Animal intranasal dosing device, system, and related methods

Abstract

A veterinary subject intranasal administration device and related systems and methods are disclosed. The veterinary subject intranasal administration device can include a first support member portion including a septum interface portion sized for insertion into a nasal passage of a veterinary subject, an actuation mechanism connected to the first support member portion, and a fluid conduit having a distal end opposite a supported end, the distal end sized for insertion into the nasal passage of the veterinary subject, the fluid conduit being flexible and configured to receive fluid from a fluid source and discharge the fluid into the nasal passage through the distal end, the distal end of the fluid conduit being unsupported and movable relative to the septum interface portion.

Description

[0001] Cross-references to related applications

[0002] This application is a divisional application of Chinese Patent Application No. 201780044424.X. This application claims the benefit of U.S. Patent Application No. 62 / 364,808, filed July 20, 2016, which is incorporated herein by reference in its entirety. Background Technology

[0003] Nitric oxide gas has antibacterial effects and, when safely administered, can be used as a therapeutic treatment for microbial infections in subjects. While numerous systems have been described for the use of nitric oxide in clinical settings, these systems are designed to deliver nitric oxide gas to subjects in a manner requiring the subject to remain still for an extended period. Unfortunately, many cases where nitric oxide therapy would be particularly beneficial do not allow subjects to remain still or immobile for the length of time required to receive an effective dose of nitric oxide gas.

[0004] For example, one such case is in the cattle industry, where Bovine Respiratory Disease Syndrome (BRDc) remains the most common disease in beef cattle fed in North America, affecting 20-40% of affected calves annually. Production losses due to BRDc include respiratory morbidity and mortality, as well as increased treatment and management costs. Its pathogenicity is associated with primary viral infection, followed by secondary bacterial infection.

[0005] Although the incidence of BRDc has been shown to decrease in animals treated with appropriate doses of nitric oxide gas, the effective commercialization of this therapy remains impractical due to time constraints in administration. Therefore, there is a need for an apparatus, system, and method for the rapid and efficient delivery of effective doses of nitric oxide gas.

[0006] The background art described herein is used to explain the context of the invention. This should not be construed as an admission or implication that, on the priority date of any claim, in the United States or any other country, any material mentioned is public, known, or part of the common general knowledge of the art to which this invention pertains. Summary of the Invention

[0007] In one aspect, devices for intranasal administration of a fluid to a veterinary subject are provided. In some embodiments, an intranasal administration device for a veterinary subject includes a first support member portion including a septum interface portion sized for insertion into a nasal passage of the veterinary subject, an actuation mechanism coupled to the first support member portion, and a fluid conduit having a distal end opposite a supported end, the distal end sized for insertion into the nasal passage of the veterinary subject, the fluid conduit being flexible and configured to receive a fluid from a fluid source and discharge the fluid into the nasal passage through the distal end, the distal end of the fluid conduit being unsupported and movable relative to the septum interface portion.

[0008] In some embodiments, an intranasal administration device for a veterinary subject includes a first member pivotally coupled to a second member, each of the first and second members including an arm, wherein the arm of the first member is pivotally coupled to the arm of the second member, a handle portion coupled to and extending proximally from the arms, and a clip coupled to and extending distally from the arms and having a distal end, wherein the distal end of the clip of the first member and the distal end of the clip of the second member are configured to pinch a nasal septum of the veterinary subject, a fluid conduit supported by the first member and having a distal end separate from the distal end of the clip of the first member, and a second fluid conduit supported by the second member and having a distal end separate from the distal end of the clip of the second member. The first and second fluid conduits extend beyond a flow constriction formed by alar folds and basal folds of the veterinary subject for delivery of fluid into the veterinary subject when the intranasal administration device is pinched to the nasal septum.

[0009] In another aspect, a method of intranasally delivering a fluid to a veterinary subject is provided. In some embodiments, the method includes opening a clamp of an intranasal administration device, the intranasal administration device including a fluid conduit; inserting the clamp and fluid conduit into a nostril of the veterinary subject; clamping a nasal septum of the veterinary subject with the clamp to retain the fluid conduit in the nasal portion of the veterinary subject; and discharging a fluid through the fluid conduit. An animal intranasal administration device can include a first support member pivotally coupled to a second support member, each of the first and second support members including an arm, wherein the arm of the first support member is pivotally coupled to the arm of the second support member; a handle portion coupled to and extending proximally from the arms; a clamp coupled to and extending distally from the arms, wherein the clamp of the first support member and the clamp of the second support member are configured to clamp a nasal septum of an animal; a first fluid conduit supported by the first support member and having a distal end; and a second fluid conduit supported by the second support member and having a distal end, wherein the first and second fluid conduits extend beyond a flow constriction formed by a wing fold and a base fold of the animal for delivering a fluid into a nasopharynx of the animal when the animal intranasal administration device is clamped to the nasal septum.

[0010] Thus, various features of the present application have been quite broadly outlined in order that the detailed description thereof that follows can be better understood, and in order that the present contribution to the art can be better appreciated. BRIEF DESCRIPTION OF DRAWINGS

[0011] The following detailed description of embodiments of the application will better be understood from the following DETAILED DESCRIPTION in connection with the appended drawings. It should be understood, however, that the application is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings.

[0012] Figure 1 is a schematic illustration of an animal intranasal administration system according to an example of the present disclosure.

[0013] Figure 2A is a schematic illustration of an animal intranasal administration system according to another example of the present disclosure.

[0014] Figure 2B is a schematic illustration of an animal intranasal administration system according to yet another example of the present disclosure.

[0015] Figure 2C is a schematic illustration of an animal intranasal administration system according to still another example of the present disclosure.

[0016] Figure 3A is a perspective view of an animal intranasal administration device according to an example of the present disclosure.

[0017] Figure 3B is engaged with the septum of an animal Figure 3A bottom view of an animal intranasal dosing device.

[0018] Figure 3C is engaged with the septum of an animal Figure 3A side view of an animal intranasal dosing device.

[0019] Figure 4 is a separate view of an animal intranasal dosing device nozzle according to an example of the disclosure.

[0020] Figure 5 is a perspective view of an animal intranasal dosing device according to another example of the disclosure.

[0021] Figures 6A-6C illustrates several aspects of an animal intranasal dosing system according to another example of the disclosure.

[0022] Figure 7 is a perspective view of an animal's head showing an intranasal dosing device coupled to the animal's nose according to another example of the disclosure.

[0023] Figure 8 and Figure 9 is Figure 7 perspective and top views of an intranasal dosing device illustrated in

[0024] Figure 10 and Figure 11 are perspective and side views of a nasal passage nozzle included in an intranasal dosing device according to another example of the disclosure.

[0025] Figure 12 is Figure 7 rear view of an intranasal dosing device illustrated in

[0026] Figure 13 is a perspective view of an animal's head showing an intranasal dosing device coupled to the animal's nose according to yet another example of the disclosure.

[0027] Figures 14 to 16 is Figure 13 perspective, top, and rear views of an intranasal dosing device illustrated in

[0028] Figure 17 is a schematic illustration of a cross-sectional head of a bovine animal.

[0029] Corresponding reference numerals indicate corresponding parts throughout the several views. While the drawings illustrate embodiments according to the present disclosure, the drawings are not necessarily drawn to scale and certain features can be exaggerated to better illustrate and explain the present disclosure. The examples set forth herein are not to be construed as limiting the scope of the application in any manner. DETAILED DESCRIPTION

[0030] Each of the following terms has the meaning associated with it in this section.

[0031] As used herein, when referring to a measurable value such as an amount, a duration, and so on, "about" means including a variation of ±20%, ±10%, ±5%, ±1%, and ±0.1% of the specified value, as such variations are appropriate to the particular context. It is understood that the use of the term "about" in relation to a numerical value encompasses support for the exact numerical value as if the term "about" were not used.

[0032] The terms "comprises", "comprising", "includes", and "including" and the like can have the meaning ascribed to them in U.S. patent law and can mean "includes", "including", and the like and are generally interpreted to be open ended terms. The term "consisting of" or "consists of" is a closed term and only includes components, structures, steps, etc. specifically listed in the specification, as well as those that are self-evident to one of ordinary skill in the art based on the disclosure.

[0033] The terms "first", "second", "third", "fourth" and the like, if any, as used in this specification are used as identifiers to describe similar elements and are not necessarily used to describe a particular sequential or chronological order. It is to be understood that any terms so used are not to be construed as limiting the scope of the embodiments described herein in any way. As used herein, the indefinite articles "a" and "an" are intended to have the meaning defined by the U.S. Patent Office in 35 U.S.C. § 112(f) and are not intended to be limiting.

[0034] The singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0035] As used herein, "NORS" can refer to a nitric oxide releasing solution or substance. In one aspect, the NO released from the NORS can be a gas.

[0036] As used herein, "gaseous nitric oxide" or "gNO" refers to exogenous nitric oxide. The gNO can be delivered to the veterinary subject itself or can be delivered through a NORS.

[0037] The term "veterinary subject" refers to a non-human animal or individual. Some non-limiting examples of veterinary subjects can include bovines, goats, swine, poultry, canines, felines, equines, bison, alpacas, llamas, sheep, and the like. In one embodiment, the veterinary subject can be a bovine. In another embodiment, the veterinary subject can be a chicken, a rooster, a duck, a goose, a pheasant, or other poultry. In another embodiment, the veterinary subject can be a domestic pig or other swine. In another embodiment, the veterinary subject can be a dog or a cat. In another embodiment, the veterinary subject can be a ferret or a mink. In yet another embodiment, the veterinary subject can be a commercially marketed animal.

[0038] The occurrence of the phrase "in one embodiment" or "in one aspect" herein does not necessarily all refer to the same embodiment or aspect.

[0039] As used herein, a "therapeutic agent" refers to an agent that can have a beneficial or positive effect on a veterinary subject when administered to the veterinary subject in an appropriate or effective amount. In one aspect, NO can be a therapeutic agent.

[0040] As used herein, an "effective amount" of an agent is an amount sufficient to accomplish a specified task or desired function of the agent. As used herein, the phrase "therapeutically effective amount" refers to an amount sufficient to, or effective for, preventing or treating a disease or condition (delaying or preventing its onset, preventing its worsening, inhibiting, reducing, or reversing it) in a subject. It should be understood that various biological factors can influence the ability of a substance to perform its intended task. Thus, in some instances, a "therapeutically effective amount" can be dependent on such biological factors. Moreover, while a veterinarian or other qualified veterinary personnel can use assessments known in the art of the technology to measure the achievement of therapeutic effects, it should be recognized that individual differences and responses to treatment can make the achievement of therapeutic effects somewhat subjective determinations. The determination of an effective amount or therapeutically effective amount is well within the capabilities of those of ordinary skill in the art of pharmaceutical science and medicine.

