Patent Application
20120247466
The purpose of this invention is to provide a device and method for drug delivery to the respiratory system.
Manifold devices and methods of delivering droplets or particles of drugs to the respiratory system, especially the lungs have been proposed. In many of these devices, the aforementioned droplets or particles are picked up due to the Venturi effect as the airstream passes over the drug supply on its way into the respiratory system. Contemporary devices suffer from several drawbacks, including the very low ratio of drug that reaches its target location (e.g. the terminal bronchioles and alveoli); and the skill and cooperation required from the patient using the device. It would be highly advantageous to provide a method of improving the delivery of the aforementioned droplets or particles to the target tissues, such as the alveolar walls of the lungs, to ensure better uptake of the drugs. Moreover, it would also be highly advantageous to prepare the lungs prior to drug dispersion for optimal drug uptake.
The invention delivers a stream of fluid that is periodically stopped by means of a valve. When a person breathes freely, normal negative pressure (NNP) is created within the airways during inhalation. A user inhaling the abovementioned stream of fluid will experience periods of relatively high negative pressure during those periods when the supply of fluid is stopped. These periods of high negative pressure have beneficial effects for various disorders and also facilitate the delivery of any drugs or medicaments in the fluid flow.
An additional effect of pulsating negative pressure prepares the lungs for improved drug uptake. Additionally, this invention creates alternating pulses of positive pressure and negative pressure. Additionally, this invention provides devices and methods for drug delivery to the sinuses.
It is one object of the present invention to disclose a device useful for facilitating delivery of drugs or medicaments to the respiratory system of a user. The device comprises a mechanism for interrupting the airflow during inhalation or exhalation performed by the user through the device by generating pressure pulses within the respiratory system of the user, such that the delivery of the drugs to the user is facilitated; the pressure pulses are selected from the group consisting of: inspiratory Negative Pressure (NP) pulses, inspiratory Positive Pressure (PP) pulses, expiratory Negative Pressure (NP) pulses, expiratory Positive Pressure (PP) pulses into the respiratory system, and any combination thereof.
It is another object of the present invention to disclose the device as define above, wherein the device is adapted for delivering the drugs to the upper respiratory tract of the respiratory system.
It is another object of the present invention to disclose the device as define above, wherein the device is adapted for delivering drugs to the lower respiratory tract of the respiratory system.
It is another object of the present invention to disclose a device useful for delivering drugs to the respiratory system of a user. The device comprises:
It is within the scope of the present invention that the air controlling mechanism is adapted to generate pressure pulses of Negative Pressure and/or Positive Pressure into the respiratory system during inspiration and/or expiration, and the drug releasing mechanism is adapted for entraining the drugs into the pressure pulses, such that uptake of the drugs by the tissues of the respiratory system is facilitated; the pressure pulses are selected from the group consisting of: inspiratory Negative Pressure (NP) pulses, inspiratory Positive Pressure (PP) pulses, expiratory Negative Pressure (NP) pulses, expiratory Positive Pressure (PP) pulses into the respiratory system, and any combination thereof.
It is another object of the present invention to disclose the device as define above, wherein the air controlling mechanism comprises means for forcing a stream of fluid towards the patient's respiratory system.
It is another object of the present invention to disclose the device as define above, wherein the device is adapted for delivery of powdered drug supplied in capsule form.
It is another object of the present invention to disclose the device as define above, wherein the air controlling mechanism comprises a shutter for interrupting the stream of air during patient's inspiration or expiration, such that a pulse of Negative Pressure is induced within the patient's respiratory system.
It is another object of the present invention to disclose the device as define above, wherein the shutter comprises a perforated rotating disc adapted to allow passage of the air through the perforation within the disc and to block and unblock the passage of the air.
It is another object of the present invention to disclose the device as define above, wherein the air controlling mechanism comprises a motor driven disc wheel adapted for synchronization with the drug releasing mechanism.
It is another object of the present invention to disclose the device as define above, wherein the drug releasing mechanism is adapted to be opened by a drop in pressure during inhalation and closed by a rise in pressure during exhalation.
It is another object of the present invention to disclose the device as define above, wherein the drug releasing mechanism comprises a drug releasing shutter for controlling release of the drugs from the container during the operation of the air controlling mechanism.
It is another object of the present invention to disclose the device as define above, wherein the device additionally comprises fluid vibrating means 26 (FVM) for vibrating the medication and the air to facilitate drug delivery, the FVM selected from the group comprising an acoustic means mechanical means or electromechanical (piezoelectric) means.
It is another object of the present invention to disclose the device as define above, wherein the FVM is located in the middle section of the device or proximally to the outlet of the container.
It is another object of the present invention to disclose the device as define above, wherein the container comprises a pressure generator for generating high pressure therein.
It is another object of the present invention to disclose the device as define above, wherein the device is pocket sized device.
It is another object of the present invention to disclose the device as define above, wherein the device is characterized by a non-drug mode in which the drug releasing mechanism does not provide drugs, and solely controls the passage of air during inhalation or exhalation of the air.
It is another object of the present invention to disclose the device as define above, wherein the device is adapted for use a s a sinusitis inhaler for use with one or both nostrils.
It is another object of the present invention to disclose the device as define above, further comprising a ratchet and pawl mechanism adapted to activate the device by lifting a pawl by the user's teeth.
It is another object of the present invention to disclose the device as define above, further comprising spirometric, chemical or other types of sensors adapted to measure parameters of the user's breath and to modify the treatment protocols of the device via a feedback mechanism, said sensors are adapted to measure parameters selected from the group consisting of: peak flow, flow rate, FEV1, spirometric parameters, inhalation pressure, exhalation pressure, inspiratory pressure, expiratory pressure, vital capacity, inhaled CO2 concentration, exhaled CO2 concentration , inhaled O2 concentration, exhaled O2 concentration, and any combination thereof.
It is another object of the present invention to disclose the device as define above, wherein the device additionally comprises means for pulling the lower jaw forward with respect to the upper jaw such that the geometry of the upper airway facilitates smooth flow of air and drug into the lungs.
