RU2796190C2 - Intranasal administration device - Google Patents

Abstract

FIELD: medical equipment.

SUBSTANCE: invention relates to medical equipment, namely to intranasal administration devices. The device contains: a manual unit containing a part for gripping and a spraying head containing a spraying device and a nozzle, while the nozzle contains a soft cone made with the possibility of introduction into the patient’s nostril for prevention of spraying of a spray outside the nostril and direction of the spray through the nostril to inner tissue; a control unit connected via fluid to the manual unit by means of one or more flexible connecting pipes made with the possibility of resistance to expansion, when a drug passes through them; one or more containers for accommodation of at least one drug, wherein containers are detachably connected to the control unit; and at least one pump located in the control unit, while the pump is made with the possibility of pumping the drug from the control unit to the spraying device, while the pump contains one or more reverse valves and a piston.

EFFECT: obtaining an intranasal administration device.

16 cl, 19 dwg

Description

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority over the earlier filing date of U.S. Provisional Application No. 62/596967, filed December 11, 2017, which is incorporated herein by reference in its entirety.

FIELD OF TECHNOLOGY

The present invention relates to vaccination devices for vaccinating patients, in particular farm animals, and more specifically relates to automated intranasal vaccination devices for vaccinating a large number of feed and domestic animals such as pigs, cattle, sheep, goats, horses, poultry, cats, dogs or aquatic species including fish.

BACKGROUND OF THE INVENTION

In industrial animal husbandry, for a variety of reasons, it is often necessary to administer substances such as drugs to animals. Usually each breeder needs to treat large numbers of animals. Treatment may often require the injection of several drugs, usually in liquid form, into each animal. Said drugs may include various antigens, drugs and/or other components, drugs, vaccines, hormones, nutritional supplements, and the like (hereinafter collectively referred to as "drug" in this document). Administration of these drugs typically involves the use of an administration device, such as a syringe or infusion machine, from which a dose of the drug is manually or automatically administered to the animal. This type of administration typically involves actuating or inflating the drug delivery device by hand to deliver the drug to the animal.

When treating a large number of animals (for example, using a manually operated device containing a needle), the operator may become tired. This can lead to many misbehaviors, such as but not limited to: (i) an operator accidentally injecting itself; (ii) administering a dose of drug when the needle has not yet penetrated the patient's skin or has not penetrated to the required depth; (iii) administering a dose after removing the needle from the patient; (iv) administering only a portion of the required dose (v); inserting a needle into a patient in a non-optimal orientation; and/or (vi) administering a double dose of one individual. Accordingly, devices have been developed in an attempt to mitigate and overcome some of the potential pitfalls in the use of needle injection, for example by using intranasal administration.

Intranasal administration allows the drug to be administered directly to the mucosal immune system via the mucosal tissue. Such intranasal drugs can be administered using spray applicators which administer the drug in the form of fine drops. This form of delivery contributes to the development of both cellular and humoral immune responses and hence protection against disease.

Some live virus vaccines are too pathogenic to be used as immunogens, and vaccinations with inactivated viruses may be less effective and cause unwanted side effects such as inflammatory reactions at the injection site. Such vaccines can be delivered intranasally by attaching the antigen to the mucosal surface of the animal. Attachment of the antigen to the mucosal surface may depend on the size of the particles, the depth of penetration of the antigen into the mucosal tissue, and the distance traveled into the nose cone. In addition, a local antibody system and interferon production mechanism has been shown to operate at the primary site of infection in the membranes of the nasal canal (see, for example, US Pat. No. 4,132,775). Thus, intranasal administration of vaccines has become the preferred way of administering both inactivated viruses and attenuated live vaccines.

In some prior art devices, an attempt has been made towards intranasal administration. For example, U.S. Patent No. 5,053,022 discloses a device for intranasal vaccination of a horse, comprising a hollow, conical, flexible tube long enough to reach the horse's tonsillar tissue and adapted to receive a syringe and a locking device that allows the flexible device to pass through the locking device until it is reached. the wider part of the cone.

WO 2001/021151 discloses administration of a single dose non-live influenza virus antigen using a nasal delivery device that contains a tip with helical channels that result in a spray when pressure is applied to the plunger.

US Pat. No. 7,296,566 describes a syringe with a spray nozzle for delivering liquid substances into the nasal passage. US Pat. No. 8,499,721 discloses an intranasal avian vaccination device comprising a beak receiving cavity into which the bird's beak is placed to receive fluid from fluid passages connected to the beak receiving cavity.

WO 2010/060462 discloses a device for nasal administration of a pharmaceutical composition comprising a cannula for insertion into the nasal cavity of an animal.

However, these other known nasal delivery devices have various drawbacks. For example, many of them are stationary, require laborious handling, are designed for single administration, etc. The anatomical difference in the length of the nasal passage between animal species may require the use of different sizes and lengths of nozzles depending on the species or size of the animal. In addition, cannulas and other insertion devices may cause excessive physical stimulation of the nasal passage. This can damage the nasal mucosa and cause infection, as well as cause unintentional movement of the animal (which can result in injury to the animal or operator). Another disadvantage of known devices is the amount of dose that can remain in the device after administration (also known as "dead volume"). This "dead volume" makes it difficult to determine the dose of drug that was actually administered to the animal.

Accordingly, there continues to be a need for improved injection devices, such as devices for quickly and efficiently injecting large numbers of animals, and methods of using the same.

SHORT DESCRIPTION

Described herein are embodiments of an improved nasal administration device for intranasally administering one or more drugs to a patient (e.g., pigs, poultry, fish, sheep, goats, horses, cattle, dogs, cats, etc.). The administration device can be used to rapidly and efficiently administer a drug to a large number of animals to prevent and/or reduce operator error, operator fatigue, and injection failure.

Accordingly, in some embodiments, the implementation of the device for intranasal administration includes a hand part containing a grip part held by the operator and a spray head containing a spray device and a nozzle, a control unit connected to the hand unit through at least one connecting tube and one or more containers for accommodating medicines connected in fluid medium to the control unit. The control unit may contain one or more pumps. The at least one connecting tube may be flexible enough to allow the handpiece to be easily operated and rigid enough to prevent the tube from expanding due to internal pressure as medications pass from the containers into the handpiece.