[0041] As used herein, a plurality of items, structural elements, compositional elements, and / or materials can be presented in a common list for convenience. However, these lists should be construed as though each member of the list is individually identified as a separate and unique member. Thus, no individual member of such list should be construed as a de facto equivalent of any other member of the same list.

[0042] Throughout this disclosure, various aspects of the application can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and does not

[0043] In one aspect, the present disclosure provides an animal intranasal administration device and related systems and methods related to a nitric oxide releasing solution (NORS) capable of reducing the presence of bacteria, viruses, or other pathogens in a veterinary subject. In one aspect, the present disclosure provides a method and apparatus for treating a subject animal by delivering a nitric oxide releasing solution to a treatment site of the veterinary subject, such as at least a portion of the upper respiratory tract of the animal.

[0044] The present disclosure allows for the delivery of nitric oxide to ambulatory veterinary subjects, or to a pipeline of veterinary subjects, where the administration protocol for delivering a nitric oxide releasing solution is completed in a short period of time. For example, the extended release and delivery of nitric oxide to the treatment site by the administered nitric oxide releasing solution allows the treated subject to remain ambulatory during treatment, or to be stationary for a very short period of time. Thus, the veterinary subject is not confined to the nitric oxide delivery device during the entire duration of the nitric oxide delivery. Rather, the nitric oxide releasing solution can be administered to the subject for a short treatment duration, and after administration, the nitric oxide releasing solution will continue to deliver an extended release of a therapeutically effective amount of nitric oxide to the subject. The ability of the subject to remain ambulatory during treatment is particularly important in cattle, as cattle or other veterinary subjects can become stressed when they are restrained, such as in a stanchion, and the stress can exacerbate and increase the incidence of BRDc. In some embodiments, it can be desirable to guide the fluid conduit without the animal fully supporting the intranasal administration device, for example in relation to a companion animal. Rather, the animal's head can be held while the fluid conduit is inserted until the depth limit surface contacts the animal's nose and the fluid is discharged, at which point the device can be removed.

[0045] In certain embodiments, the nitric oxide releasing solution is prepared prior to initiating administration to the subject by administering an acidifying or activating agent (e.g., citric acid) to the resting NORS solution. Alternatively, sodium nitrite can be administered to the resting acidified solution. Either mechanism can be selected and used based on a number of performance factors, such as shelf life, etc. For example, administering an acidifying agent to the resting solution results in a decrease in the pH of the resting solution, thereby activating the nitric oxide releasing solution to be administered to the treatment site. Importantly, the nitric oxide releasing solution can achieve prolonged production of nitric oxide, e.g., for a period of time beyond that required to administer the nitric oxide releasing solution. In one embodiment, the nitric oxide releasing solution produces nitric oxide for a period of between 1 minute and 24 hours. In one embodiment, the nitric oxide releasing solution produces nitric oxide for a period of between 10 minutes and 45 minutes. In one embodiment, the nitric oxide releasing solution produces nitric oxide for at least 15 minutes. In one embodiment, the nitric oxide releasing solution produces nitric oxide for at least 30 minutes. In another embodiment, the nitric oxide releasing solution produces nitric oxide for at least 1 hour. In another embodiment, the nitric oxide releasing solution produces nitric oxide for at least 4 hours. In another embodiment, the nitric oxide releasing solution produces nitric oxide for at least 8 hours. In another embodiment, the nitric oxide releasing solution produces nitric oxide for at least 12 hours. In another embodiment, the nitric oxide releasing solution produces nitric oxide for at least 24 hours. Thus, the administered nitric oxide releasing solution achieves continuous delivery of nitric oxide to the treatment site of the subject. It should be noted that in some embodiments, the treatment site can be at or near the location of NORS administration (e.g., the upper respiratory tract). However, in some embodiments, the treatment site (i.e., the location where nitric oxide therapy is desired) can be remote from the location of NORS administration (e.g., the lower respiratory tract).

[0046] The nitric oxide releasing solution can be administered to the subject in a variety of forms. As will be appreciated by those skilled in the art, the nitric oxide releasing solution can be administered as a liquid, a spray, a vapor, a microdroplet, a mist, or any form that provides release of nitric oxide from the solution. In one embodiment, the nitric oxide releasing solution is administered as a spray. In another embodiment, the nitric oxide releasing solution is administered as a vapor. In another embodiment, the nitric oxide is administered as a gas. The amount or dose volume of the nitric oxide releasing solution administered can vary in order to optimize the duration of nitric oxide production and delivery. In one embodiment, the amount of the nitric oxide releasing solution administered to the subject is between about 0.1 mL and 5000 mL. In another embodiment, the amount of the nitric oxide releasing solution administered to the subject is between about 10 mL and 1000 mL. In one embodiment, the amount of the nitric oxide releasing solution administered to the subject is about 2 mL. In one embodiment, the amount of the nitric oxide releasing solution administered to the subject is about 10 mL. In one embodiment, the amount of the nitric oxide releasing solution administered to the subject is about 32 mL. In another embodiment, the amount of the nitric oxide releasing solution administered to the subject is about 160 mL. These amounts or other amounts can be administered in a single spray or in multiple sprays (e.g., 2, 3, 4, 5, 6, or 8-10 sprays) over a given dose time (e.g., over a 1 minute, 30 seconds, 10 seconds, 5 seconds, 2 seconds, or any other window of time deemed appropriate or beneficial for administering a single or multiple sprays). The nitric oxide releasing solution can be re-administered one or more times as necessary to effectively treat the subject. In one embodiment, the nitric oxide releasing solution is administered to the subject once. In another embodiment, the nitric oxide releasing solution is administered to the subject multiple times, with the nitric oxide releasing solution being re-administered substantially after the extended release of nitric oxide gas from a previous dose administered is complete.

[0047] In certain embodiments, the nitric oxide releasing solution is administered directly into the upper respiratory tract of the subject. For example, in one embodiment, the nitric oxide releasing solution is sprayed into the upper respiratory tract of the subject. The solution can be administered into the upper respiratory tract of the subject once per hour, once per day, once per week, once per two weeks, once per month, once per two months, once per year, and any and all ranges therebetween as necessary to treat the subject. In one embodiment, the solution is sprayed once per week. In another embodiment, the solution is sprayed once per week for four consecutive weeks. The nitric oxide releasing solution enables extended production of nitric oxide, providing continuous delivery of therapeutic nitric oxide to the respiratory system of the subject.

[0048] The duration of administration of the nitric oxide releasing solution to the subject can vary in order to achieve the desired delivery. In one embodiment, the nitric oxide releasing solution is administered to the subject over a period of less than 5 seconds. In another embodiment, the nitric oxide releasing solution is administered to the subject over a period of about 5 seconds. In another embodiment, the nitric oxide releasing solution is administered to the subject over a period of about 30 seconds. In another embodiment, the nitric oxide releasing solution is administered to the subject over a period of about 1 minute. In another embodiment, the nitric oxide releasing solution is administered to the subject over a period of about 2 minutes. In another embodiment, the nitric oxide releasing solution is administered to the subject over a period of about 10 minutes. In another embodiment, the nitric oxide releasing solution is administered to the subject over a period of about 30 minutes.

[0049] In one aspect, the principles disclosed herein enable the treatment, prevention, or reduction of a respiratory disease or condition in a subject. Exemplary respiratory diseases or conditions that can be treated include, but are not limited to, BRDc, porcine respiratory disease complex (PRDc), and the like. In some cases, the respiratory disease or condition can be caused by bacteria (e.g., Mannheimia haemolytica, Histophilus somni, Mycobacterium), fungi, viruses (e.g., infectious bovine rhinotracheitis (IBR), bovine parainfluenza virus-3 (PI-3), and bovine respiratory syncytial virus (BRSV)), protozoa, parasites, and / or arthropods, including bacteria that have developed resistance to one or more antibiotics. Treatment of a respiratory disease by the present disclosure includes delivering a nitric oxide releasing solution into the upper respiratory tract of a subject to be treated. For example, in certain embodiments, the nitric oxide releasing solution can be sprayed, inhaled, or instilled into the respiratory tract of a subject. The nitric oxide releasing solution can be administered to the respiratory tract of a subject through the nasal or oral cavity of the subject. In one embodiment, the nitric oxide releasing solution is sprayed into the upper respiratory tract of a subject. In one embodiment, the solution is administered to a subject intranasally. In one embodiment, the solution is administered to the sinuses of a subject. The nitric oxide releasing solution enables extended production of nitric oxide, thereby providing continuous delivery of therapeutic nitric oxide to the respiratory tract of a subject.

[0050] Reference is made to Figure 1 FIG. 1 shows an animal intranasal administration system 100 according to an example of the present disclosure. The system 100 can include an animal intranasal administration device 101 that can be used to administer a fluid (e.g., a nitric oxide releasing solution) to a nostril 103 of an animal 104. The system 100 can also include a fluid source 102 for providing the fluid to the intranasal administration device 101. In one aspect, the fluid provided by the fluid source 102 and / or administered by the device 101 to the animal 104 can be in a liquid or gaseous state. In some embodiments, the liquid can be prepared to have a desired viscosity.

[0051] The intranasal administration device 101 can include a nasal passage nozzle 110 for each nostril, configured to receive fluid from a fluid source 102 fluidly coupled to the nasal passage nozzle, such as through a fluid conduit 120. The intranasal administration device 101 can also include a biasing mechanism to bias the nasal passage nozzles toward the septum 105 of the animal 104, such that the device is held in place around the septum during administration of fluid into the nasal passage of the animal. The biasing action of each nozzle toward the septum allows the nasal passage nozzle or other components of the device to effectively pinch the septum when it is on the opposite side of the septum. The device can then be held in place while it pinches the septum. The animal intranasal administration system 100 can also include a pump 121 operable to deliver fluid from the fluid source 102 to the nasal passage nozzles 110. The pump 121 can be a motorized pump powered by electricity and / or a pump operated by hand. Any pump sufficient to deliver NORS in a volume and at a rate to provide effective NO therapy can be used. In one example, NORS can be delivered at a rate sufficient to ensure delivery of the NORS liquid to the pharyngeal tonsil material in the upper airway. Other delivery parameters and characteristics, such as volume, delivery time and variation, can be selected and controlled in order to achieve a particular result, such as a particular volume of NORS can be placed at a particular physical location within the subject, for example, the set volume can be delivered at a varying pressure, or the set time can be used at a fixed pressure in order to achieve the desired volume.

[0052] In one example, a hand-operated pump (e.g., a trigger-operated vacuum hand pump) can be "inline" coupled to the fluid conduit 120 in order to deliver fluid to the device 101 without the use of electricity. In one aspect, the fluid source can be carried by the user when in use. In some embodiments, the system 100 can include one or more carrying straps 126 that can be coupled to the fluid source 102 (e.g., directly coupled or coupled through a backpack or other portable case) to facilitate carrying by the user. Thus, in certain embodiments, the system 100 can be portable and entirely powered by the user. In alternative embodiments, the fluid source can be substantially stationary, and in some cases, can be attached to a stand or other fixture. This embodiment can be advantageous when treating a large number of subjects, as it allows for the use of a large amount of nitric oxide releasing solution (i.e., from a large container).

