US20040216738A1 - Inhalation device and method - Google Patents

Inhalation device and method Download PDF

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Publication number
US20040216738A1
US20040216738A1 US10/771,525 US77152504A US2004216738A1 US 20040216738 A1 US20040216738 A1 US 20040216738A1 US 77152504 A US77152504 A US 77152504A US 2004216738 A1 US2004216738 A1 US 2004216738A1
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United States
Prior art keywords
indicator
casing
indicating
coupled
chamber
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.)
Abandoned
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US10/771,525
Inventor
David Edwards
Colleen Conlon
David Foshee
Jason Durkin
Tim Coker
Kevin Stapleton
Sarah Dreesen
Mark DeLong
Andrew Jones
Ryan McManus
Margaret Saunders
Robert Spaller
Andrew Ziegler
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.)
CORREGIDOR THERAPEUTICS Inc
Advanced Inhalation Research Inc
Civitas Therapeutics Inc
Original Assignee
Advanced Inhalation Research Inc
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Publication date
Application filed by Advanced Inhalation Research Inc filed Critical Advanced Inhalation Research Inc
Priority to US10/771,525 priority Critical patent/US20040216738A1/en
Publication of US20040216738A1 publication Critical patent/US20040216738A1/en
Assigned to CORREGIDOR THERAPEUTICS, INC. reassignment CORREGIDOR THERAPEUTICS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ALKERMES, INC.
Assigned to CIVITAS THERAPEUTICS, INC. reassignment CIVITAS THERAPEUTICS, INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: CORREGIDOR THERAPEUTICS, INC.
Abandoned legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00Inhalators
    • A61M15/0028Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/001Particle size control
    • A61M11/003Particle size control by passing the aerosol trough sieves or filters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00Inhalators
    • A61M15/0028Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/003Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A61M15/0033Details of the piercing or cutting means
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00Inhalators
    • A61M15/0028Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/003Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A61M15/0033Details of the piercing or cutting means
    • A61M15/0035Piercing means
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00Inhalators
    • A61M15/0028Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/003Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A61M15/0033Details of the piercing or cutting means
    • A61M15/0041Details of the piercing or cutting means with movable piercing or cutting means
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/06Solids
    • A61M2202/064Powder

Definitions

  • the present invention relates generally to facilitating release of powder contained in a receptacle. More specifically, the present invention relates to the administration of medication by a method and apparatus for facilitating inhalation of powder medicaments.
  • Each of these medications comes in a variety of forms, including fluids, which are commonly administered as an aerosol vapor or mist, as well as solids.
  • Inhalable solids typically take the form of fine, dry powders.
  • Specialized devices, such as inhalers, are provided to assist the patient in directing these fine powder medications into the respiratory tract.
  • U.S. Pat. No. 5,787,881 discloses an inhaler that is used with encapsulated dry powder medicaments.
  • use of this device requires numerous steps and imposes a number of inconveniences on a user.
  • the medication capsules used with the device have an aperture formed therein prior to insertion into an opening in the inhaler. Therefore, there exists a danger that an amount of medication may be lost prior to or during insertion into the device. After insertion of the capsule, use of the device requires the additional step that a cover must be closed before the medication may be inhaled.
  • Inhalation devices configured for use with a capsule containing some type of medicament are shown in U.S. Pat. No. 4,069,819 to Valentini et al. (“the '819 patent”) and U.S. Pat. No. 4,995,385 to Valentini et al. (“the '385 patent”).
  • the inhalation device described in the '385 patent was developed to overcome the drawbacks of the device described in the '819 patent. Particularly, in a large number of cases, the device described in the '819 patent experienced irregular and incomplete emptying of the capsule, thereby resulting in difficulties in properly administering the medicament in the capsule.
  • the inhalation device described in the '385 patent attempts to overcome this deficiency by tapering the nebulization chamber toward the end surface that comprises the discharge holes.
  • the nebulization chamber of the '385 patent is not cylindrical, but rather frusto-conical in form in an attempt to achieve regular complete emptying of the nebulization chamber.
  • emitted dose refers to the percentage of the dose of powder medicament that is emitted from a receptacle in the inhalation device.
  • the dispersal of the powder can be quantified by measuring the volume mean geometric diameter (VMGD) of the emitted powder.
  • volume mean geometric diameter refers to the average geometric diameter of the powder.
  • “resistance” refers to the square root of the pressure gradient across the inhaler divided by the peak inspiratory flow rate through the inhaler.
  • “low peak inspiratory flow rate” refers to a peak inspiratory flow rate of approximately 25 L/min or less. Moreover, improvements are needed to achieve high emitted doses and highly dispersed powders that are consistently reproducible, i.e., that have a low standard deviation of emitted dose percentage and VMGD, respectively.
  • FIG. 1 Another drawback of the inhalation devices described in the '819 and the '385 patents is the piercing device that is used to puncture the capsule.
  • Such conventional piercing devices are formed from circular stock, with the points created by pinching the stock at an angle, thereby creating a single sharp cutting edge.
  • Drawbacks of such a design are that the point (which must puncture the capsule material) is often rounded, lessening its effectiveness as a piercing device.
  • burrs often form on the lower edge, which can stop the piercing device from retracting from the capsule, thereby causing a device failure.
  • the holes formed by such a conventional piercing device are generally round, and do not have the appearance of being cut by a sharp edge.
  • the present invention relates to a method and apparatus for facilitating release of powder from a device.
  • a device for emitting powder includes a first casing portion, and a second casing portion removably coupled to the first casing portion.
  • a cylindrical chamber defined by a straight wall of circular cross section, is coupled to the first casing portion.
  • the chamber has a proximal end and a distal end.
  • a ring is circumferentially coupled to an inner surface of the chamber.
  • the ring is preferably disposed at approximately a midpoint of the chamber, or, alternatively, disposed adjacent the proximal end of the chamber.
  • the second casing portion includes an emitter portion disposed at the proximal end of the chamber when the first and second casing portions are coupled together.
  • the emitter portion defines at least one aperture configured to emit powder therethrough.
  • the device is configured as an inhalation device for administering powder.
  • the emitter portion is configured as an inhalation portion so that powder is dispersed in the chamber and administered to a user through the inhalation portion.
  • the inhalation portion may be configured as a mouth piece for inhalation through the mouth, or as a nose piece for inhalation through the nose.
  • One aspect of the invention comprises an optimized configuration of a device for administering powder that comprises a chamber defined by a wall and configured to hold a receptacle containing a powder, the wall defining a plurality of vents, and the inhalation device further comprising an inhalation portion defining at least one aperture for emitting powder therethrough.
  • the inhalation device is configured to have a resistance of at most 0.28 (cm H 2 O) 1/2 /L/min and to provide an emitted dose of at least 85% when the dose of powder is up to 20 mg and when the device is operated at a peak inspiratory flow rate of 25 L/min or less and at an inhalation volume of 0.75 L or less.
  • the standard deviation of the emitted dose is 10% or less.
  • the device of the present invention is configured to cause the emitted powder to be highly dispersed.
  • “highly dispersed” is meant that the VMGD of the emitted powder is substantially similar to the VMGD of the powder contained in the receptacle.
  • Highly dispersible powders have a low tendency to agglomerate, aggregate or clump together and/or, if agglomerated, aggregated or clumped together, are easily dispersed or de-agglomerated as they emit from an inhaler and are breathed in by the subject.
  • the highly dispersible particles suitable in the methods of the invention display very low aggregation compared to standard micronized powders which have similar aerodynamic diameters and which are suitable for delivery to the pulmonary system.
  • Properties that enhance dispersibility include, for example, particle charge, surface roughness, surface chemistry, relatively large geometric diameters, and the configuration of the device used to dispense the powder.
  • the powder is contained in a receptacle that is disposed in the chamber. Upon puncturing the receptacle, powder is dispersed in the chamber and emitted or inhaled from the device.
  • the device of the present invention includes means for puncturing the receptacle.
  • the means for puncturing can be configured as a staple.
  • a staple is preferably configured in a substantially U-shape, having two prongs.
  • each of the prongs has a square cross-section.
  • the substantially U-shaped staple includes a rounded portion and two prongs that define a non-planar inner edge and a non-planar outer edge of the staple, the staple being formed from a rectangular length having two end surfaces and four planar side surfaces that intersect to form four non-planar edges.
  • the inner edge of the staple is configured to be one of the non-planar edges, and the outer edge of the staple is the non-planar edge that is opposite that non-planar edge.
  • Each end surface is an angled diamond-shaped surface. In a preferred aspect, each end surface has a top point at an apex of the inner edge, and a bottom point at an apex of the outer edge, each top point forming a cutting point for one of the prongs.
  • the puncturing means can be configured as a substantially longitudinal prong comprising a puncturing surface on the distal end of the prong, a primary cutting surface running from the proximal end to the distal end of the prong and terminating at the puncturing surface, and a substantially planar face opposite to the primary cutting edge and running from the proximal end to the distal end of the prong.
  • the puncturing means comprises a substantially longitudinal prong comprising a puncturing surface on the distal end, a primary cutting surface terminating at the puncturing surface, and a face opposite to the primary cutting edge, wherein the prong is configured to create an opening in a wall by forming a hanging chad in the wall, the hanging chad having a free end formed by the puncturing surface and the primary cutting edge and a hinge coupled to the wall formed by the face.
  • the prong is configured to form a hanging chad in a wall of the receptacle having a longitudinal axis substantially parallel to the prong and a minor axis substantially perpendicular to the longitudinal axis, the hanging chad being opened to an angle of at least 30 to 45 degrees with respect to the minor axis of the receptacle.
  • the prong is configured so that at least 3 ⁇ 4 of the length of the prong can be inserted into a receptacle without breaking off chads in the receptacle.
  • the prong preferably has an angled surface at the distal end, the surface having a distal end terminating at the puncturing surface and a proximal end terminating at the substantially planar face.
  • the prong preferably is tapered, so that its distal end is smaller than its proximal end, to facilitate removing the prong from the receptacle.
  • the prong also preferably has a plurality of longitudinal faces and a plurality of longitudinal edges running from the proximal end to the distal end of the prong.
  • the cross section of the prong is a pentagon.
  • the width of the substantially planar face may be very small and the four longitudinal faces may be substantially at right angles to each other so that the prong has substantially a diamond shaped cross section.
  • the cross section of the prong is a triangle.
  • the puncturing means comprises one or more of the longitudinal prongs coupled to a base, preferably in a U-shape.
  • any of these embodiments of the longitudinal prongs may be coupled to the device for administering powder.
  • a method for dispensing powder by inhalation comprises
  • a cylindrical chamber defined by a straight wall of circular cross-section, coupled to said first casing portion, said chamber having a proximal end and a distal end and configured to receive a receptacle therein, said chamber comprising a ring circumferentially coupled to an inner surface of said chamber, and
  • a second casing portion removably coupled to said first casing portion, said second casing portion comprising an inhalation portion disposed at the proximal end of said chamber when said first and said second casing portions are coupled, said inhalation portion comprising a hemispheric region defining a plurality of apertures configured to emit powder therethrough;
  • the inhaling step is carried out by inhaling the powder through a mouthpiece into a user's mouth.
  • the inhaling step may be carried out by inhaling the powder through a nose piece into a user's nose.
  • the present invention also encompasses an indicating device comprising a body disposed within a casing and reversibly moveable between a first and a second position, an indicator moveable between a rest position and an indicating position, and a means for coupling the body and the indicator, wherein upon a first movement of the body from the first position to the second position, the means for coupling couples the body and the indicator, and upon a second movement of the body from the second position to the first position, the indicator moves from the rest position to the indicating position.
  • the present invention encompasses an indicating device comprising a body disposed within a casing and reversibly moveable between a first position and a second position, an indicator reversibly moveable between a rest position and an indicating position, a lip coupled to the indicator and a flange coupled to the body for engaging the lip, wherein upon a first movement of the body from the first position to the second position, the flange engages the lip, and upon a second movement of the body from the second position to the first position, the engagement of the lip and the flange causes the indicator to move from the rest position to the indicating position.
  • the invention further encompasses one of the previously described embodiments of a device for emitting powder comprising a means for indicating readiness of the device for emitting powder.
  • the means for indicating readiness of the device for emitting powder may comprise one of the previously described embodiments of an indicating device.
  • the invention comprises a method for indicating the readiness of a device for emitting a medicament.
  • a method for indicating the readiness of a device for emitting a medicament comprises
  • a device for dispensing a medicament comprising a casing comprising at least one aperture configured to emit powder therethrough, a body coupled to said casing and reversibly moveable between a first position and a second position, and an indicator coupled to said casing and reversibly moveable between a rest position and an indicating position;
  • the invention further comprises a method for indicating that a device for dispensing a medicament has been used.
  • a method for indicating that a device for dispensing a medicament has been used comprises
  • a device for dispensing a medicament comprising a casing comprising at least one aperture configured to emit a medicament therethrough, a body coupled to said casing and reversibly moveable between a first position and a second position, and an indicator coupled to said casing and reversibly moveable between a rest position and an indicating position;
  • One feature of the present invention is that it provides, in a low resistance inhaler with a highly dispersed powder, high emitted doses that are consistently reproducible over a range of peak inspiratory flow rates, inhalation volumes and dosage quantities.
  • the present invention improves and optimizes the emitted dose at low peak inspiratory flow rates, low inhalation volumes, and high dose ranges.
  • a particularly advantageous feature of the present invention is its ability to operate at low peak inspiratory flow rates, such as would be associated with a child, an elderly person, or a person with a respiratory disease, such as chronic obstructive pulmonary disease (COPD).
  • COPD chronic obstructive pulmonary disease
  • One advantage of the present invention is that the means for puncturing used in the device is less expensive to manufacture than conventional piercing devices.
  • Advantages of the injection molding manufacturing process used for the puncturing means include reliability, reproducibility, and design flexibility, such as the ability to make a wide variety of shapes and sizes of longitudinal prongs.
