Intranasal cryotherapy device

Abstract

An intranasal cryotherapy device with a canister with an actuator. The canister stores a coolant and compressed air and is configured to dispense the coolant and compressed air when actuated. The device also includes an intranasal catheter with a manifold with a pair of inlet ducts to receive the coolant and the compressed air and two pairs of outlet ducts to output the coolant and the compressed air. The catheter also includes a pair of tubular nostril inserts protruding away from the manifold, a pair of tubular nasal cavity inserts with a nozzle plate that protrude away from the nostril inserts, and two pairs of delivery ducts with a first end connected to one of the outlet ducts and a second end proximal to one of the nozzle plates forming a mixing chamber in an intermediary space between the second end of the delivery ducts and the nozzle plates.

Description

INTRANASAL CRYOTHERAPY DEVICE

[0001] This application claims priority to U.S. provisional patent application serial No.63 / 569,500, filed on March 25, 2024, which is hereby incorporated by reference.FIELD

[0002] The specification relates generally to cryotherapy devices, and specifically to point-of-care intranasal cryotherapy devices.BACKGROUND

[0003] Migraine headaches are a common neurological disorder that affect an estimated 1 billion people worldwide and 33 million people in the United States. The 2016 Global Burden of Disease Study and 2019 update found migraines to be the second leading cause of disability around the world, followed only by lower back pain. In the United States, migraines incur annual costs of up to $17 billion due to the direct cost of outpatient services and the indirect cost of lost productivity by individuals who suffer from migraine. In 2017, the estimated market value from the seven major migraine markets (US, France, Germany, Italy, Spain, UK, and Japan) was 3.8 billion USD at a compound annual growth rate of 13.3%. However, existing pharmacologic point-of-care treatments for migraines that focus on providing quick relief from symptoms have multiple drawbacks, for example: Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) may not be effective for severe migraines, their prolonged use can lead to gastrointestinal issues like ulcers and bleeding and are not suitable for individuals with kidney problems or certain cardiovascular conditions; acetaminophen has limited efficacy for migraine relief compared to NSAIDs and its overuse can cause liver damage; triptans are contraindicated in individuals with certain cardiovascular conditions, can cause chest tightness, dizziness and other side effects, and their overuse can lead to medication overuse headache (rebound headache) ; combination analgesics present a risk of overuse due to the inclusion of caffeine, which can lead to rebound headaches, and their longterm use can cause gastrointestinal issues and liver damage due to acetaminophen;antiemetics cause side effects like drowsiness, dry mouth, and movement disorders and are not effective for all migraineurs; ergotamine derivatives cause potential serious side effects like ergotism (blood vessel constriction) and dependence and are contraindicated in individuals with cardiovascular disease; corticosteroids are reserved for severe cases due to potential side effects like weight gain, mood changes, and increased risk of infections and are not suitable for long-term use due to systemic effects; intranasal lidocaine has limited evidence supporting its efficacy and its potential side effects include nasal discomfort and taste disturbances; and botulinum toxin injections require invasive procedures with potential side effects like neck weakness, injection site pain, and allergic reactions, and their long-term efficacy is still under investigation.SUMMARY

[0004] An aspect of the specification provides an intranasal cryotherapy device comprising a canister with an actuator, the canister configured to store a coolant and compressed air and to dispense the coolant and compressed air when actuated. The intranasal cryotherapy device also includes and an intranasal catheter including a manifold with a pair of inlet ducts configured to receive the coolant and the compressed air, and two pairs of outlet ducts configured to output the coolant and the compressed air; a pair of tubular nostril inserts protruding away from the manifold, a pair of tubular nasal cavity inserts protruding away from the nostril inserts, each of the tubular nasal cavity inserts including a nozzle plate at an outlet distal from the nostril inserts, and two pairs of delivery ducts, each pair of the delivery ducts extending through an interior of each of the tubular nostril inserts and of the nasal cavity inserts, a first end of each of the delivery ducts connected to one of the outlet ducts and a second end of each of the delivery ducts proximal to one of the nozzle plates, forming a mixing chamber in an intermediary space between the second end of the delivery ducts and the nozzle plates interior to the nasal cavity inserts.

[0005] Another aspect of the specification provides an intranasal catheter including a manifold with a pair of inlet ducts configured to receive two different fluids, and two pairs of outlet ducts configured to output the two different fluids, a pair of tubular nostril inserts protruding away from the manifold, a pair of tubular nasal cavity inserts protruding awayfrom the nostril inserts, each of the tubular nasal cavity inserts including a nozzle plate at an outlet distal from the nostril inserts, and two pairs of delivery ducts, each pair of the delivery ducts extending through an interior of each of the tubular nostril inserts and of the nasal cavity inserts, a first end of each of the delivery ducts connected to one of the outlet ducts and a second end of each of the delivery ducts proximal to one of the nozzle plates, forming a mixing chamber in an intermediary space between the second end of the delivery ducts and the nozzle plates interior to the nasal cavity inserts.