[0053] The system 100 can include one or more valves associated with the fluid source 102, the fluid conduit 120, and / or the apparatus 101 to control the flow of fluid to the nasal passage nozzles 110, such as to control the fluid dosage to the animal 104. For example, a valve 106 can be located at or near the fluid source 102, and a valve 107 can be located at or near the apparatus 101, although valves can be disposed in any suitable location. In one aspect, a valve can be associated with one or both of the nasal passage nozzles 110 to control the flow of fluid to a particular nozzle. Any other mechanism for metering out a particular volume or dosage of nitric oxide releasing solution for administration to a subject can also be used, including only the amount of time (i.e., the dosing period) and the flow rate at which the solution is administered, among others.

[0054] In some embodiments, the fluid source 102 can include the inactivated nitric oxide releasing solution 123, the activator 124, the activated nitric oxide releasing solution, and / or the nitric oxide gas. The activator 124 can be configured to activate the inactivated nitric oxide releasing solution 123 upon mixing. In one aspect, the activator 124 can be maintained separate from the inactivated nitric oxide releasing solution 123. The activator 124 can be in any suitable form, such as a solid (e.g., a powder, a tablet, and a capsule), a liquid (e.g., a solution), a gas, and the like. The fluid source 102 can also include one or more containers 122 or reservoirs for the inactivated nitric oxide releasing solution 123, the activator 124, the activated nitric oxide releasing solution, and / or the nitric oxide gas. Generally, the activator 124 and the inactivated nitric oxide releasing solution 123 can be mixed at least partially in a mixing chamber 125, which can be within the container 122. Thus, in one aspect, the inactivated nitric oxide releasing solution 123 can be activated within the container 122 and dispensed or delivered to the apparatus 101 for administration to the animal 104. A pump 121 can transport the activated nitric oxide releasing solution from the fluid source 102 to the apparatus 101. Alternatively, the activated nitric oxide releasing solution can be transported from the fluid source 102 to the apparatus 101 by pressure in the container 122 due to the generation of nitric oxide gas from the activation of the nitric oxide releasing solution. In other words, the increase in gas pressure in the container 122 due to the formation of nitric oxide can cause the activated nitric oxide releasing solution to move from the container 122 to the apparatus 101 through the fluid conduit 120 for delivery to the animal. In such embodiments, the pump 121 can not be needed, or can be utilized in the event that the pressure inside the container 122 becomes insufficient to continue dispensing the nitric oxide releasing solution at the desired rate / volume. In alternative embodiments, as described more fully below, a pump (either electrically or manually operated) can be used to create pressure within the container and facilitate administration of the nitric oxide releasing solution.

[0055] In Figures 2A-2CIn another aspect shown in FIG. 1, the activator and the inactivated nitric oxide releasing solution can be mixed at least partially in a mixing chamber external to the container (such as the container 122) of the fluid source 102. For example, as shown in FIG. 1, the intranasal delivery system 100 can include the fluid source 102 fluidly coupled to the intranasal delivery device 101 (e.g., to the nasal passage nozzle 110) by a conduit 120, which includes a conduit 120a associated with the inactivated nitric oxide releasing solution 123 and a conduit 120b associated with the activator 124, each of which can be disposed in separate containers. The conduits 120a, 120b can be combined prior to the nasal passage nozzle 110 (such as in a mixing chamber 125 internal to the fluid source 102), such that mixing of the inactivated nitric oxide releasing solution 123 and the activator 124 occurs between the fluid source 102 and the nasal passage nozzle 110. Thus, the nitric oxide releasing solution can be activated, or in other words, an activated solution can be formed during delivery or administration of the nitric oxide releasing solution to the subject. Figure 1 In another example shown in FIG. 2, the intranasal delivery system 200 can include the fluid source 202 fluidly coupled to the intranasal delivery device 201 (e.g., to the nasal passage nozzle 210) by a conduit 220, which includes a conduit 220a associated with the inactivated nitric oxide releasing solution 223 and a conduit 220b associated with the activator 224, each of which can be disposed in separate containers. The conduits 220a, 220b can be combined prior to the nasal passage nozzle 210 (such as in a mixing chamber 225 internal to the intranasal delivery device 201), such that mixing of the inactivated nitric oxide releasing solution 223 and the activator 224 occurs between the fluid source 202 and the nasal passage nozzle 210. Thus, the nitric oxide releasing solution can be activated, or in other words, an activated solution can be formed during delivery or administration of the nitric oxide releasing solution to the subject. Figure 2A In another example shown in FIG. 2, the intranasal delivery system 200 can include the fluid source 202 fluidly coupled to the intranasal delivery device 201 (e.g., to the nasal passage nozzle 210) by a conduit 220, which includes a conduit 220a associated with the inactivated nitric oxide releasing solution 223 and a conduit 220b associated with the activator 224, each of which can be disposed in separate containers. The conduits 220a, 220b can be combined prior to the nasal passage nozzle 210 (such as in a mixing chamber 225 internal to the intranasal delivery device 201), such that mixing of the inactivated nitric oxide releasing solution 223 and the activator 224 occurs between the fluid source 202 and the nasal passage nozzle 210. Thus, the nitric oxide releasing solution can be activated, or in other words, an activated solution can be formed during delivery or administration of the nitric oxide releasing solution to the subject.

[0056] In another example shown in FIG. 2, the intranasal delivery system 200 can include the fluid source 202 fluidly coupled to the intranasal delivery device 201 (e.g., to the nasal passage nozzle 210) by a conduit 220, which includes a conduit 220a associated with the inactivated nitric oxide releasing solution 223 and a conduit 220b associated with the activator 224, each of which can be disposed in separate containers. The conduits 220a, 220b can be combined prior to the nasal passage nozzle 210 (such as in a mixing chamber 225 internal to the intranasal delivery device 201), such that mixing of the inactivated nitric oxide releasing solution 223 and the activator 224 occurs between the fluid source 202 and the nasal passage nozzle 210. Thus, the nitric oxide releasing solution can be activated, or in other words, an activated solution can be formed during delivery or administration of the nitric oxide releasing solution to the subject. Figure 2B In another example shown in FIG. 2, the intranasal delivery system 200 can include the fluid source 202 fluidly coupled to the intranasal delivery device 201 (e.g., to the nasal passage nozzle 210) by a conduit 220, which includes a conduit 220a associated with the inactivated nitric oxide releasing solution 223 and a conduit 220b associated with the activator 224, each of which can be disposed in separate containers. The conduits 220a, 220b can be combined prior to the nasal passage nozzle 210 (such as in a mixing chamber 225 internal to the intranasal delivery device 201), such that mixing of the inactivated nitric oxide releasing solution 223 and the activator 224 occurs between the fluid source 202 and the nasal passage nozzle 210. Thus, the nitric oxide releasing solution can be activated, or in other words, an activated solution can be formed during delivery or administration of the nitric oxide releasing solution to the subject.

[0057] In another example shown in FIG. 2, the intranasal delivery system 200 can include the fluid source 202 fluidly coupled to the intranasal delivery device 201 (e.g., to the nasal passage nozzle 210) by a conduit 220, which includes a conduit 220a associated with the inactivated nitric oxide releasing solution 223 and a conduit 220b associated with the activator 224, each of which can be disposed in separate containers. The conduits 220a, 220b can be combined prior to the nasal passage nozzle 210 (such as in a mixing chamber 225 internal to the intranasal delivery device 201), such that mixing of the inactivated nitric oxide releasing solution 223 and the activator 224 occurs between the fluid source 202 and the nasal passage nozzle 210. Thus, the nitric oxide releasing solution can be activated, or in other words, an activated solution can be formed during delivery or administration of the nitric oxide releasing solution to the subject. Figure 2CIn yet another example shown in FIG. 4, an intranasal dosing system 400 can include a fluid source 402 fluidically coupled to an intranasal dosing device 401 (e.g., to the nasal passage nozzles 410) by a conduit 420, which includes a conduit 420a associated with an inactivated nitric oxide releasing solution 423 and a conduit 420b associated with an activator 424, each of which can be housed in separate containers. The conduits 420a, 420b can combine at the nasal passage nozzles 410 (which can form a mixing chamber) such that mixing of the inactivated nitric oxide releasing solution 423 and the activator 424 occurs at the nasal passage nozzles 410. Thus, the nasal passage nozzles 410 can include any suitable structure that can be used to adapt for introduction of solutions from multiple conduits and mixing of the inactivated nitric oxide releasing solution 423 and the activator 424. Thus, the conduits 420a, 420b can remain separate from the fluid source 402 to the nasal passage nozzles 410 such that mixing of the inactivated nitric oxide releasing solution and the activator occurs at the animal engaged by the intranasal dosing device 401. In other words, the nitric oxide releasing solution is activated or formed in vivo at the dosing site or after dispensing from the nozzle.

[0058] In one aspect, each nasal passage nozzle can receive an activation solution or an inactivated nitric oxide releasing solution such that each is separately administered to the animal. Thus, the activation solution and the inactivated nitric oxide releasing solution can be mixed at or within the animal after dispensing from the intranasal dosing device, such as within the nasal passage, to activate the nitric oxide releasing solution. In some embodiments, each nozzle can have a separate opening and support fluid connections to respective sources of activator and nitrite solution (i.e., inactivated NORS). In this way, the solutions from each source can be separately brought to the nozzle, yet simultaneously, synchronously delivered to the subject. The nozzle can have a single opening and can alternately administer the solutions, e.g., a spray of inactivated NORS (i.e., nitrite solution, citric acid), followed by a spray of activator solution (e.g., citric acid, ascorbic acid, nitrite solution, etc.).

[0059] Figures 3A-3C An animal intranasal dosing device 501 according to an example of the disclosure is shown. The intranasal dosing device 501 can include nasal passage nozzles 510a, 510b Figure 3C for each nostril 503 configured to receive fluid from a fluid source as described above. The intranasal dosing device 501 can also include a biasing mechanism 530 to bias the nasal passage nozzles 510a, 510b Figure 3B and 3C toward the septum 505 of the animal such that the device 501 is held in place around the septum 505 during administration of fluid to the nasal passages of the animal.

[0060] In one aspect, the intranasal administration device 501 can include a support member 540 having support member portions 541a, 541b coupled to and supporting the nasal passage nozzles 510a, 510b, respectively. The support member portions 541a, 541b are movable relative to one another (i.e., pivotally coupled to one another at a pivot coupling 543) to at least partially secure the nasal passage nozzles 510a, 510b within the nostrils 503 of the animal around the septum 505 and such that fluid is directed into the nasal passages of the animal. Thus, when the device 501 is engaged with the septum 505 of the animal, the nasal passage nozzles 510a, 510b can be oriented with the nozzle openings 511a, 511b aligned with the nasal passages to effect delivery of fluid to the deep nasal passages.