In a typical embodiment, the nasal administration device may comprise a spray head having one spray device and nozzle, and one or more dosing chambers in fluid communication with the spray device. In some embodiments, the administration device may further comprise one or more drug containers, each drug container being connected to a respective dosage chamber. In some embodiments, one or more flexible connecting tubes can be used to connect the dosing chambers and drug containers, and the flexible connecting tubes can be designed in such a way that they are resistant to expansion when the drug passes through them.

In another exemplary embodiment, the nasal administration device may comprise a spray head having a first spray device in fluid communication with the first nozzle and a second spray device in fluid communication with the second nozzle. The first spray device and the first nozzle may be movable relative to the second spray device and the second spray nozzle so that the distance between them may vary depending on the anatomy of the patient. In some embodiments, the first spray device may be in fluid communication with the first dosage chamber, and the second spray device may be in fluid communication with the second dosage chamber. In other embodiments, both the first and second spray devices may be connected to the same dosing chamber. In some embodiments, the administration device may further comprise two or more drug containers, each drug container being connected to a respective dosage chamber. In some embodiments, each dosing chamber is connected to a respective pump configured to pump drug from the dosing chamber to the nebulization device.

In some embodiments, the administration device is configured to administer a single drug. In other embodiments, the administration device is configured to administer multiple drugs. In some embodiments, the drug is administered by manually actuating the administration device (eg, by pulling the trigger). In some embodiments, the implementation of the drug can be entered automatically when the introduction into the nasal cavity of the patient spray head to a selected depth.

In another illustrative embodiment, the device for intranasal administration may comprise: a handpiece containing a grip portion, a spray head having a spray device, and a nozzle; one or more dosing chambers in fluid communication with the spray device; a control unit connected to one or more medicine containers; at least one flexible connecting tube fluidly connecting the hand unit with the control unit, and the flexible connecting tube is made in such a way that it is resistant to widening when the drug passes through it; at least one pump configured to pump medication from the control unit to the hand unit; one or more temperature control units operatively connected to the medicine containers; one or more control panels, configured to determine and display information related to the introduction process, and optionally transmit data in real time to a remote device; and a fault detection device configured to detect a fault in the nasal administration device.

The above and other objects, features and advantages of the present invention will become more apparent from the following detailed description, carried out with reference to the accompanying drawings.

BRIEF DESCRIPTION OF GRAPHICS

Fig. 1 is a perspective view of the handheld device of an exemplary intranasal insertion device.

Fig. 2 is a perspective view of the control unit of an example device for intranasal administration.

Fig. 3 is a perspective view of a drug container of an example of a nasal administration device.

Fig. 4 is an elevational side view of the handpiece of an exemplary intranasal insertion device.

Fig. 5 is a cross-sectional view of the hand block of FIG. 4.

Fig. 6 is an enlarged cross-sectional view of a portion of the tip of the hand block of FIG. 4.

Fig. 7-8 are exploded views of a portion of the tip of the hand block of FIG. 4.

Fig. 9 is a perspective view of the control unit of an exemplary intranasal administration device.

Fig. 10 is a partial exploded perspective view of the control unit shown in FIG. 9 with the side panel removed to show the valve assembly.

Fig. 11 is a side cross-sectional view of the control unit of FIG. 9.

Fig. 12 is a perspective view of a valve assembly of an example intranasal device.

Fig. 13 is a side elevational view of the valve assembly of claim 12.

Fig. 14 is a cross-sectional side view along the line A-A shown in FIG. 13.

Fig. 15-16 are perspective views of the control unit of an exemplary intranasal insertion device.

Fig. 17 is an elevational side view of the handpiece of an example of a nasal insertion device.

Fig. 18 is an elevational side view of the hand block of FIG. 17, used for intranasal administration of a drug to an animal.

Fig. 19 is a side elevational view of a handpiece of an example of a nasal administration device used for intranasal administration of a drug to an animal.

DETAILED DESCRIPTION

I. Definitions

For the purposes of the present disclosure, this document describes specific aspects, advantages, and novel features of embodiments of the present invention. The disclosed methods, devices and systems should not be considered limiting in any way. On the contrary, the present invention is directed to all new and non-obvious distinguishing features and aspects of the various described embodiments, individually and in various combinations and subcombinations with each other. These methods, devices and systems are not limited to any particular aspect or feature or combination thereof, nor are the described embodiments required to provide any one or more particular advantages or to solve one or more problems.

Although, for convenience of presentation, the operations of some of the described embodiments are described in particular sequential order, it should be understood that such a mode of description encompasses rearrangement unless that particular order is required by the specific wording set forth below. For example, actions described sequentially may in some cases be regrouped or performed simultaneously. In addition, for simplicity, the attached figures may not show the various ways in which the described methods can be used in combination with other methods. In addition, terms such as "provide" or "achieve" are sometimes used in the description to describe the disclosed methods. These terms are high-level abstractions of the actual actions performed. The actual actions corresponding to these terms may vary depending on the specific implementation and are easily recognizable by a person skilled in the art.

As used herein and in the claims, singular forms include plural forms unless the context clearly dictates otherwise. In addition, the term "includes" means "comprises". In addition, the term "connected" usually means physically, mechanically, chemically, magnetically and/or electrically connected or connected, and does not exclude the presence between connected or connected elements, intermediate elements in the absence of specific reverse formulations.

In the context of this document, the term "proximal" refers to the position, direction, or part of the device that is closer to the user and further from the insertion site. In the context of this document, the term "distal" refers to the position, direction, or part of the device that is further away from the user and closer to the insertion site. For example, “proximal movement” of the device refers to movement of the device away from the insertion site and towards the user (e.g., away from the patient’s body), while “distal movement” of the device refers to movement of the device away from the user and towards the insertion site. (for example, in the patient's body). The terms "longitudinal" and "axial" refer to the axis extending in the proximal and distal directions, unless otherwise defined explicitly.

The description may use specific terms such as "up", "down", "top", "bottom", "horizontal", "vertical", "left", "right", etc. These terms are used there, where applicable, to provide some clarity of description when considering spatial relationships. However, these terms are not intended to denote absolute relationships, positions and/or orientations. For example, with respect to an object, the "top" surface can become the "bottom" surface by simply flipping the object. However, this object remains the same.

