Description
Title of Invention : INTRANASAL DELIVERY DEVICES
Technical Field
[0001]
CROSS-REFERENCE
This application claims the benefit of U.S. Provisional Application No. 62/563,244 filed on September 26, 2017, which is incorporated herein by reference in its entirety.
[0002]
INCORPORATION BY REFERENCE
All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
Summary of Invention
[0003]
In some cases, the present disclosure provides a device that comprises: a nozzle having a reservoir disposed within the nozzle, a poppet valve at least partially fit into the reservoir, a retainer that is hollow and holds the poppet valve, and a manual air pump, e.g., operably linked to an upstream end of the nozzle and a downstream end of the retainer, wherein the poppet valve has one or more contacting points with the retainer. In some instances, the one or more contacting points are one or more inner ribs. In some instances, the retainer has an inner circumferential groove based from an upstream end of the retainer. In some instances, a rim of the circumferential groove of the retainer is in contact with the one or more contacting points of the poppet valve. In some instances, the retainer immobilizes the poppet valve. In some instances, when the device is activated, a portion of air from the pump flows into the retainer along the circumferential groove and travels through surface grooves of the retainer to generate a vortex into the reservoir. In some instances, the one or more air intake holes of the retainer allows outside air to enter the pump after the device is activated. In some instances, the reservoir contains a powdered therapeutic formulation. In some instances, the device is adapted to deliver at least about 85% of the powdered therapeutic formulation into a nostril of a subject after a single, two, or three times of activation of the manual air pump. In some instances, at least about 90% of the powdered therapeutic formulation is delivered into the nostril of the subject after the single, two, or three times of activation of the manual air pump. In some instances, the powdered therapeutic formulation is present in an amount of about 1 to about 30 mg. In some instances, the powdered therapeutic formulation is present in an amount of about 20 mg. In some instances, the nozzle further comprises a breakable tab positioned at the downstream end of the nozzle. In some instances, the device is a single-use device. In some instances, the poppet valve further comprises a conical top section. In some instances, the conical top section is connected to a first shelf that is connected to a first cylindrical section. In some instances, the first cylindrical section is connected to a second shelf that is connected to a second cylindrical section. In some instances, the poppet valve has one or more surface grooves. In some instances, the poppet valve has about 3 to about 20 surface grooves, for example about 8 surface grooves. In some instances, the one or more surface grooves creates a vortex in the reservoir when the device is activated. In some instances, the one or more surface grooves are present on the second shelf. In some instances, the poppet valve has about 2 to about 10 inner ribs. In some instances, the poppet valve has about 3 inner ribs. In some instances, the poppet valve is at least partially located within the reservoir. In some instances, the poppet valve is at least partially located within the manual air pump. In some instances, the poppet valve comprises a cavity. In some instances, the device is less than about 100 cm 3 in volume. In some instances, the device is less than about 50 cm 3 in volume. In some instances, the device is about 30 cm 3 in volume. In some instances, the device has a mass of less than about 20 grams. In some instances, the device has a mass less than about 10 grams. In some instances, the device has a mass of about 6-7 grams. In some instances, the reservoir has an inner diameter of less than about 10 mm. In some instances, the reservoir has an outer diameter of about 8 to about 9 mm. In some instances, the outer diameter of the reservoir is about 8.7 to about 8.9 mm. In some instances, an upstream end of the reservoir has smooth surface adapted to contact the poppet valve. In some instances, the poppet valve has an outer diameter of about 7 to about 8 mm, for example about 7.7 to about 7.9 mm. In some instances, an opening of the manual air pump is wider than an outer diameter of the poppet valve. In some instances, the retainer contains an outer circumferential rim that is wider than an opening of the manual air pump. In some instances, the retainer has two air intake holes. In some instances, the one or more air intake holes are about 0.2-0.4 mm wide. In some instances, the retainer is at least partially fit into the manual air pump. In some instances, a portion of the poppet valve fit into the nozzle is about 5 mm to about 6 mm, for example 5.7 mm to about 5.9 mm, in length parallel to an upstream to downstream axis. In some instances, the nozzle has a length parallel to an upstream to downstream axis of between 5 mm and 40 mm. In some instances, the nozzle of the device comprises a clear, lightly tint, or translucent material.
[0004]
In some cases, the present disclosure provides a method of using a device disclosed herein to deliver a powdered therapeutic formulation in a subject in need thereof, comprising positioning a nozzle of the device at least partially into a nostril of the subject and activating the manual air pump, wherein the nozzle comprises the powdered therapeutic formulation. In some instances, the method treats a disease or condition of the subject, for example migraine. In some instances, the powdered therapeutic formulation comprises an active agent disclosed herein, for example dihydroergotamine or a pharmaceutically acceptable salt thereof. In some instances, the method further comprises visually inspecting the amount of the powdered therapeutic formulation remaining in the reservoir and repeating the method until a sufficient dose is delivered.
[0005]
In some cases, the present disclosure provides a method of manufacturing the device, comprising: inserting the poppet valve in the nozzle, inserting the retainer in the manual air pump, and coupling the manual air pump to the nozzle. In some instances, the method further comprises filling the reservoir with a powdered therapeutic formulation.
Brief Description of Drawings
[0006]
[fig. 1] FIG. 1 illustrates two views of parts of a device. The device comprises a nozzle (1), a poppet valve (2), a retainer (3), and a pump (4). The device can further comprise a cap to protect the nozzle.
[0007]
[fig. 2] FIG. 2 illustrates contact and seal areas between the parts. The nozzle and the retainer are sealed. The retainer and the pump are also sealed. The poppet valve lifted by the retainer always contacts the nozzle, so there is no clearance between the nozzle and the poppet valve. This reduces a potential risk that powder prefilled in the nozzle falls into the pump.
[0008]
[fig. 3] FIG. 3 illustrates that the retainer has a tray to trap powder fallen from the nozzle. This reduces a potential risk that powder from the nozzle falls into the pump.
[0009]
[fig. 4] FIG. 4 illustrates the main flow to deliver powder and a side air flow to deliver trapped powder through the nozzle. If necessary, the pump may be activated up to 3 times to deliver powder. Air-intake holes in the retainer prevent the remaining powder in the nozzle from entering to the pump when the pump returns to the original form.
[0010]
[fig. 5] FIG. 5 illustrates measurements of the parts. The width of the thread of the pump "a" is 10.1-10.7 mm, and can be adjusted by 0.4 mm shorter or longer, in order to minimize the risk of insufficient seal between the retainer and the pump, and between the nozzle and the retainer.
[0011]
[fig. 6] FIG. 6 illustrates an assembly procedure of the device.
[0012]
[fig. 7] FIG. 7 illustrates delivered weight amounts of placebo under a normal condition and after climatic and transit conditioning in a delivery performance test of the device.