  • larger longitudinal prongs of the present invention can create larger openings in the receptacles than conventional piercing devices, which allows for higher emitted doses at low peak inspiratory flow rates, low volumes, and high dosage quantities.
  • Another advantage of the present invention is that at least one configuration of the puncturing means facilitates forming a hanging chad in the wall of the receptacle, with an opening of at least 30 to 45 degrees, to facilitate more efficient removal of powder from the receptacle and, thus, higher emitted doses than could be achieved with conventional piercing devices.
  • the means for puncturing of the present invention advantageously provides improved puncturing performance since less force is needed to puncture the receptacles, and fewer failures result than with conventional piercing devices.
  • the prongs are shaped for easy removal from the receptacle without breaking off the hanging chad formed in the wall of the receptacle.
  • Another advantage of the preferred means for puncturing is an improvement to the emitted dose rate of the inhaler.
  • the puncturing means improves the powder flow from the receptacle by increasing the size of the holes in the receptacle.
  • the puncturing means improves the peak inspiratory flow rate by opening a hanging chad in the wall of the receptacle to an angle of at least 30 to 45 degrees with respect to the wall of the receptacle. Consequently, the emitted dose of the powdered medicament delivered to a patient will be independent of how fast the patient breathes, thereby ensuring that a consistent dose of medicament is delivered each time.
  • Another advantageous feature of the present invention is the accuracy of medicament dosage delivered thereby.
  • the puncturing means allows for a greater range of puncturing depths without breaking off the chads formed in the receptacle, allowing for greater optimization of the inhaler.
  • the inhaler operates only under the inhalative power of the patient, the inhaler carries the additional advantage that no accessory device, such as a compressed air cylinder or other propellant, needs to be used in conjunction with the present invention.
  • Another advantage of the present invention is that during inhalation, the medicament is subjected to mixing in the dispersion chamber. This helps to ensure that the medicament exiting the inhaler and entering the patient's respiratory system is in the form of a fine dry powder, facilitating medicament deposition in the lungs. In addition, inhalation of finer powders is typically more comfortable for the patient.
  • Still another advantage of the present invention is that it can be used with individuals who cannot breathe hard, such as a child, an elderly person, or a person suffering from a respiratory disease, such as asthma, or individuals who are sleeping or in a coma.
  • Yet another advantage of the apparatus of the present invention is that it is reusable. To reuse, a patient removes the emptied receptacle, and replaces it with a fresh receptacle filled with the proper dose of medicament.
  • Another advantage of the present invention is that it includes a means for indicating when a device for emitting powder is ready for inhalation.
  • a means for indicating informs the user when the device is ready for use and/or when the device needs to be refilled or discarded.
  • the means for indicating could be used with a device for emitting fluticasone propionate (used to treat asthma) to indicate that the device is ready for inhalation.
  • the means for indicating could be used with an epinephrine pen for treating allergies to indicate that the pen has been used.
  • the means for indicating preferably makes an audible click so that a user will know when the device has been properly actuated.
  • the means for indicating is easy to manufacture and use.
  • FIG. 1 is a front view of one embodiment of a device of the present invention
  • FIG. 2 is a cross-section of the device shown in FIG. 1 along line 2 - 2 ;
  • FIG. 3 is an enlarged partial cross-section of one embodiment of a dispersion chamber of the present invention.
  • FIG. 4 is an enlarged partial cross-section of another embodiment of a dispersion chamber of the present invention showing one location for a ring in the dispersion chamber;
  • FIG. 5 is an enlarged partial cross-section of another embodiment of a dispersion chamber of the present invention showing another location for a ring in the dispersion chamber;
  • FIG. 6 is an enlarged partial cross-section of another embodiment of a dispersion chamber of the present invention showing another location for a ring in the dispersion chamber;
  • FIG. 7A is a top view of a preferred embodiment of a staple suitable for use with the device of the present invention.
  • FIG. 7B is a front view of the embodiment shown in FIG. 7A;
  • FIG. 7C is a side view of the embodiment shown in FIG. 7A;
  • FIG. 7D is an isometric view of the embodiment shown in FIG. 7A;
  • FIG. 8 shows the puncture obtained with the staple shown in FIGS. 7A through 7D;
  • FIG. 9A shows a partial view of another embodiment of a staple suitable for use with the device of the present invention.
  • FIG. 9B illustrates the puncture obtained with the staple shown in FIG. 9A
  • FIG. 10 is a bar graph illustrating emitted dose at peak inspiratory flow rates of 20 L/min (left bar), 40 L/min (center bar), and 60 L/min (right bar) for four dispersion chamber configurations;
  • FIG. 11 is a bar graph illustrating emitted dose at low peak inspiratory flow rates for devices with varying numbers of vents
  • FIG. 12 is a bar graph showing a comparison of mass fraction distributions obtained for 6 mg (left bar) and 50 mg (right bar) fill weights;
  • FIG. 13 is a graph showing glucose levels (mg/dL) in beagle dogs after administration of insulin using an aerosol generator and a device of the present invention with the low ring configuration substantially as shown in FIG. 4;
  • FIG. 14 is a bar graph illustrating the percentage emitted dose as a function of air volume.
  • FIG. 15 is an exploded cross-sectional view of an alternate embodiment of a device of the present invention.
  • FIG. 16A is a perspective view of an alternative embodiment of a puncturing device suitable for use with the present invention.
  • FIG. 16B is a front view of the puncturing device shown in FIG. 16A.
  • FIG. 16C is a side view of the puncturing device shown in FIG. 16A.
  • FIG. 16D is a top view of the puncturing device shown in FIG. 16A.
  • FIGS. 17A-17C are schematic diagrams of one of the prongs of the puncturing device shown in FIGS. 16 A-D being used to puncture a receptacle and create a hanging chad therein.
  • FIG. 18 is a front cross-sectional view of an alternative embodiment of the device for administering powder comprising a means for indicating the readiness of the device.
  • FIGS. 19A-19C are enlarged partial cross-sectional views of a preferred embodiment of the means for indicating readiness of the device.
  • the present invention provides an improved method and apparatus for facilitating release of powder.
  • the powder is contained in a receptacle.
  • receptacle includes but is not limited to, for example, a capsule, blister, film covered container well, chamber, and other suitable means of storing a powder known to those skilled in the art.
  • the present invention will be described below in the context of a method and apparatus for dispensing dry powder medicaments for inhalation by a patient. However, it should be apparent to one skilled in the art that the invention is not limited to such an exemplary embodiment, and could be used for other purposes.
  • an apparatus of the present invention is an inhaler that includes a chamber.
  • the chamber is configured to receive the receptacle containing the medicament.
  • the chamber includes a ring circumferentially coupled to an inner surface of the chamber. The ring is preferably disposed at approximately a midpoint of the chamber, or alternatively, adjacent the proximal end of the chamber. In proper use, air will exit the inhaler carrying a full dose of medicament in the form of a fine, dry powder.
  • Another aspect of the present invention is an optimized chamber configured to have a resistance of at most 0.28 (cm H 2 O) 1/2 /L/min and to provide an emitted dose of at least 85% when the dose of powder is up to 20 mg and when the device is operated at a peak inspiratory flow rate of 25 L/min or less and at an inhalation volume of 0.75 L or less.
  • the inhaler of the present invention is preferably configured with a means for puncturing the receptacle that improves puncturing performance, particularly with brittle receptacle material.
  • the means for puncturing the receptacle of the present invention is configured as a substantially U-shaped staple with two prongs, each prong having a sharp point and two cutting edges.
  • each prong has a square cross-section, with the staple material being bent around a face so that the innermost part of the U-shaped staple is flat.
  • the staple material is rotated 45 degrees so that it is bent around an edge so that the innermost part of the U-shaped staple is an edge.
  • the end surface of each prong is an angled diamond-shaped surface.
  • the means for puncturing the receptacle is configured as a substantially longitudinal prong comprising a puncturing surface on the distal end, a primary cutting surface running from the proximal end to the distal end of the prong and terminating at the puncturing surface, and a substantially planar face opposite to the primary cutting edge and running from the proximal end to the distal end of the prong.
  • the prong preferably has an angled surface at the distal end, the angled surface having a distal end terminating at the puncturing surface and a proximal end terminating at the substantially planar face.
  • the prong is preferably tapered so that the distal end is smaller than the proximal end, to facilitate removing the prong from a receptacle.
  • the prong also preferably has a plurality of longitudinal faces and a plurality of longitudinal edges running from the proximal end to the distal end of the prong.
  • the prong is configured to create an opening in a wall by forming a hanging chad in the wall, the hanging chad having a free end formed by the puncturing surface and the primary cutting edge and a hinge coupled to the wall formed by the face.
  • the prong is configured to open the hanging chad to an angle of at least 30 to 45 degrees between the minor axis of the receptacle and the hanging chad, wherein the minor axis is substantially perpendicular to a longitudinal axis of the receptacle, which is substantially parallel to the longitudinal prong.
  • the methods of the present invention use an inhaler to dispense powder by inhalation.
  • a user operates the device to puncture the receptacle to disperse powder in the chamber, and inhales the powder through the inhalation portion.
  • the present invention further encompasses a means for indicating readiness coupled to a device for administering powder.
  • FIG. 1 A front view of one embodiment of an inhalation device 100 of the present invention is shown in FIG. 1.
  • the rear view of device 100 is substantially identical to the front view.
  • Device 100 includes a first or lower casing portion 120 and a second or upper casing portion 130 removably coupled to first casing portion 120 .
  • Upper casing portion 130 and lower casing portion 120 include a flattened region 132 and 122 , respectively, for ease of gripping the casing for use by a patient.
  • Lower casing portion 120 preferably includes an outer casing 126 and an inner casing 124 movably received within outer casing 126 .
  • a removable cap 110 is provided at the user or inhalation end of the device.
  • Preferred materials for device 100 include Food and Drug Administration (FDA) approved, USP tested plastics.
  • FDA Food and Drug Administration
  • device 100 is manufactured using an injection molding process, the details of which would be readily apparent to one skilled in the art.
  • FIG. 2 is a cross-section of device 100 shown in FIG. 1 along line 2 - 2 .
  • device 100 includes an inhalation or emitter portion 220 .
  • Inhalation portion 220 comprises a hemispheric region 222 that defines a plurality of apertures 224 .
  • An inhalation piece 226 is provided to allow for inhalation of the medicament by a user.
  • Inhalation piece 226 can be configured as a mouth piece for inhalation through a user's mouth.
  • inhalation piece 226 can be configured as a nose piece for inhalation through a user's nose.
  • Device 100 includes a cylindrical chamber 210 that is defined by a straight wall 212 of circular cross-section.
  • Chamber 210 has a proximal end 214 and a distal end 216 .
  • a plurality of vents 218 are defined by wall 212 , and are configured for introducing air into chamber 210 to disperse powder released from a capsule 219 . It should be understood that the present invention is not limited to a particular number of vents 218 , and can be configured such that at least one vent 218 is provided. Powder released from capsule 219 is dispersed in chamber 210 and inhaled through apertures 224 and inhalation piece 226 by the user.
  • receptacles other than capsules are used, such as blisters and film covered container wells as is known in the art.
  • the volume of the receptacle is at least about 0.37 cm 3 .
  • the volume of the receptacle is at least about 0.48 cm 3 .
  • the receptacles have a volume of at least about 0.67 cm 3 or 0.95 cm 3 .
  • the receptacle is a capsule designated with a capsule size 2, 1, 0, 00, or 000. Suitable capsules can be obtained, for example, from Shionogi (Rockville, Md.).
  • Blisters can be obtained, for example, from Hueck Foils, (Wall, N.J.).
  • the receptacle encloses or stores particles, also referred to herein as powders.
  • the receptacle is filled with particles in a manner known to one skilled in the art. For example, vacuum filling or tamping technologies may be used. Generally, filling the receptacle with powder can be carried out by methods known in the art.
  • the particle or powder enclosed or stored in the receptacle have a mass of at least about 5 milligrams (mg). In another embodiment, the mass of the particles stored or enclosed in the receptacle is at least about 10 mg, and up to approximately 50 mg. In a preferred embodiment, the mass of the particles is approximately 20 mg.
  • particles used with the device have a tap density of less than about 0.4 g/cm 3 .
  • Particles having a tap density of less than about 0.4 g/cm 3 are referred to herein as “aerodynamically light”.
  • the particles have a tap density of near to or less than about 0.1 g/cm 3 .
  • Tap density is a measure of the envelope mass density characterizing a particle.
  • the envelope mass density of particles of a statistically isotropic shape is defined as the mass of the particle divided by the minimum sphere envelope volume within which it can be enclosed.
  • Features that can contribute to low tap density include irregular surface texture and hollow or porous structure. Particularly preferred particles and powders are described in U.S. Pat.
  • Device 100 includes a means for puncturing 230 that is used to puncture capsule 219 to release powder contained therein into chamber 210 .
  • means for puncturing 230 is configured as a substantially U-shaped staple having two prongs 232 .
  • each of prongs 232 is configured with a square cross-section 234 , thereby providing a sharp point and two cutting edges. This will be discussed in more detail below with respect to FIGS. 9A and 9B.
  • device 100 could alternatively be configured with the means for puncturing shown in FIGS. 7A through 7D.
  • device 100 could alternatively be configured with the means for puncturing shown in FIGS. 16A through 16D.
  • the present invention is not limited to these means for puncturing the capsule, described in detail below.
  • one, or a plurality of, straight needle-like implements could be used.
  • the means for puncturing is configured to puncture at least two holes in the capsule.
  • Means for puncturing 230 is preferably configured to be movable between a non-puncturing position (as depicted in FIG. 1) and a puncturing position. In the puncturing position, prongs 232 pierce or puncture capsule 219 to make holes therein.
