EP1237605A2 - Dispositif d'inhalation de poudre - Google Patents

Dispositif d'inhalation de poudre

Info

Publication number
EP1237605A2
EP1237605A2 EP00976224A EP00976224A EP1237605A2 EP 1237605 A2 EP1237605 A2 EP 1237605A2 EP 00976224 A EP00976224 A EP 00976224A EP 00976224 A EP00976224 A EP 00976224A EP 1237605 A2 EP1237605 A2 EP 1237605A2
Authority
EP
European Patent Office
Prior art keywords
powder
patient
vibration
walls
package
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00976224A
Other languages
German (de)
English (en)
Other versions
EP1237605A4 (fr
Inventor
Zohar Avrahami
Zeev Sohn
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
TransPharma Ltd
Original Assignee
TransPharma Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from IL13303199A external-priority patent/IL133031A0/xx
Application filed by TransPharma Ltd filed Critical TransPharma Ltd
Publication of EP1237605A2 publication Critical patent/EP1237605A2/fr
Publication of EP1237605A4 publication Critical patent/EP1237605A4/fr
Withdrawn legal-status Critical Current

Links

Definitions

  • the present invention relates generally to drug delivery devices, and specifically to devices and methods for delivery of drugs by inhalation BACKGROUND OF THE INVENTION
  • Drug delivery by inhalation is well known in the treatment of respiratory disorders, such as asthma Inhalation has also found use in delivery of systemic drugs through the lungs, wherein the drugs are absorbed directly into the blood stream without having to pass through (and be broken down by) the digestive tract
  • Ultra-fine, dry powders also known as micro- and nano-powders, are the subject of increasing interest in pharmaceutical manufacturing, because they provide a solution to many of the shortcomings of blended drugs Active drug ingredients are produced, packaged and administered to the patient as pure, dry powders, without blending them with solvents or other agents Elimination of the blending steps simplifies the manufacturing process, reduces development and manufacturing costs, makes dosage more accurate, and extends the drug's shelf life
  • Dry powder inhalers are known in the art, for delivery of dry powder medications to the lungs
  • the powder particles should be particularly fine - on the order of 4 ⁇ m in size, or less
  • the drawback of such ultra-fine, dry powders is that they are difficult to handle, tending to clump and stick in storage and to scatter when disturbed by even slight air movements
  • MicroDose Technologies Inc. offers a dry powder inhaler based on the general principles described in the above-mentioned PCT publications.
  • the MicroDose inhaler uses a piezoelectric vibrator, brought into contact with a blister pack containing the powder, to deaggregate the particles.
  • the mechanical interface for transferring the vibrations to the powder in the pack is inefficient and further increases the cost and complexity of the inhaler.
  • a dry powder for delivery to a patient by inhalation is contained in a package having an opening through which the powder flows when the patient inhales.
  • the powder is deaggregated and mobilized by application of a magnetic field.
  • the field interacts with the package, engendering rapid motion thereof, which deaggregates the powder.
  • an electrostatic valve screen is created by means of an alternating electrostatic field in a vicinity of the opening, so as to trap particles of the powder and prevent their escape from the package except during inhalation.
  • the alternating electrostatic field is applied using electrodes at either side of the opening. Only when air is made to flow through the opening at a rate above a given threshold, which is generally determined by the voltage applied between the electrodes, can the powder flow out through the electrostatic valve screen.
  • the voltage is preferably set so that the flow rate passes the threshold when the patient inhales, whereby the powder is drawn out of the package and into the patient's lungs.
  • the package comprises flexible side walls, which are made to vibrate by application of the magnetic field. The vibration of the walls deaggregates the powder in the package and generates air flow which suspends the powder in the air inside the package.
  • the side walls of the package are coupled to electrical wiring, preferably to coils in the form of electrical conductors applied to a surface of the walls in the manner of a flexible printed circuit.
  • One or more permanent magnets apply a fixed magnetic field to the package.
  • the coils on the walls of the package are driven by an alternating electrical current, generating a field that interacts with the fixed magnetic field and thus causes the walls to vibrate.
  • the walls comprise an array of coils, which are driven cooperatively to control the mode of vibration of the walls and thus regulate the air flow inside the package.
  • the external magnetic field has a component in a direction perpendicular to a coil axis, in the plane of the coils, causing the walls to vibrate along the axis.
  • the magnetic field has a component perpendicular to the plane of the coils, causing lateral vibrations.
  • the side walls of the package comprise a magnetic material, which is preferably coated on a surface of the walls. The magnetic field is applied by driving an electromagnet outside the package with an alternating current, which thus causes the walls to vibrate.
  • the flexible side walls are made to vibrate at a resonant vibration frequency thereof, in order to maximize the vibrational energy.
  • a frequency of the alternating current applied to the coils on the walls or to the electromagnet is set so as to engender the resonant vibration.