[0006] The nostril inserts may have a length of about 3 cm. The nasal cavity inserts may extend a length of about 1 cm beyond the nostril inserts. The coolant may be a perfluorocarbon. The coolant may be perfluorohexane. The coolant may further be at least one of carbon dioxide and nitrogen. The device may be used to treat migraine and / or heatstroke. The actuator may include an actuation mechanism configured to dispense a dose of the coolant and the compressed air for up to about 30 seconds.

[0007] Another aspect of the specification provides an intranasal cryotherapy device including a canister with an actuator cap, the canister configured to separately store a coolant and compressed air and to dispense a mixture of the coolant and compressed air when the actuator cap is actuated, and an intranasal catheter. The intranasal catheter includes a manifold, a cap duct fluidly connected to the manifold, the cap duct configured to connect the intranasal catheter to the actuator cap of the intranasal cryotherapy device, and two nose inserts fluidly connected to the manifold, the nose inserts configured to be inserted to the nose of a user and deliver the mixture of the coolant and compressed air to the user when the actuator cap is actuated.

[0008] Each of the nose inserts may include a nostril insert section and a nasal cavity insert section. The intranasal catheter may further include a set of ducts to regulate and direct the flow of the mixture of the coolant and compressed air through the nasal catheter. The set of ducts may include at least one duct to direct the flow of the mixture of the coolant and compressed air from the cap duct to each of the nose inserts and at least one additional duct to direct an additional fluid to the nose inserts. The device may further comprise a storage unit for the additional fluid fluidly connected to the at least one additional duct. The device may be used to treat migraine and / or heatstroke.BRIEF DESCRIPTIONS OF THE DRAWINGS

[0009] Embodiments are described with reference to the following figures. In the figures provided, certain components or details may have been omitted for clarity and conciseness. However, it is understood that these elements will be readily apparent to those skilled in the art and are considered within the scope of the disclosure.

[0010] FIG. 1 depicts a schematic drawing of an example intranasal cryotherapy device.

[0011] FIG. 2 depicts a schematic drawing of an example nasal catheter of the example device of FIG. 1 .

[0012] FIG. 3 depicts a schematic drawing of another example intranasal cryotherapy device.

[0013] FIG. 4 depicts a schematic drawing of an example canister of the example device of FIG. 3.

[0014] FIG. 5 depicts a schematic drawing of a user using an example intranasal cryotherapy device.

[0015] FIG. 6 depicts a schematic drawing of another example intranasal cryotherapy device.

[0016] FIG. 7 depicts a front plan view of another example intranasal cryotherapy device.

[0017] FIG. 8 depicts a top, back and right perspective view of an example actuator cap of the example intranasal cryotherapy device of FIG. 7.

[0018] FIG. 9 depicts a left plan view of the example actuator cap of FIG. 8.

[0019] FIG. 10 depicts a top, back and right perspective view of an example connector element of an example actuator cap.

[0020] FIG. 11 depicts a top, back and right exploded perspective view of the example actuator cap of FIG. 8 and two example connectors.

[0021] FIG. 12. depicts a left plan view of the example intranasal cryotherapy device of FIG. 7.

[0022] FIG. 13 depicts a front plan view of another example nasal catheter.DETAILED DESCRIPTION

[0023] Although mechanisms responsible for migraines remain unclear, it is thought to be a disorder of the trigeminovascular system, which is a complex network of nerves and blood vessels including the trigeminal nerve and the blood vessels surrounding the brain. Preclinical data has demonstrated that activation of the trigeminovascular system results in the release of vasoactive signaling molecules such as Calcitonin Gene-Related Peptide (CGRP), which have been shown to contribute to dilation of the blood vessels of the trigeminovascular system and to sensitization of pain receptors, contributing to pain and other symptoms of migraine. Furthermore, intravenous infusions of CGRP have been shown to cause headaches in individuals predisposed toward migraines.

[0024] Cryotherapy methods offer a non-pharmacologic alternative for treating migraines that can be optionally combined with pharmacologic treatments. It has been estimated that 27% of people with migraines self-administer various forms of external cryotherapy such as using cold compacts or directing cooling fans to the neck or forehead with limited effectiveness. While the exact mechanisms by which cryotherapy alleviates migraines are not well understood, benefits likely result from cryotherapy inducing local vasoconstriction by directly affecting the smooth muscle cells lining the vessels, which can help decrease the diameter of blood vessels normalizing blood flow, inhibit release of vasodilatory substances like CGRP and nitric oxide, and affect pain signaling pathways in the brain leading to a reduction in perception of pain associated with migraines.

[0025] An intranasal cryotherapy device configured to deliver a cooling fluid, for example, at a temperature between about 5° C and about 15° C, such as at about 10° C, to the cribriform plate, which is the thin skeletal membrane separating the brain from the nasal cavity, can enable cooling of the cribriform plate which in turn allows for efficient cooling of the brain; furthermore, said intranasal cryotherapy device may also cool down blood flowing to the brain as it passes through the nasopharynx, further helping with thecooling of the brain, the cooling of the brain ultimately inducing vasoconstriction and thereby helping alleviate an episode of migraine.