In the context of this document, the term "approximately" means the specified value and any value within 10% of the specified value. For example, "approximately 100 degrees" means any value between 90 and 110 degrees, inclusive.

The term "drug" as used herein means any material to be administered to a patient and includes, for example, antibiotics, vaccines, hormones, nutritional supplements, oils, vitamins, minerals, etc. In some embodiments, drugs have liquid form. In other embodiments, the drugs may be in powder form and may be mixed with one or more diluents in or before placement in two or more containers.

II. Exemplary Embodiments

Disclosed herein are embodiments of a nasal administration device suitable for administering one or more drugs intranasally to a patient, and methods of using the same.

Devices for intranasal administration allow you to enter the desired dose of the drug to the patient. The dose may be any desired amount of a drug or a desired amount of a combination of drugs, and is optionally used to treat a patient. Examples of drugs may include prophylactic compositions such as vaccines, therapeutic compositions such as drugs, and/or other compositions of research or medical interest such as proteins, nucleic acids, immunogens, live or inactivated viruses, reassortant live viruses, cold adapted live viruses, attenuated live viruses and/or adjuvants. The drug may also be or contain other substances that are useful for delivery or efficacy. In some embodiments, the drug may contain species-specific compositions, such as cold-adapted live equine influenza viruses, that: (i) replicate only within a certain temperature range; (ii) do not form plaques in tissue culture cells; and/or (iii) have a defined phenotype.

The advantages of intranasal drug administration include: a direct route to the bloodstream; exclusion of presystemic hepatic metabolism; bioavailability; simplicity and ease of administration; and proximity to the central nervous system. Many types of medications can be delivered intranasally, including but not limited to: local anesthetics, sedatives, hypnotics, analgesics, ketamines, opiates, glucagons, vaccines, nausea and motion sickness medications, antihistamines, antihypertensives, psychoactive drugs, antibiotics, and hormones.

Fig. 1-3 illustrate the components of an exemplary intranasal device. In certain embodiments, the nasal administration device is useful for administering drugs (including prophylactic and/or therapeutic) to various animals. Device components (eg, handpiece) can be scaled up or down for use with patients of various sizes, including immature, young, or early stage animals.

Some disclosed embodiments include: (a) a hand unit 100, a main unit or control unit 200, connected to the hand unit by at least one connecting tube 202 (see, for example, Fig. 15) and at least one container 300, removable attached to the control unit 200 and/or hand unit 100, or connected to it by one or more connecting tubes. One or more connecting tubes 202 can be flexible enough to allow the user to maneuver the hand block 100 and control unit 200, and rigid enough to prevent expansion of the connecting tube due to internal pressure when drugs pass from the container 300 or control unit 200 into the manual block. Widening of the tube can lead to inaccurate dosing of the drug. Additional details of flexible connecting tubes can be found at least in WO 2018/203203, incorporated herein by reference in its entirety.

In some embodiments, the control unit 200 may be configured to be worn by a user, such as on a belt, waist bag, vest, or carrying bag. In such embodiments, the connecting tube 202 may be flexible enough to allow the user to move the hand block 100 in any direction, long enough to allow the user to fully extend their hand holding the hand block 100, and sufficiently rigid (i.e., not stretchable and non-deformable) to prevent expansion of the tube due to pressure caused by the drug passing through the tube. Changes in pressure can deform the tubing, which lacks sufficient rigidity during drug administration, which can result in inaccurate drug dosing or a delay between pump action and drug administration to the animal. In some embodiments, the implementation of the connecting tube can be bent in all directions and is able to withstand twisting. In some embodiments, the implementation of the connecting tube can resiliently return to its original shape after bending, twisting, stretching or other deformation. For example, the tube may have an overall outside diameter of from about 1 mm to 10 mm, typically from about 4 mm to 5 mm, in size. The inner diameter may generally be from about 1 mm to 5 mm, typically from about 2 mm to 3 mm. In some embodiments, the implementation of the tube may be made of polyamide. In some embodiments, the implementation of the tube may further include a spring, allowing the tube to be flexible in all directions and at the same time resistance to increase in size. The spring may be external to the tube, internal to the tube, and/or integrally formed with the tube.

In some embodiments, the implementation of the rigidity of the connecting tube is achieved through the use of a casing in combination with an elastic tube. In some embodiments, the shroud may be formed separately and either wrapped around the resilient tube or placed within the tube. In some embodiments, the implementation of the casing may be made integral with the tube. In other embodiments, the implementation of the elastic tube may be formed from a material having rigidity, due to which it is able to withstand the forces applied during the internal passage of fluids.

In some embodiments, the connection tube 202 may be laser cut from stainless steel to form integral links having a design that allows the tube to be flexible while preventing the tube from expanding radially. After laser cutting, the resulting laser-cut steel tube is either mounted on or coated with a flexible tube made of a polymeric or elastomeric material.

With reference to FIG. 4 and 5, the hand unit 100 includes a grip portion 102 for holding by the operator and a spray head 104 including a spray device 106 and a nozzle 108. The spray device 106 may have any suitable shape, such as a straight or curved shape. In some embodiments, the implementation of the spray device 106 may be stationary relative to the part 102 for capture. In other embodiments, the implementation of the spray device 104 may be movable and/or retractable relative to the part 102 to capture. In such embodiments, retracting the nebulizer device (eg, by depressing nozzle 108 into the patient's nostril) causes a predetermined dose of drug to be released into the patient's mucosal tissue. In some embodiments shown in FIG. 6-8, the spray device 106 can be connected to the hand block using a luer connection 110.

With reference to FIG. 6-8, as noted above, the spray head 104 may include a nozzle 108 for insertion into a patient's nostril. Nozzle 108 may comprise silicone, rubber, or thermoplastic material and may be configured to: (i) insert and seal in a patient's nostril; (ii) prevent the spread of the drug outside the nostril; and (iii) directing the spray through the nostril to the internal tissue, thus ensuring maximum mucosal exposure.