  • the frequency of the alternating current is swept through a range of frequencies, preferably including the resonant frequency, and is then set at the frequency that maximizes the effectiveness of deaggregation, which is typically the frequency that maximizes the wall vibration.
  • a vibration sensor is preferably coupled to the wall and provides feedback for use in controlling the frequency of the alternating current.
  • the vibration sensor is coupled in a positive feedback loop to a driver that provides the alternating current, causing the loop to spontaneously oscillate at or near the resonant frequency.
  • the powder particles comprise an electrically- or magnetically-active component, preferably in the form of a coating on or a compound in the particles.
  • the application of the magnetic field deaggregates the particles without the necessity of vibrating the walls of the package.
  • the field is driven to alternate at or near a resonant motion frequency of the particles.
  • the electrically- active component enables charging of the particles with a low work function, by contact of the particles with a conductive area of the walls. The charged particles then interact with the electrostatic screen with enhanced efficiency.
  • a powder inhaler device operating as described hereinabove, comprises a disposable package, which is introduced into and actuated by a reusable control and power unit.
  • the package is a part of a multi-dose cartridge, which most preferably comprises multiple packets of the dry powder, which are actuated in succession.
  • the control and power unit includes a dose counter, as well as an appropriate user interface, which informs and reminds a patient as to dosage to be administered.
  • the dose counter can also be used to record patient dosage and compliance data to be read out subsequently by medical caregivers.
  • the powder is deaggregated and mobilized by the action of a mechanical impactor, which applies mechanical energy to the container periodically so as to induce resonant oscillatory motion of the container.
  • the impactor comprises an eccentric rotating element, such as a cam.
  • the impactor may comprise an electromagnetic or piezoelectric oscillating element. The impactor is positioned so as to contact the container only at or near one extreme of the container's oscillation. In this position, the impactor necessarily strikes and imparts energy to the container only in synchronization with the oscillation, even if the motion of the impactor itself is not synchronized precisely with the resonance of the container.
  • the container is configured to oscillate at two different levels of vibrational amplitude: a low level to deaggregate the powder, and a high level to aerosolize the powder.
  • the high-level vibration is induced in order to mobilize the powder when the user of the device inhales.
  • the device is configured so that when the user inhales through the device, air pressure changes induced in the device cause the vibrational amplitude to increase, most preferably by means of an increase in the driving force exerted by the impactor on the container.
  • an inhaler device for administration of a dry powder to a patient including: a package containing a dose of the dry powder; and a magnetic field generator, which produces a magnetic field in a vicinity of the package, causing motion of particles of the powder so as to deaggregate the powder in the package, whereby the powder is inhaled by the patient.
  • the package includes walls made of a flexible material, which vibrate under the influence of the magnetic field so as to impart the motion to the particles.
  • the package includes electrical wiring coupled to at least one of the walls and a control unit which drives a time-varying current through the wiring, causing the walls to vibrate due to interaction of the current with the magnetic field.
  • the wiring includes a circuit trace printed on at le::st one of the walls, which forms a plurality of coils.
  • the control unit drives the plurality of coils at respective relative phases so as to induce a desired mode of vibration of the at least one of the walls.
  • the walls include a magnetic material
  • the field generator includes an electromagnet, which produces a time-varying magnetic field, causing the walls to vibrate due to interaction of the magnetic material with the magnetic field.
  • the magnetic material includes a coating on the one or more of the walls.
  • the walls made of the flexible material include opposing side walls of the package, which vibrate in a controlled mutual phase relationship.
  • the opposing side walls are driven to vibrate in phase or alternatively, in mutually opposite phases so as to pump the powder out of the package.
  • the walls are driven to vibrate at a frequency approximately equal to a resonant vibration frequency thereof.
  • the device includes a driver circuit, which provides an alternating current of adjustable frequency to drive the vibration of the walls, and a vibration transducer coupled to one of the walls, which transducer provides feedback to the driver circuit, so that the frequency of the alternating current is adjusted such that the walls vibrate at approximately the resonant vibration frequency.
  • the driver circuit and transducer are arranged in a self-oscillating positive feedback loop.
  • the device includes a vibration sensor, which generates signals responsive to vibration of the walls, and a control unit, which receives the signals from the vibration sensor and, responsive thereto, controls the inhaler device so as to regulate an energy of vibration of the walls.