It is another object of the present invention to disclose the device as define above, wherein the drugs are selected from the group consisting of: vaporized essential oils, volatile compounds, etheric oils, terepenes, terpanols and either water miscible or water-immiscible extracts, especially oils or extracts obtained from Amyris, Balsam, Bay Rum, Black Pepper, bornyl acetate, Cajeput, Camphor, Cedarwood, Cedarleaf oil, Chamomile, chlorbutanol, Cinnamon, Clary Sage Rosewood, Clove, Eucalyptus, Frankincense, Geranium, Ginger, Lavender, Lemon, Lemon essential oils, levomenthol, Lime, Menthol, Mint, Myrrh, nutmeg oil Orange, Patchouli, Peppermint, Pine Needle, Rose Eucalyptus, rosemary, Rosewood, Sage, Sandalwood, Spearmint, Tea Tree, terpinol, turpentine oil, thymol, Ylang Ylang or any combination thereof.
It is another object of the present invention to disclose the device as define above, wherein the drugs comprise in vaporized form at least one of the group of Braochodilators, especially sympatic mimetics, alfa antagonists, anti cholinergics; nasal decongestants, such as pseudoehedrines, ephedrines; steroids; anti histamines; anti prostaglandins, alternative or homeopathic medicaments; vaso constrictors; local anesthetics; mast cell stabilizers; antibiotics, such as biocides, fungicides etc; pleasant odor; pheromones; hormone treatments, such as ADH, insulin, growth hormones; vapors, humidifiers; drying compositions; hot or cold vapors; hyper-, iso- or hypotonic vapors or any combination thereof.
It is another object of the present invention to disclose the device as define above, wherein the drugs comprise in vaporized form at least one of the group of compositions and commercial available medicaments, their derivatives, or by-products provided thereof, selected from the group consisting of: Acrivastine, Aller-Eze Clemastine, Aller-Eze nasal spray, Azatadine maleate, Azelastine nasal spray, Beclometasone nasal spray, Beclometasone nasal spray, Beconase hayfever nasal spray, Beconase hayfever relief for adults, Beconase nasal spray, Benadryl allergy relief, Benadryl, Benadryl, Benadryl plus, Brompheniramine maleate, Budesonide nasal spray, Calimal Antihistamine, Cetirizine, Chlorphenamine, Clarityn, Clemastine, Cyproheptadine hydrochloride, Desloratadine, Dexa-Rhinaspray Duo. Dimotane elixir, Dimotane plus, Dimotapp elixir, Dimotapp elixir paediatric. Dimotapp LA, Flixonase allergy nasal spray, Flixonase aqueous nasal spray, Fluticasone propionate nasal spray, Galpharm hayfever and allergy relief, Galpseud Plus, Haymine, Histafen, Ipratropium bromide nasal spray, Levocabastine nasal spray, Levocetirizine dihydrochloride, Livostin direct nasal spray, Livostin nasal spray, Loratadine, Medised, Medised, Mistamine, Mizolastine, Mizollen, Mometasone furoate nasal spray, Nasacort, Nasobec nasal spray, Nasonex nasal spray, Neoclarityn tablets/syrup, Optimine syrup, Periactin, Phenergan, Piriteze, Piriton, Pollenase hayfever nasal spray, Promethazine hydrochloride elixir, Promethazine hydrochloride, Rhinocort Aqua, Rhinolast allergy nasal spray, Rhinolast nasal spray, Rinatec nasal spray, Rino clenil nasal spray, Rynacrom allergy nasal spray, Rynacrom nasal spray, Semprex, Sodium cromoglicate nasal spray, Sudafed Plus, Syntaris nasal spray, Tavegil, Telfast 120, Terfenadine, Terfinax, Triamcinolone acetonide, Vista-Methasone, Xyzal tablets, Zirtek allergy relief tablets, Zirtek allergy tablets/solution, Afrazine, Anadin, Beechams all-in-one, Beechams products, Benylin products, Contac, Day Nurse, Dimotapp elixir, Dimotapp elixir paediatric, Dimotapp products, Galpseud, Karvol decongestant products, Lemsip products, Meggezones, Merocets Plus lozenges, Nurofen Cold and Flu, Otrivine Menthol Nasal Spray, Otrivine Metered Dose Sinusitis Spray, Otrivine products, Pseudoephedrine hydrochloride, Sterwin real lemon cold powders and other products, Strepsils Menthol and Eucalyptus and other products, Sudafed and its products, Xylometazoline nasal drops, Bactroban Nasal, Fusafungine, Locabiotal, Naseptin nasal cream, Ipratropium bromide nasal spray, Rinatec nasal spray, pseudoephedrine, propylhexedrine, L-Desoxyephedrine, xylometazoline hydrochloride or any combination thereof.
It is another object of the present invention to disclose the device as define above, further comprising means for cooling or heating the fluid prior to or during or forcing the stream of fluid towards the respiratory tract.
It is another object of the present invention to disclose the device as define above, further comprising means for mixing or activating a medicament by reacting it with one or more reactants prior to or during dispensing of the drug.
It is another object of the present invention to disclose the device as define above, additionally comprising means for forcing the stream of fluid towards the respiratory tracts.
It is another object of the present invention to disclose the device as define above, comprising additional means of inhaling a dispersed medicament.
It is another object of the present invention to disclose the device as define above, wherein any part of the device is disposable.
It is another object of the present invention to disclose the device as define above, wherein said drug releasing mechanism is adapted to control the release of at least one drug from a combination of said containers.
It is another object of the present invention to disclose the device as define above, wherein any part of the device is reusable.
It is another object of the present invention to disclose the device as define above, wherein said pressure pulses are provided according to the treatment protocol of tables 1, 2, or 3.
It is another object of the present invention to disclose the device as define above, wherein said pressure pulses are provided according to a treatment protocol which is adapted to increase the uptake of medications.
It is another object of the present invention to disclose the device as define above, wherein said pressure pulses are provided according to a treatment protocol which is adapted to improve the clinical outcome of the treatment.
It is another object of the present invention to disclose a method for efficiently delivering drugs/medicaments to the respiratory system. The method comprising steps of:
It is another object of the present invention to disclose the method as define above, wherein the device is adapted for delivering the drugs to the upper respiratory tract of the respiratory system.
It is another object of the present invention to disclose the method as define above, wherein the device is adapted for delivering drugs to the lower respiratory tract of the respiratory system.
It is another object of the present invention to disclose a method for delivering drugs. The method comprises steps of:
It is within the scope of the present invention that the air controlling mechanism is adapted to generate pressure pulses of Negative Pressure and/or Positive Pressure into the respiratory system during inspiration and/or expiration, and the drug releasing mechanism is adapted for entraining the drugs into the pressure pulses, such that uptake of the drugs by the tissues of the respiratory system is facilitated; the pressure pulses are selected from the group consisting of: inspiratory Negative Pressure (NP) pulses, inspiratory Positive Pressure (PP) pulses, expiratory Negative Pressure (NP) pulses, expiratory Positive Pressure (PP) pulses into the respiratory system, and any combination thereof.