  • a means for biasing is provided that biases the means for puncturing 230 in the non-puncturing position.
  • the means for biasing is configured as a spring 242 that biases the substantially U-shaped staple in the non-puncturing position.
  • device 100 includes inner casing 124 and outer casing 126 .
  • a spring 244 is disposed in lower casing portion 120 that biases inner casing 124 in an outward position.
  • inner casing 124 moves from the outward position to an inward position, thereby drawing lower casing portion 120 toward upper casing portion 130 .
  • Compression of spring 244 also causes compression of spring 242 , thereby causing means for puncturing 230 to move to the puncturing position.
  • springs 242 and 244 return to their biased state, thereby returning means for puncturing 230 to its non-puncturing position, and inner casing 124 to its outward position.
  • a pair of flanges 252 is disposed on first casing portion 120 .
  • a pair of grooves 254 is disposed on second casing portion 130 so that flanges 252 can be received within grooves 254 to thereby couple the first and second casing portions.
  • the first and second casing portions are coupled with a friction-fit engagement.
  • a friction-fit engagement can be achieved using the groove and flange arrangement depicted in FIG. 2.
  • Other alternative configurations for a friction-fit engagement would be readily apparent to one skilled in the art.
  • FIG. 3 is an enlarged partial cross-section of one embodiment of chamber 210 .
  • chamber 210 does not contain a ring disposed on an inner surface, and an inner diameter of chamber 210 is depicted as “X”.
  • X an inner diameter of chamber 210 is depicted as “X”.
  • Such a configuration may be referred to herein as a “straight” chamber configuration.
  • FIG. 4 is an enlarged partial cross-section of another embodiment of chamber 210 .
  • a ring 400 is circumferentially coupled to an inner surface of chamber 210 .
  • An inner diameter of ring 400 is depicted as “Y”, and is less than inner diameter X of chamber 210 .
  • ring 400 is disposed at approximately a midpoint of chamber 210 .
  • Such a configuration may be referred to herein as a “low” ring position or “low” chamber configuration.
  • ring 400 is disposed adjacent vents 218 .
  • the ring position is measured by the distance from the top of hemispheric region 222 to the bottom edge of ring 400 . This distance is depicted as “Z”.
  • the following dimensions are provided as exemplary dimensions of a device of the present invention. It should be understood by one skilled in the art that the present invention is not limited to the dimensions provided herein, or to any particular dimensions.
  • diameter X is 0.47 in.
  • diameter Y is 0.38 in.
  • distance Z is 0.49 in.
  • FIG. 6 is an enlarged partial cross-section of another embodiment of chamber 210 .
  • ring 400 is circumferentially coupled to an inner surface of chamber 210 .
  • An inner diameter of ring 400 is depicted as “Y”, and is less than inner diameter X of chamber 210 .
  • ring 400 is disposed adjacent the proximal end of chamber 210 .
  • Such a configuration may be referred to herein as a “high” ring position or a “high” chamber configuration.
  • the ring position is measured by the distance from the top of hemispheric region 222 to the bottom edge of ring 400 . This distance is depicted as “Z”.
  • diameter X is 0.47 in.
  • diameter Y is 0.38 in.
  • distance Z is 0.29 in.
  • FIG. 5 is an enlarged partial cross-section of another embodiment of chamber 210 .
  • ring 400 is circumferentially coupled to an inner surface of chamber 210 .
  • An inner diameter of ring 400 is depicted as “Y”, and is less than inner diameter X of chamber 210 .
  • ring 400 is disposed between the low ring position of FIG. 4 and the high ring position of FIG. 6.
  • Such a configuration may be referred to herein as a “mid” ring position or “mid” chamber configuration.
  • the ring position is measured by the distance from the top of hemispheric region 222 to the bottom edge of ring 400 . This distance is depicted as “Z”.
  • diameter X is 0.47 in.
  • diameter Y is 0.38 in.
  • distance Z is 0.39 in.
  • ring 400 is integral with chamber 210 .
  • ring 400 and chamber 210 are formed as a unit, such as through an injection molding, extrusion or a casting process.
  • ring 400 is attached to the inner surface of chamber 210 in a manner known to those skilled in the art, such as through the use of glue or other type of adhesive, or by using an attaching device such as a pin or screw, etc.
  • the casing of device 100 is made from a material that can be injection molded, such as a plastic material (preferably FDA approved, USP tested).
  • the material is preferably durable, easy to clean, and non-reactive with powder medicaments.
  • FIG. 15 An exploded cross-sectional view of an alternate embodiment of a device 1500 of the present invention is shown in FIG. 15.
  • Device 1500 includes a first or lower casing portion 1540 and a second or upper casing portion 1550 removably coupled to first casing portion 1540 .
  • First and second casing portions 1540 and 1550 are coupled through the use of a flange 1552 and a groove 1554 .
  • Preferred materials for device 1500 include Food and Drug Administration (FDA) approved, USP tested plastics.
  • FDA Food and Drug Administration
  • device 1500 is manufactured using an injection molding process, the details of which would be readily apparent to one skilled in the art.
  • Device 1500 includes an inhalation or emitter portion 1520 .
  • Inhalation portion 1520 comprises a hemispheric region 1522 that defines a plurality of apertures 1524 . It should be understood that the present invention is not limited to a particular number of apertures 1524 , and can be configured such that at least one aperture 1524 is provided.
  • An inhalation piece 1526 is provided to allow for inhalation of the medicament by a user.
  • Inhalation piece 1526 can be configured as a mouth piece for inhalation through a user's mouth.
  • inhalation piece 1526 can be configured as a nose piece for inhalation through a user's nose.
  • Device 1500 includes a cylindrical chamber 1510 that is defined by a straight wall 1512 of circular cross-section.
  • a plurality of vents 1518 are defined by wall 1512 , and are configured for introducing air into chamber 1510 to disperse powder released from, for example, capsule 219 as illustrated in FIG. 2. It should be understood that the present invention is not limited to a particular number of vents 1518 , and can be configured such that at least one vent 1518 is provided. Powder released from capsule 219 is dispersed in chamber 1510 and inhaled through apertures 1524 and inhalation piece 1526 by the user.
  • device 1500 can be configured with means for puncturing and means for biasing in a manner similar to that described above with respect to the embodiment shown in FIGS. 1 and 2. Means for puncturing are described in more detail below with respect to FIGS. 7A through 7D, 8 , 9 A- 9 B, 16 A- 16 D, and 17 A- 17 C. Moreover, device 1500 can be configured with the chamber designs described above with respect to FIGS. 3-6.
  • the peak inspiratory flow rates were measured with a flow meter.
  • the emitted dose measurement involved placing a capsule into four embodiments of the inhaler of the present invention for actuation into an emitted dose (ED) measurement apparatus.
  • the ED apparatus included a powder filter and a filter holder.
  • the powder collected by the ED apparatus was quantified by fluorescence spectrophotometry.
  • the straight configuration is shown in FIG.
  • the ring configuration of the present invention provides an improvement over conventional chamber designs without a ring, such as those shown in the '819 and '385 patents.
  • the low configuration produced a higher emitted dose and a lower standard deviation than the mid and high configurations.
  • FIG. 11 is a bar graph illustrating emitted dose at low peak inspiratory flow rates for devices with varying numbers of vents 218 . The measurements were taken at a flow rate of 5 L/min, with a volume of 67 cc and a 15 mg dosage. As show in FIG. 11, by decreasing the number of vents 218 , the emitted dose increases so that the device of the present invention successfully delivers a high emitted dose at a low peak inspiratory flow rate over multiple (ten) actuations. Thus, the device of the present invention achieves a high emitted dose at low peak inspiratory flow rates that is consistently reproducible with low standard deviation.
  • the ratio of the inner diameter of the ring to the inner diameter of the chamber is about 0.8.
  • inner diameter X of chamber 210 is 0.33 in. and inner diameter Y of ring 400 is 0.30 in.
  • the ratio of the inner diameter of the ring to the inner diameter of the chamber is about 0.9.
  • the ratio of the inner diameter of the ring to the inner diameter of the chamber is about 0.9 or less.
  • the device of the present invention can also be optimized for varying dosage ranges.
  • One way to do so is to vary the dimensions of chamber 210 to accommodate varying sizes of capsules.
  • a chamber having an inner diameter X of 0.33 in., inner diameter Y of 0.30 in., and distance Z of 0.57 in. can be used with size 2 and size 00 capsules.
  • chamber 210 can be scaled to accommodate varying capsule sizes, and to accommodate those capsule sizes at varying peak inspiratory flow rates.
  • the device of the present invention can be used with varying dosage ranges.
  • a highly dispersible powder was prepared and loaded into capsules to obtain a large pre-metered dose (50 mg) and a smaller pre-metered dose (6 mg).
  • the aerodynamic particle size distributions were characterized using a multistage liquid impinger that extracted air at 60 L/min after actuating the inhaler device (D). As shown in FIG.
  • FIG. 12 shows the results comparing the two particle size distributions obtained for the 6 mg (left bar) and 50 mg (right bar) doses.
  • ED used on the graph refers to emitted dose
  • FPM used on the graph refers to fine particle mass (estimate of the mass that would deposit in the lungs).
  • the fine particle fraction ⁇ 6.8 ⁇ m relative to the total dose (FPF TD ⁇ 6.8 ⁇ m) for the 6 and 50 mg doses were 74.4% and 75.0%, respectively. Similar aerodynamic particle size distributions were obtained for both doses.
  • FIG. 13 is a graph showing glucose (mg/dL) in beagle dogs after administration of human insulin using an aerosol generator and a device of the present invention with the low ring configuration substantially as shown in FIG. 4.
  • the generator is a device with proven ability for forming a respirable aerosol that results in deposition of powder in dog lungs. Metered powder is presented to a chamber where the powder is dispersed by a high velocity jet of air. The dispersed powder is directed toward a baffle to separate large agglomerates before inhalation by the dog.
  • the pharmakodynamic profile shown in FIG. 13 confirms that the device of the present invention produces a pattern of powder deposition similar to the aerosol generator.
  • the dogs were anesthetized for the dosing procedure.
  • a forced maneuver was used with dogs being ventilated at 75% of their vital capacity (approximately 100 cc/s or 6 L/min for a duration of 1 second).
  • a 4 second breath-hold was applied at the end of each inhalation.
  • a physically smaller device was used with the low ring configuration to facilitate administration. The device performed well at the low peak inspiratory flow rate with the anesthetized dogs using the forced maneuver. Based on these results, such a device could be used with a sleeping person or a person having breathing problems, such as from chronic obstructive pulmonary disease (COPD).
  • COPD chronic obstructive pulmonary disease
  • the device of the present invention relies upon the breath of the user to drive the inhalation process, yet the device is configured to work successfully at low peak inspiratory flow rates.
  • the device of the present invention has particular suitability for use with individuals who cannot breath hard, such as a child, an individual with respiratory disease, or individuals who are sleeping or in a coma.
  • the present invention further encompasses optimizing the configuration of device chamber 210 in order to maintain a low resistance of at most 0.28 (cm H 2 O) 1/2 /L/min and to achieve an emitted dose at least 85% when the receptacle contains a dose of up 10 to 50 mg of powder and when the device is operated at a peak inspiratory flow rate of 25 L/min or less and at an inhalation volume of 0.75 L or less.
  • a peak inspiratory flow rate of 25 L/min or less
  • inhalation volume 0.75 L or less.
  • ED emitted dose
  • VMGD volume mean geometric diameter
  • RODOS dry powder disperser or equivalent technique
  • chamber 210 The following dimensions of chamber 210 were varied in order to discover the optimal combination: mouthpiece hole area, mouthpiece hole number, chamber diameter (X in FIG. 4), ring diameter (Y in FIG. 4), vent area (the product of vent width, vent height, and vent number), and capsule hole area (the product of the hole area and the number of holes).
  • the capsule hole area was fixed at 0.013 square inches. It should be understood that the present invention encompasses other capsule hole areas, especially when used with different sized capsules. It was also determined that the total area of the holes in the mouthpiece was an important factor but that the number of holes in the mouthpiece did not effect the results.
  • Tables 2-4 summarize the emitted dose (ED) (in percent) and dispersion (volume mean geometric diameter (VMGD) in microns)) (with standard deviations in parentheses) achieved with each of these preferred embodiments of chambers, operated with a capsule having a dose of approximately 20 mg and at peak inspiratory flow rates from 15 L/min to 25 L/min and at inhalation volumes from 0.25 L to 0.75 L.
  • the test powder referred to herein as “standard test powder,” was a placebo powder of 84.99 wt % maltodextran, 15 wt % leucine, and 0.01 wt % rhodamine.
  • VMGD volume mean aerodynamic diameter
  • the italicized print indicates peak inspiratory flow rates and inhalation volumes at which the chambers achieved both the goal of an emitted dose of at least 85% and a dispersion of a VMGD of 11.8 ⁇ m or less.
  • these goals were achieved for peak inspiratory flow rates of 25 L/min or less and for inhalation volumes of 0.75 L or less.
  • the standard deviations were quite small for the emitted dose (on the order of approximately 10% or less) and for the VMGD (on the order of approximately 1.0 or less).
  • the present invention encompasses an optimized chamber, for a size 00 capsule, that has:
  • At least one aperture has an aggregate area of 0.018 to 0.022 square inches;
  • vent length 0.195 to 0.236 inches
  • the emitted dose of powder when used with a dose of approximately 20 mg of the standard test powder described above and operated at a peak inspiratory flow rate of 25 L/min or less and an inhalation volume of 0.75 L or less, the emitted dose of powder will be at least 85%, and the VMGD will be about 11.8 ⁇ m or less.