  • the control unit provides an alternating current of adjustable frequency to drive the vibration of the walls, and adjusts the frequency of the alternating current in order to maximize the energy of vibration.
  • the powder includes magnetized particles, and the field generator produces a time-varying magnetic field which interacts with magnetic fields of the particles, causing the particles to move.
  • a frequency of the time-varying magnetic field is adjusted so that the particles oscillate at approximately a resonant frequency thereof.
  • the package includes a multi-dose cartridge, such that multiple doses of the dry powder are administered to the patient in succession, and the device includes a dose counter which tracks the administration of the doses.
  • an inhaler device for administration of a dry powder to a patient including: a package containing a dose of the dry powder and having an opening through which the powder exits the package and is inhaled by the patient; and an electrostatic valve screen, which traps the powder inside the package by generating a time-varying electrostatic field across the opening.
  • the valve screen includes a pair of electrodes positioned on opposing sides of the opening.
  • the electrostatic valve screen allows the powder to pass through the opening when a rate of air flow through the opening exceeds a predetermined threshold, wherein the threshold is chosen such that inhalation by the patient generates an air flow through the opening in excess of the threshold.
  • the electrostatic field causes particles of the powder to oscillate in a vicinity of the opening.
  • a method for deaggregation of a dry powder for administration to a patient including applying a magnetic field so as to cause motion of particles of the powder, whereby the powder is inhaled by the patient.
  • the powder is contained in a package having walls made of a flexible material, and applying the magnetic field includes magnetically inducing vibration of the walls so as to impart the motion to the particles.
  • inducing the vibration includes driving a time-varying current in wiring coupled to at least one of the walls, which current interacts with the magnetic field to induce the vibration of the walls.
  • driving the current includes driving current in different portions of the wiring at respective, relative phases so as to induce a desired mode of vibration of the walls.
  • inducing the vibration includes applying a time-varying magnetic field, which interacts with magnetic material in the walls to induce the vibration.
  • inducing the vibration includes controlling relative phases of vibration of different ones of the walls.
  • inducing the vibration includes driving the vibration at approximately a resonant vibration frequency of the walls.
  • inducing the vibration includes sensing vibration of one of the walls and adjusting a frequency of the vibration responsive to the sensing.
  • the method includes magnetizing the particles, wherein applying the magnetic field includes applying a time-varying magnetic field which interacts with magnetic fields of the particles, causing the particles to move.
  • a method for administration of a dry powder to a patient including: providing the dry powder in a package having an opening through which the powder exits the package and is inhaled by the patient; and generating a time-varying electrostatic field across the opening so as to trap the powder inside the package until the patient inhales.
  • generating the field includes adjusting the strength of the field so as to allow the powder to pass through the opening only when a rate of air flow through the opening exceeds a predetermined threshold, wherein the threshold is chosen such that inhalation by the patient generates an air flow through the opening in excess of the threshold.
  • an inhaler device for administration of a dry powder to a patient including: a container assembly, containing a dose of the dry powder and adapted to oscillate over a predetermined oscillation path between first and second extremes; and an impactor, configured to drive the container assembly to oscillate by contacting the container assembly periodically in a vicinity of the first extreme of the oscillation path, but not in a vicinity of the second extreme, so as to deaggregate the dry powder for inhalation by the patient.
  • the container assembly is adapted to oscillate at a resonant frequency of the assembly, so that the impactor contacts the container periodically at the resonant frequency.
  • the device includes an energy source, which is coupled to drive the impactor into motion at a frequency substantially greater than the resonant frequency, wherein the motion of the impactor causes it to contact the container assembly.
  • the impactor includes an eccentric rotating element.
  • the container assembly is configured so that responsive to a flow of air over the assembly, an amplitude of oscillation of the assembly increases.
  • the flow of air is induced by the patient's inhalation.
  • an inhaler device for administration of a dry powder to a patient including: a housing, containing the powder and having an outlet adapted for the patient to inhale the powder therethrough and an inlet through which air is drawn into the housing when the patient inhales; and a deaggregation assembly inside the housing, which is adapted to apply a vibration to the powder so as to deaggregate the powder for inhalation by the patient, such that an amplitude of the vibration is increased when the patient inhales.
  • the amplitude of the vibration is increased responsive to the air flowing through the housing when the patient inhales, wherein the air flowing through the housing applies a force to the deaggregation assembly, causing the amplitude of the vibration to increase.