It is another object of the present invention to disclose the method as define above, wherein the air controlling mechanism comprises means for forcing a stream of fluid towards the patient's respiratory system.
It is another object of the present invention to disclose the method as define above, wherein the device is adapted for delivery of powdered drug supplied in capsule form.
It is another object of the present invention to disclose the method as define above, wherein the air controlling mechanism comprises a shutter for interrupting the stream of air during patient's inspiration or expiration, such that a pulse of Negative Pressure is induced within the patient's respiratory system.
It is another object of the present invention to disclose the method as define above, wherein the shutter comprises a perforated rotating disc adapted to allow passage of the air through the perforation within the disc and to block and unblock the passage of the air.
It is another object of the present invention to disclose the method as define above, wherein the air controlling mechanism comprises a motor driven disc wheel adapted for synchronization with the drug releasing mechanism.
It is another object of the present invention to disclose the method as define above, wherein the drug releasing mechanism is adapted to be opened by a drop in pressure during inhalation and closed by a rise in pressure during exhalation.
It is another object of the present invention to disclose the method as define above, wherein the drug releasing mechanism comprises a drug releasing shutter for controlling release of the drugs from the container during the operation of the air controlling mechanism.
It is another object of the present invention to disclose the method as define above, wherein the device additionally comprises fluid vibrating means 26 (FVM) for vibrating the medication and the air to facilitate drug delivery, the FVM selected from the group comprising an acoustic means mechanical means or electromechanical (piezoelectric) means.
It is another object of the present invention to disclose the method as define above, wherein the FVM is located in the middle section of the device or proximally to the outlet of the container.
It is another object of the present invention to disclose the method as define above, wherein the container comprises a pressure generator for generating high pressure therein.
It is another object of the present invention to disclose the method as define above, wherein the device is pocket sized device.
It is another object of the present invention to disclose the method as define above, wherein the device is characterized by a non-drug mode in which the drug releasing mechanism does not provide drugs, and solely controls the passage of air during inhalation or exhalation of the air.
It is another object of the present invention to disclose the method as define above, wherein the device is adapted for use a s a sinusitis inhaler for use with one or both nostrils.
It is another object of the present invention to disclose the method as define above, further comprising a ratchet and pawl mechanism adapted to activate the device by lifting a pawl by the user's teeth.
It is another object of the present invention to disclose the method as define above, further comprising spirometric, chemical or other types of sensors adapted to measure parameters of the user's breath and to modify the treatment protocols of the device via a feedback mechanism, said sensors are adapted to measure parameters selected from the group consisting of: peak flow, flow rate, FEV 1, spirometric parameters, inhalation pressure, exhalation pressure, inspiratory pressure, expiratory pressure, vital capacity, inhaled CO2 concentration, exhaled CO2 concentration , inhaled O2 concentration, exhaled O2 concentration, and any combination thereof.
It is another object of the present invention to disclose the method as define above, wherein the device additionally comprises means for pulling the lower jaw forward with respect to the upper jaw such that the geometry of the upper airway facilitates smooth flow of air and drug into the lungs.
It is another object of the present invention to disclose the method as define above, wherein the drugs are selected from the group consisting of: vaporized essential oils, volatile compounds, etheric oils, terepenes, terpanols and either water miscible or water-immiscible extracts, especially oils or extracts obtained from Amyris, Balsam, Bay Rum, Black Pepper, bornyl acetate, Cajeput, Camphor, Cedarwood, Cedarleaf oil, Chamomile, chlorbutanol, Cinnamon, Clary Sage Rosewood, Clove, Eucalyptus, Frankincense, Geranium, Ginger, Lavender, Lemon, Lemon essential oils, levomenthol, Lime, Menthol, Mint, Myrrh, nutmeg oil Orange, Patchouli, Peppermint, Pine Needle, Rose Eucalyptus, rosemary, Rosewood, Sage, Sandalwood, Spearmint, Tea Tree, terpinol, turpentine oil, thymol, Ylang Ylang or any combination thereof.
It is another object of the present invention to disclose the method as define above, wherein the drugs comprise in vaporized form at least one of the group of Braochodilators, especially sympatic mimetics, alfa antagonists, anti cholinergics; nasal decongestants, such as pseudoehedrines, ephedrines; steroids; anti histamines; anti prostaglandins, alternative or homeopathic medicaments; vaso constrictors; local anesthetics; mast cell stabilizers; antibiotics, such as biocides, fungicides etc; pleasant odor; pheromones; hormone treatments, such as ADH, insulin, growth hormones; vapors, humidifiers; drying compositions; hot or cold vapors; hyper-, iso- or hypotonic vapors or any combination thereof.
It is another object of the present invention to disclose the method as define above, wherein the drugs comprise in vaporized form at least one of the group of compositions and commercial available medicaments, their derivatives, or by-products provided thereof, selected from the group consisting of: Acrivastine, Aller-Eze Clemastine, Aller-Eze nasal spray, Azatadine maleate, Azelastine nasal spray, Beclometasone nasal spray, Beclometasone nasal spray, Beconase hayfever nasal spray, Beconase hayfever relief for adults, Beconase nasal spray, Benadryl allergy relief, Benadryl, Benadryl, Benadryl plus, Brompheniramine maleate, Budesonide nasal spray, Calimal Antihistamine, Cetirizine, Chlorphenamine, Clarityn, Clemastine, Cyproheptadine hydrochloride, Desloratadine, Dexa-Rhinaspray Duo. Dimotane elixir, Dimotane plus, Dimotapp elixir, Dimotapp elixir paediatric. Dimotapp LA, Flixonase allergy nasal spray, Flixonase aqueous nasal spray, Fluticasone propionate nasal spray, Galpharm hayfever and allergy relief, Galpseud Plus, Haymine, Histafen, Ipratropium bromide nasal spray, Levocabastine nasal spray, Levocetirizine dihydrochloride, Livostin direct nasal spray, Livostin nasal spray, Loratadine, Medised, Medised, Mistamine, Mizolastine, Mizollen, Mometasone furoate nasal spray, Nasacort, Nasobec nasal spray, Nasonex nasal spray, Neoclarityn tablets/syrup, Optimine syrup, Periactin, Phenergan, Piriteze, Piriton, Pollenase hayfever nasal spray, Promethazine hydrochloride elixir, Promethazine hydrochloride, Rhinocort Aqua, Rhinolast allergy nasal spray, Rhinolast nasal spray, Rinatec nasal spray, Rino clenil nasal spray, Rynacrom allergy nasal spray, Rynacrom nasal spray, Semprex, Sodium cromoglicate nasal spray, Sudafed Plus, Syntaris nasal spray, Tavegil, Telfast 120, Terfenadine, Terfinax, Triamcinolone acetonide, Vista-Methasone, Xyzal tablets, Zirtek allergy relief tablets, Zirtek allergy tablets/solution, Afrazine, Anadin, Beechams all-in-one, Beechams products, Benylin products, Contac, Day Nurse, Dimotapp elixir, Dimotapp elixir paediatric, Dimotapp products, Galpseud, Karvol decongestant products, Lemsip products, Meggezones, Merocets Plus lozenges, Nurofen Cold and Flu, Otrivine Menthol Nasal Spray, Otrivine Metered Dose Sinusitis Spray, Otrivine products, Pseudoephedrine hydrochloride, Sterwin real lemon cold powders and other products, Strepsils Menthol and Eucalyptus and other products, Sudafed and its products, Xylometazoline nasal drops, Bactroban Nasal, Fusafungine, Locabiotal, Naseptin nasal cream, Ipratropium bromide nasal spray, Rinatec nasal spray, pseudoephedrine, propylhexedrine, L-Desoxyephedrine, xylometazoline hydrochloride or any combination thereof.