[0061] In one aspect, the nasal passage nozzles 510a, 510b can be configured to direct fluid into the nasal passages, past nasal folds 508a, 508b that can be present in the animal, as represented in Figure 3B For example, bovine animals can have winged folds, basal folds, and straight folds. Thus, the nasal passage nozzles 510a, 510b can be configured to direct fluid into the nasal passages, past one or more of such folds, to deliver fluid to the deep nasal passages. In one example, the nasal passage nozzles 510a, 510b can be configured to extend or penetrate into the nostril beyond one or more nasal folds 508a, 508b, as shown in Figure 3B In another example, the nasal passage nozzles 510a, 510b can be positioned and oriented to direct fluid past one or more nasal folds without extending or penetrating into the nostril beyond one or more of the nasal folds. In short, given the specific anatomy of a subject, any configuration needed to effectively administer a nitric oxide release solution into the nasal passages or any other desired or designated location in the respiratory tract of any subject in a manner sufficient to allow the subject to receive an effective nitric oxide therapy can be used.

[0062] In one aspect, the support member portions 541a, 541b can be moved relative to one another by a biasing mechanism 530 to bias the nasal passage nozzles 510a, 510b around the septum 50 in directions 531a, 531b toward a fixed position. For example, the biasing mechanism 530 can include springs acting on the support member portions 541a, 541b to bias the support member portions 541a, 541b around the septum 505 toward a fixed position. Thus, the biasing mechanism 530 can cause the nasal passage nozzles 510a, 510b to sandwich the septum 505 therebetween so that the nozzles 510a, 510b are held in place in the nostril 503. While shown as springs, it should be understood that the biasing mechanism 530 can be any device, component, or mechanism sufficient to provide the desired biasing action. Further, the biasing mechanism 530 can be located at any location on the device 501 sufficient to provide the desired biasing action. In one aspect, the biasing or spring strength can be adjusted as desired to secure the device 501 to the animal without causing undue pain to the animal. In one aspect, the support member 540 can be configured to provide a gap around the tip 506 of the septum 505. For example, the support member portions 541a, 541b can include an arcuate configuration to provide a gap around the tip 506 of the septum 505, as shown in Figure 3B

[0063] The intranasal administration device 501 can include septum interface portions 512a, 512b associated with the nasal passage nozzles 510a, 510b, respectively, to interact with the septum 505 and position the nasal passage nozzles to facilitate deep penetration of the fluid into the nasal passage of the animal. For example, the septum interface portions 512a, 512b can be used to space or position the nasal passage nozzles 510a, 510b and openings 511a, 511b at a sufficient distance from the septum 505 to facilitate and maintain a spray or dispersion pattern coverage into the nasal passage without interference from the septum 505.

[0064] ​The intranasal dosing device 501 can also include a positioning member 550 configured to contact the tip 506 of the septum 505 to facilitate and maintain proper positioning and / or orientation of the nasal passage nozzles 510a, 510b within the nostril 503 of the subject such that the nasal passage nozzles 510a, 510b direct fluid in a direction that is approximately aligned with the nasal passage opening of the animal. In this manner, the positioning member 550 can act as a depth stop for maintaining proper positioning and / or orientation of the nasal passage nozzles 510a, 510b within the nostril 503 of the subject. For example, the positioning member 550 can be configured to position the nasal passage nozzles 510a, 510b such that the openings 511a, 511b are located at a depth 554 from the tip 506 of the septum 505 to properly position the nasal passage nozzles 510a, 510b at an appropriate distance relative to the nasal passage opening. In one aspect, the positioning member 550 can include an elongated portion 551 having a longitudinal axis 552 that is approximately parallel to the rotational axis 542 of movement of the support member portions 541a, 541b relative to one another. For example, the positioning member 550 can have a “T” configuration in which a base portion 553 supports the elongated portion 551. The base portion 553 can be coupled to the support member 540 at the pivotal coupling 543 of the support member portions 541a, 541b, e.g., to one or both of the support member portions 541a, 541b. The elongated portion 551 can be configured to contact the muzzle 507 of the animal to prevent or minimize sagging or downward rotation of the device 501 during use, thereby facilitating proper alignment of the nasal passage nozzles 510a, 510b.

[0065] The intranasal dosing device 501 can include a user interface 560 coupled to the support member 540 to facilitate movement of the support member portions 541a, 541b relative to one another by a user. For example, the user interface 560 can include user interface portions 561a, 561b (such as handles) coupled to the support member portions 541a, 541b, respectively, to facilitate movement of the nasal passage nozzles 510a, 510b by a user in a direction opposite the biasing directions 531a, 531b, such as by squeezing the user interface portions 561a, 561b toward one another.

[0066] In one aspect, the intranasal drug delivery device 501 may include one or more nostril nozzles 513a, 513b configured to direct fluid to a subject's nostril 503. In a particular aspect, the nostril nozzles 513a, 513b may be configured to direct fluid to the anterior nasal cavity. The nostril nozzles 513a, 513b may be coupled to a support member 540. For example, the support member 540 may include lateral extensions 544a, 544b to position the nostril nozzles 513a, 513b, respectively. In one aspect, the lateral extensions 544a, 544b may be coupled to and extend from support member portions 541a, 541b, respectively. In another aspect, the intranasal drug delivery device 501 may include one or more nasal nozzles (not shown in these figures) configured to direct fluid to an animal's nasal cavity 507. The nasal nozzle can be supported by one or more of the support member portions 541a, 541b and / or the lateral extension portions 544a, 544b. Therefore, a nitric oxide release solution can be delivered simultaneously or at least to both the nasal passage and the nostrils using a single device.

[0067] Although the intranasal drug delivery device 501 is shown as having a total of four nozzles, it should be understood that the intranasal drug delivery device according to this disclosure may include any suitable number of nozzles having a suitable dispersion or spray pattern oriented at a suitable angle to any suitable area of ​​the animal's nose, mouth, eyes, nostrils, nasal passages, etc. In other words, the nozzle dispersion or spray pattern may be particularly suited to a specific area (i.e., nasal passages, nostrils, nose, mouth, etc.) and may be oriented at any suitable angle to direct fluid onto or into that area. In one aspect, a nozzle may be configured to direct fluid onto multiple areas. For example, nostril nozzles 513a, 513b may be configured to disperse or spray fluid over the nostrils and nose. Thus, the nozzles of the intranasal drug delivery device according to this disclosure may be configured to have various dispersion or spray patterns to cover the nasal passages and the entry surfaces of the nasal passages. Therefore, nozzles used with device 501 may initiate any spray pattern known in the art to suit a given purpose or dispersion target area.

[0068] In one aspect, the intranasal drug delivery device 501 may include a fluid distribution manifold 532 fluidly coupled to a nozzle of the device 501. For clarity, in Figures 3A-3CAn external fluid coupling or conduit, such as a tube or hose, has been omitted. The fluid distribution manifold 532 can have an inlet port 533 for receiving fluid from a fluid source and outlet ports 534a, 534b, 535a, 535b for distributing fluid to various nozzles of the device 501. For example, the outlet ports 534a, 534b can be fluidically coupled to the nasal passage nozzles 510a, 510b, respectively, and the outlet ports 535a, 535b can be fluidically coupled to the nare nozzles 513a, 513b, respectively. Thus, each of the nasal passage nozzles 510a, 510b and the nare nozzles 513a, 513b can be configured to couple with a conduit to receive fluid from a fluid source. While the fluid distribution manifold 532 is shown separate from other structural components of the device 501, such as the support member 540 or the positioning member 550, it should be recognized that the fluid distribution manifold can be coupled to or integrally formed with any structural portion of the device 501, such as one or more portions of the support member 540 and / or the positioning member 550. In one aspect, as described above, the fluid distribution manifold 532 can include at least two inlet ports and a mixing chamber such that mixing of the inactivated nitric oxide releasing solution and the activating agent occurs between the fluid source and the nasal passage nozzles 510a, 510b. In another aspect, the fluid distribution manifold 532 can include one or more valves to control fluid flow to one or more nozzles of the device 501.

[0069] In one aspect, the support member 540 can have internal fluid conduits defined by one or more openings or passageways through the support member 540. For example, one or more of the support member portions 541a, 541b can include at least a portion of a fluid conduit to direct fluid from a fluid source to the respective nasal passage nozzle 510a, 510b. Similarly, one or more of the laterally extending portions 544a, 544b can include at least a portion of a fluid conduit to direct fluid from a fluid source to the respective nare nozzle 513a, 513b. Thus, such internal fluid conduits can receive fluid directly from a fluid source or after distribution from the fluid distribution manifold 532.

[0070] In one aspect, the intranasal administration device 501 can be configured to facilitate interchangeability of components. For example, the support member portions 541a, 541b can be configured to removably couple with the nozzle or spout 514a, 514b, such as by way of fasteners 515. Similarly, the laterally extending portions 544a, 544b can be configured to removably couple with the nozzle or spout 516a, 516b, such as by way of fasteners 515. Additionally, the support member portions 541a, 541b can be configured to removably couple with the user interface portions 561a, 561b. Furthermore, the biasing mechanism 530 or spring can be removably coupled to the support member 540. Thus, the nozzle, spring, handle, positioning member, and the like can be interchanged and replaced as desired to accommodate different animal species and / or different sized animals. Accordingly, the device 501 can be configured and customized for the anatomical structure of a given age of a cow. In one aspect, the intranasal administration device 501 can be disassembled to facilitate cleaning and / or servicing of the various components or assemblies of the device.

[0071] In one aspect, the nozzle or spout 514a, 514b can include or incorporate the nasal passage nozzles 510a, 510b and the septum interface portions 512a, 512b, respectively. As shown in Figures 3A-3C As shown in the figures, the spouts 514a, 514b can have a spherical or bulbous configuration that provides a curved interface surface for the septum interface portions 512a, 512b to contact the septum 505. This spherical curved surface can accommodate various septum thicknesses and maintain consistent interaction with the septum 505. The spherical surface can have a diameter configured to provide sufficient surface area for effective "grip" contact (i.e., clamping) with the septum without providing excessive pressure to the contact area of the septum, such that the device 501 is uncomfortable for the animal. The diameter of the spherical surface can also help provide sufficient space for the nasal passage nozzles 510a, 510b from the septum to provide and maintain a suitable dispersion or spray pattern.

