Patent Application
20170368273
The present invention provides an aerosol delivery device having structures and methods for providing controlled airflow and aerosol entrainment through the device to optimize aerosol delivery under a greater range of conditions.
Aerosol delivery devices of known designs and configurations previously devised and utilized for the purpose of administering aerosolizable substances and medicament dosages through conventional methods and apparatuses are known to consist basically of familiar, expected, and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded art which has been developed for the fulfillment of countless objectives and requirements. Such aerosol delivery devices make it possible to introduce substances to the respiratory system generally via simple inhalation. Some aerosol delivery devices utilize compressed air or pressurized gas, including jet nebulizers and pressurized metered dose inhaler (MDI) canisters, while others, like the present invention, do not; instead, relying on electrical energy and vibrating/heating elements to aerosolize a substance for inhalation.
As there is a myriad of ways to generate aerosol, there is also a myriad of ways to store the medicament formulation, including liquid reservoirs, pressurized canisters, cartridges, as well as in blister strips or dosage packets.
The term “aerosol” is understood in the context of the present invention to mean a preferably nebulous collection of atomized liquid droplets, fine powder particles, or vapor, often suspended in air, that can be available for inhalation. Aerosol particles can be solid or liquid fine particles and come in a variety of shapes. The term “aerosolizable substance” as used herein means any substance, including, but not limited to aqueous liquids, suspensions, and solids and those containing a pharmacologically active ingredient, which is capable of becoming an aerosol or having already become an aerosol. The term “aerosolized therapy” as used herein means any aerosolized liquid or powder, or the condensation aerosol that forms after vaporization of a substance, regardless of whether it is physiologically active. The expression “medicament formulation” used in the present invention is understood to include, apart from medicaments, also therapeutic agents or the like, in particular therefore all types of agents for inhalation, including those which are active and non-active ingredients. Aerosols may also comprise water, saline, or flavoring agents. Some substances are aerosolizable when placed in a liposomal formulation for aerosolization.
In most instances, aerosol particles with a mass median aerodynamic diameter (MMAD) between 0.5 and 5 micrometers are ideal for lung delivery; whereas, aerosol particles with a MMAD of greater than 5 micrometers have deposition in the upper airways rather than the lungs. Aerosol particles with a MMAD of 2 to 5 micrometers have deposition in the bronchi and bronchioles, and aerosol particles with a MMAD of less than 2 micrometers have deposition in the alveoli, for deep lung and or systemic delivery. Selection of MMAD is one method of targeting aerosols to different airway regions.
Most aerosol delivery occurs through the mouth, such as via a mouthpiece, hose, or facemask, but nasal delivery of aerosol is also possible with a nosepiece or prongs. Some aerosol delivery devices can also be placed in a respiratory circuit to provide aerosols to patients on mechanical ventilation.
There are numerous limitations inherent in prior aerosol delivery devices, including not being able to provide the optimal amount of airflow regulation under all conditions of aerosol delivery. Unlike the present invention, prior aerosol delivery devices do not accomplish all of the following:
A) greater control over laminar flow and or flow velocity and volume of aerosolized air for improved aerosol delivery to user airways;
B) greater and longer expansion of user airways, such as with positive pressure, so that airways are more receptive to receiving aerosolized medicament formulations;
C) selective targeting of aerosols to different regions of the airways, such as the upper airways, lower airways, and or providing systemic delivery through the pulmonary route;
D) accommodation of the full range of varying degrees of user lung function and or inspiratory ability, including, but not limited to, pediatric patients with small lung volumes, chronic obstructive pulmonary disease (COPD) patients with compromised lung function, and adult patients with healthy lung function;
E) accommodation of more medicament formulations that have potential for aerosolization; including liquids, suspensions and solids, droplets and particles, of varying sizes, shapes, weights, viscosities, and flow dynamic properties.
Therefore, prior aerosol delivery devices do not provide for enhanced efficiency of aerosol delivery under a wide range of medicament formulations, to a wide variety of users and patients, and to various regions of the airways, as the present invention does. The present invention, therefore, has the ability to improve patient treatments for a multitude of ailments and diseases. The present invention also has the ability to speed drug product delivery research and development (R&D) time, and may reduce costs associated with R&D.
In this respect, the aerosol delivery device according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in doing so provides an apparatus primarily developed for the purpose of providing controlled airflow through the device to optimize aerosol delivery under a greater range of conditions.
More pharmaceuticals are being made available for inhalation. This includes pharmaceuticals that can be delivered to the systemic circulation via the pulmonary route. As an improved drug delivery device, the present invention can improve the delivery dynamics and targeting of these drugs. Selective targeting of aerosols to one or more different airway regions can aid in the targeting of aerosolized chemotherapies against lung cancer. Selective targeting of aerosols to one or more different airway regions can also have profound military medicine applications, including biodefense to counter bioterrorism, by coating upper airways with antibiotics against anthrax or other infectious agents, or by providing anticholinergic agents to the systemic circulation via alveoli as an antidote to nerve agent exposure. The present invention also has the potential to enhance the deliverability of drug candidates in development, which has the potential to reduce drug development costs.
Therefore, it can be appreciated that there exists a continuing need for a new and improved aerosol delivery device which can be used for providing controlled airflow through the device to optimize aerosol delivery under a greater range of conditions. In this regard, the present invention substantially fulfills this need.
In view of the foregoing disadvantages inherent in the known types of aerosol delivery devices of known designs and configurations, the present invention provides an improved aerosol delivery device. As such, the general purpose of the present invention, which will be described subsequently in greater detail, is to provide a new and improved aerosol delivery device and method which has all the advantages of prior devices and none of the disadvantages.
To attain this, the present invention essentially comprises a housing with at least one airflow inlet, at least one airflow outlet, and at least one airflow passage extending therebetween. A medicinal, therapeutic, or other aerosolizable substance to be inhaled is provided. Within this housing is at least one site/element for producing and or dispensing an aerosol to be entrained by airflow through the device. At least one calibrated airflow resistance control element with adjustable settings allows regulation of airflow into, through, and or out of the invention.
The present invention is an aerosol delivery device having a structure comprising a housing, an at least one (ambient) air inlet, an at least one aerosolized air outlet, and an at least one airflow passage (extending) therebetween/therein. The aerosol delivery device further comprises an at least one aerosol generating element producing an aerosol from an at least one aerosolizable substance or formulation with the use of electrical energy and without the use of compressed/pressurized gas. The aerosol delivery device further has an at least one airflow through its housing produced by a user inhaling from this aerosol delivery device and entraining aerosol when generated. The at least one airflow is controllable in velocity, volume, or a combination thereof as the at least one air inlet, the at least one aerosolized air outlet, the at least one airflow passage, or a combination thereof undergoes an at least one physical change selected from changes in size, angle, shape, (biasing) resistance to flow, number of apertures, or a combination thereof. The at least one physical change is modulated by user/digital input to control the at least one airflow and or entrained aerosolized air and to regulate an at least one parameter selected from user inhalation resistance, user inhalation duration, user inhalation rate, aerosol delivery efficiency, targeting of aerosol to different user airway regions, or a combination thereof. In different embodiments, the aerosol delivery device has an adjustable airflow restriction of the at least one airflow through the housing, and or an adjustable negative pressure through the housing, experienced when the user inhales through the aerosol delivery device. The user can modulate the at least one physical change of the device by the act of inhaling itself when the device adjusts automatically in a non-electric analog manner, such as with valves; or automatically via sensors, circuitry, and motors. Or, the user can modulate the at least one physical change of the device by manually moving a dial, lever, or setting with the user's fingers or hand. Or, the user can modulate the at least one physical change of the device via a digital control unit by pressing a button or dial, or by voice activation, or via software programming or algorithms, or via a Smartphone or other electronic device.
There has thus been outlined, rather broadly, the more important features of the invention in order that the detailed description thereof that follows may be better understood and in order that the present contribution to the art may be better appreciated. There are, of course, additional features of the invention that will be described hereinafter and which will form the subject matter of the claims attached.