It is another object of the present invention to disclose the method as define above, further comprising means for cooling or heating the fluid prior to or during or forcing the stream of fluid towards the respiratory tract.
It is another object of the present invention to disclose the method as define above, further comprising means for mixing or activating a medicament by reacting it with one or more reactants prior to or during dispensing of the drug.
It is another object of the present invention to disclose the method as define above, additionally comprising means for forcing the stream of fluid towards the respiratory tracts.
It is another object of the present invention to disclose the method as define above, comprising additional means of inhaling a dispersed medicament.
It is another object of the present invention to disclose the method as define above, wherein any part of the device is disposable.
It is another object of the present invention to disclose the method as define above, wherein any part of the device is reusable.
It is another object of the present invention to disclose the method as define above, wherein said drug releasing mechanism is adapted to control the release of at least one drug from a combination of said containers.
It is another object of the present invention to disclose the method as define above, wherein said pressure pulses are provided according to the treatment protocol of tables 1, 2, or 3.
It is another object of the present invention to disclose the method as define above, wherein said pressure pulses are provided according to a treatment protocol which is adapted to increase the uptake of medications.
It is another object of the present invention to disclose the method as define above, wherein said pressure pulses are provided according to a treatment protocol which is adapted to improve the clinical outcome of the treatment.
a-b schematically illustrates one possible mechanical embodiment of the device;
a-b schematically illustrates an embodiment of the device using a ‘tuning fork’ resonator for nebulization;
a-b schematically illustrates an embodiment of the invention using a drug capsule;
a-b schematically illustrates further embodiments of the device invention during expiration and inspiration;
a-d are a schematic representation of different aspects of the device of the present invention.
The core of the present invention is hereby illustrated by the following drawings and explanations.
The present invention is directed to providing devices and methods for improving drug delivery to the respiratory system, including the lower respiratory tract (the lungs) and the upper respiratory tract (nose, sinuses).
The term ‘air’ refers hereinafter to any type of gas which may be delivery to the lungs of a user during inhalation and/or exhalation. For example, the term ‘air’ may refer to a pure air, a gas, or a mixture of air/gas with a drug.
The term ‘fluid’ refers hereinafter to a mixture of a gas such as air and at least one liquid or gas other than air, or air itself, or any drug or medicament in any convenient form, especially nebulized, vaporized or powdered.
According to different embodiments of the present invention, the terms ‘air’ and ‘fluid’ may refers to same substance.
The term ‘drugs’ refers hereinafter to any kind of at least one substance or medicament which may be supplied to the human respiratory system.
The term ‘inspiratory Negative Pressure’ refers to creation of Negative Pressure during inspiration, for example by closing the passage of air through the device, and then opening the passage. Negative pressure can also be reached by drawing (sucking) air pulse from the respiratory system during inspiration.
The term ‘inspiratory Positive Pressure’ refers to creation of Positive Pressure during inspiration, for example by adding pulses of air to the lungs during inspiration.
The term ‘expiratory Positive Pressure’ refers to creation of Positive Pressure during expiration, for example by adding (delivering) pulses of air to the lungs during expiration.
a-d shows schematically the effects of pulsating high negative pressure (Vacuum) pulses on the airways and subsequently on the respiratory system.
The term ‘expiratory Negative Pressure’ refers to creation of Negative Pressure during expiration, for example by drawing (sucking) pulses of air from the mouth during expiration
A patient exhales air in normal breathing, creating positive pressure in the lungs and chest cavity. Then inhalation begins, in which a Normal Negative Pressure (NNP) is created in the lungs and chest cavity. However if, whilst the patient is inspiring air, the patient blocks his airway with the tongue or the soft palate, an immediate high negative pressure will be felt in the chest cavity. This is due to expansion of the chest cavity by the diaphragm and other chest cavity muscles: air has been expelled (expiration), after which the chest wall expands to draw in more air. If no more air can enter (i.e. if the tongue and the soft palate has now blocked or stopped the air passage) then a situation of high negative pressure obtains in the lungs and chest cavity. It is clear that this can be done repeatedly, for example by blocking and unblocking air passages, thus creating a series of High Negative Pressure (HNP) pulses over the NNP in the lungs. In the present invention, devices and methods are presented for producing HNP pulses as a method of facilitating drug delivery to the airways and lungs, and/or to aid in certain conditions requiring mucous dislodgement, etc. The method works by inducing the HNP pulses by means of a device specially designed for the purpose, which also delivers drugs via nebulization or any other convenient means. Thus, as can be seen in
As will be obvious to one skilled in the art, the air flow coming from the user upon exhalation can also be intermittently blocked in similar fashion, providing a series of high positive pressure (HPP) pulses.
According to different embodiments of the present invention, the terms ‘High Negative Pressure’ and ‘Negative Pressure’ have the same meaning. Moreover, according to different embodiments of the present invention, the terms ‘High Positive Pressure’ and ‘Positive Pressure’ have the same meaning.
According to one embodiment of the present invention the system forces a stream of fluid towards the patient's respiratory tracts. The term ‘forcing’ refers hereinafter to the generation of flowing fluid either as a continuous flow or as pulses by means of vents, fans, jets, injectors, compressors, pumping means or other means known in the art adapted to force a fluid towards at least one predetermined location such as the lungs.