  • the preferred embodiment described above relates to optimizing the design of a chamber to have a have a resistance of at most 0.28 (cm H 2 O ) 1/2 /L/min and to provide an emitted dose of at least 85% when the dose of standard test powder is about 20 mg and when the device is operated at a peak inspiratory flow rate of 25 L/min or less and at an inhalation volume of 0.75 L or less
  • the invention also encompasses optimizing the chamber to have any other combination of resistance and emitted dose, at any other combination of powder type, dose weight, peak inspiratory flow rate, and inhalation volume.
  • FIGS. 7A through 7D a preferred embodiment of the means for puncturing, in the form of a staple, suitable for use in the present invention is shown.
  • the staple preferably comprises a rectangular length of material that has four planar side surfaces 730 . Each planar side surface intersects with two other planar side surfaces to create a total of four non-planar edges 736 .
  • the staple is preferably bent into a substantially U-shaped configuration, thereby having a rounded portion and two prongs 732 .
  • the prongs 732 terminate at two end surfaces 731 . As best seen in FIGS. 7A, 7C and 7 D, end surfaces 731 are diamond-shaped.
  • each prong 732 has an inner surface 738 that comprises one of the non-planar edges and an outer surface 740 that comprises the opposite non-planar edge.
  • the inner surface 738 of each prong 732 terminates at the uppermost portion 737 of the diamond-shaped end surface, thereby creating a cutting edge for the prong.
  • the outer surface 740 of the prong 732 terminates at the lowermost portion 735 of the diamond-shaped end surface.
  • FIGS. 9A and 9B depict another embodiment of a means for puncturing in the form of a staple, suitable for use in the present invention.
  • This staple preferably comprises a rectangular length of material that has four planar side surfaces. Each planar side surface intersects with two other planar side surfaces to create a total of four non-planar edges.
  • the staple is preferably bent into a substantially U-shaped configuration, thereby having a rounded portion and two prongs. The prongs terminate at two end surfaces that have a square shape.
  • each prong has an inner surface that comprises one of the planar side surfaces and an outer surface that comprises the opposite planar side surface.
  • the inner surface of each prong terminates at the uppermost portion of the square-shaped end surface, thereby creating a cutting edge for the prong.
  • the outer surface of the prong terminates at the lowermost portion of the square-shaped end surface.
  • FIG. 9B illustrates a puncture obtained from using the staple depicted in FIG. 9A.
  • the holes formed by this staple have the appearance of being cut with a sharp edge.
  • the material removed to create the hole is peeled back and remains well attached to the capsule; thereby preventing the capsule material from being inhaled by the user when the powder medicament is being dispensed.
  • FIG. 8 illustrates a puncture obtained from using the staple depicted in FIGS. 7A-7D.
  • the holes formed by the staple appear to be cut with a sharp edge, and the excess material is peeled back.
  • the effort required to puncture the capsule is lower than circular section staples, and approximately the same as a square section staple.
  • These staples are extremely inexpensive to produce, approximately one-third the cost of square section staples such as those depicted in FIG. 9A.
  • FIGS. 16A through 16D illustrate yet another preferred embodiment of a means for puncturing suitable for use in the present invention, in the form of puncturing device 1600 .
  • Puncturing device 1600 comprises two substantially longitudinal prongs 1620 coupled to a base 1610 coupled to form a U-shape.
  • Base 1610 is configured to be coupled to inhalation device 100 .
  • prongs are illustrated in the figures, it should be understood that any number of prongs 1620 could be coupled to base 1610 , depending on the number of holes desired to be made in the receptacle. For ease of discussion, only one of prongs 1620 is described in detail below.
  • Prong 1620 has a proximal end coupled to the base 1610 and a distal end having a puncturing surface 1630 for making an initial puncture hole in the receptacle.
  • puncturing surface 1630 is a sharp point, although it should be understood that puncturing surface 1630 may also have a different shape, such as a sharp edge.
  • the periphery of prong 1620 further comprises a primary cutting edge 1640 running from the proximal end to the distal end of prong 1620 and terminating at puncturing surface 1630 .
  • primary cutting edge 1640 is sharp and may have additional features to enhance its cutting ability, such as being serrated or jagged.
  • the periphery also comprises substantially planar face 1650 running from the proximal end to the distal end of prong 1620 . In a preferred embodiment substantially planar face 1650 is substantially flat, although it may also be another suitable shape, such as slightly concave.
  • Prong 1620 further comprises a plurality of longitudinal edges 1645 and a plurality of longitudinal faces 1655 disposed around the periphery and running from the proximal end to the distal end of the prong.
  • each of the longitudinal faces 1655 is substantially planar, although it should be understood that they may be other suitable shapes, such as concave.
  • each of the longitudinal edges 1645 is sharp, although it should be understood that they may also have other suitable shapes, such as being serrated, jagged, blunt, or rounded.
  • prong 1620 has a cross section substantially in the shape of a pentagon.
  • width W see FIG. 16D
  • prong 1620 may have two longitudinal edges 1645 and two longitudinal faces 1655 , in addition to primary cutting edge 1640 and substantially planar face 1650 , so that prong 1620 has a triangular cross section.
  • the distal end of prong 1620 preferably further comprises an angled face 1660 terminating in puncturing surface 1630 at its distal end and at substantially planar face 1650 at its proximal end, as best seen in FIG. 16C.
  • angled face 1660 may be at any angle, or may be comprised of a plurality of angled faces at various angles, so long as puncturing surface 1630 is located distal to the distal end of substantially planar face 1650 .
  • prong 1620 is slightly tapered so that the distal end is smaller than the proximal end. This tapering facilitates removing prong 1620 from the wall to be punctured without sticking and without detaching the chad formed in the wall.
  • the angle of the taper is approximately 0.116 degrees with respect to a longitudinal axis of the prong.
  • puncturing device 1600 is made by injection molding of a suitable metal, such as stainless steel or titanium. Injection molding facilitates making larger prongs than could be achieved in conventional piercing devices. As discussed above, larger prongs facilitate making larger holes in the receptacle in order to optimize the emitted dose and the volume mean geometric diameter. It should be understood that puncturing device 1600 may be made of another material, such as ceramic or plastic, or by another manufacturing process, such as casting or forging. Moreover, it should be understood that the other embodiments of means for puncturing 230 depicted in FIGS. 7 A-D and 9 A-B could be made by any of these manufacturing processes or materials. It should also be understood that these other embodiments of means for puncturing 230 could be coupled to a base similar to base 1610 in FIGS. 16 A-D.
  • FIGS. 17A through 17D schematically illustrate the use of prong 1620 to puncture and create a hanging chad in the wall 1710 of receptacle 1700 .
  • receptacle 1700 is illustrated in the shape of a capsule, it should be understood that the receptacle may have any other suitable shape, such as a tablet or a blister pack.
  • Receptacle 1700 has a longitudinal axis 1770 substantially parallel to prong 1620 and a minor axis 1780 substantially perpendicular to longitudinal axis 1770 .
  • FIG. 17A puncturing surface 1630 of prong 1620 initially punctures a small opening 1740 in wall 1710 .
  • prong 1620 is inserted into receptacle 1700 to a depth D, increasing the size of opening 1740 and forming chad 1750 having free end 1755 .
  • Substantially planar face 1650 forms a hinge 1760 between chad 1750 and wall 1710 so that chad 1750 is a hanging chad.
  • FIG. 17C prong 1620 is withdrawn from wall 1710 , leaving handing chad 1750 inside of receptacle 1700 .
  • the angle A between chad 1750 and minor axis 1780 , after prong 1600 has been removed from receptacle 1700 is at least 30 to 45 degrees in order to facilitate efficient emptying of the receptacle and a high emitted dose.
  • Staple # 1 and Staple # 2 Two prototype staples similar in shape to the U-shaped staple shown in FIGS. 7A-7D but with larger prongs (referred herein as Staple # 1 and Staple # 2 ) were used to puncture ten capsules.
  • Staple # 1 the mean emitted dose from the punctured capsules was approximately 81.0%, with a standard deviation of approximately 13.3%.
  • Staple # 2 the mean emitted dose was approximately 51.0%, with a standard deviation of approximately 25.3%.
  • Staple # 3 another prototype having almost the same structure as Staples # 1 and # 2 , was used to puncture capsules to varying depths. It was determined that the capsules could consistently be punctured to a depth of 0.1495 inches without causing chads to become removed.
  • Staple # 5 another prototype of puncturing device 1600 illustrated in FIGS. 16 A-D, was used to puncture capsules to varying depths. It was determined that the prongs could be inserted to a depth of at least 3 ⁇ 4 of the length L (see FIG.
  • puncturing device 1600 illustrated in FIGS. 16 A-D has significant advantages over other puncturing means because it allows greater depth of puncturing, which allows for greater optimization of the inhaler.
  • the present invention also relates to a method for dispensing powder medicaments to a user through the various embodiments of the disclosed inhalation device.
  • a receptacle containing the powder medicament e.g., a capsule 219
  • staple 230 is moved toward capsule 219 thereby puncturing capsule 219 to cause the release of powder into chamber 210 .
  • the powder is then inhaled by the user through apertures 224 and inhalation piece 226 .
  • inhalation piece 226 can be configured as either a mouth piece or a nose piece.
  • the user merely replaces emptied capsule 219 with another capsule 219 that contains a new supply of power medicament.
  • powder medicament is injected into a permanent receptacle that is formed into chamber 210 .
  • device 100 comprises a means for indicating readiness of the device for emitting powder 1800 .
  • the means for indicating readiness 1800 comprises a body 1820 coupled to inner casing 124 and disposed in outer casing 126 .
  • Body 1820 is reversibly moveable between a first position, as shown in FIGS. 18, 19A and 19 C, and a second position, as shown in FIG. 19B.
  • Body 1820 preferably is coupled to compression spring 244 so that it is biased in the first position.
  • body 1820 comprises a hollow tube of oblong cross section, although it should be understood that body 1820 may have any other suitable shape, such as a round cylinder or rod.
  • Means for indicating readiness 1800 further comprises an indicator 1810 disposed in outer casing 126 .
  • Indicator 1810 is reversibly moveable between a rest position, as shown in FIGS. 18, 19A and 19 B, and an indicating position, as shown in FIG. 19C.
  • Indicator 1810 preferably comprises a hollow ring of oblong cross section, although it should be understood that indicator may have any other suitable shape, such as a round cylinder, a rod, or a plate.
  • Means for indicating readiness 1800 further comprises a means 1830 for coupling body 1820 and indicator 1810 .
  • coupling means 1830 comprises at least one lip 1836 coupled to indicator 1810 and a corresponding at least one flange 1832 coupled to indicator 1810 .
  • Each flange 1832 preferably comprises a ratchet surface 1834 to facilitate coupling and to prevent inadvertent decoupling of each lip 1836 and each flange 1832 .
  • each flange 1832 preferable also comprises a stop 1838 to prevent indicator 1810 from riding up body 1820 beyond each flange 1832 .
  • coupling means 1830 may comprise any other suitable structure for coupling body 1820 and indicator 1810 , such as, for example, a friction fit engagement, a plurality of corresponding tangs and grooves, a clip, or a hook and loop fastener.
  • body 1820 before device 100 is actuated, body 1820 is biased in the first position and indicator 1810 is in the rest position and is substantially within outer casing 126 , so as to not be visible to the user.
  • body 1820 moves from the first position to the second position and further into outer casing 126 , as shown in FIG. 19B.
  • coupling means 1830 causes body 1820 to become coupled to indicator 1810 .
  • lip 1836 rides over ratchet surface 1834 of flange 1832 and becomes locked between flange 1832 and stop 1838 .
  • indicator 1810 makes an audible click when it becomes coupled to flange 1832 , which informs the user that the device has been actuated properly.
  • body 1820 is released and allowed to return to the first position, as shown in FIG. 19C. Because body 1820 is coupled to indicator 1810 , the movement of body 1820 to the first position causes indicator 1810 to move from the rest position to the indicating position. In the indicating position, indicator 1810 is at least partially outside of outer casing 126 so that indicator 1810 is visible to the user to indicate that device 100 is ready for inhalation. Indicator 1810 preferably has a bright color, such as, for example, green, to be easily visible.
  • indicator 1810 Upon subsequent actuations of device 100 , indicator 1810 remains coupled to body 1820 and moves between the indicating position and the rest position as body 1820 moves between the first position and the second position, respectively, as shown in FIGS. 19B and 19C.
  • indicator 1810 is equipped with a means 1840 for decoupling indicator 1810 from body 1820 , in order to return indicator 1810 to the rest position while body 1820 remains in the first position, as shown in FIG. 19A.
  • the decoupling means 1840 is configured so that applying an axial force to indicator 1810 decouples indicator 1810 from body 1820 .
  • decoupling means 1840 comprises at least one knob 1845 coupled to indicator 1810 to facilitate the user returning indicator 1810 to the rest position. It should be understood that decoupling means 1840 may have any other suitable structure, including a plurality of grooves or knobs or another type of easily graspable surface.
  • indicator 1810 is disposed almost completely within outer casing 126 while in the rest position and is disposed partially within outer casing 126 when in the indicating position.
  • indicator 1810 may be disposed substantially within outer casing 126 at both the rest position and the indicating position and may be viewable in one or both of these positions through a window in outer casing 126 .
  • indicator 1810 may be disposed in upper casing portion 130 .
  • indicator 1810 may be interchanged with body 1820 such that, for example, the body comprises a ring surrounding the indicator and the indicator is viewable through a window in the body and/or in the outer casing.
  • indicator 1810 may be disposed in the indicating position before device 100 is ready for inhalation and in the rest position when device 100 is ready for inhalation, particularly in an embodiment in which indicator 1810 is viewable through a window in outer casing 126 .
  • Means for indicating 1800 may be used with any type of inhaler, or any another type of device that utilizes a body to which is applied an axial force.
  • means for indicating 1800 may be used to indicate that an epinephrine injection pen, used for treating allergies, has been used or is ready for use.
  • means for indicating 1800 may be used to indicate that an aerosol canister inhaler has been used or is ready for use.