[0026] Additionally, by helping with the cooling of the brain, the intranasal cryotherapy device targeting the cribriform plate, may also help lowering the body’s core temperature, helping to reduce metabolic demand, decrease inflammation, and protect brain cells from damage caused by heat stroke, especially in cases where the body’s temperature has risen to dangerously high levels, for example, above 40° C. A portable intranasal cryotherapy device may serve as a supplement to first-aid personnel for treating heat stroke in settings where people may be exposed to the sun for long periods of time and where transport to a permanent medical facility may be challenging, such as, for example, at hiking trails, music festivals, summer sporting events, etc..

[0027] FIG. 1 depicts an example intranasal cryotherapy device 100. The device 100 includes a nasal catheter 104 configured to be introduced through the nose of a user reaching the nasal cavity, and to atomize a cooling fluid mix 108 in order to deliver the cooling fluid mix 108 to the cribriform plate. The device 100 further includes a canister 112 configured to store a coolant and air and to enable the user to actuate delivery of the coolant and the air to the nasal catheter 104. The nasal catheter 104 may be optionally detachable from the cryotherapy device 100, for example, to enable the user to swap the nasal catheter 104 with an alternative nasal catheter 104 of different dimensions.

[0028] FIG. 2 depicts the nasal catheter 104 of the example device 100. The nasal catheter 104 comprises a manifold 200 including one pair of inlet ducts 204-0 and 204-A (collectively referred to as the inlet ducts 204, and individually referred to as an inlet duct 204, the nomenclature is used elsewhere) divided into two pairs of outlet ducts 208-C1 and 208-A1 , and 208-C2 and 208-A2. While in FIG. 2 the inlet ducts 204 are shown dividing into the outlet ducts 208 through a T-division and while the outlet ducts 208 are shown to include 90° bends inside the manifold 200, the division of the inlet ducts 204 into the outlet ducts 208 and their arrangement within the manifold 200 may be differently configured to reduce pressure loss of fluid flowing from the inlet ducts 204 to the outlet ducts 208, for example, by including a Y-division and by removing the 90° bends. The manifold 200 may be made of a rigid or a semirigid medical-grade material such as amedical-grade polymer, for example Polyetheretherketone (PEEK), Polyethylene (PE), Polypropylene (PP), Polyethylene Terephthalate (PET), Acetal (Polyoxymethylene, POM), etc. Alternatively, the manifold 200 may be made of other rigid medical-grade materials such as, for example, stainless steel, titanium, ceramics, etc. The manifold 200 and the ducts 204 and 208 may be manufactured as a unitary piece through any known manufacturing means, such as injection molding, 3 D-printing , etc. Alternatively, the ducts 204 and 208 may be manufactured as separate pieces from the manifold 200 and subsequently be enclosed by the manifold 200 by assembling the ducts 204 and 208 into the manifold 200 or by forming the manifold 200 over the ducts 204 and 208.

[0029] The nasal catheter 104 further comprises two tubular nostril inserts 212-1 and 212-2 protruding away from the manifold 200 and two tubular nasal cavity inserts 216-1 and 216-2 concentric and partially interior to the nostril inserts 212-1 and 212-2, respectively, and protruding further away from the manifold 200 than the nostril inserts 212. The nostril inserts 212 may be made of a rigid or a semirigid medical-grade material such as, for example, a medical grade polymer, and may further optionally include an outer layer of a medical-grade cushioning material such as, for example, silicone, polyurethane, a memory foam, etc. in order to ease insertion into the nostrils, and may be secured to the manifold 200 by, for example, adhesive bonding, a threaded connection, heat staking, etc., or may alternatively be manufactured integral to the manifold 200 and, for example, optionally be further coated with the medical-grade cushioning material. The nasal cavity inserts 216 may be made of a soft, flexible medicalgrade material such as, for example, silicon, Polyurethane (PU), PE, Polyvinyl Chloride (PVC), Polytetrafluoroethylene (PTFE), Nylon, PP, etc. so that they may be easily inserted past the nasal opening into the nasal cavity. An outer diameter of the nasal cavity inserts 216 may be of about 5 / 3 mm (about 5 French) and an inner diameter of the nostril inserts 212 may be of slightly less than about 5 / 3 mm (slightly less than about 5 French) so that an interference fit connection is secured between the outer diameter of the nasal cavity inserts 216 and the inner diameter of the nostril inserts 212. Alternatively, the nasal cavity inserts 216 may be secured to the nostril inserts 212 through different means, for example, by adhesive bonding, a threaded connection, heat staking, etc. The nostril inserts 212 have a length of about 3 cm so that the nostril inserts 212 may extend theentire length of the nostril of the user when placing the nasal catheter 104 inside the user’s nose. Users with shorter nostrils may position only a portion of the nostril inserts 212 inside their nose to guarantee that the nostril inserts 212 extend the entire length of their nostrils. The nasal cavity inserts 216 have a length of about 4 cm and extend the entire length of the nostril inserts 212 from the manifold 200 to about 1 cm beyond an end of the nostril inserts 212 so that the nasal cavity inserts 216 may extend about 1 cm into the nasal cavity of the user when placing the nasal catheter 104 inside the user’s nose. Alternatively, the nasal cavity inserts 216 may have a length longer than about 1 cm and shorter than about 4 cm, for example, of about 2 cm, and extend partially into the nostril inserts 212 while protruding away from the end of the nostril inserts 212 by about 1 cm. The outer diameter, the length, and the material of the nasal cavity inserts 216 may ease their insertion past the nasal opening into the nasal cavity. The nostril insert 212-1 and the nasal cavity inserts 216 may extend away from the manifold 200 at a non-parallel angle from each other so that a width W1 between the nasal cavity inserts 216 at the end where the nasal cavity inserts 216 start protruding away from the nostril inserts 212 is smaller than a width W2 between the nostril inserts 212 at an end adjacent to the manifold 200, for example, W1 may be equal to about 0.7 cm and W2 may be equal to about 1 .2 cm, thereby orienting the inserts 212 and 216 in a direction that may ease insertion in the user’s nose. Furthermore, an outer diameter of the nostril inserts 212 at the end distal from the manifold 200 may be smaller than at the end adjacent to the manifold 200 to further ease insertion in the user’s nose.