[0072] Figure 4 Nozzles or spouts 614a, 614b are shown that are in accordance with another example of the present disclosure. As with the above-described examples, the spouts 614a, 614b can include or incorporate the nasal passage nozzles 610a, 610b and the septum interface portions 612a, 612b, respectively. Figures 3A-3CLike the spray tips 514a, 514b, the spray tips 614a, 614b can include or incorporate the nasal passage nozzles 610a, 610b and the septum interface portions 612a, 612b, respectively. In this case, the spray tips 614a, 614b have a fan-shaped configuration with arcuate surfaces for the septum interface portions 612a, 612b to contact the septum. This arcuate curved surface can accommodate various septum thicknesses and can be useful when a relatively high contact pressure is desired, as a relatively small contact area can be provided by this configuration. The size of the arcuate surface can also help provide sufficient space for the nasal passage nozzles 610a, 610b from the septum to provide and maintain a suitable dispersion or spray pattern.

[0073] Figure 5 An animal intranasal administration device 701 according to another example of the present disclosure is shown. The intranasal administration device 701 can include nasal passage nozzles 710a, 710b for each nostril configured to receive fluid from a fluid source, as described above. In one aspect, the intranasal administration device 701 can include a support member 740 having support member portions 741a, 741b coupled to and supporting the nasal passage nozzles 710a, 710b, respectively. In one aspect, the support member 740 can be elastically flexible or include an elastically flexible component. Thus, in particular aspects, one or both of the support member portions 741a, 741b can be elastically flexible and thus movable relative to one another to at least partially secure the nasal passage nozzles 710a, 710b within the nostrils of an animal around the septum and cause fluid to be directed into the nasal passage of the animal. The elastically flexible support member portions 741a, 741b can provide a biasing mechanism to bias the nozzles 710a, 710b toward the septum of the animal so that the device 701 is secured in place around the septum during administration of fluid into the nasal passage of the animal. Thus, the elastically flexible support member portions 741a, 741b can bias the nasal passage nozzles 710a, 710b around the septum 70 in directions 731a, 731b toward a secured position. When the device 701 is engaged with the septum of the animal, the nasal passage nozzles 710a, 710b can be oriented with the nozzle openings 711a, 711b aligned with the nasal passage to effect delivery of fluid to the deep nasal passage.

[0074] The intranasal dosing device 701 can also include septum interface portions 712a, 712b associated with the nasal passage nozzles 710a, 710b, respectively, to interact with the septum and position the nasal passage nozzles to facilitate deep penetration of fluid into the nasal passage of the animal. For example, the septum interface portions 712a, 712b can function to space or position the nasal passage nozzles 710a, 710b and openings 711a, 711b away from the septum to facilitate and maintain a spray or jet pattern coverage into the nasal passage without interference from the septum. The septum interface portions 712a, 712b are shown as having a spherical configuration, but can utilize any suitable configuration.

[0075] The intranasal dosing device 701 can also include a positioning member 750 configured to contact the tip of the septum to facilitate and maintain proper positioning and / or orientation of the nasal passage nozzles 710a, 710b within the nostril of the animal such that the nasal passage nozzles 710a, 710b direct fluid in a direction that is approximately aligned with the nasal passage opening of the animal. For example, the positioning member 750 can be configured to position the nasal passage nozzles 710a, 710b such that the openings 711a, 711b are located at a distance from the tip of the septum to properly position the nasal passage nozzles 710a, 710b at a suitable distance relative to the nasal passage opening. In one aspect, the positioning member 750 can be coupled to the support member 740, such as between the support member portions 741a, 741b. The positioning member 750 can be configured to contact the nares of the animal when the device 701 is engaged with the animal to prevent or minimize sagging or downward rotation of the device 701 during use, thereby facilitating proper alignment of the nasal passage nozzles 710a, 710b.

[0076] In one aspect, the intranasal dosing device 701 can include one or more nostril nozzles 713a, 713b configured to direct fluid onto the nostrils of the animal. In particular, the nostril nozzles 713a, 713b can be configured to direct fluid onto the anterior nostrils. In one aspect, the nostril nozzles 713a, 713b can be coupled to the support member 740. For example, the support member 740 can include lateral extension portions 744a, 744b to position the nostril nozzles 713a, 713b, respectively. In another aspect, the intranasal dosing device 701 can include one or more nares nozzles 717 configured to direct fluid onto the nares of the animal. The nares nozzles 717 can be coupled to the support member 740 at any suitable location.

[0077] Figures 6A-6CSeveral aspects of an animal intranasal administration system 800 according to another example of the present disclosure are shown. The system 800 can include an animal intranasal administration device 801 having any suitable configuration described above to administer fluid to a nostril of an animal. The system 800 can also include a fluid source 802 for providing fluid to the intranasal administration device 801, such as through a fluid conduit 820. The fluid source 802 can include a deactivated nitric oxide releasing solution, an activator, an activated nitric oxide releasing solution, and / or nitric oxide gas.

[0078] In one aspect, the fluid source 802 can include a container 822 or reservoir in which a deactivated nitric oxide releasing solution is disposed. The container 822 can have any desired size and shape. In one aspect, the container 822 can be adapted to hold multiple doses or administration volumes of the nitric oxide releasing solution without requiring refilling. The fluid source 802 can also have a fluid outlet port 870 that can be configured to couple with the fluid conduit 820 to deliver fluid to the device 801. The fluid outlet port 870 can be associated with a cap 871 (as shown) or with the container 822. A sump conduit 872 can be fluidly coupled to the fluid outlet port 870 to deliver fluid to the fluid outlet port 870. The sump conduit 872 will generally extend to the bottom of the container 822 to facilitate substantially emptying all fluid from the container 822. The sump conduit 872 can be associated with the cap 871 (as shown) and / or with the container 822 (e.g., molded into the side of the container 822). The fluid source 802 can also include a gas port 873 to allow gas to enter into the container 822 during use of the system 800. For example, the pump 821 can be a gas pump and can be fluidly coupled to the gas port 873 through a conduit to provide pressurized gas (e.g., air or other suitable gas) to the container 822 such that the "headspace pressure" in the container 822 causes fluid to exit the container 822 through the sump conduit 872 and the fluid outlet port 870 for delivery to the device 801 through the fluid conduit 820. The gas port 873 can be associated with the cap 871 (as shown) or with the container 822. The gas port 873 will generally be located above the fluid level of the deactivated nitric oxide releasing solution in the container 822. In one aspect, the container 822 can be pressurized to about 50 psig (typical pressure is about 30) during operation, although the system can also be configured to operate at any suitable pressure. In one aspect, the pump 821 can provide pressure to deliver a particular spray volume into the nare and into the nostril and nasal passages of the animal. In one aspect, a pressure gauge or sensor (i.e., as part of the pump 821) can monitor the pressure in the container 822 and / or the fluid conduit 820 to determine whether the nozzle has become clogged.

[0079] In one aspect, the pump 821 can be a liquid pump and can operate to pump a liquid fluid out of the container 822 without creating a headspace pressure in the container 822. The pump 821 can be a gas pump and / or a liquid pump of any suitable configuration. In one aspect, the pump 821 can be a motorized pump powered by electricity and / or a pump operated by hand. The cap 871 can be provided with a cover 874 to protect the fluid outlet port 870 and the gas port 873 when not in use. The components of the system can be constructed of metals, plastics, and other polymers compatible with the activator (e.g., citric acid, sodium nitrite), the inactivated nitric oxide releasing solution, and nitric oxide.

[0080] In one aspect, the fluid source 802 can include an activator held separate from the inactivated nitric oxide releasing solution. The activator can be configured to activate the inactivated nitric oxide releasing solution upon mixing. Once mixed, the generation of nitric oxide in the solution can create a headspace pressure sufficient to deliver the fluid from the container 822 to the device 801. Thus, with the gas pressure generated by the activation of the nitric oxide releasing solution, the fluid can be automatically dispensed from the device 801 upon mixing of the activator with the inactivated nitric oxide releasing solution.

[0081] The activator can be in any suitable form, such as a solid (e.g., powder, tablet, capsule, etc.), a liquid (e.g., a solution), a gas, etc. In one aspect, the activator in solid form can be in a dissolvable bag and / or supported by a cage 875, which can be configured to be positioned within the container 822 below the liquid level of the inactivated nitric oxide releasing solution to ensure contact or mixing with the inactivated nitric oxide releasing solution. The cage 875 can include one or more openings to facilitate mixing of the activator and the inactivated nitric oxide releasing solution. Thus, when the activator is immersed in the inactivated nitric oxide releasing solution, the activator will dissolve, thereby generating nitric oxide in the solution. The cage 875 can be coupled to the sump conduit 872 (as shown) and supported within the container 822 above the bottom of the container or just fall into the container 822. In one aspect, the cage 875 can be coupled to a rod or tube having an end positioned near the opening of the container 822. Coupling the cage 875 to the sump conduit 872 or the rod or tube can simplify removal of the cage 875.

[0082] In one aspect, the animal intranasal dosing system 800 can be provided as a kit. For example, the container 822 can have device coupling features 880 to couple with and support the device 801. The container 822 can also have a handle 881. The handle 881 can have a free end 826 that can be coupled to the body of the container 822 by coupling features 882, 883. The coupling features 882, 883 can be configured to further capture and secure the device 801 to the container 822. Fluid conduit coupling features 884 can extend from the free end 826 of the handle 881 to capture and secure the fluid conduit 820 to the container 822. Additionally, the pump 821 can be configured to removably couple with the bottom of the container 822. If the pump 821 includes electrical components, a battery pack can be included. A cover 874 can cover the cap 871 and / or the opening of the container 822 when not in use.

[0083] In use of the system 800, an animal can arrive at the corral, and a user can engage the intranasal dosing device 801 with the nostril of the animal, as further described above or below. As the device 801 is secured to the animal, the user can "hands-free" dose fluid to the animal. The fluid source 802 can be supported by the uprights of the corral, and can hold a volume (e.g., 5 gallons) of pre-mixed nitric oxide release solution in its resting state. Once the activator and the non-active nitric oxide release solution are mixed, nitric oxide gas is generated in the solution in the container 822. The activated nitric oxide release solution is then transported from the fluid source to the device 801 and dispensed or sprayed onto the treatment site or area, such as into the nasal passage of the animal. For example, the activated solution can be sprayed into the nasal passage of a cow in short, deliberate bursts. In one aspect, the animal can receive about 8 mL of one spray in each nasal passage twice, for a total of about 32 mL before being released. The duration of the treatment dose can be between about 3-5 seconds. The device 801 can be released or disengaged from the animal at the convenience of the user. The activated solution now lining the nasal passage of the animal can continue to release nitric oxide gas for up to 30 minutes or more.

