, and dispensing the composition 111 from the posterior end 110 of the dispensing element increases the targeted delivery of the composition 111 to the target region 19. In some embodiments, the discharge area 19 is further parallel to the subject's middle nasal conchae 15 and is not located within the middle nasal meatus 30. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end of the insertable portion 107. In some embodiments, the target region 19 is one or both of the olfactory clefts 23, or a portion thereof. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, and the composition is dispensed into both regions simultaneously.In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure. In some embodiments, the target region 19 is the olfactory region 23 and the middle nasal meatus 30, as well as other regions of the nasal anatomical structure, and the composition is dispensed to all regions simultaneously.

[0152] Figure 9A shows a side view of an exemplary embodiment of the target ejection point of a representative subject.

[0153] The apparatus, systems, and methods disclosed herein are advantageous over currently available intranasal delivery devices in that the disclosed apparatus are well-adapted to placement relative to the internal nasal valve.

[0154] In some embodiments, the exemplary devices disclosed herein are located either inside the intra-internal nasal valve or above the level of the intra-internal nasal valve.

[0155] In some embodiments, the internal nasal valve is located approximately 10-15 mm from the nostril opening, depending on individual variations. In some embodiments, the lower (lower) surface of the nasal valve, closer to the nostril, faces the lower end of this range. In some embodiments, the upper (upper) surface of the internal nasal valve is located an average of 2-2.5 cm from the nostril opening.

[0156] The apparatus, systems, and methods disclosed herein are advantageous over currently available intranasal delivery devices in that the disclosed apparatus are well-adapted to placement relative to the nasal opening.

[0157] In some embodiments, the exemplary devices disclosed herein are positioned more than 10 mm to 15 mm from the nostril opening.

[0158] In some embodiments, the exemplary devices disclosed herein include a 10-15 mm compartment located inside the internal nasal valve.

[0159] In some embodiments, the exemplary devices disclosed herein are designed to be located inside or above the nasal valve.

[0160] The apparatus, systems, and methods disclosed herein are advantageous over currently available intranasal delivery devices in that the disclosed apparatus has a viewpoint that is well-suited to dispensing in the anatomical structure of the patient's nose. In some embodiments, the apparatus includes increased targeted delivery of the composition because the viewpoint is located inside or above the internal nasal valve.

[0161] The devices, systems, and methods disclosed herein are advantageous over currently available intranasal delivery devices in that the disclosed devices have a discharge trajectory that is well adapted to the anatomical structure of the patient's nose and that the devices bypass anatomical obstacles. In some embodiments, the exemplary devices disclosed herein are located inside (inside) the internal nasal valve or above (above the level of) the internal nasal valve. In some embodiments, the placement of the device allows for an increased discharge trajectory. In some embodiments, the placement of the device allows for an upward or downward tendency. In some embodiments, the placement of the device also allows for direct anterior-to-downward / forward delivery of the formulation, overcoming anatomical obstacles encountered by other devices.

[0162] In one embodiment, the present disclosure provides a method for intranasal delivery of a composition 111 to a target region 19 of the nasal cavity 11 of a subject, the method comprising the step of inserting a dispensing element 110 into a dispensing area 29 of the nasal cavity 11, wherein the dispensing area 29 is located 0mm to 30mm above a horizontal line 627 intersecting the anterior surface of the internal nasal valve 13, and 0mm to 20mm anterior to an inclined line 610 intersecting the anterior surface of the middle turbinate 15 and the posterior surface of the nasal vestibule 21, and is located 0mm to 40mm below a horizontal line 621 parallel to the inferior surface of the olfactory cleft 23, or 0mm to 20mm posterior to the dorsal surface of the nasal cavity 622, or horizontal line 62 intersecting the inferior surface of the columella 10 The steps include: a step of being located 3 to 10 mm and 50 mm above, or 0 mm to 30 mm above a horizontal line 624 intersecting the superior surface of the inferior turbinate 16, or 0 mm to 3 mm above the nasal septum 24, or one or more of any combination thereof; and a step of dispensing composition 111 from a dispensing element 110 so as to bring the composition 111 into contact with a target region 19, wherein the step of dispensing composition 111 from an extrusion area 29 is to a) increase the targeted delivery of composition 111 to the target region 19, b) decrease the off-target delivery of composition 111 to the nasal cavity 11, or c) both.