[0030] Each of the nasal cavity inserts 216 includes an atomization plate 220 on an end distal from the nostril inserts 212. The atomization plates 220 may be made of a medical grade rigid material such as, for example, stainless steel, titanium, borosilicate glass, etc., and may be secured to the nasal cavity inserts 216 though, for example, adhesive bonding, a threaded connection, compression fitting, heat staking, ultrasonic welding, etc. Each of the atomization plates 220 may include at least one atomization nozzle. Alternatively, each of the atomization plates 220 may include at least one main atomization nozzle and at least two secondary atomization nozzles, for example, of a smaller diameter than a diameter of the main atomization nozzle. The atomization nozzlesmay be straight or may be angled to impart a swirl to fluid as the fluid travels through them.

[0031] The nasal catheter 104 further comprises two pairs of delivery ducts 224-C1 and 224-A1 , and 224-C2 and 224-A2, each pair of delivery ducts 224-C and 224-A being interior to a nostril insert 212 and its corresponding nasal cavity insert 216 and extending a length longer than about 3 cm and shorter than about 4 cm from the manifold 200, for example, about 3.65 cm, so that a mixing chamber 228 is formed inside the nasal cavity inserts 216 between an end of the delivery ducts 224 and the atomization plates 220, and so that a fluid flow path is formed from the inlet ducts 204 to the atomization plates 220, the fluid flow path configured to deliver a mix of two fluids to each of the atomization plates 220. The ducts 224 may be made of a flexible medical-grade material and their inner diameter may be of about 1 / 3 mm (about 1 French). Alternatively, the inner diameter of the ducts 224 may be of up to about 2 / 3 mm (up to about 2 French). The inner diameter of the outlet ducts 208 may be slightly smaller than the outer diameter of the delivery ducts 224 so that the delivery ducts 224 may be secured to the outlet ducts 208 through an interference fit connection. Alternatively, the delivery ducts 224 may be secured to the outlet ducts 208 by other means such as, adhesive bonding, a threaded connection, heat staking, etc.

[0032] FIG. 3 depicts a schematic drawing of another example intranasal cryotherapy device 300. The device 300 includes the nasal catheter 104 and further includes a canister 304 containing a coolant storage unit 306-C and an air storage unit 306-A, an intermediary duct 308, a coolant duct 312-C and an air duct 312-A, the coolant and the air ducts 312-C and 312-A being interior to the intermediary duct 308 and connecting the coolant storage unit 306-C to the inlet duct 204-C and the air storage unit 306-A to the inlet duct 204-A, respectively. The intermediary duct 308 may be made of a flexible medical-grade material of a length of about 10 cm and an outer diameter of about 5 / 3 mm (about 5 French). The two opposite ends of the intermediary duct 308 may be secured to the nasal catheter 104 and to the canister 304, respectively, by any known means, for example, adhesive bonding, a threaded connection, compression fitting, heat staking, ultrasonic welding, etc. The coolant and the air ducts 312 may be made of a flexible medical-grade material of a length longer than about 10 cm, for example of about 11 toabout 12 cm and their inner diameter may be of about 1 / 3 mm (about 1 French). Alternatively, the inner diameter of the coolant and the air ducts 312 may be of up to about 2 / 3 mm (up to about 2 French). The inner diameter of the inlet ducts 204 may be smaller than the outer diameter of the coolant and the air ducts 312 so that the coolant and the air ducts 312 may be secured to the inlet ducts 204 through an interference fit connection. Alternatively, the coolant and the air ducts 312 may be secured to the inlet ducts 204 by other means such as, adhesive bonding, a threaded connection, heat staking, etc.