In this respect, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of descriptions and should not be regarded as limiting.
As such, those skilled in the art will appreciate that the conception, upon which this disclosure is based, may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.
It is therefore an object of the present invention to provide a new and improved aerosol delivery device which has all of the advantages of the prior art aerosol delivery devices of known designs and configurations and none of the disadvantages.
It is another object of the present invention to provide a new and improved aerosol delivery device which may be easily and efficiently manufactured and marketed.
An even further object of the present invention to provide a new and improved aerosol delivery device which is of durable and reliable constructions.
Lastly, it is an object of the present invention to provide a new and improved aerosol delivery device for providing controlled airflow through the device to optimize aerosol delivery under a greater range of conditions.
These together with other objects of the invention, along with the various features of novelty which characterize the invention, are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its operating advantages and the specific objects attained by its uses, reference should be had to the accompanying drawings and descriptive matter in which there is illustrated preferred embodiments of the invention.
The invention will be better understood and objects other than those set forth above will become apparent when consideration is given to the following detailed description thereof. Such description makes reference to the annexed drawings wherein:
The same reference numerals refer to the same parts throughout the various Figures.
With reference now to the drawings, the preferred embodiments of the new and improved systems and methods of aerosol delivery with airflow regulation embodying the principles and concepts of the present invention will be described in the following preferred aerosol delivery device embodiments. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.
The at least one physical change is modulated by user/digital input to control the at least one airflow and or entrained aerosolized air and to regulate an at least one parameter selected from user inhalation resistance, user inhalation duration, user inhalation rate, aerosol delivery efficiency, targeting of aerosol to different user airway regions, or a combination thereof. In various embodiments, the aerosol delivery device has an adjustable airflow restriction of the at least one airflow through the housing, and or an adjustable negative pressure through the housing, experienced when the user inhales through the aerosol delivery device.
The aerosol delivery device 1 embodiment of
The oscillation of vibratable membrane 11, which may include bending oscillations, causes a liquid aerosolizable substance or formulation 14, stored within a liquid reservoir 15, to be atomized/nebulized as this liquid is forced through small pores of membrane 11. The formulation may be that of an active ingredient in liposomes. The resulting nebulized aerosol travels into, and diffuses within, the internal chamber or aerosol holding chamber 5. Optionally or alternatively, a liquid containing-cartridge or vial can be placed within the liquid reservoir 15 or take the place of or serve as the liquid reservoir (not shown).
One-way valves 17 and 18, preferably duckbill valves, trap the nebulized aerosol within the device until vacuum pressure, or a significant threshold vacuum pressure, generated from user inhalation, is able to open said one-way valves 17 and 18. Nebulized aerosol is thusly contained in reserve chamber 5 until airflow 27, originating at one or more airflow inlets 19, carries the aerosol through the device and out to the end user through the airflow outlet end 20 of the device.
Calibrated airflow resistance control element 21, in this embodiment, consists of a user controlled airflow resistance dial with one or more supplemental apertures 22. The user controlled airflow resistance dial 21 is flush with the airflow inlet end of the device. Rotation of dial 21 aligns supplemental aperture(s) 22 with one or more airflow inlet passages 19, thereby controlling the amount of airflow 27 allowed to enter the device and travel through these passages 19, having the affect of controlling the velocity and or volume of airflow through the device. Therefore, the number of different apertures 19, 22 is controlled and adjusted by user input. The airflow resistance settings of this device may also provide an auditory signal to the user, such as a whistle sound caused by air passing through the airflow control element.
Furthermore, the pitch of this whistle sound may vary between different airflow resistance settings and may allow the user to distinguish between such settings. Furthermore, the auditory signal may indicate for user to adjust his or her inhalation rate.
The airflow outlet end of the device may contain a mouthpiece 23 that contours to the user's lips, allowing for an airtight seal. Said mouthpiece 23 may contain an exhaust port 24, comprised of an elastomeric one-way, flap, valve, which vents user exhalation, while one-way valve 18 prevents exhalation from entering the interior of the device. An optional and or removable filter housing assembly 40 may be aligned with exhaust port 24, to allow exhaled air to pass through a filter element 41, and out of the filter housing 40 (not shown). A preferred filter element 41 may be a 3M filtrate filter, or other HEPA filter, able to capture infectious particles and aerosol particles larger than 0.3 micrometers in diameter from exhalation, thereby preventing cross contamination to nearby individuals. A contaminated filter element may be cleaned or replaced as necessary. Other user interfaces other than the mouthpiece can be envisioned, including adapters for a respiratory circuit to provide aerosols to patients on mechanical ventilation.
The interior walls of the device, such as along reserve chamber 5, may be curved and or contain spiral baffles 229 (not shown) or other baffles to generate a rotational flow of aerosolized air that enters the device. Said rotational airflow may surround the aerosol and may more efficiently carry the aerosol out of the device, while reducing impaction or adhesion of aerosol with the inner walls of the device. Other baffle designs can be used in conjunction or alternatively to allow only smaller particles, with a mass median aerodynamic diameter, MMAD, more ideal for inhalation, to exit the device.
The device also comprises an electronic drive means 28 that sends an electric drive signal through signal lines 29a and 29b to the piezoelectrical conversion unit 13 and conductive support unit 12, of the piezoelectric motor assembly 12,13. A power source 30, preferably a rechargeable battery with micro-USB power (cord) port or USB power (cord) port 37, provides the electrical energy for the electronic drive means 28. The aerosol delivery device is preferably a rechargeable device with USB, micro-USB, or mini-USB power adapter or cord. The device may further comprise a digital control unit 31, with user inputs 32, and a digital display 33, such as LCD or LED, and or electroacoustic transducer speaker (not shown). The digital control unit 31 operates the electronic drive means 28 through circuit lines 34a and 34b. The digital control unit may also contain a microprocessor or microelectronic circuit that can perform one or more functions, such as: setting the intensity of the electric drive signal, providing visual and or auditory feedback to the user and or health care worker, providing an alarm function to signal when a treatment is due, a timer function to measure the duration of treatment and or to turn off operation after a certain treatment duration, a counting function to determine the number of treatments, a function to keep track of the airflow resistance settings during treatment, a time/date function to track the treatments of one or more different medicament formulations, along with any other functions obvious to the use of this device. Furthermore, the digital control unit may utilize the USB port 37 and or memory card so that data can be interfaced with a computer or respiratory instrument.
The aerosol delivery device may also contain one or more conductivity sensing leads or panels, touch panels 36, as an integral component of the mouthpiece that forms a switching circuit with the digital control unit 31 via circuit leads 35. Conductivity sensing touch panels 36 receive bioelectricity through a living being in contact with the touch panel to complete this switching circuit, which may signal the digital control unit 31 to activate electronic drive means 28 so that the device may generate or dispense aerosol only when the user is able to receive such aerosol delivery. Said touch panels may, therefore, prevent aerosol loss when the user is not able to receive aerosol. The switching circuit may include one or more resistors, transistors, grounds, capacitors, and or any other circuit components necessary for the function of this circuit. Touch panels 36 may also or instead be pressure sensing panels that detect user contact with the device. Alternatively, airflow sensors and or pressure sensors/pressure transducers, could be used in place of, or in addition to, touch panels 36, to detect changes in airflow and negative pressure caused by user inhalation. Likewise, airflow sensors and or pressure sensors would detect and or monitor user inhalation and provide such information to the digital control unit 31 that can interpret the data so as to activate and or regulate aerosol generation via electronic drive means 28, and or to provide visual and or auditory feedback to the user and or health care worker.