Description of Embodiments
[0013]
DETAILED DESCRIPTION
The present application describes intranasal delivery devices. An intranasal delivery device can be used for administering a powdered therapeutic formulation to a person in need of treatment. Delivery of a powdered therapeutic formulation can be performed by a medical professional and/or by a subject in need of treatment (e.g., a human subject). As described herein, devices can be pre-loaded with a dry powdered therapeutic formulation. An intranasal delivery device can be a single-use device. A device described herein can comprise at least four parts, e.g., a nozzle, a retainer, a poppet valve, and a pump. A powdered therapeutic formulation can be introduced into the nozzle of a device, which can serve as a reservoir. The nozzle can be coupled with a pump. Devices described herein can provide for complete delivery of a powdered therapeutic formulation with minimal powdered therapeutic formulation remaining in the device after activation of the device. A poppet valve can be adapted to regulate airflow from a pump to a nozzle when the device is activated. A poppet valve can be adapted to prevent movement of a powdered therapeutic formulation from a reservoir in the device upstream to a pump in the device. The poppet valve can comprise slits (canals or grooves) that can be used to generate a vortex in a reservoir to enable efficient delivery of a powdered therapeutic formulation. The grooves in the poppet valve can be positioned to permit laminar air flow in the reservoir. The grooves in the poppet valve can be positioned to create spinning air flow in the reservoir when the pump is activated. Also provided are methods for treating or prevention a condition or disease with a device or a formulation disclosed herein.
[0014]
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of the ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the compositions or unit doses herein, some methods and materials are now described. Unless mentioned otherwise, the techniques employed or contemplated herein are standard methodologies. The materials, methods and examples are illustrative only and not limiting.
[0015]
The details of one or more inventive embodiments are set forth in the accompanying drawings, the claims, and the description herein. A feature, object, or advantage of an inventive embodiment disclosed and contemplated herein can be combined with that of any other embodiment disclosed and contemplated herein, unless explicitly excluded.
[0016]
Unless otherwise indicated, open terms for example "contain," "containing," "include," "including," and the like mean comprising.
[0017]
The singular forms "a", "an", and "the" are used herein to include plural references unless the context clearly dictates otherwise. Accordingly, unless the contrary is indicated, the numerical parameters set forth in this application are approximations that may vary depending upon the desired properties sought to be obtained by the present invention.
[0018]
Unless otherwise indicated, some instances herein contemplate numerical ranges. When a numerical range is provided, unless otherwise indicated, the range includes the range endpoints. Unless otherwise indicated, numerical ranges include all values and subranges therein as if explicitly written out. Unless otherwise indicated, any numerical ranges and/or values herein can be at 80-125% of the numerical ranges and/or values.
[0019]
The term "about" means the referenced numeric indication plus or minus 15% of that referenced numeric indication.
[0020]
The term "subject" as used herein refers to a mammal (e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or non-human primate, such as a monkey, chimpanzee or baboon). In a particular instance, the subject is a human subject.
[0021]
I. Devices
Overview
In some cases, the present disclosure provides a device that comprises: a nozzle having a reservoir disposed within the nozzle, a poppet valve at least partially fit into the reservoir, a retainer that is hollow and holds the poppet valve, and a manual air pump operably linked to an upstream end of the nozzle and a downstream end of the retainer, wherein the poppet valve has one or more contacting points with the retainer. In some instances, the one or more contacting points are one or more inner ribs. In some instances, the retainer has an inner circumferential groove based from an upstream end of the retainer. In some instances, a rim of the circumferential groove of the retainer is in contact with the one or more contacting points of the poppet valve. In some instances, the retainer immobilizes the poppet valve. In some instances, when the device is activated, a portion of air from the pump flows into the retainer along the circumferential groove and travels through surface grooves of the retainer to generate a vortex into the reservoir. In some instances, the one or more air intake holes of the retainer allows outside air to enter the pump after the device is activated. In some instances, the reservoir contains a powdered therapeutic formulation. In some instances, the device is adapted to deliver at least about: 70%, 75%, 80%, 85%, 90%, or 95% of the powdered therapeutic formulation into a nostril of a subject after a single, two, or three times of activation of the manual air pump. In some instances, the powdered therapeutic formulation is present in an amount of about 1 to about 30 mg, or about 1 to about 50 mg. In some instances, the powdered therapeutic formulation is present in an amount of about: 5, 10, 15, 20, 25, 30, 35, 40, or 45 mg. In some instances, the nozzle further comprises a breakable tab positioned at the downstream end of the nozzle. In some instances, the device further comprises a cap that at least partially covers the nozzle. In some instances, the cap comprises polypropylene. In some instances, the nozzle further comprises an engaging screw adaptable to secure the nozzle to the manual air pump. In some instances, the manual air pump further comprises an engaging thread adaptable to secure the manual air pump to the nozzle. In some instances, the engaging thread spans a width of about 9-12 mm, for example about: 9.7-10.3 mm, 10.1- 10.7 mm, or 10.5-11.1 mm. In some instances, the device is a single-use device. In some instances, the poppet valve further comprises a conical top section. In some instances, the conical top section is connected to a first shelf that is connected to a first cylindrical section. In some instances, the first cylindrical section is connected to a second shelf that is connected to a second cylindrical section. In some instances, the poppet valve has one or more surface grooves. In some instances, the poppet valve has about 3 to about 20 surface grooves, for example about: 4, 6, 8, 10, 12, 14, 16, or 18 surface grooves. In some instances, the one or more surface grooves creates a vortex in the reservoir when the device is activated. In some instances, the one or more surface grooves are present on the second shelf. In some instances, the poppet valve has about 2 to about 10 inner ribs. In some instances, the poppet valve has about: 3 inner ribs. In some instances, the poppet valve is at least partially located within the reservoir. In some instances, the poppet valve is at least partially located within the manual air pump. In some instances, the poppet valve comprises a cavity. In some instances, the device is less than about 100 cm 3 in volume. In some instances, the device is less than about 50 cm 3 in volume. In some instances, the device is about: 20 cm 3 or 30 cm 3 in volume. In some instances, the device has a mass of less than about 20 grams, for example about: 11, 12, 13, 14, 15, 16, 17, 18, or 19 grams. In some instances, the device has a mass less than about 10 grams, for example about: 1, 2, 3, 4, 5, 6, 7, 8, or 9 grams. In some instances, the device has a mass of about 6-7 grams. In some instances, the reservoir has an inner diameter of less than about 10 mm. In some instances, the reservoir has an outer diameter of about 8 to about 9 mm. In some instances, the outer diameter of the reservoir is about 8.7 to about 8.9 mm. In some instances, an upstream end of the reservoir has smooth surface adapted to contact the poppet valve. In some instances, the poppet valve has an outer diameter of about 7 to about 8 mm, for example about 7.7 to about 7.9 mm. In some instances, an opening of the manual air pump is wider than an outer diameter of the poppet valve. In some instances, the retainer contains an outer circumferential rim that is wider than an opening of the manual air pump. In some instances, the retainer has two air intake holes. In some instances, the one or more air intake holes are about 0.2-0.4 mm wide. In some instances, the retainer is at least partially fit into the manual air pump. In some instances, a portion of the poppet valve fit into the nozzle is about 5 mm to about 6 mm, for example about 5.7 mm to about 5.9 mm, in length parallel to an upstream to downstream axis. In some instances, the nozzle has a length parallel to an upstream to downstream axis of from about 5 mm to about 40 mm. In some instances, the nozzle of the device comprises a clear, lightly tint, or translucent material.