[0033] FIG. 4 depicts a schematic drawing of the canister 304 of the example device 300. The coolant and air storage units 306-C and 306-A are containers with open ends 400-C and 400-A, respectively, to which valves 404-C and 404-A are connected, respectively, by any known means, such as adhesive bonding, a threaded connection, compression fitting, heat staking, ultrasonic welding, etc. The coolant storage unit 306-C may store a biologically inert coolant such as, for example, a perfluorocarbon such as perfluorohexane at a pressure slightly above 1 bar, for example, at about 1 .5 bar. The coolant storage unit 306-C may be a flexible bag made of, for example, a medical-grade low-density polymer. The air storage unit 306-A may be a cartridge made of a high- strength, wear, and corrosion resistant medical-grade metal such as stainless steel, titanium, cobalt-chromium, nickel-titanium, tantalum, etc. configured to store air at an elevated pressure, for example, between about 15 bar and about 40 bar. The storage units 306 may be securely stored inside the canister 304, which may made of a high- strength, wear, and corrosion resistant metal such as stainless steel, aluminum, etc. filled with a propellant, such as, for example, nitrogen (N2), compressed air, etc. at an elevated pressure, for example between about 5 bar to about 10 bar, preferably at about 9 bar, in order to assist the expulsion of the coolant from the canister 304 when the device 100 is actuated, for example, when the valves 404 are actuated to an open position in similar fashion to bag-on-valve technology for dispensing rescue inhalers for asthma.

[0034] In an alternative embodiment, an alternative coolant storage unit may store a different biologically inert coolant such as, for example, carbon dioxide (CO2). The alternative coolant storage unit may be made, for example, of a cold-rolled uncoated low- carbon steel narrow strip such as, for example, W-No. 10338 EN 1039 DC04, and may be configured to store, for example, about 24 grams of CO2, about 33 grams of CO2,about 38 grams of CO2, about 60 grams of CO2, etc. at a fluid density of, for example, about 0.75 kg / l and at a temperature range of, for example, about -30° C to about 65° C. The alternative coolant storage unit may be configured to release the coolant when actuated without the help of a propellant. In a further alternative embodiment, a further alternative coolant storage unit may store a different biologically inert coolant such as, for example, Nitrogen (N2).

[0035] The coolant and the air ducts 312-C and 312-A are connected to the valves 404-C and 404-A, respectively, by any known means, such as adhesive bonding, a threaded connection, compression fitting, heat staking, ultrasonic welding, etc. The valves 404 are normally closed valves that prevent the coolant and compressed air from exiting the storage units 306. The canister 304 also includes an actuation mechanism (not shown) that enables the user to simultaneously open the valves 404. When the coolant valve 404-C is opened, the propellant in the canister 304 exerts pressure on the coolant storage unit 306-C and pushes the coolant out of the coolant storage unit 306-C. At the same time, when the air valve 404-A is opened, the compressed air is allowed to exit the air storage unit 306-A. The coolant and the air are then delivered through the ducts 312, 204, 208 and 224 to the mixing chambers 228 and the mix of coolant and air are delivered through the nozzle plates 220. A mix of air and coolant at a pressure of about 3 bar and at a temperature between about 5° C and about 15° C, such as, for example, at about 10° C, is jettisoned by the device 300. The mix is directed to the cribriform plate of the user and has enough kinetic energy to reach the cribriform plate when the nasal catheter 104 is inserted into the nose of the user and the user triggers the actuation mechanism.

[0036] FIG. 5 depicts a schematic drawing of a user 500 using an example device 100 or 300. As shown in the figure, the nasal catheter 104 is inserted into the user’s nose so that the nasal cavity inserts 216 extend partially into the nasal cavity of the user. The device 100, 300 is configured to direct the mix of coolant and air to the cribriform plate of the user, in order to cool the cribriform plate and the nasal cavity, thereby also cooling the brain of the user. Additionally, the mix may influence oxygenation of the user indirectly by affecting the partial pressure of oxygen in the environment. The user may actuate the device 100, 300 for about 30 seconds at a time to, for example, treat an episode of migraine or of heatstroke.

[0037] FIG. 6 depicts a schematic drawing of another example intranasal cryotherapy device 600. The device 600 does not include an intermediary duct, and its nasal catheter is directly connected to the canister.

[0038] FIG. 7 depicts a front plan view of another example intranasal cryotherapy device 700. The device 700 includes an example canister 704 configured to store a coolant and air, and an example actuator cap 708 configured to release the coolant and air when actuated by a user.

[0039] FIGS. 8 and 9 depict the example actuator cap 708. The actuator cap 708 may be made of a rigid or a semirigid medical-grade material such as a medical-grade polymer, for example Polyetheretherketone (PEEK), Polyethylene (PE), Polypropylene (PP), Polyethylene Terephthalate (PET), Acetal (Polyoxymethylene, POM), etc. Alternatively, the actuator cap 708 may be made of other rigid medical-grade materials such as, for example, stainless steel, titanium, ceramics, etc. The actuator cap 708 includes a coolant inlet 804-C, an air inlet 804-A, and an outlet 808. The actuator cap 708 further includes an internal chamber 812 to which the inlets 804 and the outlet 808 are fluidly connected, so that coolant and air may flow from the inlets 804 through the internal chamber 812 to the outlet 808. The actuator cap 708 further includes a recessed surface 816 on the top of the cap, so that the user may easily grasp the actuator cap 708 by positioning a finger on the surface 816, for example, to press the actuator cap 708. As can be seen on FIG. 9, the direction of the outlet 808 may be at an angle 0 different than a 90° angle with respect to the direction of the inlets 804.