Airflow 27 and or entrained aerosolized air passes through the device housing 10 and internal chamber 5, through an at least one airflow passage therein 16. This airflow path or passage 16 can, in some embodiments, be adjustable as well. As shown in
It is to be understood that parameters for controlling aerosol generation timing and duration, aerosol generation amount, airflow velocity, airflow volume, airflow restriction, negative pressure, user inhalation resistance, user inhalation duration, user inhalation rate, aerosol delivery efficiency, targeting of aerosol to different user airway regions, physical changes of the device, or a combination thereof may be optionally performed or indicated by the digital control unit, and any microprocessor, electronic chip or circuit thereof, via one or more pre-programmed and or programmable algorithms stored in the device or optionally accessible via wireless or blue-tooth from a software application (“app”) on a computer, Smartphone, tablet, or diagnostic device. In certain embodiments, the aerosol delivery device utilizes “machine learning” of an aerosolizable substance's properties and or a user's breathing pattern to fine-tune and adjust the algorithm(s) of the aerosol delivery device to optimize performance and aerosol delivery, and in a sense, customize that device to a specific aerosolizable substance and or specific user or patient. In some embodiments, algorithm(s) and or data generated can be stored in the device or sent via wireless internet or blue-tooth from an “app” on a computer, Smartphone, or tablet for users, patients, and their trainers or physicians to monitor the use and progress on the device. Therefore, devices of the present invention optionally have wireless and or blue-tooth connectivity microchips and hardware (not shown). In other embodiments, wireless connectivity is not present, and instead the device optionally provides data to an “app” on a computer, Smartphone, or tablet via a USB cable or memory card or thumb drive.
In an alternative embodiment of the invention, airflow sensors 36 may also provide feedback of airflow and or breathing pattern data to a digital control unit, or microprocessor 31, which can interpret the data and can adjust airflow resistance by sending an electronic signal to an electric motor controlling a calibrated airflow resistance control element, such as that described in the next figure.
In other embodiments, the piezoelectric motor assembly may also serve as, or include, or be accompanied by, or be replaced by, a heat generating element/means to raise the temperature of the air and or aerosolized liquid droplets within the device to promote reduced particle size and convection. Electrical resistance preferably provides the heat energy for the heat generating means, and so the heat generating element is foremost an electrically resistive heating element. Furthermore, this heat generating element may serve as a vaporizing element to vaporize a liquid or other substance into a condensation aerosol available for inhalation, and may be used with, or instead of, ultrasonic/vibrating mesh nebulization, or be a hybrid among them. Therefore, at least one aerosol generating element (11,12,13) may also be or instead be a heating or vaporizing element to produce and deliver aerosols of liquid medicament, e.g., flavored nicotine solutions and cannabis oils, etc. Electricity can be used to generate aerosol by vaporizing a medicament formulation with heat from an electrically resistive heating element, electrothermal transducer, or thermo-electrical converter, and allowing that vaporized substance to condense or react in the airflow of the device. The present invention provides structures, elements, and methods for vaporization to take place.
The tag reader 216 may send information through an electronic circuit 217, preferably wired to a digital control unit 218, with user inputs 219, and a digital display 220, such as LCD or LED. The digital control unit 218 controls the operation of the piezoelectric transducer 211 and or heating element 212, using power from one or more batteries or rechargeable batteries 221. Preferably, a micro or mini-USB power (cord) port or USB power (cord) port 260, provides the interface for external electrical energy for generating aerosol with this device, and or for recharging batteries 221. In this case, an alternating current (AC) wall socket outlet 52, which the device's USB (AC/DC) power adapter 50 plugs into would be utilized. Also utilized is a USB charging cable 51 which plugs into USB power adapter 50 on one end and plugs into micro-USB power (cord) port 260, or other format of port, of the device on the other end. The combination of 50, 51, 52, and 260 can power the aerosol delivery device directly, or recharge its battery or batteries 221, and at least in some instances, even when the device is in use.
The detection and or analysis of the coded medicament information 215, by the reading device 216, may allow the digital control unit 218 to turn the piezoelectric transducer 211 and or heating element 212 on for certain durations, and or may determine the desired power and frequency to operate the piezoelectric transducer 211, and may determine the desired power and temperature to heat the heating element 212, for proper delivery characteristics of that particular medicament code.
When medicament slide 214 is inserted into the aerosol delivery device, through the medicament port channel 222, an optional piercing means or mechanism 223 can remove or cause openings 224 on the top of blister packaging 213, by which medicament can be released into the first chamber 210. When activated, heating element 212 is able to vaporize the medicament substance from medicament slide 214 by sending thermal energy to the substance by conduction and or convection. In other embodiments, heating element 212 can be located on medicament slide 214 as an electrically resistive heating support, such as a metal foil support, which may even be part of blister packaging 213. As such, an aerosolizable substance or formulation or medicament may be coated on this metal foil support. After vaporization, preferably with minimal degradation products of medicament, the vapor can cool and condense to form a condensation aerosol available for inhalation. As will next be described, this vapor can be efficiently carried to an aerosol holding chamber 225 where the particles can cool further.
First chamber 210 is connected to a second chamber 225 via a narrow orifice or channel 226. Vibration of the proximal end of first chamber 210 by the vibrations caused by the optional piezoelectric transducer 211, sets up pressure variations, as well as standing waves and or acoustic waves, within the first chamber, causing air in the first chamber 210 to move back and forth through channel 226, while vortices of air are formed at channel 226, leading to second chamber 225. A synthetic jet of air 227 is thus created by these vortices, resulting in the net flow of air from first chamber 210 into second chamber 225. Vapor and condensation aerosol is entrained in this airflow and evacuated from first chamber 210, and carried to the second chamber 225, by a synthetic jet 227 via channel 226. When the aerosolizable substance is a dry powder, and the heating element does not vaporize some or all of the powder, such as when the heating element is not activated or when the heat transfer is less than 100% efficient, piezoelectric transducer 211 can still vibrate and mix air in the first chamber to disaggregate the dry powder released from blister pack 213, to form an aerosol. The aerosolized dry powder is entrained in the air and evacuated from first chamber 210, and carried to the second chamber 225, by a synthetic jet 227 via channel 226. As such, this aerosol delivery device can serve as a dry powder inhaler. In most embodiments, the aerosol delivery device is preferably a vaporizer and or nebulizer. In other words, the device can be a hybrid between vaporization and nebulization (hybrid vaporizer/nebulizer). In some embodiments, a switch can determine when the aerosol generating element performs vaporization or vibrational nebulization. In other embodiments, the digital control unit 218 or microprocessor automatically determines the amount of heating or vibrating for vaporization and or nebulization, which may also tie into information about the specific aerosolizable substance inputted by the user or obtained from the coded tag 215 and tag reader 216. Only electrical energy, and not compressed air/pressurized gas produces aerosols with this device by providing kinetic energy to heat or vibrate molecules of aerosolizable substance.
Second chamber 225 can serve as an aerosol reserve, holding, chamber. Airflow enters device chamber 225 through inlet passage 228, where it may be vortexed by the curved interior walls or spiral baffles 229 of this chamber, before exiting the device via outlet end 230. Airflow outlet end 230 can consist of a user mouthpiece 231 that contours to the user's lips, allowing for an airtight seal. Said mouthpiece 231 may optionally contain an exhaust port 232, comprised of an elastomeric one-way, flap, valve, which vents user exhalation, while optional one-way valve 233, preferably a duckbill valve, prevents exhalation from entering the interior of the device. The outlet end 230 may have interchangeable mouthpieces of different sizes to change airflow through it, or may have a mechanism to be turned to adjust airflow by modulating airflow restriction (not shown). Other user interfaces other than a small mouthpiece can be envisioned, including a hose, hose with mouthpiece, facemask, oxygen mask, nosepiece or nasal prong can be used alternatively.
The aerosol delivery device may also contain one or more airflow sensors 234, that forms a switching circuit with the digital control unit 218 via circuit leads 235. Detection of user airflow may signal the digital control unit 218 to activate and or regulate piezoelectric transducer 211 and or heating element 212 for aerosol delivery. Airflow sensors may also provide feedback of airflow and or breathing pattern data to a digital control unit, or microprocessor, 218, which can interpret the data and can adjust airflow resistance by sending an electronic signal to an electric motor 236, controlling a calibrated airflow resistance control element 237 by means of gears 238 and 239. The acoustic horn shape of this embodiment, along with its associated synthetic jet, is preferred, although one can envision other embodiments where the acoustic horn is not used. The main feature of these embodiments are, however, a calibrated airflow resistance control element 237 that controls the velocity and or volume of airflow through the device. There exist many ways to achieve this calibrated airflow resistance control element, and one such way is way is with an inhalation threshold resistance valve which regulates airflow entering chamber 225 via inlet 228, thereby, effecting the airflow through the device 27.