[0022]
In some cases, the present disclosure provides a method of using a device disclosed herein to deliver a powdered therapeutic formulation in a subject in need thereof, comprising positioning a nozzle of the device at least partially into a nostril of the subject and activating the manual air pump, wherein the nozzle comprises the powdered therapeutic formulation. In some instances, the method treats a disease or condition of the subject, for example migraine. In some instances, the powdered therapeutic formulation comprises an active agent disclosed herein, for example dihydroergotamine or a pharmaceutically acceptable salt thereof. In some instances, the method further comprises visually inspecting the amount of the powdered therapeutic formulation remaining in the reservoir and repeating the method until a sufficient dose is delivered.
[0023]
In some cases, the present disclosure provides a method of manufacturing the device, comprising: inserting the poppet valve in the nozzle, inserting the retainer in the manual air pump, and coupling the manual air pump to the nozzle. In some instances, the method further comprises filling the reservoir with a powdered therapeutic formulation.
[0024]
In some cases, a device is provided comprising: a) a nozzle having an upstream end and a downstream end adapted to allow positioning of at least a portion of said nozzle into a nostril of a subject; b) a reservoir comprising a single dose of a powdered therapeutic formulation, the reservoir having an upstream end and a downstream end, and disposed within said nozzle; c) a poppet valve having an upstream end and a downstream end, wherein the poppet valve is adapted to cause diffusion of the powdered therapeutic formulation when the device is activated; and d) a pump operably linked to the upstream end of a poppet valve, wherein the device is a single-use device. In some instances, the poppet valve is adapted to create a spinning airflow in the reservoir when the pump is activated. In some instances, the poppet valve is adapted to permit the entire wall of the reservoir to be covered by airflow when the pump is activated. In some instances, the poppet valve is at least partially located in the nozzle. In some instances, the powdered therapeutic formulation is located along the internal wall of the nozzle and between the poppet valve and internal wall of the nozzle. In some instances, the poppet valve is adapted to minimize the powdered therapeutic formulation remaining between the poppet valve and the internal wall of the nozzle when the pump is activated. In some instances, the device is adapted to deliver from about 80% to about 99% of the single dose of powdered therapeutic formulation into the nostril of the subject. In some instances, the device is adapted to deliver about 80% to about 99% of the single dose of powdered therapeutic formulation into the nostril of the subject after a single activation of the pump. In some instances, the pump comprises a flow outlet. In some instances, the poppet valve is adapted to prevent movement of the powdered therapeutic formulation through the flow outlet when the device is not activated. In some instances, the poppet valve is adapted to prevent movement of the powdered therapeutic formulation through the flow outlet when the device is activated. In some instances, the poppet valve covers the flow outlet when the device is not activated. In some instances, the poppet valve does not cover the flow outlet when the device is activated. In some instances, the poppet valve comprises a top section connected to a first cylindrical section, and the first cylindrical section is connected to a first shelf, and the first shelf is connected to a second cylindrical section.
[0025]
In some instances, the top section comprises a conical shape. In some instances, a surface of the first shelf comprises at least one groove. In some instances, the first shelf comprises at least one groove. In some instances, the first shelf comprises about 1 to 50 grooves. In some instances, the first shelf comprises about 1 to 20 grooves. In some instances, the first shelf comprises about 1 to 10 grooves. In some instances, the at least one groove lies at a 45 degree angle relative to an edge of the first shelf. In some instances, the at least one groove is adapted to permit air flow from the pump to the nozzle when the pump is engaged. In some instances, the nozzle comprises a nozzle pipe. In some instances, the poppet valve is partially located within the nozzle pipe. In some instances, the top section and first cylindrical section of the poppet valve are located within the nozzle pipe. In some instances, the second cylindrical section of the poppet valve is not located within the nozzle pipe.
[0026]
In some instances, the first shelf contacts the nozzle pipe in the pump is activated. In some instances, the pump is adapted to deliver about 2 to 7 mL of air. In some instances, the device is adapted to deliver about 1 to 50 mg of powdered therapeutic agent. In some instances, the device is less than about 50 cm 3 in volume. In some instances, the device has a mass of less than about 20 grams. In some instances, the pump is adapted to be activated by a user to force air from the pump through the flow outlet, along the surface of the at least one groove in the first shelf, into the reservoir, and out the downstream end of a nozzle. In some instances, the device is adapted to provide laminar airflow within at least a portion of a reservoir while a device is in use. In some instances, the device is adapted to deliver a powdered therapeutic formulation into the nostril of the subject by application of from about 5 to about 30 kilopascals of compressive force to a pump. In some instances, the pump further comprises a deformable volume adapted to be activated by a user. In some instances, the pump comprises a manual air pump. In some instances, the manual air pump is adapted to be activated by a user by squeezing the pump between a thumb and a forefinger, middle finger, ring finger, little finger or combination thereof. In some instances, the reservoir comprises an inner diameter of less than about 10 mm. In some instances, the nozzle further comprises a length perpendicular to an upstream to downstream axis of about 5 mm to about 20 mm. In some instances, the nozzle further comprises a length parallel to an upstream to downstream axis of about 5 mm to about 40 mm.
[0027]
In some instances, the pump further comprises a flow inlet, wherein said flow inlet is less than 10% of the size of a flow outlet. In some instances, said flow inlet is about 0.1 to 2 mm in diameter. In some instances, the nozzle further comprises an airtight cap positioned on the upstream end of a nozzle and adapted to prevent outside air from contacting a powdered therapeutic formulation. In some instances, the nozzle further comprises a removable or breakable tab positioned at the downstream end of the nozzle, and adapted to prevent a flow of air through a nozzle. In some instances, the downstream end of the nozzle further comprises a nozzle hole.
[0028]
In some instances, the poppet valve is adapted to provide laminar airflow along at least a portion of the reservoir. In some instances, sufficient flow of air is generated by a compression force of at least 20 kilopascals applied to the pump. In some instances, the nozzle is comprised of a substantially clear or translucent material. In some instances, the nozzle further comprises a thread adaptable to secure the nozzle to the pump.