The present invention discloses a device useful for facilitating delivery of drugs to the respiratory system of a user. The device comprises a mechanism for interrupting the airflow during inhalation or exhalation performed by the user through the device by generating pressure pulses within the respiratory system of the user, such that the delivery of the drugs to the user is facilitated. The pressure pulses may be selected from the group consisting of: inspiratory Negative Pressure (NP) pulses, inspiratory Positive Pressure (PP) pulses, expiratory Negative Pressure (NP) pulses, expiratory Positive Pressure (PP) pulses into said respiratory system, and any combination thereof.
According to some embodiments, the device may deliver the drugs to the upper respiratory tract of the respiratory system. According to other embodiments, the device may deliver drugs to the lower respiratory tract of the respiratory system.
According to different embodiments of the present invention, the present invention discloses a device useful for delivering drugs to the respiratory system of a user. The device comprises:
The air controlling mechanism is adapted to generate pressure pulses of Negative Pressure and/or Positive Pressure into the respiratory system during inspiration and/or expiration, and the drug releasing mechanism is adapted for entraining the drugs into the pressure pulses, such that uptake of the drugs by the tissues of the respiratory system is facilitated. The pressure pulses may be selected from the group consisting of: inspiratory Negative Pressure (NP) pulses, inspiratory Positive Pressure (PP) pulses, expiratory Negative Pressure (NP) pulses, expiratory Positive Pressure (PP) pulses into said respiratory system, and any combination thereof.
In one embodiment of the invention a device is employed for introducing air and medicaments during inspiration (whilst the patient breathes in). The device has a shutter mechanism which opens and closes in a predetermined manner. When the shutter is open, air may enter the airways, and the normal negative pressure (NNP) is experienced by the airways. When the shutter closes, the aforementioned HNP is produced in the airways due to continued chest cavity expansion with a lack of fluid intake. This can be explained by the Boyle-Mariotte law according to which p1V1=p2V2. This has a mechanical effect of narrowing the airways, and when the shutter is reopened, a ‘rebound effect’ takes place. The rebound effect, which comprises a series of pressure waves passing through tissue, is described by Avni in U.S. patent application 61/250,528, and this document is herein incorporated by reference in its entirety. Said tissue rebound will have profound effects on facilitation of blood supply, oxygenation, perfusion, CO2 and NO production and other physiologically important functions of cells and tissues. In addition, and possibly as a consequence of the aforementioned, drugs which are introduced in the airstream penetrate the lungs further towards the terminal bronchioles and alveoli; and also, the drug particles impinge and impact on the tissue walls, and increased rates and efficiency of drug uptake is achieved.
It is herein acknowledged that, having described the principle of the invention, many embodiments may be envisaged and reduced to practice. Some of these embodiments are found in
In
In
The device also comprises a drug releasing mechanism 28 adapted to control the passage of the drugs from the container.
According to some embodiments, by means of rotation of a cogwheel, a shutter may be alternately opened and closed thus provided alternate NNP and HNP pulses. Following this, a slow release of the drug combines with HNP pulses may be provided. By this means the amount of drug delivered may be metered to an exact dose.
According to some embodiments, a dry powder drug capsule or container may also be used to administer the drug to the patient. A button is depressed by the user as in a standard inhaler. Meanwhile a rotating disc is activated that alternately blocks or opens a passage allowing or disallowing fluid flow out of the device. As the user inhales, alternating pulses of NNP and HNP are thereby administered, the NNP pulses allowing fluid flow and medicine delivery to the patient, and the HNP parts of the cycle increasing the negative pressure in the chest cavity and lungs. The next NNP pulse induces a rebound effect on the respiratory tissues due to the sudden inrush of fluid. Depressing the aforementioned button presses the piston which in turn raises the pressure in the container, to improve and create initial high velocity of the drug pulses while still keeping slow release. A similar mechanism (not shown here) can be adapted to administer liquid medication in the form of aerosol droplets, as shown in
Another embodiment of the device is shown in
In another embodiment of the device, the resistance of the device to the flow of the exhaled airstream can be controlled according to a predetermined program. This resistance control may be implemented by narrowing of the airstream conduit at the device's outlet in the mouthpiece, at the location of drug pickup by the airstream, at the device's air inlet or at any other location along the device's exhaled airstream path. This resistance control may also, or alternatively, be implemented by increasing resistance to rotation of the turbine while the latter is rotating due to the exhaled airstream. This turbine resistance control may be automatic, based on changes in air pressure or flow, or based on data provided by one or more sensors that monitor biological information such as gas levels in the exhaled air. The turbine resistance control may, alternatively, be manual, by setting of a shutter, valve or other mechanisms, or by replacing parts that affect flow resistance such as the mouthpiece.
According to some embodiment, the sensors of the present invention may be connected to a feedback mechanism which may modify the treatment protocols of the device via a feedback mechanism. The feedback mechanism may receive physiological or other data from the sensors, and operate the drug releasing mechanism or the air controlling mechanism accordingly.
In another embodiment of the device, the size and/or shape of the mouthpiece can be controlled, in order to affect the way the patient's lips are placed around the mouthpiece and/or the angle of the jaw and/or how large the mouth is opened when using the device. As an example, the mouthpiece can be designed with notches for the upper and lower teeth, in order to pull the lower jaw forward such that the geometry of the upper airway facilitates the smooth flow of the air and drug into the lungs. Control of the size and shape of the mouth is also important as it affects the chest cavity and airways resonance and acoustics, similar to the phenomenon known in singing and playing wind instruments, and improves drug dispersion in the lungs.
In another embodiment, there is an element in the device that vibrates and creates vibrational frequency(ies) in the inhaled or exhaled airstream.
It is within provision of the invention that as part of a protocol, the pressure introduced into the lungs be reduced and increased at a certain frequency, to create pulses of positive and negative pressure in the patient lungs.
As seen in
It is one provision of the invention that the user's natural inspiration be intermittently blocked by means of blocking the incoming airflow, with a shutter or the like. By this means a series of repeating ambient and low pressures are introduced into the respiratory passages. It is also within provision of the invention that expiration be similarly blocked, producing a similar series of high positive and ambient pressures. As will be clear to one skilled in the art this will tend to release mucous blockages, increase uptake, and provide for better gas exchange.
Reference is now made to
Moreover, the drug releasing mechanism may be activated in a synchronization of predetermined treatment protocols, such that each drug is released according to the same treatment protocol, or according to different treatment protocols.