  • the amplitude of the vibration of the deaggregation assembly is not sufficient to mobilize the powder substantially, so that the powder remains inside the housing, whereas when the patient inhales, the amplitude of the vibration is increased sufficiently to aerosolize the powder
  • the amplitude of the vibration of the deaggregation assembly is increased to a greater degree in response to a greater strength of inhalation by the patient
  • a method for administration of a dry powder to a patient including providing a dose of the dry powder in a container assembly, which is adapted to oscillate over a predetermined oscillation path between first and second extremes, and driving the container assembly to oscillate by striking the container assembly periodically in a vicinity of the first extreme of the oscillation path, but not in a vicinity of the second extreme, so as to deaggregate the dry powder for inhalation by the patient
  • a method for administration of a dry powder to a patient by inhalation including applying a vibration to the powder at an initial vibration amplitude so as to deaggregate the powder p ⁇ or to the inhalation by the patient, and increasing the amplitude of the vibration du ⁇ ng the inhalation by the patient so as to aerosolize the powder
  • Fig 1 is a schematic, partly cutaway, picto ⁇ al illustration of an inhaler device, in accordance with a preferred embodiment of the present invention
  • Fig 2 is a schematic, sectional illustration showing details of a powder package within the inhaler of Fig 1, in accordance with a preferred embodiment of the present invention
  • Figs 3A, 3B and 4 are schematic illustrations showing operating modes of the package of Fig 2, in accordance with preferred embodiments of the present invention
  • Fig 5 is a schematic illustration showing details of an inhaler device, in accordance with another preferred embodiment of the present invention.
  • Fig 6A is a schematic, sectional illustration of a particle of a dry powder for delivery to a patient by inhalation, in accordance with a preferred embodiment of the present invention
  • Fig. 6B is a schematic illustration showing details of an inhaler device for delivery of the powder of Fig. 6 A, in accordance with a preferred embodiment of the present invention
  • Fig. 7 is a schematic, pictorial illustration of a multi-dose powder dispenser cartridge, in accordance with a preferred embodiment of the present invention
  • Fig. 8 is a block diagram that schematically illustrates dose counting circuitry used in an inhaler device, in accordance with a preferred embodiment of the present invention
  • Fig. 9 is a flow chart that schematically illustrates a method for tracking dosage of a medication administered by inhalation, in accordance with a preferred embodiment of the present invention
  • Fig. 10 is a block diagram that schematically illustrates frequency control circuitry used in driving an inhaler device, in accordance with a preferred embodiment of the present invention
  • Fig. 11 is a block diagram that schematically illustrates frequency control circuitry used in driving an inhaler device, in accordance with another preferred embodiment of the present invention.
  • Fig. 12 is a schematic, sectional illustration showing details of a powder package, in accordance with another preferred embodiment of the present invention.
  • Fig. 13 is a schematic, sectional view of an inhaler device, in accordance with still another preferred embodiment of the present invention.
  • Fig. 14 is a schematic end view of an impactor for use in the device of Fig. 13, in accordance with a preferred embodiment of the present invention.
  • Figs. 1 and 2 schematically illustrate an inhaler device 20, in accordance with a preferred embodiment of the present invention.
  • Fig. 1 is a schematic, partly cutaway, pictorial view
  • Fig. 2 is a sectional detail view.
  • Device 20 comprises a powder package 22, preferably in the form of a disposable, replaceable cartridge, which is inserted into a device housing 24.
  • Package 22 comprises side walls 23 and 25, which enclose a volume 26 in which a medication in the form of a dry powder 66 is contained.
  • the side walls preferably comprise a flexible plastic material, such as Mylar, on which electrical conductors are printed, in the manner of a printed circuit, as is known in the art.
  • the electrical conductors form one or more coils or current loops on each of the side walls.
  • coils 28, 30, 32 and 34 are printed on wall 23, and coils 58, 60, 62 and 64 are p ⁇ nted on wall 25
  • Different numbers of coils or loops, as well as coils and loops of different shapes and forms, may similarly be used
  • Permanent magnets 36 and 38 are placed adjacent to package 22 and produce a generally static magnetic field in and around the package More preferably the poles of the magnets are configured to create a magnetic field component perpendicular to the axes of the coils, I e , in the plane of the walls In a preferred embodiment, the poles are configured as a North-North pair, with the coils in the gap between the poles A control umt 40, powered by a battery 42, d ⁇ ves an alternating current through the coils, which interacts with the magnetic fields of magnets 36 and 38 so as to induce vibrations in walls 23 and 25, as desc ⁇ bed further hereinbelow Preferablv, the frequency of the alternating current is adjusted so that the walls are d ⁇ ven to vibrate at a dominant resonant vibrational frequency of the walls, as further desc ⁇ bed hereinbelow
  • control unit 40 t ⁇ ggers the vibrations responsive to a signal from a flow sensor (not shown), so as to synchronize the deaggregation with inhalation by the patient