[0029]
In some cases, a method of using a device to deliver a powdered therapeutic formulation is provided, wherein said method comprises positioning a nozzle of a device into a nostril of a subject and activating a pump, and wherein said device is a single-use device that comprises: a) a nozzle having an upstream end and a downstream end, said nozzle adapted to allow position of at least a portion of said nozzle into a nostril of a subject; b) a reservoir comprising a dose of a powdered therapeutic formulation and having an upstream end and a downstream end, operably linked to and disposed within said nozzle; c) a poppet valve having an upstream end and a downstream end, wherein the poppet valve is adapted to cause diffusion of the powdered therapeutic formulation when the device is activated; d) a retainer having inner ribs linked to the poppet valve; and e) a pump operably linked to the upstream end of the retainer. In some instances, the device is a single-use device. In some instances, the nozzle and the reservoir of the device comprise clear or translucent material. In some instances, the method further comprises visually inspecting the amount of powdered therapeutic formulation remaining in a reservoir and repeating the method until a sufficient dose is delivered. In some instances, the method further comprises activating the pump to produce laminar flow along at least a portion of a reservoir. In some instances, the method further comprises delivering between 1 mg and 50 mg of a powdered therapeutic formulation to the nostril of the subject. In some instances, the method further comprises delivering about 80%- 99% of the single dose of powdered therapeutic formulation to the nostril of the subject. In some instances, the method further comprises compressing the manual air pump with about 5-30 kilopascals of force. In some instances, the method further comprises removing a cover from the nozzle before the nozzle is positioned in the nostril of the subject.
[0030]
In some cases, a method of manufacturing a device for delivering a powdered therapeutic formulation to a subject, wherein said method comprises providing a powdered therapeutic formulation to a reservoir and subsequently coupling a nozzle to a pump, wherein said device comprises: a) a nozzle having an upstream end and a downstream end, said nozzle adapted to allow positioning of at least a portion of said nozzle into a nostril of a subject; b) a reservoir comprising a dose of a powdered therapeutic formulation and having an upstream end and a downstream end, operably linked to and disposed within said nozzle; c) a poppet valve having an upstream end and a downstream end, wherein the poppet valve is adapted to cause diffusion of the powdered therapeutic formulation when the device is activated; d) a retainer having inner ribs linked to the poppet valve; and e) a pump operably linked to the upstream end of the retainer.
[0031]
In some instances, the device does not comprise a flow inlet when the removable cover positioned at the downstream end of the nozzle is not removed. In some instances, the reservoir for a powdered therapeutic formulation is a closed system when the removable cover is not removed, thereby increasing the stability of a powdered therapeutic formulation within the reservoir. In some instances, the device comprises a flow inlet when the removable cover positioned at the downstream end of the nozzle is removed. In some instances, the downstream end of the nozzle further comprises a nozzle hole and the nozzle hole comprises the flow inlet.
[0032]
In some instances, the poppet valve comprises an inner inlet section and the inner inlet section is connected to a first cylindrical section, and the first cylindrical section is connected to a first shelf, and the first shelf is connected to a second cylindrical section. In some instances the poppet valve further comprises an inner inlet section and the inner inlet section is connected to the top section. In some instances, the poppet valve comprises a poppet valve cavity. In some instances, the poppet valve cavity comprises a hollow chamber within the poppet valve, an opening at the upstream end of the poppet valve cavity, and an opening at the downstream end of the poppet valve cavity. In some instances, the poppet valve cavity spans the entire length of the poppet valve. In some instances, the poppet valve cavity and the opening at the upstream end of the poppet valve cavity is connected to the reservoir and the opening at the downstream end of the poppet valve cavity is connected to the pump.
[0033]
Device height
The devices disclosed herein can be of any convenient dimensions for application of a powdered therapeutic formulation contained therein. For example, a device can be about: 3-15 cm, 4-15 cm, 5-15 cm, 6-15 cm, 7-15 cm, 8-15 cm, 3-10 cm, 3-9 cm, or 3-8 cm in height. A device can be about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, about 9 cm, about 10 cm, about 11 cm, about 12 cm, about 13 cm, about 14 cm, or about 15 cm in height. A device can be more than: about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, about 9 cm, about 10 cm, about 11 cm, about 12 cm, about 13 cm, about 14 cm, or about 15 cm in height. A device can be less than: about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, about 9 cm, about 10 cm, about 11 cm, about 12 cm, about 13 cm, about 14 cm, or about 15 cm in height. Dimensions for the device can be chosen based on the amount of powdered therapeutic formulation to be delivered, ease of use, ease of portability, or manufacturing convenience.
[0034]
Device volume
As described herein, a device can be configured to be a small size such that it can easily be stored or transported. A device can be between about 1 and 100 cm 3 in volume, between about 5 and 90 cm 3 in volume, between about 10 and 80 cm 3 in volume, between about 25 and 80 cm 3 in volume, between about 50 and 100 cm 3 in volume, between about 1 and 50 cm 3 in volume, between about 5 and 75 cm 3 in volume, between about 1 and 25 cm 3 in volume, between about 5 and 50 cm 3 in volume, between about 10 and 50 cm 3 in volume, or between about 25 and 50 cm 3 in volume. A device can be at least about: 1, 2, 5, 10, 25, 30, 40, 50, 75, or 100 cm 3 in volume. A device can be less than about: 250, 200, 175, 150, 125, 100, 75, 70, 65, 60, 55, 50, 40, 30, 25, 10, 5, 2, or 1 cm 3 in volume.
[0035]
Device width
At its widest point, the device can be between about 0.5-5 cm in width. The device at its widest point can be about: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 cm in width. The device at its widest point can be more than about: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 cm in width. The device at its widest point can be less than about: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 cm in width.
[0036]
Device mass
A device can be configured to be lightweight. For example, a device can have a total mass of between about 1 and about 50 grams, between about 5 and about 40 grams, between about 10 and about 35 grams, between about 10 and about 30 grams, between about 10 and about 25 grams, between about 1 and about 10 grams, between about 1 about 5 grams, or between about 10 and about 20 grams. A device can have a total mass of less than about: 100 grams, 90 grams, 80 grams, 75 grams, 70 grams, 65 grams, 60 grams, 55 grams, 50 grams, 45 grams, 40 grams, 35 grams, 30 grams, 25 grams, 20 grams, 10 grams, 9 grams, 8 grams, 7 grams, 6 gram, 5 grams, 4 grams, 3 grams, 2 grams, 1 gram, 0.5 gram, or less. A device can have a total mass of more than about: 0.5 gram, 1 gram, 2 grams, 3 grams, 4 grams, 5 grams, 6 grams, 7 grams, 8 grams, 9 grams, 10 grams, 11 grams, 12, grams, 13 grams, 14 grams, 15 grams, 16 grams, 17 grams, 18 grams, 19 grams, 20 grams, 25 grams, 30 grams, 35 grams, 40 grams, 45 grams, 50 grams, 55 grams, 60 grams, 65 grams, 70 grams, 75 grams, 80 grams, 85 grams, 90 grams, 95 grams, or 100 grams. A device can a have a total mass of about: 1 gram, 2 grams, 3 grams, 4 grams, 5 grams, 6 grams, 7 grams, 8 grams, 9 grams, 10 grams, 11 grams, 12, grams, 13 grams, 14 grams, 15 grams, 16 grams, 17 grams, 18 grams, 19 grams, 20 grams, 25 grams, 30 grams, 35 grams, 40 grams, 45 grams, 50 grams, 55 grams, 60 grams, 65 grams, 70 grams, 75 grams, 80 grams, 85 grams, 90 grams, 95 grams, or 100 grams. Total mass can be the mass of a device without a powdered therapeutic formulation or the mass of a device with a powdered therapeutic formulation.