The airflow resistance valve assembly is comprised of a rotatable cap 240 with an integrally formed cylindrical wall slidably received through a cylindrical housing 241. Gear 239 is connected to, or forms the top of, rotatable cap 240. Gear 239, and or the top of cap 240, contains one or more air inlet ports 242 that allow airflow to enter airflow resistance control element 237, which allows airflow to enter chamber 225 via inlet 228, when this valve is open. Rotatable cap 240 also has a tubular guide 243 extending through it. The tubular guide has female threads 244 that is designed to receive the male threads of a thin rod 245. A load calibrated, coiled spring 246, or other resilient or biasing member, is positioned inside of the rotatable cap 240, around the tubular guide 243 and thin rod 245. A circular disc 247, along thin rod 245, is located within a chamber region 248, adjacent to reserve chamber 225, and serves as the actuator piston of threshold resistance valve 237. As spring 246 puts outward pressure on rotatable cap 240, circular disc 247 is pulled against the proximal surface of chamber 248, thereby blocking this chamber's proximal aperture 249, which in some embodiments can serve as a Venturi or Venturi-like structure or function.
Upon inhalation, when a threshold level of negative pressure, vacuum pressure, is applied on the valve assembly, the threshold valve will open as the spring compresses and the actuator piston moves away from its resting position. Cap 240 is able to slide within cylindrical housing 241, commensurate with gear 239 being able to slide along gear 238. When the threshold valve is open, ambient air enters the device through air inlets 242, and passes through chamber 248 and reserve chamber 225, entraining aerosolized particles, and carrying these particles out of the device through outlet 230. The threshold valve closes when negative pressure within chamber 225, and chamber 248, can no longer overcome the tension of the spring. The threshold valve 237 also serves as a calibrated airflow resistance control element. As electric motor 236 turns gears 238 and 239, cap 240 is rotated like a dial. When the cap is rotated, the distance that the thin rod 245 screws into the tubular guide 243 of the cap also changes, thereby affecting the space between the cap 240 and the cylindrical housing 241, and thus, the compression of the spring 246. By varying the tension of the spring, one can control inhalation resistance, negative pressure, and the velocity and or volume of airflow through the device, which may allow for aerosol delivery with sustained maximal inspiration/inhalation. The number of partial or full revolutions that the electric motor 236 must spin in order to turn gears 238 and 239, and thus, cap 240, necessary to adjust the tension of load calibrated spring 246, is programmed into the digital control unit 218. Thus, digital control unit 218 can automatically adjust airflow resistance settings based on user inputs 219, or from data signals generated from airflow sensor 234. Other embodiments may utilize a manual means for adjusting calibrated airflow resistance settings.
The digital control unit 218 may also contain a microprocessor that can perform one or more functions, such as: providing an alarm function to signal when a treatment is due, a timer function to measure the duration of treatment and or to turn off operation after a certain treatment duration, a counting function to determine the number of treatments, a function to keep track of the airflow resistance settings during treatment, a time/date function to track the treatments of one or more different medicament formulations, the ability to store settings for different medicament formulations, along with any other functions obvious to the use of this device. The digital control unit 218 may have an electronic speaker 250 that provides auditory feedback to the user regarding the user's progress and or to adjust the user's inhalation rate or breathing pattern, and or to provide the user with incentive. The electronic speaker may provide human sounding words to provide such auditory feedback, and may also voice aloud device settings and functions. The aerosol delivery device can train the user on proper inhalation technique for optimized aerosol delivery efficiency, or overcome any incorrect inhalation technique. The digital control unit may contain a memory card (not shown) so that data can be interfaced with a computer or respiratory instrument.
This embodiment utilizes a medicament strip with a single medicament blister. One can envision other embodiments where multiple blisters are housed on the strip, or a device that can hold and use multiple unit dosages of medicament(s), sequentially. Other embodiments can include cartridges. Some embodiments can include at least two different aerosolizable substances or formulation dosages that can be aerosolized separately and or simultaneously with this device. Some of these embodiments have control or selection means to control or select which of these at least two different aerosolizable substances or formulations are to be aerosolized and delivered at any given time or times; selected manually or by digital control. This is desirable when having two or more life saving emergency drugs, such as epinephrine and an anticholinergic such as atropine, such as if a soldier is exposed to nerve agent or anaphylaxis causing agent.
It is to be understood that parameters for controlling aerosol generation timing and duration, aerosol generation amount, airflow velocity, airflow volume, airflow restriction, negative pressure, user inhalation resistance, user inhalation duration, user inhalation rate, aerosol delivery efficiency, targeting of aerosol to different user airway regions, physical changes of the device, or a combination thereof may be performed by the digital control unit, and any microprocessor, electronic chip or circuit thereof, via one or more pre-programmed and or programmable algorithms stored in the device or optionally accessible via wireless or blue-tooth from an software “app” on a computer, Smartphone, tablet, or diagnostic device. In certain embodiments, the aerosol delivery device utilizes “machine learning” of an aerosolizable substance's properties and or a user's breathing pattern to fine-tune and adjust the algorithm(s) of the aerosol delivery device to optimize performance and aerosol delivery, and in a sense, customize that device to a specific aerosolizable substance and or specific user or patient. In some embodiments, algorithm(s) and or data generated can be stored in the device or sent via wireless internet or blue-tooth from an “app” on a computer, Smartphone, or tablet for users, patients, and their trainers or physicians to monitor the use and progress on the device. Therefore, devices of the present invention optionally have wireless and or blue-tooth connectivity microchips and hardware (not shown).
Other embodiments may rely on one or more solenoid valves under the control of a digital control unit. These other conceivable embodiments are not shown and are not meant to be limiting.
The embodiments presented and other conceivable embodiments can include a threshold that either lets airflow into the device or aerosol chamber or some other airflow path, and or lets airflow out of the device or aerosol chamber or some other airflow path. When the threshold is overcome, the airflow path opens. It is desirable to have an adjustable airflow resistance and or negative pressure threshold. It may also be desirable to have a threshold associated with inhalation and or exhalation that actuates or activates aerosol generation or aerosol discharge of the device. The present invention can accomplish this with structures, functions, properties, and methods amenable to do so.
Increased airflow resistance and or increased negative pressure settings of this invention require an increased inhalation effort (negative pressures above 1 cm of water, and preferably above 3 cm of water) and can provide exercise to the muscles involved in respiration. The breathing exercise therapy provided by this device can also help maintain lung elasticity. Some embodiments can have the ability to bypass or remove or nearly remove airflow resistance or negative pressure resistance thresholds.
Embodiments of this invention may utilize flow throttling structures, and flow throttling structures that indicate airflow and or inhalation is taking place, and even to what extent. Such flow throttling structures, such as a Venturi, ball, disc, flap, weight, impeller, springs, compressible materials, or moveable baffle can serve as inhalation and or exhalation incentive, and could conceivably take the place of an incentive spirometer if calibrated with indicia and can be visualized.
Other embodiments can be adapted to provide positive expiratory pressure (PEP) therapy, such as with an exhalation threshold resistance valve or PEP valve.
Some embodiments can include a vibratable/oscillatable aperture mesh/membrane, to atomize/nebulize aerosol from a liquid substance, such as when said liquid comes in contact with/passes through the mesh, the source of vibration/oscillation being chosen from vibratory means chosen from the class of electro-mechanical vibratory means including, but not limited to, piezoelectric elements, including piezoelectric transducers, piezoelectric pumps, and piezoelectric motors, the vibratory mesh element including regions of one or more different curvatures and pores of one or more different sizes, oscillations including bending oscillations, such as of the vibratable mesh. Oscillations can be adapted to occur at ultrasonic frequencies.