  • device 20 uses an electrostatic valve screen to prevent escape of particles of powder 66 through openings 41 and 43 except when the patient inhales
  • the screen takes advantage of the fact that the particles in volume 26 typicallv acquire an electrostatic charge by contact with the walls of package 22
  • a high-voltage generator 52 is coupled via contacts 48 and 50 to drive electrodes 44 and 46, respectively, at opposite sides of opening 41, and similarly via contacts 68 and 70 to drive electrodes 74 and 76, respectively, at the sides of opening 43 (Although only a single pair of electrodes is shown at the sides of each opening 41 and 43 it will be understood that multiple electrodes may similarly be used for this purpose )
  • the generator drives the electrodes to produce an alternating electrostatic field in openings 41 and 43 having a peak amplitude of about 3000 volts, at a frequency between 1 and 100 Hz If the dimensions of package 22 and the characte ⁇ stics of the field are approp ⁇ ately chosen, the electrostatic valve screen and the coils on side walls 23 and 25 can be driven at the
  • the threshold level is a function of the field strength and frequency and may be adjusted by varying one or both of these parameters.
  • the threshold air flow velocity is set to about 1 liter/min, and the actual flow rate exceeds this velocity only when the patient inhales.
  • valves as are known in the art, may be used to close off openings 41 and 43 during times other than the inhalation portion of the patient's breath cycle.
  • Figs. 3 A and 3B are schematic illustrations showing vibration of side walls 23 and 25 when control unit 40 drives the coils thereon, in accordance with preferred embodiments of the present invention.
  • the solid lines show the side walls at one extremum of their vibration, and the dashed lines show the opposite extremum.
  • the amplitude of the vibration i.e., the distance between the extrema is exaggerated for clarity of illustration.
  • Fig. 4A is a schematic illustration showing another mode of vibration of side walls 23 and 25, in accordance with a preferred embodiment of the present invention.
  • coils 28, 30, 58 and 60 are driven in opposite phase to coils 32, 34, 62 and 64, thus inducing a higher-order vibrational mode of the walls.
  • Other vibrational modes can similarly be induced by appropriately varying the phases and, optionally, amplitudes of the currents used to drive the various coils.
  • Fig. 5 is a schematic illustration showing details of an inhalation device 80, in accordance with another preferred embodiment of the present invention.
  • Device 80 is largely similar to device 20, described hereinabove, except that it uses a different technique to induce vibration of walls 23 and 25.
  • a package 82 is similar in construction to package 22, except that this package has a magnetic coating 84 on the walls.
  • the coating preferably comprises iron (Fe) or a ferrous compound, for example iron cobalt or gamma Fe203, which are widely used in the magnetic recording field.
  • Electromagnets 86 and 88, respectively comprising coils 90 and 92, are placed at either side of package 82.
  • a driver 94 provides an alternating current to the coils, which thus generate a time-varying magnetic field.
  • the field interacts with coating 84 on the side walls, inducing vibration of the walls.
  • coating 84 on the side walls, inducing vibration of the walls.
  • Driver 94 may further control the phase of the currents supplied to the coils so as to vary the spatial distribution of the magnet field and thus affect the vibrational mode of the walls, as described hereinabove.
  • Fig. 6A is a schematic, sectional illustration of a particle of powder 96, in accordance with still another preferred embodiment of the present invention.
  • the particle preferably comprises a magnetic or electrically-active coating 99 applied around a core 98 containing a medication to be administered to a patient.
  • the particle may comprise a magnetic core, to which the medication is applied as a coating.
  • the coating is of the electrically-active type, it preferably comprises a substance such as sodium, potassium or calcium, which acquires electrical charge with a low work function by contact with a conductive area of the walls of package 22 or with a suitable electrode in the package.
  • the powder can then be more effectively trapped by the electrostatic valve screen, typically at a lower voltage than would otherwise be required.
  • Fig. 6B is a schematic illustration showing details of an inhalation device 100 for use with particles of powder 96 having a magnetic coating 99, in accordance with a preferred embodiment of the present invention.
  • Device 100 and a powder package 102 therein are substantially similar in design and operation to device 80 and package 82 shown in Fig. 5, except that package 102 does not require magnetic coating 84 on its side walls. Instead, coating 99 of the particles of powder 96 interacts with the time-varying magnetic field generated by coils 90 and 92, causing deaggregation and suspension of the particles in volume 26 There is no need for vibration of side walls 23 and 25 for this purpose, as there is in the other embodiments described hereinabove
  • FIG 7 is a schematic, pictorial illustration showing a multi-dose powder dispenser cartridge 120, in accordance with a preferred embodiment of the present invention
  • Cartridge 120 comprises a row of conjoined packets 122 containing a medication in dry powder form, to be dispensed by inhalation using a suitable device having the general form and function of device 20, shown in Fig 1