  • Means for indicating 1800 may be used with both single-use and multiple-use devices.
  • a device containing a plurality of inhalation chambers and a plurality of receptacles may comprise a plurality means for indicating 800 .

Abstract

Inhalation device and associated method for facilitating inhalation by a patient of powder medicaments contained in a receptacle. The inhalation device has a chamber for receiving the receptacle. A ring is circumferentially coupled to an inner surface of the chamber to achieve a higher reproducible emitted dose of medicament from the receptacle. The inhalation device also includes an improved implement for puncturing the receptacle, requiring less force and experiencing fewer failures. The inhalation device also includes a means for indicating readiness.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • The present application is a divisional of Application Ser. No. 10/268,059, filed Oct. 10, 2002, which is a continuation-in-part of Application Ser. No. 09/835,302, filed Apr. 16, 2001, the entirety of each of which is incorporated herein by reference.[0001]
  • BACKGROUND OF THE INVENTION
  • 1. Field of the Invention [0002]
  • The present invention relates generally to facilitating release of powder contained in a receptacle. More specifically, the present invention relates to the administration of medication by a method and apparatus for facilitating inhalation of powder medicaments. [0003]
  • 2. Related Art [0004]
  • In the medical field, it is often desirable to administer various forms of medication to patients. Well known methods of introducing medication into the human body include the oral ingestion of capsules and tablets, intravenous injection through hypodermic needles, and numerous others. In one method, certain medications may be inhaled into a patient's respiratory tract and lungs through the nose or mouth. Certain of these medications, such as bronchodilators, corticosteroids, etc., for the treatment of asthma and other respiratory anomalies, may be aimed at the respiratory tract directly. Others are inhaled for purposes of systemic treatment, i.e. for treatment of any area of the body through absorption from the respiratory tract through the lung tissue, into the deep lungs, and into the bloodstream. Each of these medications comes in a variety of forms, including fluids, which are commonly administered as an aerosol vapor or mist, as well as solids. Inhalable solids typically take the form of fine, dry powders. Specialized devices, such as inhalers, are provided to assist the patient in directing these fine powder medications into the respiratory tract. [0005]
  • Various types of inhalers are known for the administration of dry powder medicaments. However, each of these inhalers suffers certain drawbacks. For example, U.S. Pat. No. 5,787,881 discloses an inhaler that is used with encapsulated dry powder medicaments. However, use of this device requires numerous steps and imposes a number of inconveniences on a user. For example, the medication capsules used with the device have an aperture formed therein prior to insertion into an opening in the inhaler. Therefore, there exists a danger that an amount of medication may be lost prior to or during insertion into the device. After insertion of the capsule, use of the device requires the additional step that a cover must be closed before the medication may be inhaled. [0006]
  • Inhalation devices configured for use with a capsule containing some type of medicament are shown in U.S. Pat. No. 4,069,819 to Valentini et al. (“the '819 patent”) and U.S. Pat. No. 4,995,385 to Valentini et al. (“the '385 patent”). The inhalation device described in the '385 patent was developed to overcome the drawbacks of the device described in the '819 patent. Particularly, in a large number of cases, the device described in the '819 patent experienced irregular and incomplete emptying of the capsule, thereby resulting in difficulties in properly administering the medicament in the capsule. The inhalation device described in the '385 patent attempts to overcome this deficiency by tapering the nebulization chamber toward the end surface that comprises the discharge holes. Thus, the nebulization chamber of the '385 patent is not cylindrical, but rather frusto-conical in form in an attempt to achieve regular complete emptying of the nebulization chamber. [0007]
  • However, further improvements in the design of inhalation devices are needed to achieve high emitted doses and highly dispersed powders while maintaining low resistance, especially when the inhaler is used with high doses and is operated at low peak inspiratory flow rates (PIFR) and low inhalation volumes. As used herein, “emitted dose” (ED) refers to the percentage of the dose of powder medicament that is emitted from a receptacle in the inhalation device. The dispersal of the powder can be quantified by measuring the volume mean geometric diameter (VMGD) of the emitted powder. As used herein “volume mean geometric diameter” refers to the average geometric diameter of the powder. As used herein, “resistance” refers to the square root of the pressure gradient across the inhaler divided by the peak inspiratory flow rate through the inhaler. As used herein “low peak inspiratory flow rate” refers to a peak inspiratory flow rate of approximately 25 L/min or less. Moreover, improvements are needed to achieve high emitted doses and highly dispersed powders that are consistently reproducible, i.e., that have a low standard deviation of emitted dose percentage and VMGD, respectively. [0008]
  • Another drawback of the inhalation devices described in the '819 and the '385 patents is the piercing device that is used to puncture the capsule. Such conventional piercing devices are formed from circular stock, with the points created by pinching the stock at an angle, thereby creating a single sharp cutting edge. Drawbacks of such a design are that the point (which must puncture the capsule material) is often rounded, lessening its effectiveness as a piercing device. Moreover, burrs often form on the lower edge, which can stop the piercing device from retracting from the capsule, thereby causing a device failure. The holes formed by such a conventional piercing device are generally round, and do not have the appearance of being cut by a sharp edge. With such a conventional design, the capsule is often crushed, rather than punctured or pierced. If such a conventional piercing device is used with brittle capsule materials such as gelatin, pieces of capsule material of a size that can be inhaled are usually broken off from the capsule. Thus, conventional piercing devices are less than optimal, particularly for brittle capsule material. [0009]
  • Another drawback of conventional inhalation devices is that they have no means for indicating when the powder in the inhaler is ready for inhalation by the user. It is desirable to have a means for indicating to the user that a dose of powder is ready for inhalation. For example, it would be desirable for a patient using a device for dispensing fluticasone propionate (used to treat asthma) to know when the device is ready for inhalation. [0010]
  • Thus, there is a need in the art for an improved method and apparatus for inhalation of dry powder medicaments. What is needed is an inhaler that provides for a higher emitted dose that is consistently reproducible with low standard deviation. Such a need is particularly acute for low peak inspiratory flow rates, and for high dosage ranges. There is a further need in the art for an improved means for puncturing the capsule containing the medicament. The present invention, the description of which is fully set forth below, solves the need in the art for such improved methods and apparatus. [0011]
  • SUMMARY OF THE INVENTION
  • The present invention relates to a method and apparatus for facilitating release of powder from a device. In one aspect of the invention, a device for emitting powder is provided. The device includes a first casing portion, and a second casing portion removably coupled to the first casing portion. A cylindrical chamber, defined by a straight wall of circular cross section, is coupled to the first casing portion. The chamber has a proximal end and a distal end. A ring is circumferentially coupled to an inner surface of the chamber. The ring is preferably disposed at approximately a midpoint of the chamber, or, alternatively, disposed adjacent the proximal end of the chamber. The second casing portion includes an emitter portion disposed at the proximal end of the chamber when the first and second casing portions are coupled together. The emitter portion defines at least one aperture configured to emit powder therethrough. [0012]
  • In another aspect of the present invention, the device is configured as an inhalation device for administering powder. In this aspect of the present invention, the emitter portion is configured as an inhalation portion so that powder is dispersed in the chamber and administered to a user through the inhalation portion. The inhalation portion may be configured as a mouth piece for inhalation through the mouth, or as a nose piece for inhalation through the nose. [0013]
  • One aspect of the invention comprises an optimized configuration of a device for administering powder that comprises a chamber defined by a wall and configured to hold a receptacle containing a powder, the wall defining a plurality of vents, and the inhalation device further comprising an inhalation portion defining at least one aperture for emitting powder therethrough. The inhalation device is configured to have a resistance of at most 0.28 (cm H[0014] 2O)1/2/L/min and to provide an emitted dose of at least 85% when the dose of powder is up to 20 mg and when the device is operated at a peak inspiratory flow rate of 25 L/min or less and at an inhalation volume of 0.75 L or less. Preferably the standard deviation of the emitted dose is 10% or less.
  • In another aspect, the device of the present invention is configured to cause the emitted powder to be highly dispersed. By “highly dispersed” is meant that the VMGD of the emitted powder is substantially similar to the VMGD of the powder contained in the receptacle. Highly dispersible powders have a low tendency to agglomerate, aggregate or clump together and/or, if agglomerated, aggregated or clumped together, are easily dispersed or de-agglomerated as they emit from an inhaler and are breathed in by the subject. Typically, the highly dispersible particles suitable in the methods of the invention display very low aggregation compared to standard micronized powders which have similar aerodynamic diameters and which are suitable for delivery to the pulmonary system. Properties that enhance dispersibility include, for example, particle charge, surface roughness, surface chemistry, relatively large geometric diameters, and the configuration of the device used to dispense the powder. [0015]
  • In another aspect of the invention, the powder is contained in a receptacle that is disposed in the chamber. Upon puncturing the receptacle, powder is dispersed in the chamber and emitted or inhaled from the device. [0016]
  • In yet another aspect of the present invention, the device of the present invention includes means for puncturing the receptacle. In one embodiment, the means for puncturing can be configured as a staple. Such a staple is preferably configured in a substantially U-shape, having two prongs. In one aspect of the present invention, each of the prongs has a square cross-section. In another aspect of the present invention, the substantially U-shaped staple includes a rounded portion and two prongs that define a non-planar inner edge and a non-planar outer edge of the staple, the staple being formed from a rectangular length having two end surfaces and four planar side surfaces that intersect to form four non-planar edges. The inner edge of the staple is configured to be one of the non-planar edges, and the outer edge of the staple is the non-planar edge that is opposite that non-planar edge. Each end surface is an angled diamond-shaped surface. In a preferred aspect, each end surface has a top point at an apex of the inner edge, and a bottom point at an apex of the outer edge, each top point forming a cutting point for one of the prongs. [0017]
  • In another embodiment, the puncturing means can be configured as a substantially longitudinal prong comprising a puncturing surface on the distal end of the prong, a primary cutting surface running from the proximal end to the distal end of the prong and terminating at the puncturing surface, and a substantially planar face opposite to the primary cutting edge and running from the proximal end to the distal end of the prong. Another embodiment of the puncturing means comprises a substantially longitudinal prong comprising a puncturing surface on the distal end, a primary cutting surface terminating at the puncturing surface, and a face opposite to the primary cutting edge, wherein the prong is configured to create an opening in a wall by forming a hanging chad in the wall, the hanging chad having a free end formed by the puncturing surface and the primary cutting edge and a hinge coupled to the wall formed by the face. In another embodiment, the prong is configured to form a hanging chad in a wall of the receptacle having a longitudinal axis substantially parallel to the prong and a minor axis substantially perpendicular to the longitudinal axis, the hanging chad being opened to an angle of at least 30 to 45 degrees with respect to the minor axis of the receptacle. In another embodiment the prong is configured so that at least ¾ of the length of the prong can be inserted into a receptacle without breaking off chads in the receptacle. [0018]
  • In each of these embodiments, the prong preferably has an angled surface at the distal end, the surface having a distal end terminating at the puncturing surface and a proximal end terminating at the substantially planar face. In addition, the prong preferably is tapered, so that its distal end is smaller than its proximal end, to facilitate removing the prong from the receptacle. The prong also preferably has a plurality of longitudinal faces and a plurality of longitudinal edges running from the proximal end to the distal end of the prong. In one embodiment, the cross section of the prong is a pentagon. In a related embodiment, the width of the substantially planar face may be very small and the four longitudinal faces may be substantially at right angles to each other so that the prong has substantially a diamond shaped cross section. In another embodiment, the cross section of the prong is a triangle. [0019]
  • In another embodiment of the invention, the puncturing means comprises one or more of the longitudinal prongs coupled to a base, preferably in a U-shape. In another aspect of the invention, any of these embodiments of the longitudinal prongs may be coupled to the device for administering powder. [0020]
  • In still a further aspect of the present invention, a method for dispensing powder by inhalation is provided. Such a method comprises [0021]
  • providing a powder inhalation device, the device comprising [0022]
  • a first casing portion, [0023]
  • a cylindrical chamber, defined by a straight wall of circular cross-section, coupled to said first casing portion, said chamber having a proximal end and a distal end and configured to receive a receptacle therein, said chamber comprising a ring circumferentially coupled to an inner surface of said chamber, and [0024]
  • a second casing portion removably coupled to said first casing portion, said second casing portion comprising an inhalation portion disposed at the proximal end of said chamber when said first and said second casing portions are coupled, said inhalation portion comprising a hemispheric region defining a plurality of apertures configured to emit powder therethrough; [0025]
  • puncturing the receptacle to allow release of powder into said chamber; and [0026]
  • dispersing powder through inhalation of the powder through said inhalation portion. [0027]
  • In one aspect of the present invention, the inhaling step is carried out by inhaling the powder through a mouthpiece into a user's mouth. Alternatively, the inhaling step may be carried out by inhaling the powder through a nose piece into a user's nose. [0028]
  • The present invention also encompasses an indicating device comprising a body disposed within a casing and reversibly moveable between a first and a second position, an indicator moveable between a rest position and an indicating position, and a means for coupling the body and the indicator, wherein upon a first movement of the body from the first position to the second position, the means for coupling couples the body and the indicator, and upon a second movement of the body from the second position to the first position, the indicator moves from the rest position to the indicating position. [0029]
  • In another embodiment, the present invention encompasses an indicating device comprising a body disposed within a casing and reversibly moveable between a first position and a second position, an indicator reversibly moveable between a rest position and an indicating position, a lip coupled to the indicator and a flange coupled to the body for engaging the lip, wherein upon a first movement of the body from the first position to the second position, the flange engages the lip, and upon a second movement of the body from the second position to the first position, the engagement of the lip and the flange causes the indicator to move from the rest position to the indicating position. [0030]