Some embodiments are adapted to force a liquid through at least one small orifice, such as part of a spray nozzle, ejection actuator, or aperture mesh, to cause aerosolization of that liquid, the means for moving the liquid is chosen from physical means chosen from the class of mechanical/electro-mechanical means including, but not limited to, pumps, such as electric pumps, hydraulic pumps, and piezoelectric pumps, pistons, injectors, piezoelectric elements, piezo-inkjets, thermal inkjets, thermal bubble jets, synthetic jets, solenoids, and valves.
Some embodiments are adapted to control the activity of at least one aerosol generating element, chosen from among aerosol generating elements, including, but not limited to, spray nozzles, ejection actuators, aperture meshes, vibratable plates, and heating/vaporizing elements.
The settings of most embodiments are adapted to be adjustable and adjusted by any physical means, including, but not limited to, rotatable means, slidable means, manual means, mechanical means, electro-mechanical means, including electric motors, analog control means, digital control means, and microprocessor control means.
Some embodiments include an aerosol delivery device with an at least one controller/microprocessor adapted to adjust airflow resistance settings, such as by electric motorized means, the controller/microprocessor adapted to adjust the airflow resistance settings based on input received from at least one electronic sensor, being chosen from the class of electronic sensors, including, but not limited to, pressure transducers, piezoelectric sensors, and other airflow sensors, such sensors adapted to provide the controller/microprocessor with at least some user or patient information chosen from the class of breathing information, including, but not limited to, inhaled air volume, exhaled air volume, inhaled airflow rate, exhaled airflow rate, breathing cycle patterns, and other lung function parameters of spirometry, such as tidal volume, forced vital capacity, and lung capacity, in this manner, the device is able to adjust to the properties of the user, such as for optimized aerosol delivery, the device is adapted to display these measured parameters allowing the device to serve as a pulmonary diagnostic tool/instrument.
Some embodiments include an aerosol delivery device with an at least one controller/microprocessor adapted to modulate the operation of at least one aerosol generating element, the controller adapted to modulate the operation of the at least one aerosol generating element based on input received from at least one electronic sensor, being chosen from the class of electronic sensors, including, but not limited to, conductivity sensing leads, pressure transducers, piezoelectric sensors, and other airflow sensors, such sensors adapted to provide the controller/microprocessor with at least some user or patient information chosen from the class of breathing information, including, but not limited to, inhaled air volume, exhaled air volume, inhaled airflow rate, exhaled airflow rate, breathing cycle patterns, and other lung function parameters of spirometry, such as tidal volume, forced vital capacity, and lung capacity, in this manner, the device is able to adjust to the properties of the user, such as for optimized aerosol delivery, the device also allows aerosol generation to be breath/touch activated and synchronized with portions of the breathing cycle.
Some embodiments are adapted to modulate aerosol particle size, such as by modulating the size and number of nozzle/mesh orifices and or oscillations, and or as well as temperature.
Some embodiments are adapted to modulate aerosol particle size by modulating the operation of at least one aerosol generating element, including, but not limited to, its frequency and intensity, aerosol generating elements are chosen from among sites of aerosol generation, including, but not limited to, spray nozzles, ejection actuators, aperture meshes, vibratable plates, and vaporizing elements.
Some embodiments include a heating element that raises the temperature of the air and aerosol within the device, such as above that of ambient air, said heating element adapted to help evaporate aerosol droplets to reduce particle size, said heating element also produce convection currents that are adapted to help move aerosolized air, the activity and temperature of the heating element adapted to be controlled by electronic means as the heating element is adapted to be an electrically resistive heating element.
Some embodiments can include a valved aerosol holding chamber to retain aerosol within the device until/between periods of user inhalation, the chamber/region also being valved to prevent user exhalation from entering far into the interior of the device, valves chosen from fluid regulating devices chosen from the class of valves including, but not limited to, elastomeric valves, one-way valves, flap valves, duckbill vales, pistons, and threshold valves.
Some embodiments include vaporization means to vaporize a therapeutic substance to produce a condensation aerosol available for inhalation, vaporization means chosen from the class of vaporization elements including, but not limited to, electrically resistive heating elements, electrostatic chargers, elements producing thermal radiation, elements that transfer thermal energy by conduction, elements that transfer thermal energy by convection, elements releasing exothermic energy from chemical reactions, laser producing elements, and elements producing electromagnetic radiation, such as microwaves, radio frequency waves, and infrared waves.
Some embodiments include means to electronically store data, algorithms, and or programs, the electronically stored data is chosen from the types of electronic data including, but not limited to data records, such as time, date, time and or date of treatment, treatment duration, airflow resistance settings, flow rate, flow volume, number of dosages used and unused, dosage amounts, medicament information, such as name and serial number, breathing pattern information, user's progress, device program information, such as device temperature settings, frequency settings, airflow settings, timing settings, aerosolization settings for a particular type of medicament, and other user settings, such as alarm settings and password protection, said electronic data is adapted to be stored and accessed from an Electrically Erasable Programmable Read-Only Memory, EEPROM, and flash memory chips, and or USB ports or other ports.
Most embodiments will conserve the aerosolizable substance or formulation by incorporating a pump or drive system or aerosol generating element that is breath-activated, and may be turned on and off depending on the stage in the user's breathing cycle. The breathing cycle includes the stages of inhalation, pause, and exhalation.
The purpose is for the device to be responsive to inhalation, that it may activate the pump, drive, or aerosol generating element during inhalation, and inactivate the pump, drive, or aerosol generating element when inhalation is no longer detected, i.e., during exhalation, or with a timer.
The invention is an aerosol delivery device having a structure comprising a housing, an at least one ambient/unaerosolized air inlet, an at least one aerosolized air outlet, and an at least one airflow passage therein the device or housing and or extending at least partially therebetween the at least one ambient/unaerosolized air inlet and the at least one aerosolized air outlet. The aerosol delivery device further comprises an at least one aerosol generating element that produces an aerosol from an at least one aerosolizable substance or formulation with the use of electrical energy and without the use of compressed/pressurized gas. The aerosol delivery device further has an at least one airflow through its housing produced by a user inhaling from the aerosol delivery device and entraining the aerosol when generated; wherein the at least one airflow is controllable in velocity, volume, or a combination thereof as the at least one ambient/unaerosolized air inlet, the at least one aerosolized air outlet, the at least one airflow passage, or a combination thereof undergoes an at least one physical change selected from changes in size, angle, shape, biasing resistance to flow, number of apertures, shunting of airflow, or a combination thereof. The at least one physical change is modulated by user/digital input to control the at least one airflow and to regulate an at least one parameter selected from user inhalation resistance, user inhalation duration, user inhalation rate, aerosol delivery efficiency, targeting of aerosol to different user airway regions, or a combination thereof.
In preferred embodiments, the user/digital input is selected from user inhalation, user touch, user speech/sound, user programming, user selection, or a combination thereof.
In preferred embodiments, the aerosol delivery device further comprises at least two physical change settings when the at least one physical change is modulated by user/digital input.
In preferred embodiments, the aerosol delivery device further comprises marked/digitized indicia, preferably calibrated indicia, adapted to be presented to the user and further representing the at least one parameter selected from user inhalation resistance, user inhalation duration, user inhalation rate, aerosol delivery efficiency, targeting of aerosol to different user airway regions, or a combination thereof.
In preferred embodiments, the aerosol delivery device further comprises an at least one airflow sensor, pressure sensor, or a combination thereof.
In preferred embodiments, the aerosol delivery device further comprises an at least one airflow indicator, pressure indicator, or a combination thereof.
The aerosol delivery device generally comprises an at least one airflow valve, pressure valve, or a combination thereof.