  • Each of packets 122 takes the place of package 22 in device 20, and functions in a generally similar manner
  • the packets are inserted in succession, as needed, into the inhaler device, preferably without separating the packets in the row one from another
  • cartridge 120 is disposable, and is thrown away after the doses in all of packets 122 have been exhausted, whereas the inhalation device with control and power electronics is reused indefinitely
  • one of packets 122 is slid into an operating position inside the inhaler device.
  • Protective strips 134 and 136 are peeled away, uncovering air openings 141 and 143.
  • An alternating electrical current is driven through coils 128 and 158 on upper and lower walls 123 and 125, respectively, of the packet, via contacts 124. (For simplicity of illustration, the contacts for coils 158 are not shown in the figure.) As described hereinabove, the alternating current causes walls 123 and 125 to vibrate, thereby deaggregating the powder
  • a transducer 130 serves as a vibration sensor, generating signals responsive to the vibration of wall 123, which signals are received via contacts 132 by a controller of the inhalation device, such as control unit 40 of device 20
  • the transducer signals are used in controlling the alternating current applied to the coils, most preferably to adjust the frequency of the current so as to maximize the energy of wall vibration, as described further hereinbelow
  • transducer 130 comprises a pick-up coil, in which a current flows responsive to movement of the coil in the external magnetic field applied to packet 122, for example, by magnets 36 and 38
  • transducer 130 may comprise an accelerometer or a microphone, which senses acoustic radiation produced by vibration of the walls of the packet (in which case the transducer may also be positioned adjacent to, rather than on, wall 123).
  • Cartridge 120 is advantageous in that it allows multiple doses to be dispensed in succession, conveniently and reliably. Other cartridge shapes and configurations may similarly be used for this purpose.
  • packets may be a
  • Figs. 8 and 9 schematically illustrate circuitry and methods used in automatically tracking dosage administered by an inhaler device, in accordance with a preferred embodiment of the present invention.
  • Fig. 8 is a block diagram of circuitry used for this purpose
  • Fig. 9 is a flow chart illustrating the tracking method.
  • the circuitry and method are preferably, although not necessarily, used in conjunction with a multi-dose cartridge, such as cartridge 120 shown in Fig. 7.
  • a cell presence detector 160 detects that the packet is properly positioned in a dispensing position in the inhaler device.
  • Detector 160 preferably detects an electrical resistance between contacts 124 or 132 on the packet and, assuming the resistance to be within a predetermined range, notifies control unit 40 of the presence of the packet.
  • detector 160 may detect a short circuit between suitable, dedicated terminals on the packet (not shown in the figures). Further alternatively, detector 160 may sense the position of packet 122 mechanically or optically, using sensing methods known in the art.
  • control unit 40 determines that the packet is suitably positioned, it enables the inhaler device to operate.
  • the device is then actuated by means of operational keys 164 and/or by a flow sensor (not shown), so as to apply electrical current to coils 128 and 158.
  • electrostatic valve screens are applied at openings 141 and 143, as described hereinabove, to keep the powder in the packet until it is inhaled by the patient.
  • a dose counter 162 typically comprising a memory segment associated with control unit 40, is incremented to record that the medication was administered.
  • the time and date of the dose as provided by a real-time clock 168, are also recorded in the memory.
  • control unit 40 waits for detector 160 to indicate that a new packet 122 has been moved into position before allowing the device to be actuated again.
  • Fig. 10 is a block diagram that schematically illustrates circuitry used in controlling the frequency of the electrical current applied to coils 128 and 158, in accordance with a prefe ⁇ ed embodiment of the present invention
  • the purpose of controlUng the frequency is typically to maximize the vibrational energy of walls 123 and 125 for a given input power to the coils Such maximal energy is generally achieved when the frequency is such that the walls vibrate at a mechanical resonant frequency thereof
  • the resonant frequency may vary from packet to packet or from cartridge to cartridge as a result of differences in the dimensions and materials of the packets
  • the circuitry of Fig 10 is useful in adjusting the frequency for each packet It will be understood that such circuitry may be applied, as well, to drive the coils of packet 22, shown in Figs 1 and 2
  • Control unit 40 receives signals from transducer 130, indicative of the amplitude and frequency of vibration of the wall of packet 122
  • the signals are processed to determine the energy of vibration of the wall, which is generally maximal when the wall is d ⁇ ven to vibrate at its mechanical resonant frequency, as noted above
  • the control umt vanes the frequency of an oscillator 170 (which may also be implemented in software running on the control umt itself), which frequency is supplied to a d ⁇ ver amplifier 172, coupled to coil 128 As the frequency is swept through the resonant frequency of the wall, the control umt detects a corresponding peak m the vibrational energy sensed by sensor 130 and locks onto the peak frequency