[0084] Further, the animal intranasal dosing systems 100, 800 can be used in conjunction with any of the intranasal dosing devices according to the present application. Reference is made below to the Figures 7 to 16An additional example of an intranasal dosing device is described. Generally, the embodiments of the intranasal dosing device described below include a fluid conduit that includes a nasal passage nozzle at its distal end. The distal end of the fluid conduit is separated from the septum interface portion so that the nasal passage nozzle can move relative to the clip when the first and second support member portions or clip are closed. The movement can be in the lateral direction and / or in the anterior / posterior direction. The nasal passage nozzle can move into alignment with and into the nasovaginal canal. As used herein, the terms "open" and "closed" mean to separate the clip or bring the clip closer together, respectively. Thus, the clip is opened to enable its insertion into the nostril and closed to pinch the animal's nasal septum. The fluid conduit is fixed to the intranasal dosing device so that the angle formed by the centerline of the fluid conduit at its distal end is smaller when the clip is open and increases when the clip is closed.

[0085] In some embodiments, the fluid conduit is formed of a flexible material. The fluid conduit has a length between its distal end and the area where the fluid conduit is supported by the intranasal dosing device that is sufficient to allow the flexible fluid conduit to bend when the clip is closed due to contact with the tissues of the veterinary subject. Example flexible materials include PVC and vinyl. The combination of self-alignment of the fluid conduit to the nasal septum and / or nasovaginal canal with the depth of insertion of the nasal passage nozzle into the nostril enhances delivery of the fluid into the nasopharynx. In some cases, it is desirable to substantially coat the animal's turbinate, faucial tonsil material, and nasopharynx. As used herein, the nasopharynx is substantially coated when at least 50% of its surface is coated with fluid. Of course, to the extent possible, the nasopharynx should be substantially coated without disturbing or causing trauma to the animal. In some embodiments, the clip is sized and configured to minimally obstruct the animal's breathing during the intervention and the clip is blunted to reduce the likelihood of tissue damage. The distal end of the clip can include a septum interface member that is twice as wide as it is thick to enable pinching while permitting substantially unobstructed breathing of the animal.

[0086] Reference is now made to Figures 7 to 17 , Figure 7is a perspective view of the head of an animal 104 with an intranasal administration device 900 comprising two fluid conduits 918, 919 extending into the nostrils of the animal's nose 902. The intervention is carried out by administering fluid into the nasopharynx 1164 of the animal 104 by means of at least one of the fluid conduits 918, 919. An exemplary intervention includes delivering nitric oxide (in various embodiments described above and variations thereof, including liquid, gas, gas-releasing solution, and combinations thereof) to the nasopharynx to prevent, control, and / or treat bovine respiratory disease in a bovine animal. While the present invention can be described with reference to a particular animal species and disease, the present invention is suitable for any other treatment in an intranasal manner to a subject of any other animal species.

[0087] A schematic illustration of a dissected head of a bovine animal is shown in Figure 17 which shows the alar fold 1150 and the basal fold 1152 at the nose 104 of the animal. The folds form a nasal constriction at the nasal vestibule 1154 which inhibits entry into the nasal passage's ventral meatus 1166. Figure 17 Further shown are the locations of the dorsal concha 1156, the middle concha 1158, the nasal septum 1160, and the soft palate 1162 of a bovine animal. The intranasal administration device according to the present disclosure comprises a fluid conduit, e.g., a tube, which extends through the nasal constriction into the ventral meatus 1166 of the nasal passage to facilitate the discharge of fluid in a direction parallel to the nasal septum 1160, which enables the fluid to reach the nasopharynx 1164. The intranasal administration device 900, 1000 is structured such that the fluid conduit 918, 919 and the nasal passage nozzle 920, 921 are inserted into the ventral meatus 1166 medially and posteriorly to effectively reach into the cavity of interest.

[0088] Reference is now made to Figures 8 to 12 The intranasal administration device 900 comprises fluid conduits 918, 919, nasal passage nozzles 920, 921 inserted at the distal ends of the fluid conduits 918, 919 (best shown in Figure 10 and Figure 11The actuator 928 includes a first member 930 pivotally coupled to a second member 931 via a connector mechanism 964. Clamping members 980 and 981 extend distally from the first and second members 930 and 931, respectively. The first member 930 includes a first arm 932 having an opening (not shown) at one end and a protrusion 934 at the opposite end. The protrusion 934 includes an elongated fluid conduit support opening 938 through which a fluid conduit 918 passes. The portion of the fluid conduit 918 that contacts the elongated fluid conduit support opening 938 can be referred to as the “supported portion” of the fluid conduit 918, which is opposite its distal end, in which a nasal nozzle 920 is positioned. Therefore, the distal end is unsupported and movable relative to the septum interface portion. The distance between the supported portion and the flexible portion of the fluid conduit affects the potential amount of movement of the distal end relative to the distal end of the septum interface portion. In some embodiments, a distance of about 2 inches or more provides sufficient flexibility. In some embodiments, a distance of about 3 inches or more provides sufficient flexibility. The force causing this movement of the distal end is a result of insertion into the nasal passage and contact with the nasal septum during insertion; therefore, the magnitude of this force should be small enough to avoid causing pain to the animal.

[0089] A first handle member 942 extends from the first arm 932 and includes a first handle portion 944 and a second handle portion 946. The second member 931 includes a second arm 933 having an opening (not shown) at one end thereof and a protrusion 935 at an opposite end. The protrusion 935 includes an elongated fluid conduit support opening 939 through which the fluid conduit 919 passes. A second handle member 943 extends from the second arm 933 and includes a first handle portion 945 and a second handle portion 947. The first and second handle members 942, 943 form a handle 948, also referred to as a user interface. In use, a user compresses the handle 948 against a tension provided by a biasing mechanism 954 to cause the clamping members 980, 981 to open, allowing their insertion into a nostril of an animal, and upon release of the compression force by the user biasing mechanism 954, to cause the clamping members 980, 981 to close, clamping the nasal septum 1160. The first handle portions 944, 945 are disposed to extend proximally from the pivot point of the joint mechanism 964 to the second handle portions 946, 947 to enhance actuation leverage. The second handle portions 946, 947 have a greater contact surface than the first handle portions 944, 945 to increase user comfort when compressing them to open the clamping members 980, 981. The second handle portions 946, 947 can have a spherical contact surface, can include a spherical shape, and can further include any shape having a curve cut into a circular arc to correspond to a user's finger to distribute the force applied by the user. Alternatively or additionally, the second handle portions 946, 947 can have an elongated shape to distribute the force along its length.

[0090] The angle 929 (shown in Figure 9 FIG. 6) formed by the centerlines 940, 941 of the elongated fluid conduit support openings 938, 939 is greater when the clamping members 980, 981 are closed than when the clamping members 980, 981 are open. First and second securing members 950, 951 are disposed in the first handle portions 944, 945 to secure the biasing mechanism 954. An example biasing mechanism 954 includes a spring, as shown. The arms 932, 933 have reduced thickness portions 936, 937 at their ends, and have openings (not shown) in the reduced thickness portions 936, 937 through which bolts 978 pass. The bolts 978 are secured by nuts 974. The joint mechanism 964 is formed by the reduced thickness portions 936, 937, the nuts 974, and the bolts 978.

[0091] In the present embodiment, a depth adjuster 958 or positioning member is provided that can be secured to the first and second members 930, 931 at any of a plurality of positions by a bolt 978. The depth adjuster 958 includes two slots 962 traversed by the bolt 978 and a depth stop surface 960. The depth adjuster 958 can be moved proximally or distally to set a desired insertion depth of the clamping members 980, 981, and thus the fluid conduits 918, 919, into the nostril of the animal. The depth stop surface 960 contacts the nose of the animal at the desired insertion depth to stop forward or distal movement of the intranasal administration device 900.

[0092] The first and second clamping members 980, 981 extend distally from the actuation mechanism 928 and include septum interface members 990, 991 at their distal ends that are configured to form a pinch point 996 when the first and second clamping members 980, 981 are closed. In the present embodiment, the clamping members 980, 981 include straight clamping member portions 988, 989 and curved clamping member portions 984, 985 coupled to the first and second arms 932, 933; and the septum interface members 990, 991. In the present embodiment, the curved clamping member portions 984, 985 curve outwardly and then inwardly, thus extending on both sides of the centerline of the straight clamping member portions 988, 989. The septum interface members 990, 991 have blunted edges to prevent tissue trauma and are curved and generally flat perpendicular to the curve. As shown, the septum interface members 990, 991 are about twice as wide as they are thick to achieve a pinch while permitting generally unobstructed breathing by the animal. The flat profile increases the ability of the animal to breathe. The thickness of the septum interface members 990, 991 (across the flat profile) is sufficient to prevent tissue trauma at the pinch point 996. These characteristics can depend on the age and weight of the animal and the weight of the intranasal administration device 900, which together determine the minimum biasing force needed to pinch the intranasal administration device 900 to the nasal septum.

[0093] As Figure 9As shown in FIG. 9, the fluid conduits 918, 919 are supported by the first and second members 930 and 931 through the elongated fluid conduit support openings 938, 939. The distal ends of the fluid conduits 918, 919 extend beyond the pinch point 996, and thus the nasal passage nozzles 920, 921 are also positioned distal of the septum interface members 990, 991. The depth of insertion of the fluid conduits can be adjusted to achieve the proper depth of insertion by sliding the fluid conduits 918, 919 within the elongated fluid conduit support openings 938, 939 or by cutting the fluid conduits 918, 919. Distance A is defined by the longitudinal distance between the depth limiting surface 960 and the pinch point 996. A transverse line 994 is shown passing through the pinch point 996 to better illustrate distance A. Longitudinal distance B is defined by the depth limiting surface 960 and the distal end of the fluid conduits 918, 919. A transverse line 998 is shown passing through the nasal passage nozzles 920, 921 to better illustrate distance B. In some embodiments, for bovine animals weighing between 400 and 700 pounds, distance A is between 1 and 3 inches, more preferably between 1 1 / 2 and 2 1 / 2 inches, and distance B is between 2 and 6 inches, more preferably between 3 and 5 inches, and even more preferably between 3 1 / 2 and 4 1 / 2 inches. The elongated fluid conduit support openings 938 and 939 are at least partially disposed under the clamping members 980, 981 to facilitate alignment of the fluid conduits with the nasal passages. In addition to providing support, the elongated fluid conduit support openings 938 and 939 also establish an angle between the fluid conduits that changes as the device is opened or closed. In some embodiments, the angle includes an angle between 35 and 60 degrees when the clamping members are in contact with each other, as shown in FIG. 9B. In some embodiments, the angle includes an angle between about 40 and 50 degrees when the clamping members are in contact with each other. The fluid conduits 918, 919 and the nasal passage nozzles 920, 921 are designed to be inserted into the left and right nasal passages at an angle / orientation that is substantially aligned with the longitudinal direction of the nasal passages. This orientation reduces tissue trauma and aids in depth of insertion and animal acceptance. Figure 9