[0037]
Device Delivery Efficiency
As described herein, a device can be configured to deliver a substantial fraction of a single dose of a powdered therapeutic formulation (powdered formulation) into a nostril of a subject. A device can be configured to deliver a substantial fraction of an amount of powdered therapeutic formulation residing within the device into a nostril of a subject. A powdered therapeutic formulation or a substantial fraction thereof can be delivered after a single activation of a device. Activation of a device can be, for example, compression of a flexible vial that serves as a manual air pump. A substantial fraction of a powdered therapeutic formulation can be delivered after multiple activations of a device, such as, for example 2, 3, 4, 5, 6, 7, 8, 9, or 10 activations. Multiple activations of a device can constitute a single use of a device. The substantial fraction of powdered therapeutic formulation that can be delivered by a device can be at least about: 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94.5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.5%, 99.6%, 99.7%, 99.8% 99.9%, 99.95%, or 100% of the amount of powdered therapeutic formulation such as the amount in a single dose or the amount residing in the device. The substantial fraction of powdered therapeutic formulation that can be delivered by a device can be about: 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94.5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.5%, 99.6%, 99.7%, 99.8% 99.9%, 99.95%, or 100% of the amount of powdered therapeutic formulation such as the amount in a single dose or the amount residing in the device. In some instances, about: 60-100%, 60-99%, 60-95%, 60-90%, 60-85%, 60-80%, 60-75%, 60-70%, 70-100%, 70-99%, 70-95%, 70-90%, 70-85%, 70-80%, 75-100%, 75-99%, 75-95%, 75-90%, 75-85%, 75-80%, 80-100%, 80-99%, 80-95%, 80-90%, 80-85%, 85-100%, 85-99%, 85-95%, 85-90%, 90-100%, 90-99%, 90-95%, 95-100%, or 95-99% of the amount of powdered therapeutic formulation is expelled from the device after the first activation. In such instances, a second activation can result in expulsion of substantially all of the powdered therapeutic formulation. The remainder of 1% or less of the powdered therapeutic formulation in the device, typically as a residual powder on the walls of the chamber, can constitute delivery of substantially all of the powdered therapeutic formulation.
[0038]
A. Nozzle
Provided herein are nozzles adapted to deliver a powdered therapeutic formulation to a nostril of a subject. In some instances, a nozzle is adapted to be placed partially or completely into a nostril of a subject during use. In some instances, a nozzle is adapted to be placed externally and adjacent to a nostril, totally or partially covering the opening of a nostril.
[0039]
Nozzle shape
A nozzle disclosed herein is not limited to a particular shape. A nozzle can be of a uniform width such as in the shape of a cylinder, a cuboid, a rhombohedron, or a parallelepiped. A nozzle can also be a funnel or frustum shape, with a wide end and a narrow end. The shape of a nozzle can be wider at the upstream end and narrower at the downstream end. A nozzle can be wider at the downstream end and narrower at the upstream end. In some instances, the widest and narrowest sections of a nozzle, however, are not being at any end. For example, the widest section of a nozzle can be at any position along the upstream to downstream axis. In nozzles where the widest section is found mid-length along the axis, the widest section can function as a stop that prevents the nozzle from being inserted further into a nostril. In some instances, a nozzle is composed of two or more shapes such as any of the shapes provided herein. For example, a nozzle can include a cylinder shaped portion and a cone shaped portion. The nozzle can include a section, e.g., a nozzle pipe, designed for insertion into a nostril and a section, e.g., a nozzle base, designed for attachment to a pump, for example, attachment to the throat of a flexible vial.
[0040]
Nozzle material
A nozzle can be composed of a variety of polymers, plastics, rubber, silicones, metal, composites, any other materials described herein as suitable for use in the manufacture of a device applicator, or any other material suitable for use as an applicator nozzle. A nozzle can be made of one material or type of material. A nozzle can be composed two or more different materials or types of materials. All or a portion of a nozzle can be a biocompatible material or a hypoallergenic material. In some instances, a nozzle is comprised of one or more of cyclic olefin copolymer (COC), silicone, styrene butadiene block copolymer (SBC), polyacetal, polyoxymethylene, acrylates, polyethylenes, polyurethane, hydrogel, polyester (e.g., DACRONB from E. I. Du Pont de Nemours and Company, Wilmington, Del.), polypropylene, polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), polyether ether ketone (PEEK), nylon, extruded collagen, polymer foam, rubber, silicone rubber, polyethylene terephthalate, ultra high molecular weight polyethylene, polycarbonate urethane, polyimides, aluminum, stainless steel, nickel-titanium alloy (e.g., Nitinol), titanium, stainless steel, or cobalt-chrome alloy (e.g., ELGILOYB from Elgin Specialty Metals, Elgin, Ill.; CONICHROMEB from Carpenter Metals Corp., Wyomissing, Pa.).
[0041]
Nozzle opaqueness
A nozzle can be composed partially or entirely of clear or translucent materials. The use of a clear or translucent nozzle can allow for the visual inspection of the nozzle to ascertain whether there is appreciable residual powdered therapeutic formulation (powdered formulation) remaining in a reservoir after use. If, upon inspection, a subject notices that there is a residual powdered therapeutic formulation in a reservoir, the subject can activate a pump once or multiple times and then check by visual inspection of the clear or translucent nozzle to see if there was sufficient delivery. This process can be repeated as needed to ensure that an adequate dose is delivered. The nozzle can be composed partially or entirely of opaque or substantially opaque materials. For example, if the device contains a light-sensitive powdered therapeutic formulation, an opaque nozzle or substantially opaque material can protect the light-sensitive powdered therapeutic formulation from exposure to light.
[0042]
Nozzle rigidity
A nozzle material can be a soft, pliable or malleable material such that the nozzle can conform to the shape of a nostril of a subject. A nozzle can be composed of rigid, substantially rigid, flexible, or substantially flexible materials, or a combination thereof. A nozzle can be a rigid material such as a polymer, plastic, silicone, metal, or a composite at one end, and a soft, malleable, or pliable material at another end, such as, for example the end of the nozzle that is placed in the nostril. The soft, pliable, or malleable material can provide the advantage of reducing the likelihood of injury during contact between a nostril of a subject and the nozzle. The reduction of likelihood of an injury can be useful if a device is used by a third party such as a doctor, a nurse, a nursing home attendant, an emergency medical technician, a paramedic, a parent, a guardian or other caregiver to deliver a powdered therapeutic formulation to a subject (e.g., a child or an elderly person).