  • Fig 11 is a block diagram that schematically illustrates a circuit for use in controlling the frequency of the current applied to coils 128 and 158, in accordance with another preferred embodiment of the present invention
  • transducer 130 and d ⁇ ver amplifier 172 are included in a positive feedback loop, coupled by a phase compensation network, as is known in the art
  • the loop tends to oscillate at a resonant frequency that is determined by the resonant vibration frequency of wall 123, since at this frequency the output signal of transducer 130 is typically maximized
  • maximal vibration of the walls of packet 122 (or, similarly, of packet 22) is achieved without the need for active frequency control by control umt 40
  • Fig 12 is a schematic, sectional illustration of a powder package 180, in accordance with another preferred embodiment of the present invention
  • the package has the form of a blister pack, for ease of manufacture, formed from an upper layer 182 and a lower layer 184 of a suitable plastic material
  • a p ⁇ nted circuit coil 190 is formed on an outer surface of package 180 at one end thereof, which end is positioned between magnets 36 and 38. The other end of the package is held in a holding clip 188.
  • FIG. 13 is a schematic, sectional illustration of a powder inhaler device 200, in accordance with a preferred embodiment of the present invention.
  • Device 200 comprises a base 201, which contains a source of mechanical energy, in this case a motor 202.
  • the motor is powered by a battery 203 and is actuated by a user-operated switch 204.
  • An air flow guide 211 mates with base 201 at a connection joint 212.
  • an oscillating powder container assembly 206 holds a powder which is administered to a patient when the patient places a proximal end 213 of the guide in his or her mouth and inhales.
  • container assembly 206 and guide 211 are disposable elements.
  • Assembly 206 is mounted to rotate back and forth about a joint 208. The rotation is induced by contact between an eccentric impactor 205, which is driven by motor 202, and a distal region 210 of the container assembly. Powder for administration to the patient is held in a pocket 207. Motor 202 drives impactor 205 to rotate, so that the impactor contacts region 210 periodically. The motion of the impactor striking the container assembly causes the assembly to oscillate about joint 208 at a resonant frequency that is determined by the mass and other mechanical properties of the assembly.
  • assembly 206 includes a flexible portion 209, which enhances the resonant oscillation. Oscillation of assembly 206 deaggregates and mobilizes the powder in pocket 207.
  • Fig. 14 is a schematic end view of impactor 205, in accordance with a preferred embodiment of the present invention.
  • the impactor has an asymmetric protrusion 220, which strikes region 210 as the impactor rotates, thus imparting mechanical energy to assembly 206.
  • Contact between protrusion 220 and region 210 causes assembly 206 to rotate about joint 208 in a counterclockwise direction (in the view of Fig. 13), so that region 210 moves away from impactor 205.
  • the force of gravity then causes assembly 206 to rotate back clockwise, at the resonant oscillatory frequency of the assembly, so that region 210 again contacts the impactor and is struck by protrusion 220.
  • the force of counter-rotation is enhanced by mechanical deformation of assembly 206 (particularly of portion 209 of the assembly).
  • device 200 may be configured so that other forces contribute to the counter-rotation of assembly 206, including air pressure changes within guide 211, as described below.
  • the resonant frequency of assembly 206 is in the range of 50 to 500 Hz.
  • Impactor 205 preferably moves at a frequency between 100 Hz and 20 kHz. (Although the higher speeds in this range may not be practical using a rotating impactor driven by a miniature motor, as shown in Figs. 13 and 14, these high speeds can be attained using impactors of other types, such as electromagnetic or piezoelectric oscillating elements.)
  • the frequency of motion of impactor 205 is preferably chosen to be substantially greater than the resonant frequency of assembly 206. As a result, every time region 210 moves in toward the impactor, the impactor strikes and imparts energy to the region.
  • motor 202 and impactor 205 may be arranged so as to cause vibration of device 200 as a whole, thereby deaggregating the powder in the container assembly. Such vibration may be induced, for example, by an intentional imbalance of the impactor.
  • Fig. 13 it will be observed that when the patient inhales through proximal end 213 of guide 211, air flows into the guide through an inlet 214.
  • the air flows over pocket 207 so as to carry the powder into the patient's mouth.
  • the inlet is positioned and configured so that the air flow also exerts pressure on assembly 206, driving region 210 against impactor 205 with increased force.
  • the container assembly oscillates with increased amplitude while the patient inhales.
  • device 200 is designed so that while the air inside guide 21 1 is still, assembly 206 oscillates at a relatively low amplitude, which is only sufficient to deaggregate the powder in the container assembly.
  • the inherent oscillation of the container assembly (before the patient inhales) is sufficient to aerosolize the powder, but the powder remains sealed within the device until the patient actually inhales
  • an electrostatic valve screen is used for this purpose, as described above
  • a mechamcal seal can be used to retain the powder inside the device The patient's inhalation provides the force needed to overcome the seal or, alternatively, triggers another mechamsm that releases the seal