The external shape of the nozzle 108 may vary significantly depending on the drug being administered and the patient's anatomy, and may include, for example, a cylindrical or conical configuration. The illustrated embodiments show a conical nozzle; however, in other embodiments, the nozzle 108 may have a substantially uniform cylindrical outer portion. The length of the nozzle 108 may vary depending on the location of the target insertion site. To dose animals with longer, narrower nasal passages, the nozzle may have a cylindrical outer surface having a radius ranging from about 1.0 millimeters to about 10 millimeters and a longitudinal length ranging from about 70 millimeters to about 180 millimeters.

In some embodiments, (see, for example, FIG. 19), the nasal spray head 104 may comprise two spray devices, each connected to a nozzle configured to: (i) insert into an animal's nostril; (ii) preventing the spray from spraying outside the nostrils; and (iii) directing the spray through the nostril to the internal mucosal tissue. The distance between the two spray devices, and hence between the two nozzles, can be adjusted so that it can vary depending on the distance between the animal's nostrils, thereby maximizing mucosal exposure and contact with the drug being sprayed. In particular embodiments, the intranasal administration device is configured to administer a separate drug through each nozzle. As described in more detail below, the spray head embodiments are removable so that they can be replaced. For example, a dual nozzle spray head can be replaced with a single nozzle spray head for use with selected animals.

Spray head 104, spray nozzle 108, and/or spray device 106 may be made from a flexible material or a substantially rigid material, depending on the application chosen or the anatomy of the selected patient species. For example, a substantially rigid material may be selected for use with ruminants, which may have relatively short and uncomplicated intranasal passageways, for the purpose of delivering a dose to a dose target or coordinate. Alternatively, a more flexible spray head, spray nozzle, and/or spray device may be selected for use with horses that have longer intranasal canals and that may also have a blind-ended nasal canal (such as a nasal diverticulum) that may need to be bypassed. to deliver the dose to the desired target or dose location coordinate.

The nebulizer head 104 (including the nebulizer 108 and/or nebulizer 106) may contain materials that are compatible with the drug being administered and that will not degrade such that the drug will not be altered by heat, light, ultraviolet radiation, etc. e. For example, the spray head may contain glass, polymeric materials such as polyethylene, polypropylene, polyurethane, polyvinyl chloride, rubber, silicone, and/or metals or alloys.

In some embodiments shown in FIG. 8, the spray head 104 may further comprise a movable head 112 that covers the spray device 106. The movable head 112 may be movable between an extended position and a retracted position. In some embodiments, moving the movable head 112 to a retracted position allows medicament to pass through the nebulizer 106 (eg, by opening a valve associated with the nebulizer). In such embodiments, retracting the movable head 112 (eg, by pushing it into the patient's nostril) causes a predetermined dose of drug to be released into the patient's mucosal tissue. In some embodiments, the entire spray head 104, including the movable head 112, the spray device 106, and the nozzle 108, is a removable and replaceable unit that can be connected to the hand unit 100.

In some embodiments, the implementation of the minimum dosage may be from about 1 ml to about 1.5 ml. In some embodiments, the implementation of the minimum dose can be "squeezed" through the device for intranasal administration using a dose pusher.

Typically, drugs are administered in liquid form (eg, spray). In some embodiments, containers 300 are provided with a ready-to-use liquid medication. In other embodiments, the drug to be administered is administered in dry form (eg, as a sprayable powder). In such embodiments, the drug is contained in the containers in dry form. In other embodiments, containers 300 are provided with a drug (eg, in dried or powdered form) that requires processing or preparation prior to use (eg, by adding water or other solvent to it). Accordingly, in some embodiments, containers 300 may be internally divided into two or more compartments to hold one or more powdered drugs and one or more diluents. Prior to administration of the drug(s), one or more diluents may be mixed with the powder to provide a ready-to-use drug.

In some embodiments, containers 300 may be formed separately and may be releasably connected to control unit 200. In such embodiments, empty containers may either be refilled or replaced with full containers. In other embodiments, containers 300 may be integrally formed as part of hand unit 100, control unit 200, or both, and may be refilled with a suitable liquid medication upon emptying. In some embodiments, containers 300 may be made of a rigid material (eg, metal or rigid polymeric material). In other embodiments, containers 300 may be made from a flexible material (eg, polyethylene film or flexible polymeric material). In some embodiments, containers 300 may be transparent or substantially transparent, allowing the user to see the content and the level of content within. In other embodiments, containers 300 may be translucent, such as when the drug(s) they contain is light sensitive.

In some embodiments, each drug can be administered by manually actuating the intranasal device, for example, by manually depressing and/or retracting the trigger 114 located on the grip portion 102 of the hand block 100. Suitable triggers 114 can be a lever or a button. In such embodiments, each actuation of the trigger 114 actuates the motor of the device to deliver a predetermined amount of drug to be administered. In some embodiments, the device may be configured to sequentially deliver doses of two or more different drugs. In such embodiments, a first trigger pull will administer the selected dose of the first drug, and a second trigger pull will administer the selected dose of the second drug.

In other embodiments, the implementation of each dose can be entered automatically (for example, without pulling the trigger). In such embodiments, the spray head 104 of the handpiece 100 may further comprise a means, such as a measuring device or a contact sensor, for identifying that the spray head 104 (e.g., spray head nozzle 108) has reached a selected location (e.g., depth) in the nasal cavity. patient. Once the spray head 104 has reached the selected location, the control unit 200 may activate a pump 204 (see, for example, FIG. 11) configured to deliver a predetermined dose of drug through the hand unit 100 and to the patient.

It is noteworthy that the administration of the drug may be required for animals of different sizes. This may require spray heads 104 of various types, shapes and sizes. Accordingly, in certain embodiments, the nasal administration device is configured to change spray heads (e.g., change nozzle or spray device) for maintenance, to prevent delivery of contaminants between individual patients, and/or to adjust their type and size. In certain embodiments, the entire spray head 104 of the handpiece is interchangeable, allowing the user to quickly and easily switch between types of spray nozzles, for example, between nozzles of different lengths and/or widths, between fixed and movable nozzles, and/or replace damaged nozzles.