  • The invention further encompasses one of the previously described embodiments of a device for emitting powder comprising a means for indicating readiness of the device for emitting powder. The means for indicating readiness of the device for emitting powder may comprise one of the previously described embodiments of an indicating device. [0031]
  • In addition, the invention comprises a method for indicating the readiness of a device for emitting a medicament. Such a method comprises [0032]
  • providing a device for dispensing a medicament, the device comprising a casing comprising at least one aperture configured to emit powder therethrough, a body coupled to said casing and reversibly moveable between a first position and a second position, and an indicator coupled to said casing and reversibly moveable between a rest position and an indicating position; [0033]
  • applying an axial force to said body to move said body from said first position to said second position, which readies the powder for dispensing and couples said body to said indicator; [0034]
  • releasing said axial force from said body to allow said body to move from said second position to said first position, which moves said indicator to said indicating position; and [0035]
  • dispensing the medicament from said device. [0036]
  • The invention further comprises a method for indicating that a device for dispensing a medicament has been used. Such a method comprises [0037]
  • providing a device for dispensing a medicament, the device comprising a casing comprising at least one aperture configured to emit a medicament therethrough, a body coupled to said casing and reversibly moveable between a first position and a second position, and an indicator coupled to said casing and reversibly moveable between a rest position and an indicating position; [0038]
  • applying an axial force to said body to move said body from said first position to said second position, which couples said body to said indicator; [0039]
  • dispensing the medicament from the device; [0040]
  • releasing said axial force from said body to allow said body to move from said second position to said first position, which moves said indicator to said indicating position to indicate that the device has been used. [0041]
  • Features and Advantages
  • One feature of the present invention is that it provides, in a low resistance inhaler with a highly dispersed powder, high emitted doses that are consistently reproducible over a range of peak inspiratory flow rates, inhalation volumes and dosage quantities. Advantageously, the present invention improves and optimizes the emitted dose at low peak inspiratory flow rates, low inhalation volumes, and high dose ranges. A particularly advantageous feature of the present invention is its ability to operate at low peak inspiratory flow rates, such as would be associated with a child, an elderly person, or a person with a respiratory disease, such as chronic obstructive pulmonary disease (COPD). [0042]
  • One advantage of the present invention is that the means for puncturing used in the device is less expensive to manufacture than conventional piercing devices. Advantages of the injection molding manufacturing process used for the puncturing means include reliability, reproducibility, and design flexibility, such as the ability to make a wide variety of shapes and sizes of longitudinal prongs. For example, larger longitudinal prongs of the present invention can create larger openings in the receptacles than conventional piercing devices, which allows for higher emitted doses at low peak inspiratory flow rates, low volumes, and high dosage quantities. Another advantage of the present invention is that at least one configuration of the puncturing means facilitates forming a hanging chad in the wall of the receptacle, with an opening of at least 30 to 45 degrees, to facilitate more efficient removal of powder from the receptacle and, thus, higher emitted doses than could be achieved with conventional piercing devices. Moreover, the means for puncturing of the present invention advantageously provides improved puncturing performance since less force is needed to puncture the receptacles, and fewer failures result than with conventional piercing devices. Yet another advantage is that the prongs are shaped for easy removal from the receptacle without breaking off the hanging chad formed in the wall of the receptacle. [0043]
  • Another advantage of the preferred means for puncturing is an improvement to the emitted dose rate of the inhaler. In one aspect of the invention, the puncturing means improves the powder flow from the receptacle by increasing the size of the holes in the receptacle. In another aspect of the invention, the puncturing means improves the peak inspiratory flow rate by opening a hanging chad in the wall of the receptacle to an angle of at least 30 to 45 degrees with respect to the wall of the receptacle. Consequently, the emitted dose of the powdered medicament delivered to a patient will be independent of how fast the patient breathes, thereby ensuring that a consistent dose of medicament is delivered each time. Another advantageous feature of the present invention is the accuracy of medicament dosage delivered thereby. Since only one dosage of medication is present in the inhaler during each use, the possibility of overdose is eliminated, and the medicament need not be metered prior to delivery. A patient may simply inhale all medicament present in the device. Yet another advantage is the design of the puncturing means allows for a greater range of puncturing depths without breaking off the chads formed in the receptacle, allowing for greater optimization of the inhaler. [0044]
  • Because the present invention operates only under the inhalative power of the patient, the inhaler carries the additional advantage that no accessory device, such as a compressed air cylinder or other propellant, needs to be used in conjunction with the present invention. [0045]
  • Another advantage of the present invention is that during inhalation, the medicament is subjected to mixing in the dispersion chamber. This helps to ensure that the medicament exiting the inhaler and entering the patient's respiratory system is in the form of a fine dry powder, facilitating medicament deposition in the lungs. In addition, inhalation of finer powders is typically more comfortable for the patient. [0046]
  • Still another advantage of the present invention is that it can be used with individuals who cannot breathe hard, such as a child, an elderly person, or a person suffering from a respiratory disease, such as asthma, or individuals who are sleeping or in a coma. [0047]
  • Yet another advantage of the apparatus of the present invention is that it is reusable. To reuse, a patient removes the emptied receptacle, and replaces it with a fresh receptacle filled with the proper dose of medicament. [0048]
  • Another advantage of the present invention is that it includes a means for indicating when a device for emitting powder is ready for inhalation. Such a means for indicating informs the user when the device is ready for use and/or when the device needs to be refilled or discarded. For example, the means for indicating could be used with a device for emitting fluticasone propionate (used to treat asthma) to indicate that the device is ready for inhalation. Alternatively, the means for indicating could be used with an epinephrine pen for treating allergies to indicate that the pen has been used. In addition, the means for indicating preferably makes an audible click so that a user will know when the device has been properly actuated. Also, the means for indicating is easy to manufacture and use.[0049]
  • BRIEF DESCRIPTION OF THE FIGURES
  • The present invention is described with reference to the accompanying drawings. In the drawings, like reference numbers indicate identical or functionally similar elements. [0050]
  • FIG. 1 is a front view of one embodiment of a device of the present invention; [0051]
  • FIG. 2 is a cross-section of the device shown in FIG. 1 along line [0052] 2-2;
  • FIG. 3 is an enlarged partial cross-section of one embodiment of a dispersion chamber of the present invention; [0053]
  • FIG. 4 is an enlarged partial cross-section of another embodiment of a dispersion chamber of the present invention showing one location for a ring in the dispersion chamber; [0054]
  • FIG. 5 is an enlarged partial cross-section of another embodiment of a dispersion chamber of the present invention showing another location for a ring in the dispersion chamber; [0055]
  • FIG. 6 is an enlarged partial cross-section of another embodiment of a dispersion chamber of the present invention showing another location for a ring in the dispersion chamber; [0056]
  • FIG. 7A is a top view of a preferred embodiment of a staple suitable for use with the device of the present invention; [0057]
  • FIG. 7B is a front view of the embodiment shown in FIG. 7A; [0058]
  • FIG. 7C is a side view of the embodiment shown in FIG. 7A; [0059]
  • FIG. 7D is an isometric view of the embodiment shown in FIG. 7A; [0060]
  • FIG. 8 shows the puncture obtained with the staple shown in FIGS. 7A through 7D; [0061]
  • FIG. 9A shows a partial view of another embodiment of a staple suitable for use with the device of the present invention; [0062]
  • FIG. 9B illustrates the puncture obtained with the staple shown in FIG. 9A; [0063]
  • FIG. 10 is a bar graph illustrating emitted dose at peak inspiratory flow rates of 20 L/min (left bar), 40 L/min (center bar), and 60 L/min (right bar) for four dispersion chamber configurations; [0064]
  • FIG. 11 is a bar graph illustrating emitted dose at low peak inspiratory flow rates for devices with varying numbers of vents; [0065]
  • FIG. 12 is a bar graph showing a comparison of mass fraction distributions obtained for 6 mg (left bar) and 50 mg (right bar) fill weights; [0066]
  • FIG. 13 is a graph showing glucose levels (mg/dL) in beagle dogs after administration of insulin using an aerosol generator and a device of the present invention with the low ring configuration substantially as shown in FIG. 4; [0067]
  • FIG. 14 is a bar graph illustrating the percentage emitted dose as a function of air volume; and [0068]
  • FIG. 15 is an exploded cross-sectional view of an alternate embodiment of a device of the present invention. [0069]
  • FIG. 16A is a perspective view of an alternative embodiment of a puncturing device suitable for use with the present invention. [0070]
  • FIG. 16B is a front view of the puncturing device shown in FIG. 16A. [0071]
  • FIG. 16C is a side view of the puncturing device shown in FIG. 16A. [0072]
  • FIG. 16D is a top view of the puncturing device shown in FIG. 16A. [0073]
  • FIGS. 17A-17C are schematic diagrams of one of the prongs of the puncturing device shown in FIGS. [0074] 16A-D being used to puncture a receptacle and create a hanging chad therein.
  • FIG. 18 is a front cross-sectional view of an alternative embodiment of the device for administering powder comprising a means for indicating the readiness of the device. [0075]
  • FIGS. 19A-19C are enlarged partial cross-sectional views of a preferred embodiment of the means for indicating readiness of the device.[0076]
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Overview
  • The present invention provides an improved method and apparatus for facilitating release of powder. In a preferred embodiment, the powder is contained in a receptacle. As used herein, the termn “receptacle” includes but is not limited to, for example, a capsule, blister, film covered container well, chamber, and other suitable means of storing a powder known to those skilled in the art. The present invention will be described below in the context of a method and apparatus for dispensing dry powder medicaments for inhalation by a patient. However, it should be apparent to one skilled in the art that the invention is not limited to such an exemplary embodiment, and could be used for other purposes. [0077]
  • As will be described in more detail below, an apparatus of the present invention is an inhaler that includes a chamber. In one embodiment, the chamber is configured to receive the receptacle containing the medicament. To improve the emptying of the receptacle and provide a higher reproducible emitted dose, the chamber includes a ring circumferentially coupled to an inner surface of the chamber. The ring is preferably disposed at approximately a midpoint of the chamber, or alternatively, adjacent the proximal end of the chamber. In proper use, air will exit the inhaler carrying a full dose of medicament in the form of a fine, dry powder. [0078]
  • Another aspect of the present invention is an optimized chamber configured to have a resistance of at most 0.28 (cm H[0079] 2O)1/2/L/min and to provide an emitted dose of at least 85% when the dose of powder is up to 20 mg and when the device is operated at a peak inspiratory flow rate of 25 L/min or less and at an inhalation volume of 0.75 L or less.
  • The inhaler of the present invention is preferably configured with a means for puncturing the receptacle that improves puncturing performance, particularly with brittle receptacle material. In one preferred embodiment, the means for puncturing the receptacle of the present invention is configured as a substantially U-shaped staple with two prongs, each prong having a sharp point and two cutting edges. In one such embodiment, each prong has a square cross-section, with the staple material being bent around a face so that the innermost part of the U-shaped staple is flat. In another such embodiment, the staple material is rotated 45 degrees so that it is bent around an edge so that the innermost part of the U-shaped staple is an edge. In such an embodiment, the end surface of each prong is an angled diamond-shaped surface. [0080]
  • In another preferred embodiment, the means for puncturing the receptacle is configured as a substantially longitudinal prong comprising a puncturing surface on the distal end, a primary cutting surface running from the proximal end to the distal end of the prong and terminating at the puncturing surface, and a substantially planar face opposite to the primary cutting edge and running from the proximal end to the distal end of the prong. The prong preferably has an angled surface at the distal end, the angled surface having a distal end terminating at the puncturing surface and a proximal end terminating at the substantially planar face. In addition, the prong is preferably tapered so that the distal end is smaller than the proximal end, to facilitate removing the prong from a receptacle. The prong also preferably has a plurality of longitudinal faces and a plurality of longitudinal edges running from the proximal end to the distal end of the prong. [0081]
  • The prong is configured to create an opening in a wall by forming a hanging chad in the wall, the hanging chad having a free end formed by the puncturing surface and the primary cutting edge and a hinge coupled to the wall formed by the face. In a preferred embodiment, the prong is configured to open the hanging chad to an angle of at least 30 to 45 degrees between the minor axis of the receptacle and the hanging chad, wherein the minor axis is substantially perpendicular to a longitudinal axis of the receptacle, which is substantially parallel to the longitudinal prong. [0082]
  • The methods of the present invention use an inhaler to dispense powder by inhalation. As will be discussed in greater detail below, a user operates the device to puncture the receptacle to disperse powder in the chamber, and inhales the powder through the inhalation portion. The present invention further encompasses a means for indicating readiness coupled to a device for administering powder. [0083]
  • Inhaler and Associated Method of the Present Invention
  • A front view of one embodiment of an [0084] inhalation device 100 of the present invention is shown in FIG. 1. The rear view of device 100 is substantially identical to the front view. Device 100 includes a first or lower casing portion 120 and a second or upper casing portion 130 removably coupled to first casing portion 120 . Upper casing portion 130 and lower casing portion 120 include a flattened region 132 and 122, respectively, for ease of gripping the casing for use by a patient. Lower casing portion 120 preferably includes an outer casing 126 and an inner casing 124 movably received within outer casing 126. A removable cap 110 is provided at the user or inhalation end of the device.
  • Preferred materials for [0085] device 100 include Food and Drug Administration (FDA) approved, USP tested plastics. Preferably, device 100 is manufactured using an injection molding process, the details of which would be readily apparent to one skilled in the art.
  • FIG. 2 is a cross-section of [0086] device 100 shown in FIG. 1 along line 2-2. As shown in FIG. 2, device 100 includes an inhalation or emitter portion 220. Inhalation portion 220 comprises a hemispheric region 222 that defines a plurality of apertures 224. It should be understood that the present invention is not limited to a particular number of apertures 224, and can be configured such that at least one aperture 224 is provided. An inhalation piece 226 is provided to allow for inhalation of the medicament by a user. Inhalation piece 226 can be configured as a mouth piece for inhalation through a user's mouth. Alternatively, inhalation piece 226 can be configured as a nose piece for inhalation through a user's nose.