[0163] In some embodiments, the discharge area 29 is located 0 to 30 mm above a horizontal line 627 intersecting the anterior surface of the internal nasal valve 13, 0 to 20 mm anterior to an inclined line 610 intersecting the anterior surface of the middle turbinate 15 and the posterior surface of the nasal vestibule 21, 0 to 40 mm below a horizontal line 621 parallel to the inferior surface of the olfactory cleft 23, 0 to 20 mm posterior to the dorsal surface of the nasal dorsum 622, 10 mm and 50 mm above a horizontal line intersecting the inferior surface of the columella 623, 0 to 30 mm above a horizontal line 624 intersecting the superior surface of the inferior turbinate 16, 0 to 3 mm from the nasal septum 24, or one or more of any combination thereof. In some embodiments, the subject engagement portion 106 prevents the distal end 128 from moving within or away from the discharge area 29 when the subject engagement portion 106 is fixed to the columella region 10. In some embodiments, the discharge area 29 is aligned with the olfactory cleft 23, defined by a linear vector between the olfactory cleft 23 and the distal end 128 of the insertable portion 107.

[0164] In some embodiments, dispensing composition 111 from the discharge area 29 increases the targeted accumulation of composition 111 in the olfactory cleft 23. In some embodiments, the subject engagement portion 106 is fixed to the columella region 10 when the subject engagement portion 106 is in contact with the lower side, left side, and right side of the columella 10 simultaneously. In some embodiments, dispensing composition 111 from the discharge area 29 increases the targeted accumulation of composition 111 on a respiratory surface such as the middle turbinate 15. In some embodiments, the discharge area 29 is an irregular quadrilateral or irregular quadrilateral comprising (i) a lower side surface 29A which is a 10-25 mm line 627 extending posteriorly and horizontally from the anterior surface of the internal nasal valve 13; (ii) an anterior side surface 29B which is a 10-35 mm line extending upward from the anterior surface of the internal nasal valve 13 and parallel to the dorsal nasal interior 622; (iii) an upper side surface 29C which is a 10-25 mm line extending posteriorly and horizontally from a point in the dorsal nasal interior 622 located 0-10...

Claims

1. A device for intranasal delivery to a subject, wherein the device is transitionable from a first configuration to a second configuration, and the device is a. Two insertable parts, each configured to be inserted into the nasal passage of the subject, wherein each of the two insertable parts has a distal end and a proximal end, b. One or more dispensing elements, each of one or two dispensing elements having one or more dispensing elements that emerge from a corresponding insertable portion when the device transitions from the first configuration to the second configuration, c. A subject engagement portion that engages with the columella region of the subject so as to fix the distal end of each insertable portion within the discharge area of ​​the subject's nasal passage, wherein the discharge area is i. Located 0 mm to 30 mm above the horizontal line intersecting the anterior surface of the internal nasal valve, ii. The subject engagement portion is located 0 mm to 20 mm anterior to the inclined line that intersects the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule, d. A trigger release unit connected to the subject engagement portion and The subject engagement portion is provided, and when pressure is applied to the nasal columella region of the subject, i. The apparatus is changed from the first configuration to the second configuration. ii. Release the trigger release unit and allow the device to operate in order to deliver the composition to the subject from either or both of the insertable portions. A device configured in such a way.

2. A device for intranasal delivery to a subject, wherein the device is a. A housing having an insertable portion with a distal end and a proximal end, b. A subject engagement portion that engages with the columella region of the subject so as to fix the distal end of the insertable portion within the discharge area of ​​the subject's nasal passage, wherein the discharge area is i. Located 0 mm to 30 mm above the horizontal line intersecting the anterior surface of the internal nasal valve, ii. The subject engagement portion located 0 mm to 20 mm anterior to the inclined line where the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule intersect. A device equipped with the following features.

3. The aforementioned discharge area is provided. vii. Is it located 0 mm to 40 mm below the horizontal line parallel to the lower surface of the olfactory cleft? viiii. Is it located 0mm to 20mm posterior to the dorsum of the nose? ix. Is it located 10 mm to 50 mm above the horizontal line that intersects the lower surface of the columella? x. Is it located 0 mm to 30 mm above the horizontal line that intersects with the upper surface of the inferior turbinate? xi. Located 0mm to 5mm from the nasal septum, or xi. In any combination of those, The apparatus according to claim 2.