In some embodiments, the nasal administration device is configured to allow the user to control and/or adjust the spread of the aerosol (distance and diameter) according to the anatomy of the animal being treated and/or vaccinated, as described in more detail below.

The size of the spray droplets can be adjusted to beneficially influence drug delivery in terms of mucosal absorption of the drug. Accordingly, in certain embodiments, the nasal administration device further comprises a mechanism for controlling and/or adjusting the size of the spray droplets. In some embodiments, this spray drop adjustment can be achieved by adjusting the pressure applied by the pump or motor using a pulse width modulation (PWM) controller. This allows different drop sizes to be used for animals of different sizes and ages, eg using smaller drops for smaller and/or younger animals. In addition, this allows the droplet size to be adjusted for different drugs and/or vaccine components having different viscosities, which can affect the droplet size generated.

Particle sizes can affect the amount and rate of drug absorption. Drug particles having a diameter of less than about 1 μm may remain suspended during administration because the time required for the particle to diffuse into the airway wall tends to be longer than the time to complete the inspiratory phase of normal breathing. Deposition of the drug in the lungs can be facilitated by the use of particles having a diameter of approximately 3 μm. Larger particles greater than about 5 microns in diameter often deposit in the upper respiratory tract. Accordingly, in certain embodiments, the nasal administration device can be configured to generate drug droplets that are greater than 0 to about 250 microns in size. In some embodiments, the nasal administration device is designed to deliver a dose of about 0.25 ml to about 2 ml of drug to each animal in each nebulization process.

The nasal administration device may further comprise a means for delivering the drug from its respective container 300 to the handpiece 100 and to the nostril(s) of the patient. With reference to FIG. 11, in some embodiments, control unit 200 includes a pump 204. Pump 204 may be driven by one or more motors 206 that may rotate one or more drive shafts 208 connected to the pumps. Pump 204 may be a piston or plunger pump. The pump 204 may be in fluid communication with one or more containers 300 and may be configured to draw and/or eject the same or different predetermined amounts of drug from each container 300 and deliver them to the handpiece 100 and thus to the spray head 104 The target amounts of each drug may be equal or may differ depending on the type of drug being administered. The nasal administration device may further comprise one or more motors configured to drive various components of the device, such as one or more pumps.

In some embodiments, the device for intranasal administration may include two or more pumps 204 located in the control unit 200, with the number of pumps equal to the number of containers 300, and each pump 204 is connected to a separate container 300. In this configuration, each pump 204 is made with the possibility of pushing and/or removing a given amount of the drug from its corresponding container 300 and sequentially delivering the drug to the spray head 104 of the hand unit 100 and the patient in accordance with the given order of administration.

In some embodiments, the nasal administration device may be designed to be suitable for remote locations with limited power supply. In some embodiments, the nasal administration device may be electrically actuated. In some embodiments, the nasal administration device may further comprise a power source located, for example, in the control unit 200, the hand unit 100, or both. In some embodiments, the power supply may be located as a separate power supply unit electrically connected to the inserter. In some embodiments, the power supply is rechargeable. In other embodiments, the power supply may be disposable (eg, disposable batteries). In some embodiments, the inserter further comprises a power meter configured to display the amount of electricity remaining and/or send an alert when a selected power level is reached, which may interfere with operation of the inserter.

In some embodiments, the nasal administration device may further comprise an infusion alarm configured to electrically actuate the valves and/or one or more pumps 204. For example, in embodiments containing a single pump, after drug A is administered, the injection monitor may close a valve located at the drug outlet of container A and open a valve located at the drug outlet of container B. Thus, when the pump is actuated, it can only withdraw the drug from the container B containing the valve in the open position. Alternatively, in embodiments containing two or more valves, with each valve associated with a separate container 300, after drug A is administered, the injection alarm may turn off pump A associated with container A and actuate pump B associated with the second capacity B. Thus, the pumps can be actuated according to the order of introduction. The administration alarm may be further configured to signal (eg, in a visible, audible, and/or tactile manner, eg, by vibration) that a drug has been administered and indicate that the next drug is ready for administration.

In some embodiments, the intranasal administration device further comprises a dosing chamber associated with each drug holding container 300 and a piston for pushing/pulling the drug out of said dosing chamber, the drug being automatically loaded into the dosing chamber immediately upon delivery of a dose of drug. animal. In a specific embodiment, there is a separate dosing chamber located in the hand unit 100 that holds a single drug prior to each delivery according to the desired delivery order. In an alternative embodiment, there are multiple dosing chambers, each fluidly connected to a respective container 300, and each dosing chamber is filled with one type of drug, which is then delivered to the spray head 104 according to the delivery order. Further details of examples of dosing chambers can be found at least in WO 2018/203203.

In some embodiments, the amount of drug administered is controlled by an encoder. In some embodiments, an encoder may be coupled to a drive shaft or piston 208 of pump 204 (eg, located on a hand or control portion). The encoder is configured to, by detecting the amount of rotation of the motor, set the position of the piston head to enable the introduction of a given amount of drug. This feature is useful for setting different volumes of drugs to be administered. The volume of dose may be determined for each patient or class of patient, but for some embodiments it typically varies from greater than 0 milliliters to about 10 milliliters, typically from 0.05 milliliters to 5 milliliters.

In some embodiments, the nasal administration device further comprises a control panel. The control panel may be configured to display to the user the necessary information related to the administration process and enable him to control various functions of the administration process. The control panel may optionally transmit real-time information to the remote device, thus enabling data storage and/or remote control of the device. In some embodiments, the control panel may control, for example, the amount of each drug administered and/or the order in which different drugs are administered. The control panel can display information such as the amount of drug remaining in each container and/or the number of patients who received the drug, total administration time, motor rotation information, etc. As shown in FIG. . 2, in some embodiments, the control panel 210 is located on the control unit 200. In other embodiments, the control panel may be located on the hand unit 100.

In some embodiments, the nasal administration device further comprises a volume adjustment device for setting and confirming different dose volumes to be administered. In some embodiments, the volume adjusting device may include, for example, an encoder, an electrical meter, sensors, and indicators for measuring amounts of drugs. In other embodiments, the volume control device may comprise a simple fixed piston and plunger that can be adjusted (eg, manually or electrically) to deliver different amounts.