  • [0087] Device 100 includes a cylindrical chamber 210 that is defined by a straight wall 212 of circular cross-section. Chamber 210 has a proximal end 214 and a distal end 216. A plurality of vents 218 are defined by wall 212, and are configured for introducing air into chamber 210 to disperse powder released from a capsule 219. It should be understood that the present invention is not limited to a particular number of vents 218, and can be configured such that at least one vent 218 is provided. Powder released from capsule 219 is dispersed in chamber 210 and inhaled through apertures 224 and inhalation piece 226 by the user.
  • In other embodiments of the invention, receptacles other than capsules are used, such as blisters and film covered container wells as is known in the art. In one embodiment, the volume of the receptacle is at least about 0.37 cm[0088] 3. In another embodiment, the volume of the receptacle is at least about 0.48 cm3. In yet another embodiment, the receptacles have a volume of at least about 0.67 cm3 or 0.95 cm3. In one embodiment of the invention, the receptacle is a capsule designated with a capsule size 2, 1, 0, 00, or 000. Suitable capsules can be obtained, for example, from Shionogi (Rockville, Md.). Blisters can be obtained, for example, from Hueck Foils, (Wall, N.J.).
  • The receptacle encloses or stores particles, also referred to herein as powders. The receptacle is filled with particles in a manner known to one skilled in the art. For example, vacuum filling or tamping technologies may be used. Generally, filling the receptacle with powder can be carried out by methods known in the art. In one embodiment of the invention, the particle or powder enclosed or stored in the receptacle have a mass of at least about 5 milligrams (mg). In another embodiment, the mass of the particles stored or enclosed in the receptacle is at least about 10 mg, and up to approximately 50 mg. In a preferred embodiment, the mass of the particles is approximately 20 mg. [0089]
  • In one embodiment of the present invention, particles used with the device have a tap density of less than about 0.4 g/cm[0090] 3. Particles having a tap density of less than about 0.4 g/cm3 are referred to herein as “aerodynamically light”. In a preferred embodiment, the particles have a tap density of near to or less than about 0.1 g/cm3. Tap density is a measure of the envelope mass density characterizing a particle. The envelope mass density of particles of a statistically isotropic shape is defined as the mass of the particle divided by the minimum sphere envelope volume within which it can be enclosed. Features that can contribute to low tap density include irregular surface texture and hollow or porous structure. Particularly preferred particles and powders are described in U.S. Pat. Nos. 6,136,295, 5,985,309, 5,874,064, and 5,855,913, and U.S. patent application Ser. No. 09/591,307, filed Jun. 9, 2000 entitled “High Efficient Delivery of a Large Therapeutic Mass Aerosol”, the entirety of each of the foregoing patents and patent applications is hereby incorporated herein by reference.
  • [0091] Device 100 includes a means for puncturing 230 that is used to puncture capsule 219 to release powder contained therein into chamber 210. In the embodiment shown in FIG. 1, means for puncturing 230 is configured as a substantially U-shaped staple having two prongs 232. In this embodiment, each of prongs 232 is configured with a square cross-section 234, thereby providing a sharp point and two cutting edges. This will be discussed in more detail below with respect to FIGS. 9A and 9B. As discussed in more detail below, device 100 could alternatively be configured with the means for puncturing shown in FIGS. 7A through 7D. Also, device 100 could alternatively be configured with the means for puncturing shown in FIGS. 16A through 16D. As can be readily appreciated by one skilled in the art, the present invention is not limited to these means for puncturing the capsule, described in detail below. For example, one, or a plurality of, straight needle-like implements could be used. Preferably, the means for puncturing is configured to puncture at least two holes in the capsule.
  • Means for puncturing [0092] 230 is preferably configured to be movable between a non-puncturing position (as depicted in FIG. 1) and a puncturing position. In the puncturing position, prongs 232 pierce or puncture capsule 219 to make holes therein. In a preferred embodiment, a means for biasing is provided that biases the means for puncturing 230 in the non-puncturing position. In the embodiment shown in FIG. 2, the means for biasing is configured as a spring 242 that biases the substantially U-shaped staple in the non-puncturing position.
  • As noted with respect to FIG. 1, [0093] device 100 includes inner casing 124 and outer casing 126. As shown in FIG. 2, a spring 244 is disposed in lower casing portion 120 that biases inner casing 124 in an outward position. Upon compression of spring 244, inner casing 124 moves from the outward position to an inward position, thereby drawing lower casing portion 120 toward upper casing portion 130. Compression of spring 244 also causes compression of spring 242, thereby causing means for puncturing 230 to move to the puncturing position. Upon release of compression, springs 242 and 244 return to their biased state, thereby returning means for puncturing 230 to its non-puncturing position, and inner casing 124 to its outward position.
  • A pair of [0094] flanges 252 is disposed on first casing portion 120. A pair of grooves 254 is disposed on second casing portion 130 so that flanges 252 can be received within grooves 254 to thereby couple the first and second casing portions. Preferably, the first and second casing portions are coupled with a friction-fit engagement. A friction-fit engagement can be achieved using the groove and flange arrangement depicted in FIG. 2. Other alternative configurations for a friction-fit engagement would be readily apparent to one skilled in the art.
  • FIG. 3 is an enlarged partial cross-section of one embodiment of [0095] chamber 210. In the embodiment shown in FIG. 3, chamber 210 does not contain a ring disposed on an inner surface, and an inner diameter of chamber 210 is depicted as “X”. Such a configuration may be referred to herein as a “straight” chamber configuration.
  • FIG. 4 is an enlarged partial cross-section of another embodiment of [0096] chamber 210. In the embodiment shown in FIG. 4, a ring 400 is circumferentially coupled to an inner surface of chamber 210. An inner diameter of ring 400 is depicted as “Y”, and is less than inner diameter X of chamber 210. In the embodiment shown in FIG. 4, ring 400 is disposed at approximately a midpoint of chamber 210. Such a configuration may be referred to herein as a “low” ring position or “low” chamber configuration. As shown in FIG. 4, in the low ring position, ring 400 is disposed adjacent vents 218. The ring position is measured by the distance from the top of hemispheric region 222 to the bottom edge of ring 400. This distance is depicted as “Z”. The following dimensions are provided as exemplary dimensions of a device of the present invention. It should be understood by one skilled in the art that the present invention is not limited to the dimensions provided herein, or to any particular dimensions. In one embodiment of the chamber 210 shown in FIG. 4, diameter X is 0.47 in., diameter Y is 0.38 in., and distance Z is 0.49 in.
  • FIG. 6 is an enlarged partial cross-section of another embodiment of [0097] chamber 210. In the embodiment shown in FIG. 6, ring 400 is circumferentially coupled to an inner surface of chamber 210. An inner diameter of ring 400 is depicted as “Y”, and is less than inner diameter X of chamber 210. In the embodiment shown in FIG. 6, ring 400 is disposed adjacent the proximal end of chamber 210. Such a configuration may be referred to herein as a “high” ring position or a “high” chamber configuration. The ring position is measured by the distance from the top of hemispheric region 222 to the bottom edge of ring 400. This distance is depicted as “Z”. The following dimensions are provided as exemplary dimensions of a device of the present invention. It should be understood by one skilled in the art that the present invention is not limited to the dimensions provided herein, or to any particular dimensions. In one embodiment of the chamber 210 shown in FIG. 6, diameter X is 0.47 in., diameter Y is 0.38 in., and distance Z is 0.29 in.
  • FIG. 5 is an enlarged partial cross-section of another embodiment of [0098] chamber 210. In the embodiment shown in FIG. 5, ring 400 is circumferentially coupled to an inner surface of chamber 210. An inner diameter of ring 400 is depicted as “Y”, and is less than inner diameter X of chamber 210. In the embodiment shown in FIG. 5, ring 400 is disposed between the low ring position of FIG. 4 and the high ring position of FIG. 6. Such a configuration may be referred to herein as a “mid” ring position or “mid” chamber configuration. The ring position is measured by the distance from the top of hemispheric region 222 to the bottom edge of ring 400. This distance is depicted as “Z”. The following dimensions are provided as exemplary dimensions of a device of the present invention. It should be understood by one skilled in the art that the present invention is not limited to the dimensions provided herein, or to any particular dimensions. In one embodiment of the chamber 210 shown in FIG. 5, diameter X is 0.47 in., diameter Y is 0.38 in., and distance Z is 0.39 in.
  • In one embodiment of the present invention, [0099] ring 400 is integral with chamber 210. In such an embodiment, ring 400 and chamber 210 are formed as a unit, such as through an injection molding, extrusion or a casting process. In another embodiment of the present invention, ring 400 is attached to the inner surface of chamber 210 in a manner known to those skilled in the art, such as through the use of glue or other type of adhesive, or by using an attaching device such as a pin or screw, etc. Preferably, the casing of device 100 is made from a material that can be injection molded, such as a plastic material (preferably FDA approved, USP tested). As would be readily apparent to one skilled in the art, the material is preferably durable, easy to clean, and non-reactive with powder medicaments.
  • An exploded cross-sectional view of an alternate embodiment of a [0100] device 1500 of the present invention is shown in FIG. 15. Device 1500 includes a first or lower casing portion 1540 and a second or upper casing portion 1550 removably coupled to first casing portion 1540. First and second casing portions 1540 and 1550 are coupled through the use of a flange 1552 and a groove 1554. Preferred materials for device 1500 include Food and Drug Administration (FDA) approved, USP tested plastics. Preferably, device 1500 is manufactured using an injection molding process, the details of which would be readily apparent to one skilled in the art.
  • [0101] Device 1500 includes an inhalation or emitter portion 1520. Inhalation portion 1520 comprises a hemispheric region 1522 that defines a plurality of apertures 1524. It should be understood that the present invention is not limited to a particular number of apertures 1524, and can be configured such that at least one aperture 1524 is provided. An inhalation piece 1526 is provided to allow for inhalation of the medicament by a user. Inhalation piece 1526 can be configured as a mouth piece for inhalation through a user's mouth. Alternatively, inhalation piece 1526 can be configured as a nose piece for inhalation through a user's nose.
  • [0102] Device 1500 includes a cylindrical chamber 1510 that is defined by a straight wall 1512 of circular cross-section. A plurality of vents 1518 are defined by wall 1512, and are configured for introducing air into chamber 1510 to disperse powder released from, for example, capsule 219 as illustrated in FIG. 2. It should be understood that the present invention is not limited to a particular number of vents 1518, and can be configured such that at least one vent 1518 is provided. Powder released from capsule 219 is dispersed in chamber 1510 and inhaled through apertures 1524 and inhalation piece 1526 by the user.
  • As would be readily apparent to one skilled in the art, [0103] device 1500 can be configured with means for puncturing and means for biasing in a manner similar to that described above with respect to the embodiment shown in FIGS. 1 and 2. Means for puncturing are described in more detail below with respect to FIGS. 7A through 7D, 8, 9A-9B, 16A-16D, and 17A-17C. Moreover, device 1500 can be configured with the chamber designs described above with respect to FIGS. 3-6.
  • FIG. 10 is a bar graph illustrating emitted dose at peak inspiratory flow rates of 20 L/min (left bar), 40 L/min (center bar), and 60 L/min (right bar) for a total volume of 2L for four dispersion chamber configurations (standard deviations shown; sample size n=3). The peak inspiratory flow rates were measured with a flow meter. The emitted dose measurement involved placing a capsule into four embodiments of the inhaler of the present invention for actuation into an emitted dose (ED) measurement apparatus. The ED apparatus included a powder filter and a filter holder. The powder collected by the ED apparatus was quantified by fluorescence spectrophotometry. The straight configuration is shown in FIG. 3; the low configuration is shown in FIG. 4; the mid configuration is shown in FIG. 5; and the high configuration is shown in FIG. 6. As can be seen from FIG. 10, each of the low, mid, and high configurations demonstrated a higher emitted dose at each of the three flow rates than the straight (no ring) configuration. Thus, the ring configuration of the present invention provides an improvement over conventional chamber designs without a ring, such as those shown in the '819 and '385 patents. At each of the flow rates shown in FIG. 10, the low configuration produced a higher emitted dose and a lower standard deviation than the mid and high configurations. [0104]
  • FIG. 11 is a bar graph illustrating emitted dose at low peak inspiratory flow rates for devices with varying numbers of [0105] vents 218. The measurements were taken at a flow rate of 5 L/min, with a volume of 67 cc and a 15 mg dosage. As show in FIG. 11, by decreasing the number of vents 218, the emitted dose increases so that the device of the present invention successfully delivers a high emitted dose at a low peak inspiratory flow rate over multiple (ten) actuations. Thus, the device of the present invention achieves a high emitted dose at low peak inspiratory flow rates that is consistently reproducible with low standard deviation.
  • Experiments were conducted to evaluate the emitted dose as a function of air volume drawn through the inhaler. The inhaler was operated at a constant flow rate of 30 L/min for a 5 mg dose. The volume of air through the inhaler was varied by varying the actuation time. Volumes of 0.5, 1.0, 1.5, 2.0 and 3.0 L were investigated. FIG. 14 shows the percentage emitted dose as a function of air volume (n=3, standard deviations shown). The emitted dose remained constant across the range of volumes and was consistently reproducible with low standard deviation. [0106]
  • In the embodiments having the inner diameter X of [0107] chamber 210 of 0.47 in. and the inner diameter Y of ring 400 of 0.38 in., the ratio of the inner diameter of the ring to the inner diameter of the chamber is about 0.8. By modifying the inner diameters of the ring and the chamber, it is possible to optimize the emitted dose at varying flow rates. As reported in Annals of the ICRP, Human respiratory tract model for radiological protection, 24 (1-3), Elsevier Science, Inc., New York, 1994, the peak inspiratory flow rate for a tidal breathing seated adult male is 300 mLs (18 L/min) for a volume of 750 mL. In one embodiment of a device of the present invention optimized for low peak inspiratory flow rates, inner diameter X of chamber 210 is 0.33 in. and inner diameter Y of ring 400 is 0.30 in. In such an embodiment, the ratio of the inner diameter of the ring to the inner diameter of the chamber is about 0.9. Preferably, the ratio of the inner diameter of the ring to the inner diameter of the chamber is about 0.9 or less.