In preferred embodiments, the aerosol delivery device further comprises an at least one aerosolizable substance or formulation or liposomal formulation, said at least one aerosolizable substance or formulation preferably comprises epinephrine, bronchodilator, anticholinergic, nicotine, cannabinoid, opioid, insulin, antibiotic, prostacyclin, interluekin, cytokine, vaccine, immunosuppressant, immunomodulator, immunotherapy, chemotherapy, or combination, analogue, or derivative thereof.
In preferred embodiments the aerosol delivery device further comprises an at least one holding/storage area, chamber, reservoir, or combination thereof for the at least one aerosolizable substance or formulation.
In most embodiments, the aerosol delivery device further comprises an at least one power button/switch.
In some embodiments, the aerosol delivery device further comprises an at least one airflow filter.
In some embodiments of the aerosol delivery device, the at least one airflow through the device housing produced by the user inhaling from the aerosol delivery device interacts with at least one additional airflow through the device housing produced by the user inhaling from said aerosol delivery device so that these airflows meet in at least partially counterposing directions to at least partially negatively interfere with each other; the resulting at least partial negative interference is adapted to change/control or reduce the velocity and or trajectory of at least one of these airflows.
In some embodiments of the aerosol delivery device, the at least one airflow through the device housing produced by the user inhaling from the aerosol delivery device interacts with at least one additional airflow through the device housing produced by the user inhaling from the aerosol delivery device so that these airflows meet in at least somewhat parallel directions to at least partially positively interfere with each other; the resulting at least partial positive interference adapted to enhance the velocity and trajectory of at least one of these airflows; and in some embodiments serves as a “turbo boost” to aerosol entrainment and delivery.
In some embodiments of the aerosol delivery device, an at least one angle of incidence between at least two of the at least one airflow through the device housing produced by the user inhaling from the aerosol delivery device is modulated by user/digital input to control the at least one airflow.
In some embodiments of the aerosol delivery device, an at least one angle of incidence between at least two of the at least one airflow through the device housing produced by the user inhaling from the aerosol delivery device is modulated automatically by airflow, user inhalation rate, user inhalation force, airflow sensor relay feedback or a combination thereof.
In some embodiments of the aerosol delivery device, an at least one angle of incidence between at least two of the at least one airflow through the device housing produced by the user inhaling from the aerosol delivery device is modulated to limit/restrict airflow, airflow velocity, airflow volume, or a combination thereof.
In some embodiments of the aerosol delivery device, an at least one angle of incidence between at least two of the at least one airflow through the device housing produced by the user inhaling from the aerosol delivery device is modulated to control/change airflow, airflow velocity, airflow volume, or a combination thereof.
Most embodiments of the aerosol delivery device further comprising an at least one dial, switch, valve, lever, or a combination thereof to control the at least one airflow through the device and or aerosol chamber.
Some embodiments of the aerosol delivery device further comprise at least two aerosol generating settings to vary the amount and or properties of aerosol generated by the at least one aerosol generating element.
Some embodiments of the aerosol delivery device further comprise at least two aerosol generating settings to vary the amount and or properties of aerosol generated by the at least one aerosol generating element; the selection of the at least two aerosol generating settings determined automatically by airflow, user inhalation rate, user inhalation force, or a combination thereof.
Some embodiments of the aerosol delivery device further comprise at least two aerosol generating settings to vary the amount and or properties of aerosol generated by the at least one aerosol generating element; the selection of the at least two aerosol generating settings determined automatically by airflow, user inhalation rate, user inhalation force, type of said aerosolizable substance/formulation, or a combination thereof, by a relay/feedback from an at least one airflow sensor, pressure sensor, (substance ID) reader, or a combination thereof.
Some embodiments of the aerosol delivery device are further adapted to provide for a sustained maximal inhalation when a user or patient is able to sustain for a period of inhalation a negative pressure, airflow rate, or a combination thereof that is at least as great as the negative pressure threshold setting, airflow rate threshold setting, or a combination thereof selected by the user/digital input.
Some embodiments of the aerosol delivery device are further adapted to provide strength training of the muscles involved in respiration and help maintain lung elasticity.
Some embodiments of the aerosol delivery device are further adapted to provide incentive inhalation feedback to the user; the incentive inhalation feedback is selected from visual incentive signals, auditory incentive signals, vibrations, or a combination thereof.
Preferred embodiments of the aerosol delivery device are further adapted to only allow ambient/unaerosolized air to enter when the user is inhaling or inhaling sufficiently or inhaling above a threshold from the aerosol delivery device.
Preferred embodiments of the aerosol delivery device have aerosol generation that is activated/actuated and coordinated with the breathing cycle so that the aerosolizable substance or formulation is conserved until/between periods of user inhalation.
Some embodiments of the aerosol delivery device are further adapted to provide proper breathing technique training for optimized aerosol delivery.
Preferred embodiments of the aerosol delivery device are further adapted to limit/constrain airflow, airflow velocity, airflow volume, airflow rate, user inhalation rate, user generated negative pressure, or a combination thereof to a range conducive for aerosol delivery efficiency, accuracy and precision, and limiting or preventing deviation; limiting or preventing intra-user and or inter-user variability when using said aerosol delivery device.
Preferred embodiments of the aerosol delivery device are further adapted to selectively target aerosols to one or more different airway regions; one or more different airway regions comprising the upper airways, upper respiratory tract, nasal cavity, pharynx, larynx, lower airways, lower respiratory tract, trachea, bronchi, lungs, bronchioles, deep lung, alveoli where systemic exchange takes place, or a combination thereof.
Different embodiments of the aerosol delivery device are further adapted to receive electrical energy from an electrical wall socket/outlet, battery, rechargeable battery, or a combination thereof to power said at least one aerosol generating element.
Most embodiments with at least one rechargeable battery are further adapted to receive electrical energy to recharge the at least one associated battery, such as a lithium battery (a non-limiting example) that powers the at least one aerosol generating element. The electrical energy is received via an at least one power adapter, AC/DC power adapter, AC power connector, AC adapter inlet/socket, AC adapter outlet, AC power adapter, AC adapter power cord, AC power cord, DC power connectors, DC adapter inlet/socket, DC adapter outlet, DC power adapter, DC adapter power cord, DC power cord, male USB fitting, female USB fitting, USB adapter inlet/socket, USB adapter outlet, USB power adapter, USB power cord, USB cord, male micro-USB fitting, female micro-USB fitting, micro-USB adapter inlet/socket, micro-USB adapter outlet, micro-USB power adapter, micro-USB power cord, micro-USB cord, male mini-USB fitting, female mini-USB fitting, mini-USB adapter inlet/socket, mini-USB adapter outlet, mini-USB power adapter, mini-USB power cord, mini-USB cord, fuel cell, micro-turbine, wireless power transfer source, inductive coupling receiver, capacitive coupling receiver, charging pad/surface, or a combination or derivative thereof.
In preferred embodiments, the at least one ambient/unaerosolized air inlet, the at least one aerosolized air out, and the at least one airflow passage therebetween/therein are structurally associated with an at least one aerosol chamber of the aerosol delivery device. Some embodiments of the device can have at least two aerosol chambers.
The aerosol delivery device is not associated with nor having compressed/pressurized gas.
In some embodiments, the aerosol delivery device comprises at least two different aerosolizable substances or formulations (or dosages thereof) and is able to aerosolize these at least two different aerosolizable substances or formulations separately, sequentially, or simultaneously. The selection of aerosolization of one or both of these two different aerosolizable substances or formulations (or dosages thereof) can be selected by user/digital input, such as providing signal to an at least one aerosol generating element and or blister strip, packaging, vial, reservoir, or cartridge that contains or releases said at least one aerosolizable substance or formulation (or dosage thereof).