[0043]
Nozzle/nasal insertion
In some instances, a nozzle is of a size to substantially fit inside a nostril of a subject. For example, at least about: 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or 95% of the nozzle can fit inside a nostril of a subject during use of a device. Less than about: 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or 95% of the nozzle can fit inside a nostril of a subject during use of a device. Between about 5% and about 90% of the nozzle of a device can fit inside the nostril of a subject during use of a device. In some instances, between about: 5% and 75%, 10% and 50%, 10% and 30%, 20% and 60%, or 30% and 90% of the nozzle of a device can fit inside the nostril of a subject during use of a device. About: 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or 95% of the nozzle can fit inside a nostril of a subject during use of a device.
[0044]
Nozzle pipe/nasal insertion
The nozzle can comprise a nozzle pipe for insertion into a nostril and a base section, e.g., for attachment to a pump. In some instances, a nozzle pipe is of a size to substantially fit inside a nostril of a subject. For example, at least about: 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or 95% of the nozzle pipe can fit inside a nostril of a subject during use of a device. Less than about: 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or 95% of the nozzle pipe can fit inside a nostril of a subject during use of a device. Between about 5% and about 90% of the nozzle pipe of a device can fit inside the nostril of a subject during use of a device. In some instances, between about: 5% and 75%, 10% and 50%, 10% and 30%, 20% and 60%, or 30% and 90% of the nozzle pipe of a device can fit inside the nostril of a subject during use of a device. About: 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or 95% of the nozzle pipe can fit inside a nostril of a subject during use of a device. In some instances, a nozzle base section can fit inside a nostril of a subject. For example, at least about: 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or 95% of the nozzle base can fit inside a nostril of a subject during use of a device. Less than about: 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or 95% of the nozzle base can fit inside a nostril of a subject during use of a device. Between about 5% and about 90% of the nozzle base of a device can fit inside the nostril of a subject during use of a device. In some instances, between about: 5% and 75%, 10% and 50%, 10% and 30%, 20% and 60%, or 30% and 90% of the nozzle base of a device can fit inside the nostril of a subject during use of a device. About: 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or 95% of the nozzle base can fit inside a nostril of a subject during use of a device. Alternatively, in some instances, the nozzle base section does not fit inside a nostril of the subject.
[0045]
Nozzle length
The length of nozzle can be measured from an upstream end to a downstream end, where upstream and downstream denote the direction of flow of air or other propellant during operation of a device (i.e., air or other propellant can flow from upstream to downstream). The length of a nozzle can include the length of a nozzle pipe and a nozzle base section. The length of nozzle can be the length of a nozzle pipe. The upstream to downstream length of the nozzle can be less than about 5 cm, less than about 4.5 cm, less than about 4 cm, less than about 3.5 cm, less than about 3 cm, less than about 2.5 cm, less than about 2 cm, less than about 1.5 cm, less than about 1.0 cm, or less than about 0.5 cm. The length of the nozzle can be between about 0.5 cm and 5 cm, between about 1 cm and 5 cm, between about 1 cm and 4 cm, between about 1 cm and 3 cm, between about 2 cm and 5 cm, or between about 2 cm and 4 cm in length. The length of the nozzle can be about: 0.5 cm, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, or 5 cm. The length of the nozzle can be more than about: 0.5 cm, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, or 5 cm.
[0046]
Nozzle pipe length
A nozzle can comprise a nozzle pipe for insertion into a nostril and a throat section for attachment to a pump. The length of a nozzle pipe can be measured from an upstream end to a downstream end, where upstream and downstream denote the direction of flow of air or other propellant during operation of a device (i.e., air or other propellant can flow from upstream to downstream). The upstream to downstream length of the nozzle pipe can be less than about 5 cm, less than about 4.5 cm, less than about 4 cm, less than about 3.5 cm, less than about 3 cm, less than about 2.5 cm, less than about 2 cm, less than about 1.5 cm, or less than about 1.0 cm. The length of the nozzle pipe can be between about 0.5 cm and 5 cm, between about 1 cm and 5 cm, between about 1 cm and 4 cm, between about 1 cm and 3 cm, between about 2 cm and 5 cm, or between about 2 cm and 4 cm in length. The length of the nozzle pipe can be about: 0.5 cm, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, or 5 cm. The length of the nozzle pipe can be more than about: 0.5 cm, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, or 5 cm.
[0047]
External nozzle width
In some instances, the external width perpendicular to the upstream to downstream axis of the nozzle at its widest section is about: 0.1 cm to 4 cm, 1 cm to 4 cm, 1 cm to 3 cm, 1 cm to 2 cm, 2 cm to 4 cm, or 2 cm to 3 cm, 0.1 cm to 2 cm, 0.5 cm to 2 cm, or 1 cm to 2 cm. In some instances, the external width perpendicular to the upstream to downstream axis of the nozzle at its widest section is no more than about: 0.5 cm, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, or 5 cm wide. In some instances, the external width perpendicular to the upstream to downstream axis of the nozzle at its widest section is about: 0.1 cm, 0.2 cm, 0.3 cm, 0.4 cm, 0.5 cm, 0.6 cm, 0.7 cm, 0.8 cm, 0.9 cm, 1.0 cm, 1.2 cm, 1.4 cm, 1.6 cm, 1.8 cm, 2.0 cm, 2.2 cm, 2.4 cm, 2.6 cm, 2.8 cm, 3 cm, 3.2 cm, 3.4 cm, 3.6 cm, 3.8 cm, 4 cm, 4.2 cm, 4.4 cm, 4.6 cm, 4.8 cm, or 5 cm. In some instances, the external width perpendicular to the upstream to downstream axis of the nozzle at its widest section is more than about: 0.1 cm, 0.2 cm, 0.3 cm, 0.4 cm, 0.5 cm, 0.6 cm, 0.7 cm, 0.8 cm, 0.9 cm, 1.0 cm, 1.2 cm, 1.4 cm, 1.6 cm, 1.8 cm, 2.0 cm, 2.2 cm, 2.4 cm, 2.6 cm, 2.8 cm, 3 cm, 3.2 cm, 3.4 cm, 3.6 cm, 3.8 cm, 4 cm, 4.2 cm, 4.4 cm, 4.6 cm, 4.8 cm, or 5 cm.