In some embodiments, each container 300 may include a valve configured to actuate between an open configuration and a closed configuration. In the open configuration, the drug can pass through the valve, and in the closed configuration, the passage of the drug through the valve is prevented. For example, in an open configuration, medication can pass from container 300 to control unit 200, and in a closed configuration, medication cannot pass from container 300 to control unit 200. In some embodiments, the valves are check valves or check valves that allow the drug to pass through in only one direction. In other embodiments, the valves may be configured to be electrically actuated between open and closed configurations (eg, via a microprocessor). In other embodiments, the valves may be configured to be manually actuated (eg, by pressing a button, flipping a switch, or turning a lever). The valves may be configured to allow fluid to flow in only one direction (e.g., from a container to a dosing chamber), thereby preventing backflow of drug into the container, thereby preventing contamination of the containers, and prolonging the shelf life of said containers so that they can be reused if some drug remains after the administration procedure.

With reference to FIG. 12-14, the nasal administration device may include two or more check valves (eg, check valves, inlet check valves, lift check valves, etc.) located in pump 204 of control unit 200, for example. In some embodiments, the valves are check valves or check valves that allow the drug to pass through them in only one direction. For example, the first check valve 212 may allow the passage of drug from the container 300 to the control unit 200, but prevent backflow from the control unit 200 to the tank 300, and the second check valve 214 may allow the passage of drug from the control unit 200 to the manual unit 100, but prevents reverse flow from the hand block 100 to the control block 200. The specific embodiment shown in FIG. 12-14 includes valves 212, 214, each of which includes a spring 216 and a stopper 218 (which may be any of a variety of shapes including, for example, spherical, disc-shaped, conical, etc.). Spring 216 applies a compressive force to stopper 218, urging the valve to the closed position and preventing medicament from flowing through the valve. If the external pressure on the valve (eg, in the connecting tubes 202) is less than the opening (or "trip") pressure of the check valve (eg, less than the force applied by the spring 216), the valve remains closed. This may prevent fluid from flowing from the reservoirs into the control unit 200 until a pump is activated to increase fluid pressure and/or prevent fluid from flowing from the control unit 200 into the hand unit 100. If the external pressure is greater than the check valve set pressure, the drug may push the stopper 218 against the spring 216, compressing the spring and allowing the drug to flow through the valve in one direction.

In other embodiments, the valves may be configured to be electrically actuated between open and closed configurations (eg, via a microprocessor). In other embodiments, the valves may be configured to be manually actuated (eg, by pressing a button, flipping a switch, or turning a lever).

In some embodiments, the nasal administration device may be configured to spray two or more drugs into the animal's nostril(s) and may comprise: (i) a handpiece 100 having a grip portion 102 for holding by an operator; (ii) a control unit 200 fluidly connected to the hand unit 100 using two or more connecting tubes 202; (iii) two or more containers 300, respectively, each for holding a single medicinal product; (iv) power supply; (v) an injection signaling device for identifying that the drug has been completely administered and determining the next drug to be administered; and (vi) a control panel for defining and displaying the various functions of the administration process. Each container 300 can be releasably connected to the control unit 200. The administration device may further comprise two or more pumps 204. Drugs may be administered sequentially or simultaneously.

In some embodiments, the nasal administration device may be configured to administer two or more different drugs to a patient. In specific embodiments, the implementation of the device for intranasal administration may contain three main subsystems: (1) a hand block 100 containing a single or double spray nozzle, check valves, a printed circuit board (PCB) and a screen; (2) a control unit containing a motor, a pump, check valves, a circuit board, medication containers, a position sensor, a temperature sensor, a pressure sensor, an RFID scanner, Bluetooth, or any RF transmitter, and a power source (such as batteries); and (3) tubing and electrical wires connecting the hand unit 100 and the control unit 200.

In some embodiments, each vaccination element and/or drug administered by the intranasal device is a solution or suspension, such as an aqueous solution, an aqueous suspension, an emulsion, or a solution containing an organic solvent or suspension aid. In other embodiments, the drug may comprise at least one antigen, live virus, attenuated virus, inactivated virus, conjugated antigen, conjugated virus, DNA, RNA, bacteria, yeast, or any combination thereof. In yet other embodiments, the drug may contain antibiotics, steroids, respiratory agents, or any combination thereof.

In particular embodiments, each container 300 of the nasal administration device further comprises an identification tag. The identification tag can be any tag suitable for conveying information (eg RFID code, QR code, barcode, color sticker, etc.). In some embodiments, the identification label indicates, for example, the type of drug in each container, the amount of drug to be administered from each container, the date of manufacture and/or expiration date. Accordingly, in some embodiments, the nasal administration device further comprises a reader configured to read identification marks and transmit data to a control unit and/or a remote unit.

In some embodiments, the reader unit may be configured to emit or receive light. In such embodiments, identification tags may be comprised of light absorbing materials and/or reflective materials. For example, the first container may contain a light-absorbing sticker (eg, a black sticker) and the second container may contain a reflective sticker (eg, a white sticker). When the container is connected to the control unit, the reading unit can read the identification tag to distinguish between the first and second containers and determine the contents and/or the required dosage for each container. The reader unit can then transmit this information to the control unit and/or the remote unit.

In some embodiments, each animal may be implanted with an RFID tag. An animal's RFID tag can be scanned prior to administration to verify that the animal has not already received the drug. During or after the insertion process, the animal's RFID tag can be registered and the data transferred to a management system (eg, smartphone, cloud storage or local server).

When administering the drug to a large number of animals, the user may need to hold the administration device for a long time. Accordingly, in certain embodiments, the weight of the hand block 100 is made as light as possible, for example, from about 150 to about 200 grams, such as 160 grams, 170 grams, 180 grams, or 190 grams.

In some embodiments, the nasal administration device further comprises one or more heating blocks for heating the drug to be administered. Preheating some drugs to the animal's approximate body temperature before administration may improve drug absorption. In some embodiments, each heating block may be connected to a respective container 300. In other embodiments, the heating block may be located along the connecting tube 202 or within the hand block 100. The temperature control unit used may be selected according to system requirements. In some embodiments, the heat used to raise the temperature may be generated by a motor or engine of the nasal administration device and/or a Peltier device or other thermoelectric cooling device. This can reduce power consumption, as well as reduce the cost and improve the efficiency of the device.