[0040] FIG. 10 depicts an example connector element 1000 that can be included within the internal chamber 812 of example actuator cap 708. The connector element 1000 can be made of a rigid or semirigid medical-grade material such as, for example, a medicalgrade polymer. The connector 1000 includes a coolant inlet connector 1004-C, an air inlet connector 1004-A, and an outlet connector 1008. The inlet connectors 1004 are configured to be connected to the inlets 804, and the outlet connector 1008 is configured to be connected to the outlet 808. The connector element 1000 further includes a directing passage or set of passages 1012 that fluidly connect the coolant inlet connectors 1004 to the outlet connector 108, to direct and regulate the fluid flow of the coolant and the airfrom the inlet connectors 1004 to the outlet connector 1008, for example, by maintaining the flow laminar, by minimizing pressure loss, by making the flow turbulent, etc. The outlet connector 1008 can include an outlet nozzle or set of nozzles to further regulate the flow of the coolant and air as they exit the actuator cap 708 through the outlet 808. The passage or set of passages 1012 can be configured to mix the coolant and the air, or alternatively, to maintain the flow of coolant separate from the flow of air as the coolant and air are delivered from the inlet connectors 1004 to the outlet connector 108. If the passage or set of passages 1012 are configured to mix the coolant and the air, the outlet connector 108 can be provided with at least one outlet nozzle to regulate the flow of the mix as the mix exits the actuator cap 708 through the outlet 808. If the passage or set of passages 1012 are configured to maintain the flow of the coolant and air separate from each other, the outlet connector 108 can be provided with at least two outlet nozzles, each of which is configured to independently regulate the flow of the coolant or air as the coolant and air exit the actuator cap 708 through the outlet 808.

[0041] FIG. 11 depicts an exploded view of the example actuator cap 708 and two example connectors 1100-C and 1 100-A. The connectors 1100 may be made of a rigid or a semirigid medical-grade material such as, for example, a medical grade polymer. The coolant connector 1100-C and the air connector 1100-A are configured to fluidly connect the coolant inlet 804-C and the air inlet 804-A of the actuator cap 708 to a coolant storage unit and an air storage unit, respectively. Each of the connectors 1100 includes a cap receiving member 1 104 configured to receive an inlet 804 and a storage unit connecting member 1 112 configured to connect to an end of a storage unit. Each of the connectors 1100 further includes a duct 1116 that fluidly connects the cap receiving member 1104 to the storage unit connecting member 1112. Each of the connectors 1 100 further includes a valve member (not depicted) within the duct 11 16 to selectively allow or prevent pressurized fluid stored in the storage unit to flow from the storage unit to the cap inlet 804 through the connector 1100. Each of the connectors 1 100 may further include a biasing member 1120, for example, a coil spring, configured to bias the inlet 804 in a first position when the inlet 804 is received within the cap receiving member 1104. In the first position, the valve member is maintained in a closed state, preventing the fluid stored in the storage unit from being expelled. When the user presses theexample actuator cap 708 in an actuating direction AD1 with sufficient force, for example, of about 10 to about 40 N, the force of the biasing members is overcome and the inlets 804 are pressed onto a second position within the cap receiving members 1104 of the connectors 1100, and the valve member is set to an open state, allowing the fluids stored in the storage units to be expelled through the actuator cap 708. Alternatively, the actuator cap 708 may be configured differently, for example, the valve members within the ducts 1116 and the biasing members 1 120 may be configured so that the valve members are opened when the user twists the cap 708 open in a rotary motion, for example in the alternative actuating direction AD2, for example, with of a turn. It will be apparent to a person of skill in the art that for the actuator cap 708 to be configured to be actuated by a twist in the alternative actuating direction AD2, the valve members may be configured to work with alternative biasing members or without them, for example, as part of a rotary valve mechanism, a threaded plunger mechanism, a twist-actuated spring valve mechanism, etc. An actuator cap 708 that is configured to dispense its fluids with a twist motion can be beneficial in being easy to be actuated by a user that would not be able to actuate the actuator cap 708 by pressing the cap in the actuating direction AD1 , for example, for a continuous or large-dose dispensing event of for example, of about 30 seconds at a time, due to the sustained force required to maintain the cap 708 pressed in the actuating direction AD1 for the continuous or large-dose dispensing event and / or due to a decrease in temperature of the cap 708 as a result of the coolant flowing through it for the continuous or large-dose dispensing event that may result in discomfort to the user if the cap 708 is actuated by pressing. Furthermore, an alternative actuator cap may be configured to be actuated both when pressed in the actuating direction AD1 and when twisted in the actuating direction AD2, for example, to allow for different dispensing modes, such as a discrete or small-dose dispensing mode when pressed in the actuating direction AD1 to dispense, for example, for about 1 to about 5 seconds at a time, and a continuous (or large-dose) dispensing mode when twisted in the actuating direction AD2 to dispense, for example, for about 30 seconds at a time. FIG. 12 depicts another view of the example intranasal cryotherapy device 700. In FIG. 12, an inlet 804 is shown inserted into a cap receiving member 1 104, as discussed above. FIG. 12 further shows the canister 704 including a canister cover 1200. The canister cover 1200, which may bemade of a high-strength, wear, and corrosion resistant metal such as stainless steel, aluminum, etc. The canister cover 1200 can be crimped to the body of the canister 704 to seal the canister 704. The canister cover 1200 has a top end 1204 that is configured to engage with and support the connectors 1100, for example, by interference fitting, by means of a threaded connection, by adhesive bonding, etc. The top end 1204 is provided with a pair of apertures so that the inlets 804 can be inserted through the canister cover 1200 into the connectors 1 100.