[0048]
In some instances, the external width perpendicular to the upstream to downstream axis of the nozzle at its narrowest section is no more than about: 0.1 cm, 0.25 cm, 0.5 cm, 0.75 cm, 1.0 cm, 1.5 cm, 2.0 cm, 2.5 cm, or 3.0 cm. In some instances, the external width perpendicular to the upstream to downstream axis of the nozzle at its narrowest section lies within the range of about: 0.5 cm to 3.0 cm; 1.0 to 2.5 cm, 1.0 to 2.0 cm, 0.1 cm to 2.0 cm, or 0.5 cm to 1.5 cm. In some instances, the external width perpendicular to the upstream to downstream axis of the nozzle at its narrowest section is about: 0.1 cm, 0.2 cm, 0.3 cm, 0.4 cm, 0.5 cm, 0.6 cm, 0.7 cm, 0.8 cm, 0.9 cm, 1.0 cm, 1.2 cm, 1.4 cm, 1.6 cm, 1.8 cm, 2.0 cm, 2.2 cm, 2.4 cm, 2.6 cm, 2.8 cm, 3 cm, 3.2 cm, 3.4 cm, 3.6 cm, 3.8 cm, 4 cm, 4.2 cm, 4.4 cm, 4.6 cm, 4.8 cm, or 5 cm. In some instances, the external width perpendicular to the upstream to downstream axis of the nozzle at its narrowest section is more than about: 0.1 cm, 0.2 cm, 0.3 cm, 0.4 cm, 0.5 cm, 0.6 cm, 0.7 cm, 0.8 cm, 0.9 cm, 1.0 cm, 1.2 cm, 1.4 cm, 1.6 cm, 1.8 cm, 2.0 cm, 2.2 cm, 2.4 cm, 2.6 cm, 2.8 cm, 3 cm, 3.2 cm, 3.4 cm, 3.6 cm, 3.8 cm, 4 cm, 4.2 cm, 4.4 cm, 4.6 cm, 4.8 cm, or 5 cm.
[0049]
The width of the nozzle can vary continuously, can vary in a step-wise fashion, does not vary, or a combination thereof. The inner width or the outer width of the nozzle can vary continuously, can vary in a step-wise fashion, does not vary, or a combination thereof. The upstream and downstream ends of the nozzle can be the same width or different. In some instances, the narrowest end is the end that is placed in a nostril of a subject before and during administration. In some instances, the widest and narrowest sections of a nozzle are at the ends. For example, the widest section of a nozzle can be at the upstream end and the narrowest section of the nozzle can be at the downstream end, or vice versa. In some instances, the widest and/or narrowest sections of a nozzle are not at the end. In some instances, the widest section of a nozzle houses a powdered therapeutic formulation reservoir. In some instances, the widest section of a nozzle is a nozzle base for attachment to a manual air pump.
[0050]
Internal nozzle width
In some instances, the internal width perpendicular to the upstream to downstream axis of the nozzle at its widest section is between about: 0.1 cm to 4 cm, 1 cm to 4 cm, 1 cm to 3 cm, 1 cm to 2 cm, 2 cm to 4 cm, 2 cm to about 3 cm, 0.1 cm to 2 cm, 0.5 cm to 2 cm, or 1 cm to 2 cm. In some instances, the internal width perpendicular to the upstream to downstream axis of the nozzle at its widest section is no more than about: 0.5 cm, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, or 5 cm wide. In some instances, the internal width perpendicular to the upstream to downstream axis of the nozzle at its widest section is more than about: 0.5 cm, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, or 5 cm wide. In some instances, the internal width perpendicular to the upstream to downstream axis of the nozzle at its widest section is about: 0.1 cm, 0.2 cm, 0.3 cm, 0.4 cm, 0.5 cm, 0.6 cm, 0.7 cm, 0.8 cm, 0.9 cm, 1.0 cm, 1.2 cm, 1.4 cm, 1.6 cm, 1.8 cm, 2.0 cm, 2.2 cm, 2.4 cm, 2.6 cm, 2.8 cm, 3 cm, 3.2 cm, 3.4 cm, 3.6 cm, 3.8 cm, 4 cm, 4.2 cm, 4.4 cm, 4.6 cm, 4.8 cm, or 5 cm.
[0051]
In some instances, the internal width perpendicular to the upstream to downstream axis of the nozzle at its narrowest section is no more than about: 0.1 cm, 0.25 cm, 0.5 cm, 0.75 cm, 1.0 cm, 1.5 cm, 2.0 cm, 2.5 cm, or 3.0 cm. In some instances, the internal width perpendicular to the upstream to downstream axis of the nozzle at its narrowest section is more than about: 0.1 cm, 0.25 cm, 0.5 cm, 0.75 cm, 1.0 cm, 1.5 cm, 2.0 cm, 2.5 cm, or 3.0 cm. In some instances, the internal width perpendicular to the upstream to downstream axis of the nozzle at its narrowest section lies within the range of about: 0.5 cm to 3.0 cm; 1.0 to 2.5 cm, 1.0 to 2.0 cm, 0.1 cm to 2.0 cm, or 0.5 cm to 1.5 cm. In some instances, the internal width perpendicular to the upstream to downstream axis of the nozzle at its narrowest section is about: 0.1 cm, 0.2 cm, 0.3 cm, 0.4 cm, 0.5 cm, 0.6 cm, 0.7 cm, 0.8 cm, 0.9 cm, 1.0 cm, 1.2 cm, 1.4 cm, 1.6 cm, 1.8 cm, 2.0 cm, 2.2 cm, 2.4 cm, 2.6 cm, 2.8 cm, 3 cm, 3.2 cm, 3.4 cm, 3.6 cm, 3.8 cm, 4 cm, 4.2 cm, 4.4 cm, 4.6 cm, 4.8 cm, or 5 cm.
[0052]
Nozzle internal volume
The nozzle can be hollow and can contain an internal volume. The internal volume of a nozzle can be about: 5 cm 3 or less, 4 cm 3 or less, 3 cm 3 or less, 2 cm 3 or less, 1 cm 3 or less, 0.5 cm 3 or less. In some instances, the internal volume of a nozzle is between about 1 cm 3 and about 5 cm 3, between about 1 cm 3 and about 4 cm 3, between about 1 cm 3 and about 3 cm 3, between about 1 cm 3 and about 2 cm 3, between about 0.1 cm 3 and 2 cm 3, and between about 0.1 cm 3 and about 1 cm 3. The internal volume of the nozzle can be about: 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, or 5.0 cm 3. The internal volume of the nozzle can be more than about: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 cm 3. The internal volume of the nozzle can be less than about: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 cm 3.
Claims
[Claim 1]
A device, wherein the device comprises:
a nozzle having a reservoir disposed within the nozzle,
a poppet valve at least partially fit into the reservoir,
a retainer that is hollow and holds the poppet valve, and
a manual air pump operably linked to an upstream end of the nozzle and a downstream end of the retainer,
wherein the poppet valve has one or more contacting points with the retainer.