According to some embodiments, the drug releasing mechanism is adapted to control the release of at least one drug from a combination of said containers as illustrated in
In
In
In
It is within provision of the device to provide a ‘pocket inhaler’ which may be useful with or without medication. Without medication, the device is used to introduce pressure fluctuations into the lungs, thereby vibrating and massaging the air passages, dislodging mucous, increasing perfusion and the like as will be obvious to one skilled in the art. The device may also be used for drug delivery, by means of introducing a medicament into the fluid stream that flows in pulses into the user's airways.
As shown in
In
In
In
A similar embodiment is shown in
In
In
In
In
In
In
In
In
In certain embodiments of the device, the act of depressing a canister or other lever on the device will cause the periodic blockage and passage of fluid through the device; for example one possible mechanism may utilize a gearwheel and cam adapted to convert rotational into linear motion of a fluid-blocking gate or door. Obviously a rack-and-pinion mechanism could also be used, as could a variety of other mechanisms that will be obvious to one skilled in the art.
Reference is now made to
Spacer 123 comprises an air controlling mechanism 130 for controlling passage of air during inhalation or exhalation.
In this figure illustrated a rotating mechanism which provides passage of air only when aperture 132 and mouthpiece 134 are fluidly connected to each other, so as to provide passage of air. By the rotation air controlling mechanism 130, pulses of air are generated during inhalation. These pulses may be Negative Pressure pulses and Positive Pressure pulses, or any combination thereof.
According to some embodiments, air controlling mechanism 130 may be actuated by en electric motor 140 which is powered by batteries.
Reference is now made to
According to another embodiment, the air controlling mechanism may be driven by manual rotation of switch 152 which provides potential energy to a spring 157, so as to control the closing/opening of passage 153 while the potential energy of spring is released.
According to another embodiment, the air controlling mechanism may be driven by electric power batteries 154, so as to control the closing/opening of passage 155.
According to the embodiment of
Reference is now made to
It should be mentioned the according to this embodiment, the shutter 163 is not closed till the end, so as to provide passage air which rotates cogwheel 161.
The device of this embodiment may be used with drug and without drug. When a drug is used, there is a mixture of the air with the drug, and each pulse comprises a pulse of air with a drug. The device of this embodiment may also be actuated in inspiration and expiration, while Negative and Positive Pressure pulses are generated.
Reference is now made to
According to this embodiment, the drug is provided and mixed with the air by via channel 165. Therefore, the drug is provided to the user in a continuous manner. According to
According to the embodiment of
According to another embodiment of the device with a cogwheel, the air controlling mechanism is adapted to generate pressure pulses of Negative Pressure and/or Positive Pressure into the respiratory system during inspiration and/or expiration, and the drug releasing mechanism is adapted for entraining the drugs into the pressure pulses, such that uptake of the drugs by the tissues of the respiratory system is facilitated. The pressure pulses may be selected from the group consisting of: inspiratory Negative Pressure (NP) pulses, inspiratory Positive Pressure (PP) pulses, expiratory Negative Pressure (NP) pulses, expiratory Positive Pressure (PP) pulses into said respiratory system, and any combination thereof.
Reference is now made to
According to another embodiment of the present invention, the device may be actuated with drugs.
According to this embodiment, drug releasing mechanism 175 may provide the drug with the pulses of air during inhalation, and may not provide the drug with the pulses of air during exhalation. This may be performed in an automatic manner without intervention of the user.
Reference is now made to
By using the device of
According to one embodiment of the present invention, the device may be actuated without drugs. The pulses which are generated by the device of
According to some embodiments of the present invention, the pressure pulses are provided according to a treatment protocol which is adapted to increase the uptake of medications and/or to improve the clinical outcome of the treatment.
For purposes of the current invention, the terms ‘protocol’ or ‘treatment protocol’ or therapeutic protocol’ refers hereinafter to a description of the therapeutic procedure unlimitedly defining frequency and amplitude of the provided fluid pressure pulses (FPP), treatment period, and medicines optionally inserted into the air flow.
According to some embodiments of the present invention, fluid pressure pulses (FPP) can be provided to the mouth cavity of a patient at a predetermined frequency according to a protocol of Table 1.
The treatment via the device of the present invention may be performed by delivering series of air packets (discrete wavetrains of different repetition frequencies and pulse amplitudes) according to predetermined protocols in Table 1. The frequencies may be electronically controlled. This ensures accurate frequency and pressure delivery of each air packet. The air packets are delivered for a pre-specified time period.
Without wishing to be bound by theory discrete wavetrains of different repetition frequencies and pulse amplitudes result in specific therapeutic effects on the various components of the lung tissue, e.g. Bronchial smooth muscles and blood vessels relaxation, mucus clearance of the airways, reduction of the pulmonary vascular pressure etc.
By using the device and the protocols of the present invention, and generating and delivering discrete wave trains of different repetition frequencies and pulse amplitudes, will increase the uptake of medications.
According to some embodiments, the present invention supplies fluid pressure pulses (FPP) to the mouth cavity of a patient at a predetermined frequency and pressure in a predetermined manner which is not dependent upon the natural breathing rate of the patient.
According to other embodiments, the protocols of the present invention are tailor made protocols for diseases such as: asthma, COPD, CF. Other diseases of the airway are within the scope of the present invention, as well. In accordance with proposed technical solution, the profile of the pressure comprises alternation of pneumatic pulse sequences of high and low amplitudes corresponding to inhalation and exhalation, respectively. Amplitude and repetition rate of the pneumatic pulses are preprogrammed by a patient or a doctor according to the treated disease.
According to some embodiments of the present invention, means and methods of accurately measuring the frequency characteristics of the FPPs are provided. It is a further purpose of the invention to provide means and methods of relaying the aforementioned data to the microprocessor of the device, and to process the data, such that the operation of the device can be adjusted or calibrated or attenuated by the patient or doctor. Similarly, it is a core purpose of the invention to provide means and methods of accurately measuring the pressure amplitude of the FPPs. It is a further purpose of the invention to provide means and methods of relaying the aforementioned data to the microprocessor of the device, and to process the data, such that the operation of the device can be adjusted or calibrated or attenuated by the patient or doctor. It is a core purpose of the invention to provide means and methods of controlling pressure variations positively or negatively in order to improve treatment by means of the FPPs. It is a further purpose of the invention to provide means and methods of relaying the aforementioned data to the microprocessor of the device, and to process the data, such that the operation of the device can be adjusted or calibrated or attenuated by the patient or doctor.