The invention is also an aerosol delivery device having a structure comprising a housing, an at least one air inlet, an at least one aerosolized air outlet, and an at least one airflow passage therebetween/therein. The aerosol delivery device further comprises an at least one aerosol generating element producing an aerosol from an at least one aerosolizable substance or formulation with the use of electrical energy to produce vaporizing heat, vibration, or a combination thereof, without the use of compressed/pressurized gas. The aerosol delivery device further has an at least one airflow through its housing produced by a user inhaling from the aerosol delivery device, preferably its mouthpiece, and entraining the aerosol when generated. The aerosol delivery device further has an at least one rechargeable battery that at least powers the at least one aerosol generating element. The at least one rechargeable battery receives electrical energy via an at least one power adapter, AC/DC power adapter, AC power connector, AC adapter inlet/socket, AC adapter outlet, AC power adapter, AC adapter power cord, AC power cord, DC power connectors, DC adapter inlet/socket, DC adapter outlet, DC power adapter, DC adapter power cord, DC power cord, male USB fitting, female USB fitting, USB adapter inlet/socket, USB adapter outlet, USB power adapter, USB power cord, USB cord, male micro-USB fitting, female micro-USB fitting, micro-USB adapter inlet/socket, micro-USB adapter outlet, micro-USB power adapter, micro-USB power cord, micro-USB cord, male mini-USB fitting, female mini-USB fitting, mini-USB adapter inlet/socket, mini-USB adapter outlet, mini-USB power adapter, mini-USB power cord, mini-USB cord, fuel cell, micro-turbine, wireless power transfer source, inductive coupling receiver, capacitive coupling receiver, charging pad/surface, or a combination or derivative thereof.
The invention is also an aerosol delivery device having a structure comprising a housing, an at least one air inlet, an at least one aerosolized air outlet, preferably with user interface such as a mouthpiece, and an at least one airflow passage therebetween/therein. The aerosol delivery device further comprises an at least one aerosol generating element producing an aerosol from an at least one aerosolizable substance or formulation with the use of electrical energy and without the use of compressed/pressurized gas. The aerosol delivery device further has an at least one airflow through its housing produced by a user inhaling from the aerosol delivery device and entraining the aerosol when generated. The aerosol delivery device further has an adjustable airflow restriction of the at least one airflow as the at least one air inlet, the at least one aerosolized air outlet, the at least one airflow passage, or a combination thereof undergoes an at least one physical change selected from changes in size, angle, shape, biasing resistance to flow, number of apertures, shunting of airflow, or a combination thereof; said at least one physical change is modulated by user/digital input to control the adjustable airflow restriction and to regulate an at least one parameter selected from user inhalation resistance, user inhalation duration, user inhalation rate, aerosol delivery efficiency, targeting of aerosol to different user airway regions, or a combination thereof.
The invention is also an aerosol delivery device having a structure comprising a housing, an at least one air inlet, an at least one aerosolized air outlet with user interface, and an at least one airflow passage therebetween/therein. The aerosol delivery device further comprises an at least one aerosol generating element producing an aerosol from an at least one aerosolizable substance or formulation with the use of electrical energy and without the use of compressed/pressurized gas. The aerosol delivery device further has an at least one airflow through the housing produced by a user inhaling from the aerosol delivery device and entraining aerosol when generated. The aerosol delivery device further has an at least one negative pressure within the device housing produced by a user inhaling from the aerosol delivery device; wherein the at least one negative pressure is adjustable as said at least one air inlet, said at least one aerosolized air outlet, said at least one airflow passage, or a combination thereof undergoes an at least one physical change selected from changes in size, angle, shape, biasing resistance to flow, number of apertures, shunting of airflow, or a combination thereof; said at least one physical change is modulated by user/digital input to control the at least one negative pressure and to regulate an at least one parameter selected from user inhalation resistance, user inhalation duration, user inhalation rate, aerosol delivery efficiency, targeting of aerosol to different user airway regions, or a combination thereof.
For patients with adequate lung function that can achieve greater inhalation effort, the different airflow resistance settings and or different negative pressure settings of this novel aerosol delivery device can have profound effects on aerosol delivery dynamics. Aerosol generation and aerosol delivery occur when enough negative pressure builds within the device to cause actuation. After building up the necessary negative pressure required for valve actuation, aerosol is generated at the precise moment that the valve opens to allow a rapid stream of ambient air into the device for entraining and efficiently carrying out this aerosol as a bolus. Choosing different settings can allow this bolus to be sustained as a stream over different lengths of inhalation time corresponding to different airflow resistance settings and or different negative pressures that can be sustained and selected by the user or patient. Moreover, by having actuation of aerosolization and aerosol entrainment associated with different airflow resistance settings and or different negative pressure settings, this novel aerosol delivery device can be used to selectively target aerosols to one or more different airway regions. In effect, aerosol actuation, entrainment, and delivery occur when one or more different airways are optimally expanded with the desired pressure for enhanced drug targeting and delivery efficiency. The aerosol delivery device is thus adapted to selectively target aerosols to one or more different airway regions by selecting different negative pressure threshold settings of actuation of aerosolization. The one or more different airway regions are chosen from the regions, including, but not limited to, the upper airways, upper respiratory tract, nasal cavity, pharynx, larynx, lower airways, lower respiratory tract, trachea, bronchi, lungs, bronchioles, deep lung, and alveoli where systemic exchange takes place.
More pharmaceuticals are being made available for inhalation. This includes pharmaceuticals that can be delivered to the systemic circulation via the pulmonary route, such as insulin. As an improved drug delivery device, the present invention can improve the delivery dynamics and targeting of these drugs. Selective targeting of aerosols to one or more different airway regions can aid in the targeting of aerosolized chemotherapies against lung cancer, including targeting an airway region having a tumor. Selective targeting of aerosols to one or more different airway regions can also have profound lifesaving and medical military applications, including biodefense to counter bioterrorism, by coating upper airways with antibiotics against anthrax or other infectious agents, or by providing anticholinergic agents to the systemic circulation via alveoli as an antidote to nerve agent exposure. The present invention also has the potential to enhance the deliverability of drug candidates in development, which has the potential to reduce drug development costs. Therefore, the present invention fulfills important unmet other needs, and has applications that transcend beyond medication delivery to asthma, COPD, and cystic fibrosis patients that have trouble breathing, and opens the way for treating countless other patients, including those with the ability to generate greater negative pressures.
The present invention is able to deliver aerosols of various substances that include, but are not limited to: unformulated active pharmaceutical ingredient, formulated active pharmaceutical ingredient, pharmaceutical inactive or excipient ingredient, non-biological materials, biological materials, plant material or extracts, animal material or extracts, cellular material or extracts, cultured cell line material or extracts, cells, stem cells, bacterial material or extracts, fungal material or extracts, viral material or extracts, peptides, polypeptides, recombinant proteins, glycoproteins, sugars, monosaccharides, disaccharides, and polysaccharides, lipids, fatty acids and prostaglandins, prostacyclins and prostacyclin analogues, cholesterol, lipoproteins, vesicles, liposomes, nutrients/supplements, holistic substances, antibodies/immunoglobulins and or fragments thereof, immunosuppressants, immunotherapies, water, water soluble substances, antipsychotics, water insoluble substances, vitamins, coenzymes, enzymes, substrates, inhibitors, hormones, steroids, amino acids, neurotransmitters, cell signaling molecules, antibiotics, NSAIDs, cellular receptors and or receptor fragments, ion channels/ion channel fragments, ligands/ligand fragments, single stranded/double stranded nucleotides, deoxyribonucleic acids and or ribonucleic acids, small interfering RNA, siRNA, transcription factors, transcription inhibitors, translation factors, translation inhibitors, vaccines, antihistamines, anti-inflammatory substances, cytotoxic substances, anti-toxins, anti-venoms, anticoagulants, vasodilators, bronchodilators, stimulants, anti-depressants, analgesics, anesthetics, therapeutic gases, including, but not limited to nitric oxide, nitrous oxide, hydrogen sulfide, carbon monoxide, carbon dioxide, nitrogen, cyclopropane, helium, and oxygen, diatomic molecules and gases, electrolytes, ionic substances, non-ionic substances, minerals, salts, hydrates, anhydrates, naturally occurring non-organic molecules or compounds, synthetic/modified non-organic molecules or compounds, naturally occurring organic molecules or compounds, synthetic/modified organic molecules or compounds, medical/diagnostic probes/tracers, fluorescent substances, magnetic substances, radioisotopes or radioactive substances, nanoparticles, from any phase of any of these aforementioned materials, solid phases, liquid phases, gaseous phases, polymers of any of these aforementioned materials, precursors of any of these aforementioned materials, derivatives of any of these aforementioned materials, enantiomers of any of these aforementioned materials, stereoisomers of any of these aforementioned materials, hybrid molecules of any of these aforementioned materials, combinations of any of these aforementioned materials, suspensions, mixtures/solutions of any of these aforementioned materials.