[0094] Figure 10 and 11 ​These are perspective and side views of an embodiment of a nasal nozzle 920, identical to that of a nasal nozzle 921. The nasal nozzle 920 includes a head 922 connected to a body 924 having a plurality of ribs 925 configured to secure the body 924 within a distal end of a fluid conduit 918. The head 922 has an outer diameter perpendicular to its longitudinal axis that is substantially equal to the diameter of the fluid conduit 918. The head 922 may be hemispherical. In various examples, the diameter of the head 922 is between about 0.300 and 0.450 inches, more preferably between about 0.350 and 0.400 inches, and even more preferably between about 0.370 and 0.380 inches. In some embodiments, the body 924 has a diameter between about 0.220 and 0.280 inches, and more preferably between about 0.240 and 0.260 inches. Figure 11 As shown, the nasal channel nozzle 920 also includes a distal cavity 926 having an orifice 923 at its distal end and an intermediate cavity 927 having a diameter larger than that of the distal cavity 926, wherein a tapered transition portion therebetween is configured to constrict and stabilize the fluid before discharge. As shown, the distal cavity 926 is cylindrical. It is estimated that fluid discharged through the distal cavity 926 exhibits a complete tapered jet pattern with a circular impact region and a uniformly distributed jet angle of 55 degrees at a pressure of 29 psi (PSI), thereby discharging 0.13 gallons per minute (GPM) of fluid at said pressure with an average droplet diameter of 270 micrometers. As shown, the distal cavity 926 has a cylindrical shape. In other embodiments, other shapes may be used to produce jet patterns with different impact regions. For example, an elliptical pattern may be desired. The diameter of the distal cavity 926 can be varied to increase the discharge capacity to above or below 0.13 GPM. In some embodiments, the emission capacity is between about 0.12 and 0.26 GPM. In some embodiments, the emission pressure at the nozzle opening of the nasal channel nozzle is between about 20 and 25 PSI. In some embodiments, the average droplet diameter is between about 260 and 300 micrometers. The nasal channel nozzle may be fitted with a rotary table. Exemplary rotary tables include X-shaped, disc-shaped, and spiral rotary tables, which are configured to uniformly distribute fluid to produce a complete conical spray shape.

[0095] A pump is fluidly connected between a reservoir for the fluid and the intranasal delivery device. The pump can be controlled to vary the pressure and dispensing time, and it can be configured to produce a dose volume of fluid between approximately 30 and 35 ml at a nozzle pressure of approximately 20 to 25 PSI, wherein the fluid has a density similar to that of water. Larger or smaller dose volumes will be suitable for animals of different sizes. The density similar to that of water can be between 0.8 and 1.2 g / cm³. 3 between.

[0096] Figure 13 is a perspective view of the head of an animal 104 showing another embodiment of an intranasal administration device, designated by the numeral 1000, showing the Figures 14 to 16 intranasal administration device 1000 differs from the intranasal administration devices 101, 201, 301, 401, 501, 701, 801, and 900 in that the grip and handle have different characteristics. The intranasal administration device 1000 includes the actuation mechanism 928 with a handle 1004 and grips 1020, 1021. The handle 1004 includes first and second handle members 1012, 1013. The first handle member 1012 extends from the first arm 932 and includes a first handle portion 944 and a second handle portion 1016. The second handle member 1013 extends from the second arm 933 and includes a first handle portion 945 and a second handle portion 1017. The second handle portions 1016, 1017 are transverse bars extending from the first handle portions 944, 945, and they can have any desired length sufficient to enable operation of the handle 1004 by permitting the user to grasp the second portions 1016, 1017 without interference from the fluid conduits 918, 919. Depending on the relative position of the pump system, the second handle portions 1016, 1017 can face upward or downward in order to limit interference with the fluid conduits. The handle 1004 is also referred to as a user interface. The grips 1020, 1021 include straight grip portions 1022, 1023 and curved grip portions 1024, 1025. In comparison to the intranasal administration device 900, the grips 1020, 1021 are curved inward and none of their portions extend beyond the longitudinal axis of the straight grip portions 1022, 1023. The curved portions of the grips can interfere with the nostrils of the animal and can also prevent or interfere with the breathing of the animal.

[0097] In one embodiment, a dose volume of fluid between about 30 and 35 milliliters at a nozzle tip discharge pressure of about 20 to 25 PSI is delivered to a bovine animal weighing between 400 and 700 pounds by means of the intranasal delivery device 900. The fluid includes a colored dye and has a density similar to that of water. Upon dissection of the head of the animal, it is observed that the nasopharynx of the animal is substantially coated.

[0098] In some embodiments, a method for delivering a fluid intranasally to a veterinary subject, the method comprising: opening a grip of an intranasal administration device 900, 1000; inserting the grip into a nostril of the veterinary subject while inserting a distal end of a fluid conduit into the ventral meatus medially and posteriorly; pinching a nasal septum of the veterinary subject by means of the grip; and discharging the fluid through the fluid conduit.

[0099] Inserting the clip and fluid conduit into the nostril of the veterinary subject includes inserting the fluid conduit through a flow constriction formed by the alar fold and the basal fold of the veterinary subject. Inserting the clip and fluid conduit into the nostril of the veterinary subject can include moving the intranasal administration device toward the veterinary subject until a depth stop surface of the intranasal administration device contacts the nose of the veterinary subject.

[0100] The fluid can include a nitric oxide releasing solution or a nitric oxide gas or a combination of a nitric oxide releasing solution and a nitric oxide gas. After the fluid is delivered, the clip is released, and the intranasal administration device is removed.

[0101] Embodiments of the present invention have been described that include an actuation mechanism, two clips, and two fluid conduits. In various embodiments, the actuation mechanism can include a ratchet mechanism including a gear and a pawl mounted on the base, and a release lever for releasing the pawl from the gear, whereby a user brings the first and second members together to clamp the device, and movement of the release lever effects separation of the first and second members to release the device. Other actuation mechanisms known in the art can also be used.

[0102] The following examples relate to other embodiments:

[0103] In one example, an animal intranasal administration device can include a nasal passage nozzle for a nostril configured to receive a fluid from a fluid source, a support structure opposite the nasal passage nozzle, and a biasing mechanism for biasing the nasal passage nozzle and the support structure toward the septum so that the device is secured in place around the septum during administration of the fluid into the nasal passage.

[0104] In one example, the support structure includes a second nasal passage nozzle.

[0105] In one example, the biasing mechanism includes a spring to bias the nasal passage nozzle toward the septum.

[0106] In one example, the animal intranasal administration device can further include a support member having a first support member portion and a second support member portion each supporting a nozzle, wherein the first support member portion and the second support member portion are movable relative to each other by the biasing mechanism.

[0107] In one example, the biasing mechanism includes a resilient flexibility of at least one of the first support member portion and the second support member portion.

[0108] In one example, the first and second support member portions are pivotally coupled to each other.

[0109] In one example, the animal intranasal dosing device can further include a positioning member configured to contact a tip of the septum to facilitate and maintain proper positioning of the nasal passage nozzles.

[0110] In one example, the nasal passage nozzles are oriented with the nozzle openings aligned with the nasal passage when the device is engaged with the septum.

[0111] In one example, the nasal passage nozzles are configured to direct fluid into the nasal passage past the nasal folds.

[0112] In one example, the nasal passage nozzles are configured to extend into the nostril beyond the nasal folds.

[0113] In one example, the nasal folds include at least one of alar folds, basal folds, and straight folds.

[0114] In one example, the animal intranasal dosing device can further include a fluid distribution manifold fluidly coupled to the nasal passage nozzles, the fluid distribution manifold having an inlet port for receiving fluid from a fluid source and outlet ports for distributing fluid to the nasal passage nozzles.

[0115] In one example, the animal intranasal dosing device can further include a septum interface portion associated with each of the nasal passage nozzles to interact with the septum and position the nasal passage nozzles to facilitate directing fluid into the nasal passage.

[0116] In one example, the animal intranasal dosing device can further include a user interface to facilitate movement of the nasal passage nozzles by a user in a direction opposite the biasing direction.

[0117] In one example, the fluid is selected from the group consisting of a liquid, a gas, a gel, or a combination thereof.

[0118] In one example, an animal intranasal dosing device can include a support member having a first support member portion and a second support member portion, a first nasal passage nozzle, and a second nasal passage nozzle, wherein the first and second support member portions are movable relative to one another to at least partially position the first and second nasal passage nozzles within a nostril of an animal around a septum and to direct fluid into a nasal passage of the animal.

[0119] In one example, the first and second support member portions are biased toward a fixed position around the septum.

[0120] In one example, the animal intranasal dosing device can further include a spring to bias the first and second support member portions toward the fixed position.

[0121] In one example, at least one of the first and second support member portions is elastically flexible to bias the at least one of the first and second support member portions toward the fixed position.

[0122] In one example, the support member is configured to provide a void around the tip of the septum.

[0123] In one example, the first and second support member portions comprise an arcuate configuration to provide a void around the tip of the septum.

[0124] In one example, the first and second nasal passage nozzles are oriented with the nozzle openings aligned with the nasal passages of the animal when the device is engaged with the animal.

[0125] In one example, the fluid conduit is external to the support member.

[0126] In one example, at least one of the first and second support member portions comprises at least a portion of the conduit. Thus, the distal end of the conduit protrudes from and is not supported by the first and second support member portions.

[0127] In one example, the user interface comprises a first user interface portion coupled to the first support member portion and a second user interface portion coupled to the second support member portion, and wherein the first and second user interface portions are movable relative to one another to facilitate movement of the first and second support member portions relative to one another.

[0128] In one example, an animal intranasal administration system can comprise any of the animal intranasal administration devices described herein. The animal intranasal administration system can further comprise a pump operable to deliver fluid from a fluid source to the first and second nasal passage nozzles. The pump is configured to pump at least one of a liquid and a gas.

[0129] In one example, the pump of the animal intranasal administration system comprises a motorized pump, a manual pump, or a combination thereof.

[0130] In one example, the fluid source comprises an activated nitric oxide releasing solution.

[0131] In one example, the fluid source comprises an inactivated nitric oxide releasing solution.

[0132] In one example, the fluid source comprises a container in which an inactivated nitric oxide releasing solution is disposed, and wherein the inactivated nitric oxide releasing solution is activatable within the container.

[0133] In one example, the fluid is configured to be dispensed from the fluid source to the first and second nasal passage nozzles due to pressure within the container resulting from activation of the nitric oxide releasing solution upon activation of the nitric oxide releasing solution.

[0134] In one example, the animal intranasal administration system can further include a cage for holding the activating agent prior to mixing the activating agent with the inactivated nitric oxide releasing solution, wherein the cage is configured to facilitate mixing of the activating agent and the inactivated nitric oxide releasing solution.

[0135] In one example, the cage is supported within the container above the bottom of the container.

[0136] In one example, the fluid source further includes an activating agent maintained separate from the inactivated nitric oxide releasing solution and configured to activate the inactivated nitric oxide releasing solution upon mixing.

[0137] In one example, the fluid source is fluidly coupled to the first and second nasal passage nozzles by a first conduit associated with the inactivated nitric oxide releasing solution and a second conduit associated with the activating agent.