In a particular embodiment, the nasal administration device may be configured to meet any or all of the following requirements:

(1) The device can inject 3 L (approximately 2.55 kg) of medication over 6 hours. The operator is expected to carry 1 to 2 liters of medication and refill from a central storage base as needed.

(2) The heating system is capable of heating 3 kg of medicine.

(3) The drug is a mineral oil emulsion protein with a specific heat capacity of 2130 J/kg. The medication should be heated to approximately 38°C. For example, when heated from about 28°C to about 38°C, the total heat demand is 54315 J or 0.15 kWh (Q=2.55*2130*10). In addition, the pumping and cooling energy of the pump motor must be taken into account, which can add an additional 40-50,000 J to the energy consumed.

(4) If the working day is 6 hours, a heating power of 2.5W is required (P=54315/(6*3600). The spray pump is also expected to add approximately 3W more to the load, and thus the total power consumption will be approximately 5-6 watts.

(5) Fluid temperature when spraying is within +/- 1°C of preselected temperature.

(6) The total weight of equipment, including grafting material, must not exceed 5 kg in weight and 5 liters in volume.

(7) The heating system prevents the drug from overheating with a thermocouple switch.

(8) The heating system is safe for the user.

In a particular embodiment, the intranasal administration device may comprise two main subsystems: (i) a medicament storage and heating system housed in a backpack or belt; and (ii) a hand unit fed from it. In such embodiments, the drug is pumped through a heating device to bring it to the selected temperature and then administered in precise dosages.

In some embodiments, a small lithium ion battery 138 may be used to power a Peltier device that adds or removes heat from the drug until the desired temperature is reached. make it unusable. Thus, the battery power of the device can be used more efficiently since the batteries are required to supply only a portion of the heating power. Peltier devices operate best when a minimum "temperature gap" is maintained (eg temperature difference between hot side and cold side). For example, in some embodiments, this backlash may be approximately 10°C, which is small enough to allow efficient operation of the device with Peltier elements. In an exemplary embodiment, a thermal coefficient (COPh) of approximately 3 can be achieved, thereby reducing battery requirements to 1/3 of the battery power required for a battery-only system. In practical terms, this energy load can be realized, for example, using a lithium-ion battery weighing approximately 50 g with dimensions of 50x50x10 mm, with a capacity of 2500 mAh and a power of 1.8-2 W.

In some embodiments, the Peltier device can be used in conjunction with the heat generated by the motor of the nasal insertion device by capturing this heat and using it as an additional heat input to the "cold side" of the Peltier device. An example motor may be approximately 60% efficient, and thus 1-2 watts of heat may be generated in the motor case. This additional heat can be used by the Peltier device and thus can increase the overall performance of the heat pump, as well as significantly reduce the energy balance of the battery.

Accordingly, in particular embodiments, the nasal administration device comprises a heat generation unit based on heating assisted by a Peltier motor/pump. The amount of drug administered by the heating device assisted by the Peltier motor/pump is particularly important. Therefore, the device for intranasal administration may require calibration before the first use or before each use. Accordingly, in some embodiments, the implementation of the device further comprises an encoder for calibrating the position of the piston or pump in order to obtain an accurate calibration.

Many known intranasal devices use manual dosing calibration, which can lead to large variations in the amount of drug due to, for example, operator error and inaccuracies in cylinder dosing techniques. In comparison, in some embodiments of the present device, the current encoder can be capable of a resolution of 5 degrees in the radial direction, which results in a linear piston movement of no more than 0.0006 mm and thus provides high dosing accuracy. However, dosage deviations can occur over time due to manufacturing tolerances resulting in differences in cylinder volume and/or some degrees of freedom between moving mechanical parts that change due to corrosion and friction. Accordingly, in some embodiments, each nasal administration device may be calibrated at the time of manufacture and optionally further calibrated by the end user prior to each use or periodically.

Accordingly, in some embodiments, the nasal administration device further comprises an automated calibration system allowing the end user to calibrate the nasal administration device. In such embodiments, the automated calibration system may comprise a sealed container with electrodes at the bottom and top, the dimensions of the container and thus the distance between the electrodes being known. To calibrate the device, the user may switch the intranasal device into "calibration mode" to have the device inject (eg, by spraying) a predetermined dose of test fluid (eg, 1 cc of water) into a sealed container. Once the fluid reaches the top electrode, the calibration system notifies the device and stops injecting. The calibration system determines the number of doses that were required to fill a known volume of the container, calculates the volume of each dose and compares it with the specified volume of each dose. This allows the calibration system to determine if there is any dose discrepancy and automatically calibrate the intranasal device according to the measured discrepancy.

In some embodiments, the nasal administration device further comprises a control unit configured to detect faults such as partial dosing, clogging, air bubbles in the tubes, leakage and/or empty containers during the administration procedure. The control unit can further detect faults in various components of the intranasal device such as low power, faulty pump(s), broken tube(s), etc.

Incomplete dosing and other malfunctions can occur due to human error (for example, when the user removes the spray nozzle from the patient's nasal passage before all the drug has been injected) or due to mechanical failure (for example, the piston does not move all the way forward in dosing chamber to expel the drug, clogging of the tubes or spray nozzle, for example, due to dirt or fluid viscosity, and air bubbles entering the system, which can change the total volume of drug to be injected). Regardless of the cause, incomplete administration results in the patient receiving only a fraction of the prescribed dose of drug. These malfunctions may prevent accurate drug administration to the patient or increase the duration of each administration.