According to some embodiments, a protocol of Fluid Pressure Pulses (FPPs) useful for improving a patient's wellness is herein disclosed. The aforementioned protocol comprises sequences of individual FPPs, which are possibly different from each other. The fluid pressure pulses are administered to said patient's airway. The invention comprises protocols which can be asynchronous or synchronous, i.e., delivered in a way which may be independent of the patient's natural inspiratory cycle, cardiac cycle or other physiological functions, or dependent upon them, respectively. The above mentioned protocol may further be administered to the mouth cavity of a patient at a predetermined frequency and pressure in a predetermined manner which may be synchronous or asynchronous.
It is further within provision of the invention to provide the aforementioned FPPs wherein said FPPs comprise a given pressure amplitude, volume, duration and waveform; and further wherein said sequences of FPPs comprise a given frequency and duration.
According to different embodiments of the present invention, disease- and symptom- specific protocols with accompanying devices, based on applying fluid (e.g., gas, air, aerosols etc.) pressure pulses (FPP) to the mouth cavity of a patient at predetermined frequencies and intervals are provided. The FPPs themselves may, in some cases, be vibrationally modulated, that is to say, within each pressure pulse, representing a packet or bolus of air, different vibrations can be set up (140 in
In exemplary embodiments of the present invention the aforementioned FPPs are created by means of airflow oscillation means described and illustrated herein.
Reference is now made to
The pulses produced by the cutout shapes described above may be of almost unlimited form. As an example, a radial cutout will allow full pressure ‘at once’ with some inevitable delay and ‘smearing’ of the expected square wave due to diffusion. The resultant pressure waveform may be fit by the expression
where P0 is a constant, D is the diffusion constant of air, t is the time, and l is the distance from pulsehaler to the point of measurement.
The FPPs may be of positive pressure relative to the ambient atmosphere, negative pressure relative to the ambient atmosphere or any dynamic combination thereof.
The sequenced flow of packets of air (the FPPs) are facilitated into the airway of the patient, in a precise sequence, combination and manner (Protocol, exemplified in table 1), which is determined e.g., by the disease or symptom to be treated.
The protocols can be likened, by analogy, to tunes and chords made up by combinations of musical notes in a series. These ‘notes’ are produced by an ADD or other instrument which produces vibrating columns of air. A good analogy for the ADD would be a musical organ or similar device. Each series of notes (i.e., a musical note produced by a number of vibrations which is a multiple of the number producing some other overtones or undertones) can be a harmonic chord, which itself can be built up into a “tune”. Each “tune” is suitable for the treatment of a specific symptom or disease. Lung diseases such as COPD, Asthma, Cystic Fibrosis and others can be treated in this way. Each disease has its own protocol of FPPs, which has been developed in relation to the effect on the tissues in question. For example, in order to clear Cystic Fibrosis mucus, a pressure impulse of particular pressure p1 and amplitude a1 at a certain frequency ω1 impinging upon the viscous mucus characteristic of CF has the effect of lowering its viscosity. Another pressure impulse of particular pressure p2,amplitude a2 and frequency ω2 has a direct effect of compressing the lung tissue momentarily, and a further particular pressure impulse of pressure p3 (which may be negative) amplitude a3 and frequency ω3, releases the tissue resiliently, thereby “flinging” the now less viscous mucus off the tissue wall, and unblocking it. A further example of the effects of the device would be frequencies directed to stimulating ciliary movement, assisting in expulsion of excess mucous, and others. The particular frequencies of the supplied FPPs, also influence the effect of the treatment. Likewise, the abovementioned amplitude-modulated FPPs (
It is within provision of the invention that the device be provided with means for sensing the inhalation and exhalation stages of the subject's respiratory cycle. In this way, the device can provide a different sequence of FPPs on inhalation vs. exhalation. It is further within provision of the invention that different patient conditions be treated by different protocols, each of which may have one set of sequences of FPPs for use during inhalation, another set of sequences used during exhalation, and possibly a third set of sequences used during the intervals between inhalation and exhalation.
Devices for sensing of inhalation vs. exhalation will be well known to those skilled in the art, for example comprising pressure sensors, CO2 sensors, NO sensors, and others.
It is herein acknowledged that in some embodiments of the present invention, the protocols comprise not only the aforementioned sequences of FPPs, but also means and methods are provided to contemporaneously or simultaneously deliver streams of air with predetermined oscillating frequency into the patients airway, which persist for periods of time throughout or partially throughout the FPP sequences that are being delivered. Such airstreams can be likened to the drone of a Scottish bagpipe which produces a continuous stream of vibrating air at a predetermined frequency, whilst the chanter of the bagpipe produces the tune or melody. Certain particular predetermined oscillating frequencies of the aforementioned persistent streams of air are useful in stimulating NO production in certain tissues, promoting gas exchange and other therapeutically useful effects. Thus, some of the protocols of the invention will include the delivery of these drone-like vibrating airstreams in parallel to the predetermined sequences of FPPs.
The protocols exert their effects at the body organ level (e.g., lungs), the tissue level (e.g., bronchial smooth muscle relaxation, gas exchange at the alveolar membrane level), the cellular level (e.g., stimulation of epithelial NO production at the cellular level), the nervous system, parasympathetic nervous system, sympathetic nervous system, and others. There are several interrelated modes of interaction between the FPPs, including the setting up of resonating frequencies and harmonics with the natural resonances of different tissues.
An important facet of the invention is that means and methods are provided to design and implement any protocol for disease, based on sequences of FPPs. This is done by accumulating data from subjects provided with appropriate physiological sensors. In some embodiments the data will be fed back to fine tune the designed protocol. Protocols of the invention include particular frequencies and multiple harmonics or overtones thereof and are envisaged to cover the whole of relevant frequencies.
Mechanical resonance is the tendency of a mechanical system to absorb more energy when the frequency of its oscillations matches the system's natural frequency of vibration (its resonance frequency or resonant frequency) than it does at other frequencies. It is herein acknowledged that some of the protocols of the present invention provide FPPs at the natural frequency of target tissues in the patient to facilitate the therapeutic effects of the treatment protocols.
It is within provision of the invention to provide effects currently achieved by conventional medicines, such as increased cardiac output, decreased arterial resistance, decreased capillary resistance, increase in vascular elasticity, and the like, increase/decrease in sympathetic/parasympathetic response, and the like.