[0042] FIG. 13 depicts a front plan view of another example nasal catheter 1300 that may be made of a rigid or a semirigid medical-grade material such as, for example, a medical grade polymer, and may further optionally include an outer layer of a medicalgrade cushioning material such as, for example, silicone, polyurethane, a memory foam, etc. The nasal catheter 1300 includes a cap duct 1304 to connect the nasal catheter 1300 to an outlet of an actuator cap such as outlet 808 of the example actuator cap 708 of the example intranasal cryotherapy device 700. The nasal catheter 1300 further includes left and right nose inserts 1308-L and 1308-R, respectively, each of which can include a nostril insert section and a nasal cavity insert section configured for ease of insertion of the nose inserts 1308 into the nose of a user. The nasal cavity insert section may be made of a soft, flexible medical-grade material such as, for example, silicon, Polyurethane (PU), PE, Polyvinyl Chloride (PVC), Polytetrafluoroethylene (PTFE), Nylon, PP, etc. to be easily inserted past the nasal opening into the nasal cavity. The nasal catheter 1300 further includes a manifold 1312 to which the cap duct 1304 and the nose inserts 1308 are fluidly connected, so that fluid flowing from an intranasal cryotherapy device such as device 700 when the actuator cap 708 is actuated is directed through the nasal catheter to each of the nose inserts 1308. The nasal catheter 1300 can further include a set of bifurcated ducts 1316 to regulate and direct the fluid flow through the nasal catheter 1300. The bifurcated ducts 1316 may be made of a flexible medical-grade material. If the device 700 is configured to deliver a mix of coolant and air to the nasal catheter 1300, such as, by mixing the coolant and air in the internal chamber 812 of the actuator cap 708, for example, through the passage or set of passages 1012, the nasal catheter 1300 can include at least one bifurcated duct 1316 with a first end to receive the mix of the coolant and air from the outlet 808 and a second and third ends opposite the first end so that themix is directed towards exits of each of the nose inserts 1308. If the device 700 is configured to deliver the coolant and air separately to the nasal catheter 1300, the nasal catheter can include at least two bifurcated ducts 1316 so that the coolant and the air are separately directed towards exits of each of the nose inserts 1308. Furthermore, each of the nose inserts 1308 can further include a nozzle plate to regulate the flow (pressure, velocity, droplet size, direction of flow, imparting a swirl, etc.) of the coolant and air as they are delivered to the user. A mixing chamber can be defined by a gap interior to each of the nose inserts 1308 between the exit of each nose insert 1308 and corresponding ends of the bifurcated ducts 1316 that deliver the coolant and air to the exit of the nose inserts 1308, where the coolant and air may be mixed.

[0043] Although the invention has been described with reference to certain specific embodiments, various modifications thereof will be apparent to those skilled in the art without departing from the spirit and scope of the invention as outlined in the claims appended thereto. For example, while the example devices 100, 300 and 700 connected to 1300 have been shown to be configured to deliver a mix of a coolant and air to the cribriform plate of a user to cool the brain of the user, a alternative devices may be configured to include additional ducts and storage units to deliver an additional fluid or fluids such as, for example, supplementary air, oxygen, a pharmaceutical agent, etc. or combinations thereof to the cribriform plate of the user in addition to a mix of coolant and air. Furthermore, additional external ducts may be provided, for example, configured to be connected to additional internal ducts of alternative nasal catheters, for example, by connecting at the manifold of the alternative intranasal catheters, and additional external storage units may also be provided to store and deliver the additional fluid or fluids to the user. Additionally, while the example coolant storage unit 306-C and the canister 304 have been disclosed to function together to dispense coolant when the coolant valve 404- C is opened, alternatively, the coolant storage unit 30-6 may be differently configured, for example, by being made of a high-strength, wear, and corrosion resistant medical-grade metal such as stainless steel, titanium, cobalt-chromium, nickel-titanium, tantalum, etc. and storing the coolant at an elevated pressure, for example, at a pressure between about 2 bar and about 10 bar so that when the coolant valve 404-C is opened, the coolant is delivered by the device without the need of an additional propellant. Additionally, whilethe example ducts 312, 204 and 208, and 224 have been described as separate elements that are assembled together, they may alternatively be manufactured as a single unit and assembled into the other elements of the device.