4. The apparatus according to claim 2 or 3, wherein the apparatus is configured to dispense fluid from there as laminar flow.

5. The device according to any one of claims 2 to 4, wherein the insertable portion, when inserted into the nasal passage of the subject, opens or expands the internal nasal flap by pushing up the superior lateral nasal cartilage and surrounding tissues and separating them from the nasal septum.

6. The device according to any one of claims 2 to 5, wherein the insertable portion, when inserted into the nasal passage of the subject, is located proximal to the nasal septum.

7. The apparatus according to any one of claims 2 to 6, wherein the subject engagement portion prevents the distal end from moving within or away from the discharge area when the subject engagement portion is fixed to the columella region.

8. The apparatus according to any one of claims 2 to 7, wherein the discharge area is in line with the olfactory cleft, defined by a linear vector between the olfactory cleft and the distal end of the insertable portion.

9. The apparatus according to any one of claims 2 to 8, wherein the apparatus is configured to dispense the composition from the dispensing area such that at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 99% of the composition to be dispensed is delivered to a target area or a target sub-area.

10. The apparatus according to any one of claims 2 to 9, wherein the composition is dispensed from the discharge area to increase the target accumulation of the composition in the olfactory cleft.

11. The apparatus according to any one of claims 2 to 10, wherein the composition is dispensed from the dispensing area to increase the target accumulation of the composition on a surface with a respiratory area, such as the middle turbinate.

12. The apparatus according to any one of claims 2 to 11, wherein the composition is dispensed from the dispensing area to increase the target accumulation of the composition in two or more regions or partial regions of the nasal passage.

13. The apparatus according to any one of claims 2 to 12, wherein the subject engagement portion is fixed to the columella region when the subject engagement portion simultaneously contacts the lower side surface of the columella, the left side surface of the columella, and the right side surface of the columella.

14. The apparatus according to any one of claims 2 to 13, wherein the subject engagement portion limits the insertion depth of the insertable portion into the nasal passage.

15. The apparatus according to any one of claims 2 to 14, wherein the insertable portion incorporates one or more dispensing channels connected to one or more dispensing ports configured to deliver a composition to one or more regions or subregions of the nasal passage of the subject.

16. The apparatus according to any one of claims 2 to 15, wherein the insertable portion comprises a dispensing element for delivering a composition to a region or partial region of the nasal passage of the subject.

17. The apparatus according to any one of claims 2 to 16, wherein the housing comprises a trigger, and when pressure is applied to the trigger, the trigger activates the apparatus to dispense a composition into the subject from the insertable portion or dispensing element.

18. The apparatus according to any one of claims 2 to 17, wherein the subject engagement portion comprises a trigger connected to the housing and the subject engagement portion, and when pressure from the subject engagement portion is applied to the nasal columella region, the trigger activates the apparatus to dispense a composition to the subject from the insertable portion or dispensing element.

19. A method for intranasal delivery of a composition to a target region of the nasal cavity of a subject, wherein the method is: a. A step of inserting a dispensing element into the discharge area of ​​the nasal cavity, wherein the discharge area is b. Located 0 mm to 30 mm above the horizontal line intersecting the anterior surface of the internal nasal valve, c. Located 0 mm to 20 mm anterior to the inclined line that intersects the anterior surface of the middle turbinate and the posterior surface of the nasal vestibule, i. Is it located 0 mm to 40 mm below the horizontal line parallel to the lower surface of the olfactory cleft? ii. Is it located 0 mm to 20 mm posterior to the dorsum of the nose? iii. Are they located 10 mm and 50 mm above the horizontal line that intersects the lower surface of the columella? iv. Is it located 0 mm to 30 mm above the horizontal line that intersects with the upper surface of the inferior turbinate? v. Located 0 mm to 3 mm from the nasal septum, or vi. Any combination of them One or more of the processes, d. A step of dispensing the composition from the dispensing element so as to bring the composition into contact with the target region, wherein the step of dispensing the composition from the dispensing area is a) to increase the targeted delivery of the composition to the target region, b) to decrease the off-target delivery of the composition to the nasal cavity, or c) both. Methods that include...

20. The method according to claim 19, wherein the target region is one or both of the olfactory fissures or a portion thereof, and the target delivery of the composition to the target region is increased by dispensing the composition from the front end of the dispensing element.

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