It is within provision of the invention that clinical improvement can be attained during and/or after use of the device in a number of diseases and syndromes. The following is a partial list of such illnesses in which it is envisaged that the device may be of service:
Diseases :Lung diseases; Obstructive Lung Diseases; COPD; Asthma; Bronchitis; Restrictive Lung Diseases (e.g., asbestosis, radiation fibrosis, ARDS); Cystic Fibrosis; Upper Respiratory Tract Infection; Sinusitis; Pharyngitis; Laryngitis; Otitis Media; Lower Respiratory Tract Infections; Pneumonia; Lung tumors; Cardiovascular Diseases; Coronary heart disease; Cardiomyopathy (CM), e.g.: Hypertrophic CM; Dilated CM; Hypertensive CM; Congestive Heart Failure; Inflammatory heart disease; Endocarditis ;Myocarditis; Cardiac Arrhythmias, e.g.: Atrial fibrillation Atrial flutter; Supraventricular Tachycardia; A-V blocks; Systemic Hypertension; Pulmonary hypertension; Atherosclerosis; Atherosclerosis of the Carotid arteries; Sleep apnea; Fibromyalgia. It is further within provision of the invention that a number of biological responses can be attained through use of the device and the protocols mentioned above. The following is a partial list of such effects.
Biological Effects: Smooth muscle relaxation; Pain blocking; Nitric Oxide release; Angiogenesis Shear forces exerted on fibroblasts facilitate tissue regeneration; Relief of dyspnea (neural effect?)
Blood circulation; Improved perfusion through diseased capillaries; Improved alveolar gas exchange; Sympathetic function, Parasympathetic function, Autonomic balance; General influence on the nerves system and function; Change the chemical balance; Improvement of poorly functioning natural processes.
Protocols for Inspiration and Expiration:
In some embodiments of the present invention, a sensor at an opening of the device detects inspiration and expiration and accordingly signals the controller. The controller selects, alters or changes the FPP protocol that will be provided to the patient according to the predetermined programme.
If, for example, the 34 Hz frequency widens the bronchioles during inspiration, and 5 Hz during expiration facilitates expectoration, the appropriate frequencies will be provided. As a result, the bronchioles are widened and expectoration is increased.
If, for example, FPPs provided at a frequency of 40 Hz improve blood circulation during inspiration, and gas exchange is improved during expiration upon application of 8 Hz FPPs, then those frequencies will be automatically selected. Such a therapeutic treatment will be beneficial, because one will have, for example, lowered pulmonary pressure and improved oxygenation.
It is an embodiment of the present invention to provide and disclose sensors and methods of using them to detect gases exhaled during respiration which then transfer signals to the controller. The controller can alter and change the frequency or frequencies of the provided FPPs of the specific protocol or select a protocol at the beginning of treatment. The FPP supply to the patient's airway can be generated by Turbine-like devices, CPAP-like devices, BILEVEL like devices, breathing and respiration devices, assisted breathing and similar for inspiration and expiration. Similarly, it is envisaged that the FPPs of the applied protocols can be of positive pressure, negative pressure, or a combination of both. Means and methods of providing resistance and perturbations to the natural breathing patterns of an individual patient are herein provided with protocols. Means and methods of selecting and generating such FPP protocols characterized by supplying FPPs of various frequencies , pressures and other characteristics, tailored according to the patients condition at the beginning of the therapy and during it's progress are provided. Thus the invention herein disclosed provides a non limited solution to pulmonary, respiration related and critical care patients.
Table 2 is a more detailed example of selected protocols for Asthma treatment, COPD or CF. It should be noted that for each condition, a series of FPPs are administered of predetermined Hz and duration. The RPM in the table refers to the revolutions of the revolving disc of exemplary embodiments of the invention, but any convenient means of producing the FPP's can be employed and remain within the scope of the invention. It should further be noted that each protocol has a predetermined Hz and duration of the FPP application which is selected because they have been found to beneficially effect certain physiological characteristics such as blood circulation, mucus transport, gas exchange, Functional residual capacity and relaxation smooth muscles. mucus transport in the upper bronchial region, blood circulation, Functional / residual capacity. The
The above description has, in a non limited manner, described an Air Delivery Device (ADD) and protocols for the application of the aforementioned Fluid Pressure Pulses (FPPs) to the airways of patients in need. It is envisaged that a person skilled in the art will be able, by learning from the disclosure herein provided, to provide means and methods for treating a wide number of diseases, symptoms and conditions, itionally to COPD, Asthma and Cystic Fibrosis. Such diseases symptoms and conditions include: Sinusitis, Nasal Congestion, Pneumonia, Emphysema, Interstitial fibrosis, Pulmonary hypertension or Sarcoidosis.
It is furthermore envisaged that the above mentioned ADD and protocols will be useful in improving a patient's condition as measured by parameters, indices and scales selected from the group consisting of mental and physical health, quality of life, lung function, drug uptake, heart function, cardio- vascular efficiency, pulmonary efficiency, lung volume, oxygen uptake, gas exchange, NO production, carbon monoxide diffusion or any combination thereof.
As further examples of possible protocols, we present below mathematical representations of protocols which represent pressure as a function of time. The mathematical representation of the pressure as a function of time may take the form of triangle waves, square waves, sine waves. and others, all possibly modulating one another. Thus for example possible pressure sequences include but are not limited to:
P(t)=A sin−1(sin (ω1t))+B×θ(sin (ω2t))+C
where θ(t) is the Heaviside step function,
and others as will be obvious to one skilled in the art. The constants A, B, C, ω1, and ω2 are chosen for instance such that 0.01 Hz≦ω1≦1 Hz, 0.1 Hz≦ω2≦10 Hz, 10 mmHg≦A≦250 mmHg, 10 mmHg≦B≦250 mmHg , and −250 mmHg≦C≦250 mmHg. Change high herz to 250 Hz
It is within provision of the invention to provide enhancement of sporting performance and/or post-event recuperation. Since the device has been clinically demonstrated to cause dramatic improvements in e.g. 6 minute walk tests (see below), it is likely that improvements in blood oxygen levels and the like due to use of the device will provide similar improvements in the realm of sport and recreation.
It is within provision of the invention that the protocols used in operation of the device provide specific levels of pressure based on the expiratory resistance of the subject.
According to some embodiments, table 3 below indicates a specific embodiment of the therapeutic protocols according to which the device of the present invention may be activated.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/IL2010/001017 | 12/2/2010 | WO | 00 | 6/4/2012 |
| Number | Date | Country | |
|---|---|---|---|
| 61265775 | Dec 2009 | US |