Examples of pharmaceutical aerosols that can be delivered by the present invention include, but are not limited to: acebutolol, acetaminophen, adrenaline (epinephrine), alprazolam, amantadine, amiloride, amitriptyline, amoxicillin, anticholinergic agent, apomorphine diacetate, apomorphine hydrochloride, atropine, azatadine, betahistine, brompheniramine, bumetanide, buprenorphine, bupropion hydrochloride, butalbital, butorphanol, carbinoxamine maleate, celecoxib, chlordiazepoxide, chlorpheniramine, chlorzoxazone, ciclesonide, ciclosporin, citalopram, clomipramine, clonazepam, clozapine, codeine, cyclobenzaprine, cyproheptadine, dapsone, dextran sulfate, diazepam, diclofenac ethyl ester, diflunisal, disopyramide, doxepin, estradiol, ephedrine, estazolam, ethacrynic acid, fenfluramine, fenoprofen, flecainide, flunitrazepam, galanthamine, granisetron, haloperidol, hydromorphone, hydroxychloroquine, hyoscyamine, ibuprofen, imipramine, indomethacin ethyl ester, indomethacin methyl ester, insulin, interleukin, isocarboxazid, ketamine, ketoprofen, ketoprofen ethyl ester, ketoprofen methyl ester, ketorolac ethyl ester, ketorolac methyl ester, ketotifen, lamotrigine, lidocaine, loperamide, loratadine, loxapine, maprotiline, memantine, meperidine, metaproterenol, methoxsalen, metoprolol, mexiletine HC1, midazolam, mirtazapine, morphine, nalbuphine, naloxone, naproxen, naratriptan, nicotine, norepinephrine, nortriptyline, olanzapine, orphenadrine, oxycodone, paroxetine, pergolide, phenytoin, pindolol, piribedil, pramipexole, procainamide, prochloperazine, propafenone, propranolol, pyrilamine, quetiapine, quinidine, racepinephrine, rizatriptan, ropinirole, sertraline, selegiline, sildenafil, spironolactone, tacrine, tadalafil, terbutaline, testosterone, thalidomide, theophylline, tocainide, toremifene, trazodone, triazolam, trifluoperazine, valproic acid, venlafaxine, vitamin E, zaleplon, zotepine, amoxapine, atenolol, benztropine, caffeine, doxylamine, estradiol 17-acetate, flurazepam, flurbiprofen, hydroxyzine, ibutilide, indomethacin norcholine ester, ketorolac norcholine ester, melatonin, metoclopramide, nabumetone, perphenazine, protriptyline HCl, quinine, triamterene, trimipramine, zonisamide, bergapten, chlorpromazine, colchicine, diltiazem, donepezil, eletriptan, estradiol-3,17-diacetate, efavirenz, esmolol, fentanyl, flunisolide, fluoxetine, hyoscyamine, indomethacin, isotretinoin, linezolid, meclizine, paracoxib, pioglitazone, rofecoxib, sumatriptan, tetrahydrocannabinol, tolterodine, tramadol, tranylcypromine, trimipramine maleate, valdecoxib, vardenafil, verapamil, zolmitriptan, zolpidem, zopiclone, bromazepam, buspirone, cinnarizine, dipyridamole, naltrexone, sotalol, telmisartan, temazepam, albuterol, apomorphine hydrochloride diacetate, carbinoxamine, clonidine, diphenhydramine, thambutol, fluticasone proprionate, fluconazole, lovastatin, lorazepam N,O-diacetyl, methadone, nefazodone, oxybutynin, promazine, promethazine, sibutramine, tamoxifen, tolfenamic acid, aripiprazole, astemizole, benazepril, clemastine, estradiol 17-heptanoate, fluphenazine, protriptyline, ethambutal, frovatriptan, pyrilamine maleate, scopolamine, tacrolimus, triamcinolene acetonide, epinephrine, and any analogues, derivatives, and combinations thereof.
Antibiotic active pharmaceutical ingredient examples for aerosolization with this device, include, but are not limited to: polyketide antibiotics; macrolide antibiotics, including, but not limited to, clarithromycin, erthythromycin, azithromycin, dirithromycin, roxithromycin, telithromycin, carbomycin A, josamycin, kitasamycin, midecamycin, oleandomycin, solithromycin, spiramycin, troleandomycin; beta-lactam antibiotics; penicillin drugs including, but not limited to amoxicillin, ampicillin, talampicillin, bacampicillin, lenampicillin, mezlocillin, sultamicillin, temocillin; cephem/cephalosporin antibiotics including, but not limited to, cefaclor, cefadroxil, cefalexin, cefpodoxime proxetil, cefixime, cefdinir, ceftibuten, cefotiam hexetyl, cefetamet pivoxil, cefuroxime axetil; penem antibiotics including, but not limited to, faropenem, ritipenem; monobactam antibiotics; sulfonamide antibiotics; lincosamide antibiotics including, but not limited to, lincomycin or clindamycin; aminoglycoside antibiotics including, but not limited to amikacin, tobramycin, paromomycin; tetracycline antibiotics including, but not limited to, tetracycline, minocycline, doxycycline; quinolone antibiotics including, but not limited to, ofloxacin, levofloxacin, norfloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin, fleroxacin, sparfloxacin, temafloxacin, nadifloxacin, grepafloxacin, baloflaxacin, prulifloxacin, pazufloxacin; nitroimidazole antibiotics including, but not limited to, metronidazole, tinidazole; nitrofuran antibiotics including, but not limited to, nitrofurantoin, furazolidone, nifurtoinol; rifamycin antibiotics including, but not limited to, rifampicin, rifabutin, rifapentine, rifaximin; glycopeptide antibiotics including, but not limited to vancomycin, ramoplanin; and any salts, solvates, polymorphs, racemic mixtures, enantiomers, derivatives, mixtures and combinations thereof.
Other embodiments of aerosol delivery devices within the scope of the present invention include motorized or electronic controlled adjustable negative pressure threshold valves of actuation, which employ the use of solenoid valves and pressure sensors and the necessary circuitry, buttons, and power elements to accomplish this. Even further conceivable aerosol delivery device embodiments can include a moveable seal that exists in a position that allows aerosol delivery to occur until moved out of position by actuation of the valve during inhalation, so that aerosolization does not occur during inhalation, but occurs during exhalation. These other conceivable embodiments are not shown and are not meant to be limiting.
There are methods for using the aerosol delivery device disclosed in the present invention, as well as, methods to produce the desired aerosolized therapies and aerosol delivery dynamics when using the present invention.
As to the manner of usage and operation of the present invention, the same should be apparent from the above description. Accordingly, no further discussion relating to the manner of usage and operation will be provided.
With respect to the above description then, it is to be realized that the optimum dimensional relationships for the parts of the invention, to include variations in size, materials, shape, form, function and manner of operation, assembly and use, are deemed readily apparent and obvious to one skilled in the art, and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention.
Therefore, the foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.
Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.
The present application is a continuation-in-part of pending U.S. patent application Ser. No. 13/969,847 filed on Aug. 19, 2013, which is a continuation-in-part of U.S. patent application Ser. No. 12/806,874 filed on Aug. 23, 2010, now abandoned, the subject matter of which applications is incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 13969847 | Aug 2013 | US |
| Child | 15672021 | US | |
| Parent | 12806874 | Aug 2010 | US |
| Child | 13969847 | US |