[0044] A person skilled in the art will now appreciate that the teachings herein can improve the treatment of migraine by using the disclosed example devices or modifications thereof, which enable targeted cryotherapy that efficiently cools the brain, without the need of a pharmacologic treatment, which can often have undesirable sideeffects. Additionally, the device may be used to help treat an episode of heatstroke. Additionally, the disclosed example devices or modifications thereof may be manufactured to be compact and highly portable, facilitating a user to use the device outside a dedicated medical facility. Furthermore, the disclosed nasal catheter or modifications thereof, by having nasal cavity inserts of reduced measurements that reach only partially into the nasal cavity, may be minimally invasive and non-intimidating to use by a user, thereby facilitating its use by the user without the need of assistance by expert medical personnel. Additionally, the disclosed design of the nasal catheter or modifications thereof may enable a single nasal catheter design to be used by a wide variety of users of different sizes.

[0045] The scope of the claims should not be limited by the embodiments set forth in the above examples but should be given the broadest interpretation consistent with the description as a whole.

[0046] It should be recognized that features and aspects of the various examples provided above can be combined into further examples that also fall within the scope of the present disclosure. In addition, the figures are not to scale and may have size and shape exaggerated for illustrative purposes.

Claims

CLAIMS1 . An intranasal cryotherapy device comprising: a canister with an actuator, the canister configured to store a coolant and compressed air and to dispense the coolant and compressed air when actuated; and an intranasal catheter including: a manifold with: a pair of inlet ducts configured to receive the coolant and the compressed air; and two pairs of outlet ducts configured to output the coolant and the compressed air; a pair of tubular nostril inserts protruding away from the manifold; a pair of tubular nasal cavity inserts protruding away from the nostril inserts, each of the tubular nasal cavity inserts including a nozzle plate at an outlet distal from the nostril inserts; and two pairs of delivery ducts, each pair of the delivery ducts extending through an interior of each of the tubular nostril inserts and of the nasal cavity inserts, a first end of each of the delivery ducts connected to one of the outlet ducts and a second end of each of the delivery ducts proximal to one of the nozzle plates, forming a mixing chamber in an intermediary space between the second end of the delivery ducts and the nozzle plates interior to the nasal cavity inserts.

2. The device of claim 1 wherein the nostril inserts have a length of about 3 cm.

3. The device of claim 1 wherein the nasal cavity inserts extend a length of about 1 cm beyond the nostril inserts.

4. The device of claim 1 wherein the coolant is a perfluorocarbon.

5. The device of claim 2 wherein the coolant is perfluorohexane.

6. The device of claim 1 wherein the coolant is at least one of carbon dioxide and nitrogen.

7. The use of the device of claim 1 to treat migraine.

8. The use of the device of claim 1 to treat heatstroke.

9. The device of claim 1 wherein the actuator includes an actuation mechanism configured to dispense a dose of the coolant and the compressed air for up to about 30 seconds.

10. An intranasal catheter including: a manifold with: a pair of inlet ducts configured to receive two different fluids; and two pairs of outlet ducts configured to output the two different fluids; a pair of tubular nostril inserts protruding away from the manifold; a pair of tubular nasal cavity inserts protruding away from the nostril inserts, each of the tubular nasal cavity inserts including a nozzle plate at an outlet distal from the nostril inserts; and two pairs of delivery ducts, each pair of the delivery ducts extending through an interior of each of the tubular nostril inserts and of the nasal cavity inserts, a first end of each of the delivery ducts connected to one of the outlet ducts and a second end of each of the delivery ducts proximal to one of the nozzle plates, forming a mixing chamber in an intermediary space between the second end of the delivery ducts and the nozzle plates interior to the nasal cavity inserts.11 . The intranasal catheter of claim 10 wherein the nostril inserts have a length of about 3 cm.

12. The intranasal catheter of claim 10 wherein the nasal cavity inserts extend a length of about 1 cm beyond the nostril inserts.

13. The use of the intranasal catheter of claim 10 as part of a cryotherapy device to treat migraine.

14. The use of the intranasal catheter of claim 10 as part of a cryotherapy device to treat heatstroke.

15. An intranasal cryotherapy device comprising: a canister with an actuator cap, the canister configured to separately store a coolant and compressed air and to dispense a mixture of the coolant and compressed air when the actuator cap is actuated; and an intranasal catheter including: a manifold; a cap duct fluidly connected to the manifold, the cap duct configured to connect the intranasal catheter to the actuator cap of the intranasal cryotherapy device; and two nose inserts fluidly connected to the manifold, the nose inserts configured to be inserted to the nose of a user and deliver the mixture of the coolant and compressed air to the user when the actuator cap is actuated.

16. The intranasal cryotherapy device of claim 15 wherein each of the nose inserts includes a nostril insert section and a nasal cavity insert section.

17. The intranasal cryotherapy device of claim 15 wherein the intranasal catheter further includes a set of ducts to regulate and direct a flow of the mixture of the coolant and compressed air through the nasal catheter.

18. The intranasal cryotherapy device of claim 17 wherein the set of ducts includes at least one duct to direct the flow of the mixture of the coolant and compressed air from the cap duct to each of the nose inserts and at least one additional duct to direct an additional fluid to the nose inserts.

19. The intranasal cryotherapy device of claim 18 further comprising a storage unit for the additional fluid fluidly connected to the at least one additional duct.

20. The use of the device of claim 15 to treat at least one of migraine and heatstroke.

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