[0138] In one example, the first and second conduits combine prior to the first and second nasal passage nozzles such that mixing of the inactivated nitric oxide releasing solution and the activating agent occurs between the fluid source and the first and second nasal passage nozzles.

[0139] In one example, the first and second conduits combine at the first and second nasal passage nozzles such that mixing of the inactivated nitric oxide releasing solution and the activating agent occurs at the first and second nasal passage nozzles.

[0140] In one example, the first and second conduits remain separate from the fluid source to the first and second nasal passage nozzles such that mixing of the inactivated nitric oxide releasing solution and the activating agent occurs at the animal.

[0141] In one example, the fluid source includes a nitric oxide gas.

[0142] In one example, the animal includes a domesticated animal.

[0143] In one example, the domesticated animal includes a bovine, a pig, a horse, a sheep, or a goat.

[0144] In one example, a method of administering a fluid to a nostril of an animal can include providing an animal intranasal administration device including a support member having a first support member portion and a second support member portion, a first nasal passage nozzle coupled to the first support member portion, and a second nasal passage nozzle coupled to the second support member portion, wherein the first support member portion and the second support member portion are movable relative to one another to at least partially secure the first and second nasal passage nozzles within a nostril of an animal around a septum and to direct the fluid into a nasal passage of the animal; engaging the device with the nostril of the animal; and dispensing the fluid from the device into the nostril of the animal.

[0145] In one example, the amount of nitric oxide releasing solution dispensed to the animal is between about 0.1 mL and about 5000 mL.

[0146] In one example, the amount of nitric oxide releasing solution dispensed to the animal is between about 10 mL and 1000 mL.

[0147] In one example, the amount of nitric oxide releasing solution dispensed to the animal is about 2 mL.

[0148] In one example, the amount of nitric oxide releasing solution dispensed to the animal is about 10 mL.

[0149] In one example, the amount of nitric oxide releasing solution dispensed to the animal is about 32 mL.

[0150] In one example, the amount of nitric oxide releasing solution dispensed to the animal is 160 mL.

[0151] In one example, the fluid source comprises an inactivated nitric oxide releasing solution.

[0152] In one example, the method can further comprise activating the inactivated nitric oxide releasing solution.

[0153] In one example, the fluid is dispensed using gas pressure generated by activation of the nitric oxide releasing solution.

[0154] In one example, activating the inactivated nitric oxide releasing solution occurs prior to dispensing the fluid from the device into the nostril of the animal.

[0155] In one example, activating the inactivated nitric oxide releasing solution occurs while dispensing the fluid from the device into the nostril of the animal.

[0156] In one example, activating the inactivated nitric oxide releasing solution occurs after dispensing the fluid from the device into the nostril of the animal.

[0157] It should be noted that no particular order is required in the methods disclosed herein, but generally in some embodiments, the method steps can be performed sequentially.

[0158] It should be understood, of course, that the foregoing relates to the principles of the present application, which can be practiced or carried out in various ways. It is recognized that variations and modifications of the herein disclosed concepts and specific embodiments thereof can be made and that such modifications and variations are also intended to be within the spirit and scope of the application. Accordingly, the appended claims are intended to cover all such modifications and arrangements. Therefore, although the present application has been described in detail with respect to particular embodiments thereof, it will be apparent to those skilled in the art that various modifications and changes can be made therein without departing from the spirit and scope of the application.

Claims

1. An intranasal drug delivery device (900, 1000) for use in veterinary subjects (104), comprising: The first support member portion (980) includes a septal interface portion (990, 991) sized for insertion into the nasal passage of the veterinary subject (104); An actuation mechanism (928) includes a first member (930) having a first arm (932) pivotally coupled to a second arm (933) of a second member (931), wherein the first member is connected to the first support member portion (980); and A fluid conduit (918, 919) having a distal end opposite a supported end, the distal end being sized for insertion into the nasal passage of the veterinary subject (104), the fluid conduit (918, 919) being flexible and sized and configured to receive fluid from a fluid source (102) and discharge the fluid into the nasal passage through the distal end, the distal end of the fluid conduit (918, 919) being unsupported and movable relative to the septal interface portion (990, 991).

2. The intranasal drug delivery device (900, 1000) according to claim 1, further comprising a nasal passage nozzle (920, 921) supported by the distal end of the fluid conduit (918, 919).

3. The intranasal drug delivery device (900, 1000) according to claim 1, wherein, The actuation mechanism (928) includes a biasing mechanism (954) that provides a biasing force to bias the first support member portion (980) toward the nasal septum of the veterinary subject (104) and clamp the intranasal delivery device (900, 1000) around the nasal septum.

4. The intranasal drug delivery device (900, 1000) according to claim 3, wherein, The actuation mechanism (928) includes a user interface (948) that can be operated by a user to overcome the bias force and thereby release the intranasal drug delivery device (900, 1000) from the nasal septum.

5. The intranasal drug delivery device (900, 1000) according to claim 1, wherein, The supported end of the fluid conduit (918, 919) is attached to the actuation mechanism (928) and separated from the first support member portion (980).

6. The intranasal drug delivery device (900, 1000) according to claim 1, wherein, The supported end of the fluid conduit (918, 919) is attached to the first support member portion (980) and separated from the partition interface portion (990, 991).

7. The intranasal drug delivery device (900, 1000) according to any one of claims 1-6, wherein, The partition interface portion (990, 991) includes a width and a thickness measured perpendicular to the width, wherein the width is at least twice the thickness.

8. The intranasal drug delivery device (900, 1000) according to any one of claims 1-6, wherein, The actuation mechanism (928) includes a depth limiting surface (960) configured to contact the nose of the veterinary subject (104) and thereby determine the insertion depth of the distal end of the fluid conduit (918, 919).

9. The intranasal drug delivery device (900, 1000) according to any one of claims 1-6, wherein, The actuation mechanism (928) includes elongated fluid conduit support openings (938, 939), and the distance between the elongated fluid conduit support openings (938, 939) is between 3 inches and 4 inches.

10. The intranasal drug delivery device (900, 1000) according to claim 1, wherein, The actuation mechanism (928) includes pivotally connected components (930, 931), each of which includes an arm (932, 933) having an elongated fluid conduit support opening (938, 939) angled relative to the arm (932, 933) at an angle of less than 90 degrees to facilitate the insertion of the fluid conduit (918, 919) in the middle and at the rear until the fluid conduit (918, 919) enters the nasal passage of the veterinary subject (104).

11. The intranasal drug delivery device (900, 1000) according to any one of claims 1-6, further comprising a second support member portion (981) having a second septum interface portion, a second fluid conduit having a second distal end, and a second nasal passage nozzle supported by the second distal end of the second fluid conduit.

12. The intranasal drug delivery device (900, 1000) according to claim 11, wherein, The actuation mechanism (928) includes elongated fluid conduit support openings (938, 939), through which the fluid conduit and the second fluid conduit pass respectively, and wherein when the septum interface portion and the second septum interface portion are in contact with each other, the centerline of the elongated fluid conduit support openings (938, 939) forms an angle between 40 degrees and 60 degrees.

13. The intranasal drug delivery device (900, 1000) according to claim 12, wherein, The distance between the support openings (938, 939) of the elongated fluid conduit is between 2 inches and 5 inches.

14. The intranasal drug delivery device (900, 1000) according to claim 13, wherein, The distance between the elongated fluid conduit support openings (938, 939) is between 3 inches and 4 inches.

15. The intranasal drug delivery device (900, 1000) according to claim 11, wherein, The fluid conduits (918, 919) are formed of a flexible material and are configured to self-align with the nasal passage of the veterinary subject (104) during insertion into the nasal passage.

16. The intranasal drug delivery device (900, 1000) according to claim 1, wherein, The distal end of the fluid conduit (918, 919) is sized to extend into the nostril of the veterinary subject (104) at least one inch beyond the septal interface portion (990, 991).

17. An intranasal drug delivery device (900, 1000), comprising: The first component (930) includes a first arm (932) pivotally connected to a second arm (933) of the second component (931); A first support member portion and a second support member portion are respectively connected to the first arm (932) and the second arm (933) and extend distally from the first arm (932) and the second arm (933) and have distal ends, wherein the distal ends of the first support member portion (980) of the first member (930) and the distal ends of the second support member portion (981) of the second member (931) are configured to clamp the nasal septum of the veterinary subject (104); A first fluid conduit, supported by the first member (930) and having a distal end separated from the distal end of the first support member portion (980) of the first member (930); as well as The second fluid conduit is supported by the second member (931) and has a distal end that is separated from the distal end of the second support member portion (981) of the second member (931). The first and second fluid conduits are sized to extend beyond the fluid contraction formed by the wing folds and basal folds of the veterinary subject (104) when the intranasal delivery device (900, 1000) is clamped to the nasal septum, in order to deliver fluid into the veterinary subject (104).

18. The intranasal drug delivery device (900, 1000) according to claim 17, wherein, When the intranasal delivery device (900, 1000) is clamped to the nasal septum, the first fluid conduit and the second fluid conduit are sized to extend into the nasal cavity.

19. The intranasal drug delivery device (900, 1000) according to claim 17, wherein, Each support member portion includes a straight portion (988, 989) extending from the arm (932, 933), a curved portion (984, 985) extending from the straight portion, and a partition interface portion (990, 991) extending from the curved portion.

20. The intranasal drug delivery device (900, 1000) according to claim 19, wherein, The septum interface portion (990, 991) of the support member portion includes a width measured perpendicular to the nasal septum and a thickness measured perpendicular to the width, wherein the width is at least twice the thickness.

21. The intranasal drug delivery device (900, 1000) according to claim 19, wherein, The partition interface portions (990, 991) are curved and flattened perpendicular to the curve.

22. The intranasal drug delivery device (900, 1000) according to any one of claims 17-21, further comprising a nasal nozzle (920, 921) disposed at the distal ends of the first fluid conduit and the second fluid conduit and configured to dispense the fluid in a conical pattern.

23. The intranasal drug delivery device (900, 1000) according to claim 22, wherein, The distal ends of the first and second fluid conduits are configured to bend upon contact with the tissues of the veterinary subject (104).

24. The intranasal drug delivery device (900, 1000) according to claim 23, wherein, The bending of the distal ends of the first and second fluid conduits away from the septal interface portions (990, 991) moves the nasal channel nozzles (920, 921).

25. The intranasal drug delivery device (900, 1000) of claim 17 further includes a pump (121) configured to dispense a dose volume of fluid between 30 and 35 ml at a nozzle tip discharge pressure between 20 psi and 25 psi.

26. The intranasal drug delivery device (900, 1000) according to claim 17, wherein, The first fluid conduit and the second fluid conduit are supported by the first member (930) and the second member (931) and are not supported by the first member (930) and the second member (931) on the distal side.

Images