In some embodiments, the nasal administration device further comprises a fault detection system that can be configured to detect the above-described, as well as others, faults and send an alert to the user. Such a fault detection system may include various mechanisms, for example, a probe on the spray head or head of the spray head that detects premature withdrawal of the device before completion of the injection, a probe connected to the dosing chamber that detects if the plunger head has moved all the way to the end of the dosing chamber, a probe on the piston head, which detects whether the piston head moves in the opposite direction before moving the piston head to the very end of the dosing chamber (indicating, for example, incomplete injection), a sensor that detects no movement or too slow piston movement (for example, using an encoder and internal timing), which may indicate a clog, and/or a sensor detecting too fast piston movement (for example, using an encoder and internal timing), which may indicate an air bubble or leak. The fault detection system may further function to calculate the amount of drug remaining in each container (for example, by multiplying the number of doses by the dosage of administration), measure the current used to drive the motor, which may correspond to the presence of an air bubble, leak, or blockage, and etc. The fault detection system may further be configured to measure the duration of each dose and/or electrical current used, any additional duration and/or current used in excess of a particular amount may indicate a blockage in the system and which - either a decrease in duration and/or current used beyond a specific value may indicate the presence of an air bubble or leak in the system, or the consumption of drug in the container.

In some embodiments, the nasal administration device further comprises a purge procedure to remove blockages that may occur in the spray nozzle or spray head. The purge procedure may include spraying water or other cleaning fluid through a clogged spray nozzle, the water or cleaning fluid being contained in a container connected in parallel to the handpiece so that the purge procedure can be performed as part of the insertion procedure without the need to stop and clean the device. For example, an example of a device for intranasal administration may include a hand unit fluidly connected to a control unit that contains two containers. One container can hold the medication and the other can hold the cleaning solution. In use, the nasal administration device may be configured to alternate doses of medication and doses of cleaning fluid such that a user can administer a dose of medication to a patient, remove the spray nozzle from the patient, remove the dose of cleaning solution (e.g., to the ground), and proceed to next patient.

The above-described embodiments of the nasal administration device may be used in the following exemplary manner. The nozzle(s) of the spray head can be inserted into the nostril(s) of the patient. In some embodiments, the user may depress the spray head into the patient's nostril(s), thereby initiating the administration of a dose of drug. In other embodiments, the user may activate a trigger, thereby administering a dose of drug. The spray head can then be removed from the patient's nostril(s) and the user can move on to the next patient.

Although the above embodiments relate to animal patients, embodiments of the nasal administration devices disclosed above can also be used for nasal administration of a drug to human patients. In such embodiments, the spray head, spray nozzle, and/or spray device may be constructed from a substantially rigid material based on relatively short and uncomplicated intranasal passageways to deliver a dose to a dose target or coordinate.

In view of the many possible embodiments to which the principles of the present disclosure may apply, it should be recognized that the illustrated embodiments are merely preferred examples and should not be construed as limiting the scope of the present invention. On the contrary, the scope of the present invention is defined by the following claims.

Claims (30)

1. A device for intranasal administration, comprising: a hand-held unit comprising a gripping portion and a spray head comprising a spray device and a nozzle, the nozzle comprising a soft cone capable of being inserted into a patient's nostril to prevent the spray from spraying outside the nostril and directing the spray through the nostril to the internal tissue; a control unit in fluid communication with the hand unit via one or more flexible connecting tubes configured to resist expansion as a drug passes through them; one or more containers for accommodating at least one drug, the containers being releasably connected to the control unit; And at least one pump located in the control unit, wherein the pump is configured to pump medicine from the control unit to the nebulization device, the pump comprising one or more check valves and a piston. 2. Device according to claim. 1, characterized in that the drug is released automatically when the soft cone reaches a predetermined depth inside the patient's nostril. 3. The device according to any one of paragraphs. 1 or 2, characterized in that the spray head comprises a first spray device connected to the first nozzle and a second spray device connected to the second nozzle, wherein the first spray device and the first nozzle are movable relative to the second spray device and the second nozzle for adjusting the distance between them depending on the distance between the two nostrils of the patient. 4. The device according to claim 3, characterized in that the first spray device and the first nozzle are configured to deliver the first drug, and the second spray device and the second nozzle are configured to deliver the second drug. 5. The device according to p. 3, characterized in that the first and second nozzles contain the first and second soft cones, respectively, each soft cone is made with the possibility of: (i) insertion into the patient's nostril; (ii) preventing the spray from being sprayed outside the nostril; and (iii) directing the spray through the nostril to the internal mucosal tissue. 6. The device according to any one of paragraphs. 1-5, characterized in that the hand unit further comprises a trigger configured to release a predetermined amount of drug into the nostril of the patient and, thus, onto his mucous tissue. 7. The device according to any one of paragraphs. 1-6, characterized in that retracting the spray head triggers the release of a predetermined amount of said vaccination element into the patient's nostril and thus onto his mucous tissue. 8. The device according to any one of paragraphs. 1-7, characterized in that the device is configured to adjust at least one of the distance and the diameter of the spray in accordance with the anatomy of the patient. 9. The device according to any one of paragraphs. 1-8, characterized in that it additionally contains an RFID system configured to record each administration of the drug. 10. The device according to any one of paragraphs. 1-9, characterized in that it additionally contains a control panel configured to determine and display information related to the process of intranasal administration. 11. The device according to any one of paragraphs. 1-10, characterized in that it additionally contains a mechanism for adjusting the size of the spray drops. 12. The device according to any one of paragraphs. 1-11, characterized in that it additionally contains a signaling device for determining whether a full dose of the drug has been delivered. 13. The device according to any one of paragraphs. 1-12, characterized in that it additionally contains one or more valves, with each valve connected to the container. 14. The device according to any one of paragraphs. 1-13, characterized in that it additionally contains a fault detection system. 15. A device for intranasal administration, comprising: a hand-held unit having a gripping portion and a spray head comprising a spray device and a nozzle, the nozzle including a soft cone capable of being inserted into a patient's nostril to prevent the spray from spraying outside the nostril and directing the spray through the nostril to the internal tissue; one or more dosing chambers in fluid communication with the spray device; a control unit in fluid communication with one or more medicine containers; at least one flexible connection tube fluidly connecting the hand unit to the control unit, the flexible connection tube being configured to resist expansion when a drug passes through it; at least one pump configured to pump medication from the control unit to the hand unit; one or more temperature control units operatively connected to the medicine containers; one or more control panels configured to determine and display information related to the insertion process and optionally transmit data in real time to a remote device; And a fault detection system configured to detect faults in the nasal administration device. 16. A method of using a device for intranasal administration of drugs, including: provision of the device according to paragraph 1 and application of this apparatus.

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