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  • Medicinal Preparation (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

L'invention concerne un dispositif (20) d'inhalation servant à administrer une poudre sèche (66) à un patient. Le dispositif comprend un conditionnement (22) contenant une dose de la poudre sèche, et un générateur (36, 38) de champ magnétique qui produit un champ magnétique à proximité du conditionnement. Le champ magnétique provoque un déplacement des particules de poudre qui désagrège la poudre dans le conditionnement ; la poudre est ensuite inhalée par le patient. De préférence, le conditionnement comprend des parois (23, 25) faites d'une matière flexible, qui vibrent sous l'action du champ magnétique de manière à imprimer ce mouvement aux particules.
EP00976224A 1999-11-18 2000-11-15 Dispositif d'inhalation de poudre Withdrawn EP1237605A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IL13303199A IL133031A0 (en) 1999-06-04 1999-11-18 Powder inhaler
IL13303199 1999-11-18
PCT/IL2000/000753 WO2001036015A2 (fr) 1999-06-04 2000-11-15 Dispositif d'inhalation de poudre

Publications (2)

Publication Number Publication Date
EP1237605A2 true EP1237605A2 (fr) 2002-09-11
EP1237605A4 EP1237605A4 (fr) 2003-10-22

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP00976224A Withdrawn EP1237605A4 (fr) 1999-11-18 2000-11-15 Dispositif d'inhalation de poudre

Country Status (1)

Country Link
EP (1) EP1237605A4 (fr)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3708933A1 (de) * 1987-03-19 1988-09-29 Heinrich Prof Dr Ing Reents Verfahren mit den dazu gehoerigen vorrichtungen zur dosierung feiner und fester werkstoff- und wirkstoffteilchen mit hilfe schwingungserzeugender systeme
US5558085A (en) * 1993-01-29 1996-09-24 Aradigm Corporation Intrapulmonary delivery of peptide drugs
US5694920A (en) * 1996-01-25 1997-12-09 Abrams; Andrew L. Inhalation device

Also Published As

Publication number Publication date
EP1237605A4 (fr) 2003-10-22

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