[Claim 2]
The device of claim 1, wherein the one or more contacting points are one or more inner ribs.
[Claim 3]
The device of claim 1 or 2, wherein the retainer has an inner circumferential groove based from an upstream end of the retainer.
[Claim 4]
The device of claim 3, wherein a rim of the circumferential groove of the retainer is in contact with the one or more contacting points of the poppet valve.
[Claim 5]
The device of any preceding claim, wherein the retainer immobilizes the poppet valve.
[Claim 6]
The device of any preceding claim, wherein when the device is activated, a portion of air from the pump flows into the retainer along the circumferential groove and travels through surface grooves of the retainer to generate a vortex into the reservoir.
[Claim 7]
The device of any preceding claim, wherein after the device is activated, the one or more air intake holes of the retainer allows outside air to enter the pump.
[Claim 8]
The device of any preceding claim, wherein the reservoir contains a powdered therapeutic formulation.
[Claim 9]
The device of claim 8, wherein the device is adapted to deliver at least about 85% of the powdered therapeutic formulation into a nostril of a subject after a single, two, or three times of activation of the manual air pump.
[Claim 10]
The device of claim 8, wherein at least about 90% of the powdered therapeutic formulation is delivered into the nostril of the subject after the single, two, or three times of activation of the manual air pump.
[Claim 11]
The device of any one of claims 8 to 10, wherein the powdered therapeutic formulation is present in an amount of about 1 mg to about 30 mg.
[Claim 12]
The device of any one of claims 8 to 10, wherein the powdered therapeutic formulation is present in an amount of about 20 mg.
[Claim 13]
The device of any preceding claim, wherein the nozzle further comprises a breakable tab positioned at the downstream end of the nozzle.
[Claim 14]
The device of any preceding claim, wherein the device is a single-use device.
[Claim 15]
The device of any preceding claim, wherein the poppet valve further comprises a conical top section.
[Claim 16]
The device of claim 15, wherein the conical top section is connected to a first shelf that is connected to a first cylindrical section.
[Claim 17]
The device of claim 15, wherein the first cylindrical section is connected to a second shelf that is connected to a second cylindrical section.
[Claim 18]
The device of any preceding claim, wherein the poppet valve has one or more surface grooves.
[Claim 19]
The device of claim 18, wherein the poppet valve has about 3 to about 20 surface grooves.
[Claim 20]
The device of claim 19, wherein the poppet valve has about 8 surface grooves.
[Claim 21]
The device of any one of claims 18 to 20, wherein the one or more surface grooves creates a vortex in the reservoir when the device is activated.
[Claim 22]
The device of any one of claims 18 to 21, wherein the one or more surface grooves are present on the second shelf.
[Claim 23]
The device of any preceding claim, wherein the poppet valve has about 2 to about 10 inner ribs.
[Claim 24]
The device of claim 23, wherein the poppet valve has about 3 inner ribs.
[Claim 25]
The device of any preceding claim, wherein the poppet valve is at least partially located within the reservoir.
[Claim 26]
The device of any preceding claim, wherein the poppet valve is at least partially located within the manual air pump.
[Claim 27]
The device of any preceding claim, wherein the poppet valve comprises a cavity.
[Claim 28]
The device of any preceding claim, wherein the device is less than about 100 cm 3 in volume.
[Claim 29]
The device of claim 28, wherein the device is less than about 50 cm 3 in volume.
[Claim 30]
The device of claim 28, wherein the device is about 30 cm 3 in volume.
[Claim 31]
The device of any preceding claim, wherein the device has a mass of less than about 20 grams.
[Claim 32]
The device of claim 31, wherein the device has a mass less than about 10 grams.
[Claim 33]
The device of claim 31, wherein the device has a mass of about 6 grams to about 7 grams.
[Claim 34]
The device of any preceding claim, wherein the reservoir has an inner diameter of less than about 10 mm.
[Claim 35]
The device of any preceding claim, wherein the reservoir has an outer diameter of about 8 mm to about 9 mm.
[Claim 36]
The device of claim 35, wherein the outer diameter of the reservoir is about 8.7 mm to about 8.9 mm.
[Claim 37]
The device of any preceding claim, wherein an upstream end of the reservoir has smooth surface adapted to contact the poppet valve.
[Claim 38]
The device of any preceding claim, wherein the poppet valve has an outer diameter of about 7 mm to about 8 mm.
[Claim 39]
The device of claim 38, wherein the outer diameter of the poppet valve is about 7.7 mm to about 7.9 mm.
[Claim 40]
The device of any preceding claim, wherein an opening of the manual air pump is wider than an outer diameter of the poppet valve.
[Claim 41]
The device of any preceding claim, wherein the retainer contains an outer circumferential rim that is wider than an opening of the manual air pump.
[Claim 42]
The device of any preceding claim, wherein the retainer has two air intake holes.
[Claim 43]
The device of any preceding claim, wherein the one or more air intake holes are about 0.2 mm to about 0.4 mm wide.
[Claim 44]
The device of any preceding claim, wherein the retainer is at least partially fit into the manual air pump.
[Claim 45]
The device of any preceding claim, wherein a portion of the poppet valve fit into the nozzle is about 5 mm to about 6 mm in length parallel to an upstream to downstream axis.
[Claim 46]
The device of claim 45, wherein the portion of the poppet valve fit into the nozzle is about 5.7 mm to about 5.9 mm in length parallel to an upstream to downstream axis.
[Claim 47]
The device of any preceding claim, wherein the nozzle has a length parallel to an upstream to downstream axis of about 5 mm to about 40 mm.
[Claim 48]
The device of any preceding claim, wherein the nozzle of the device comprises a clear, lightly tint, or translucent material.
[Claim 49]
A method of using a device of any one of claims 1-48 to deliver a powdered therapeutic formulation to a subject in need thereof, comprising positioning a nozzle of the device at least partially into a nostril of the subject and activating the manual air pump, wherein the nozzle comprises the powdered therapeutic formulation.
[Claim 50]
The method of claim 49, wherein the method treats a disease or condition of the subject.
[Claim 51]
The method of claim 50, wherein the disease or condition is migraine.
[Claim 52]
The method of any one of claims 49 to 51, wherein the powdered therapeutic formulation comprises an active agent.
[Claim 53]
The method of claim 52, wherein the active agent is dihydroergotamine or a pharmaceutically acceptable salt thereof.
[Claim 54]
The method of any one of claims 49 to 53, further comprising visually inspecting the amount of the powdered therapeutic formulation remaining in the reservoir and repeating the method of claim 49 until a sufficient dose is delivered.
[Claim 55]
A method of manufacturing a device of any one of claims 1-48, comprising:
inserting the poppet valve in the nozzle,
inserting the retainer in the manual air pump, and
coupling the manual air pump to the nozzle.
[Claim 56]
The method of claim 55, further comprising filling the reservoir with a powdered therapeutic formulation.