  • The device of the present invention can also be optimized for varying dosage ranges. One way to do so is to vary the dimensions of [0108] chamber 210 to accommodate varying sizes of capsules. For example, a chamber having an inner diameter X of 0.33 in., inner diameter Y of 0.30 in., and distance Z of 0.57 in. can be used with size 2 and size 00 capsules. It should be readily apparent to one skilled in the art that chamber 210 can be scaled to accommodate varying capsule sizes, and to accommodate those capsule sizes at varying peak inspiratory flow rates.
  • The device of the present invention can be used with varying dosage ranges. A highly dispersible powder was prepared and loaded into capsules to obtain a large pre-metered dose (50 mg) and a smaller pre-metered dose (6 mg). The particle size characteristics of the powder were as follows: VMGD=10.6 μm; ρ=0.11 g/cc; and Da=3.5 μm, where VMGD is the volume mean geometric diameter, p is the powder density, and Da is the mean aerodynamic diameter. The aerodynamic particle size distributions were characterized using a multistage liquid impinger that extracted air at 60 L/min after actuating the inhaler device (D). As shown in FIG. 12, the mass fraction was measured at D, the induction port (IP) of the impactor, stages S[0109] 1-S4, and the filter cutoff (SF). Size 2 capsules were used for the 6 mg dose and size 000 capsules were used for the 50 mg dose. FIG. 12 shows the results comparing the two particle size distributions obtained for the 6 mg (left bar) and 50 mg (right bar) doses. “ED” used on the graph refers to emitted dose, and FPM used on the graph refers to fine particle mass (estimate of the mass that would deposit in the lungs). The fine particle fraction <6.8 μm relative to the total dose (FPFTD<6.8 μm) for the 6 and 50 mg doses were 74.4% and 75.0%, respectively. Similar aerodynamic particle size distributions were obtained for both doses.
  • FIG. 13 is a graph showing glucose (mg/dL) in beagle dogs after administration of human insulin using an aerosol generator and a device of the present invention with the low ring configuration substantially as shown in FIG. 4. The generator is a device with proven ability for forming a respirable aerosol that results in deposition of powder in dog lungs. Metered powder is presented to a chamber where the powder is dispersed by a high velocity jet of air. The dispersed powder is directed toward a baffle to separate large agglomerates before inhalation by the dog. The pharmakodynamic profile shown in FIG.[0110] 13 confirms that the device of the present invention produces a pattern of powder deposition similar to the aerosol generator.
  • The dogs were anesthetized for the dosing procedure. A forced maneuver was used with dogs being ventilated at 75% of their vital capacity (approximately 100 cc/s or 6 L/min for a duration of 1 second). A 4 second breath-hold was applied at the end of each inhalation. A physically smaller device was used with the low ring configuration to facilitate administration. The device performed well at the low peak inspiratory flow rate with the anesthetized dogs using the forced maneuver. Based on these results, such a device could be used with a sleeping person or a person having breathing problems, such as from chronic obstructive pulmonary disease (COPD). [0111]
  • As can be seen from the description above, the device of the present invention relies upon the breath of the user to drive the inhalation process, yet the device is configured to work successfully at low peak inspiratory flow rates. As such, the device of the present invention has particular suitability for use with individuals who cannot breath hard, such as a child, an individual with respiratory disease, or individuals who are sleeping or in a coma. [0112]
  • The present invention further encompasses optimizing the configuration of [0113] device chamber 210 in order to maintain a low resistance of at most 0.28 (cm H2O)1/2/L/min and to achieve an emitted dose at least 85% when the receptacle contains a dose of up 10 to 50 mg of powder and when the device is operated at a peak inspiratory flow rate of 25 L/min or less and at an inhalation volume of 0.75 L or less. Experiments were performed on various chamber configurations, using size 00 capsules filled with a 20 mg dose of standard test powder. The various configurations were tested for emitted dose (ED), using known methods described above, at peak inspiratory flow rates ranging from 15 L/min to 25 L/min and at inhalation volumes ranging from 0.25 L/min to 0.75 L/min. In addition, the dispersion of the powder was quantified by measuring the volume mean geometric diameter (VMGD) of the emitted powder, by employing a RODOS dry powder disperser (or equivalent technique) such that at about 1 Bar, particles of the dry powder emitted from the RODOS orifice with geometric diameters, as measured by a HELOS or other laser diffraction system, are less than about 1.5 times the geometric particle size as measured at 4 Bar. In addition, the resistance of each chamber was measured using methods that will be apparent to one of ordinary skill in the art.
  • The following dimensions of [0114] chamber 210 were varied in order to discover the optimal combination: mouthpiece hole area, mouthpiece hole number, chamber diameter (X in FIG. 4), ring diameter (Y in FIG. 4), vent area (the product of vent width, vent height, and vent number), and capsule hole area (the product of the hole area and the number of holes). Initially, it was discovered that it is always desirable to maximize the capsule hole area. Accordingly, the capsule hole area was fixed at 0.013 square inches. It should be understood that the present invention encompasses other capsule hole areas, especially when used with different sized capsules. It was also determined that the total area of the holes in the mouthpiece was an important factor but that the number of holes in the mouthpiece did not effect the results.
  • Next, 130 chambers were tested, each having a different combination of mouthpiece hole area, chamber diameter, ring diameter, and vent area. During the testing it was discovered that each of these dimensions have competing effects on the emitted dose, the volume mean geometric diameter, and the resistance of the chamber. For example, increasing the vent area has a positive impact on (i.e., decreases) resistance, but has a negative effect on (i.e., decreases) emitted dose and has a negative effect on (i.e., increases) volume mean geometric diameter. Other dimensions have similar competing effects. In addition, as shown in FIGS. 20A to [0115] 20C and discussed in detail below, the vent area and the chamber diameter have combinational effects on the properties of the chamber. Other combinations of dimensions have similar combinational effects.
  • Of the [0116] 130 chambers tested, three preferred embodiments of chambers were identified that achieved the desired characteristics. The pertinent dimensions of each of those chambers is described in Table 1.
    TABLE 1
    Aspects of Preferred Embodiments of Chambers
    Chamber F Chamber H Chamber I
    Resistance (cm 0.27 0.22 0.19
    H2O)1/2/L/min
    Mouthpiece Hole 0.020 0.022 0.022
    Area (sq. in.)
    Chamber Diameter 0.440 0.436 0.440
    (in.)
    Ring Diameter (in.) 0.400 0.380 0.400
    Vent Area (sq. in.) 0.014 0.020 0.024
    Vent Number (in.) 3 4 5
    Vent Width (in.) 0.020 0.025 0.020
    Vent Length (in.) 0.236 0.195 0.236
  • Tables 2-4 summarize the emitted dose (ED) (in percent) and dispersion (volume mean geometric diameter (VMGD) in microns)) (with standard deviations in parentheses) achieved with each of these preferred embodiments of chambers, operated with a capsule having a dose of approximately 20 mg and at peak inspiratory flow rates from 15 L/min to 25 L/min and at inhalation volumes from 0.25 L to 0.75 L. The test powder, referred to herein as “standard test powder,” was a placebo powder of 84.99 wt % maltodextran, 15 wt % leucine, and 0.01 wt % rhodamine. It had a VMGD of 12 μm measured using the RODOS at 1 bar and an aerodynamic size (volume mean aerodynamic diameter or VMAD) of 3 μm measured using an 8 stage Anderson Cascade Impactor. The goal emitted dose was at least 85%. The goal dispersion for the standard test powder was a VMGD of 11.8 μm or less, although it should be understood that this goal would vary depending on the type of powder used. [0117]
    TABLE 2
    Chamber F
    Volume →
    Flow 0.25 L 0.5 L 0.75 L
    Rate VMGD ED VMGD ED VMGD ED
    15 15.0 (0.8) 67 (14) 13.5 (0.8) 87 (6) 16.4 (1.6) 93 (3)
    L/min
    20 10.2 (0.5) 66 (9)  9.3 (0.6) 89 (4)  9.0 (0.6) 88 (10)
    L/min
    25  9.3 (0.6) 77 (8)  7.8 (0.3) 91 (5)  7.9 (0.5) 93 (3)
    L/min
  • [0118]
    TABLE 3
    Chamber H
    Volume →
    Flow 0.25 L 0.5 L 0.75 L
    Rate VMGD ED VMGD ED VMGD ED
    15 16.1 (0.8) 57 (9) 15.7 (0.7) 78 (11) 14.6 (1.1) 90 (4)
    L/min
    20 12.0 (0.6) 66 (9) 10.4 (0.6) 81 (7) 10.2 (0.4) 89 (8)
    L/min
    25 10.4 (0.6) 75 (11)  8.1 (0.3) 94 (4)  8.2 (0.3) 97 (1)
    L/min
  • [0119]
    TABLE 4
    Chamber I
    Volume →
    Flow 0.25 L 0.5 L 0.75 L
    Rate VMGD ED VMGD ED VMGD ED
    15 18.2 (0.7) 49 (8) 19.3 (1.3) 69 (12) 18.2 (1.9) 79 (12)
    L/min
    20 13.4 (0.5) 43 (13) 12.7 (1.0) 71 (10) 12.5 (0.6) 83 (9)
    L/min
    25 12.0 (0.4) 65 (8) 10.0 (0.4) 85 (7)  9.7 (0.3) 87 (9)
    L/min
  • In Tables 2-4, the italicized print indicates peak inspiratory flow rates and inhalation volumes at which the chambers achieved both the goal of an emitted dose of at least 85% and a dispersion of a VMGD of 11.8 μm or less. As is apparent from Tables 2-4, these goals were achieved for peak inspiratory flow rates of 25 L/min or less and for inhalation volumes of 0.75 L or less. Moreover, the standard deviations were quite small for the emitted dose (on the order of approximately 10% or less) and for the VMGD (on the order of approximately 1.0 or less). [0120]
  • In addition, statistical analysis was used to extrapolate the results from these three chambers into ranges of variables that would consistently yield the desired emitted dose and volume mean geometric diameter. For example, optimized combinations of chamber diameter, vent area, and mouthpiece hole area were determined. It should be apparent to one of ordinary skill in the art that optimization analysis could be performed for other variable combinations, and for other capsule sizes and powders, in order to optimize the design of the chambers. [0121]
  • Having done a thorough analysis, it has been determined that the present invention encompasses an optimized chamber, for a size 00 capsule, that has: [0122]
  • at least one aperture has an aggregate area of 0.018 to 0.022 square inches; or [0123]
  • a ring inner diameter of 0.380 to 0.400 inches; or [0124]
  • a chamber inner diameter of 0.400 to 0.440 inches; or [0125]
  • three to five vents; or [0126]
  • a vent width of 0.020 to 0.025 inches; or [0127]
  • a vent length of 0.195 to 0.236 inches; or [0128]
  • a total vent area of 0.014 to 0.024 square inches, [0129]
  • and that when used with a dose of approximately 20 mg of the standard test powder described above and operated at a peak inspiratory flow rate of 25 L/min or less and an inhalation volume of 0.75 L or less, the emitted dose of powder will be at least 85%, and the VMGD will be about 11.8 μm or less. [0130]
  • While the preferred embodiment described above relates to optimizing the design of a chamber to have a have a resistance of at most 0.28 (cm H[0131] 2O )1/2/L/min and to provide an emitted dose of at least 85% when the dose of standard test powder is about 20 mg and when the device is operated at a peak inspiratory flow rate of 25 L/min or less and at an inhalation volume of 0.75 L or less, it should be understood that the invention also encompasses optimizing the chamber to have any other combination of resistance and emitted dose, at any other combination of powder type, dose weight, peak inspiratory flow rate, and inhalation volume.
  • Turning now to FIGS. 7A through 7D, a preferred embodiment of the means for puncturing, in the form of a staple, suitable for use in the present invention is shown. The staple preferably comprises a rectangular length of material that has four planar side surfaces [0132] 730. Each planar side surface intersects with two other planar side surfaces to create a total of four non-planar edges 736. The staple is preferably bent into a substantially U-shaped configuration, thereby having a rounded portion and two prongs 732. The prongs 732 terminate at two end surfaces 731. As best seen in FIGS. 7A, 7C and 7D, end surfaces 731 are diamond-shaped.
  • The diamond-shaped end surfaces are created by bending the material about a non-planar edge. This configuration is best shown in FIGS. 7B and 7D. As can be seen, each [0133] prong 732 has an inner surface 738 that comprises one of the non-planar edges and an outer surface 740 that comprises the opposite non-planar edge. The inner surface 738 of each prong 732 terminates at the uppermost portion 737 of the diamond-shaped end surface, thereby creating a cutting edge for the prong. The outer surface 740 of the prong 732 terminates at the lowermost portion 735 of the diamond-shaped end surface.
  • FIGS. 9A and 9B depict another embodiment of a means for puncturing in the form of a staple, suitable for use in the present invention. This staple preferably comprises a rectangular length of material that has four planar side surfaces. Each planar side surface intersects with two other planar side surfaces to create a total of four non-planar edges. The staple is preferably bent into a substantially U-shaped configuration, thereby having a rounded portion and two prongs. The prongs terminate at two end surfaces that have a square shape. [0134]
  • The square-shaped end surfaces are created by bending the material about a planar side surface. As shown in FIG. 9A, each prong has an inner surface that comprises one of the planar side surfaces and an outer surface that comprises the opposite planar side surface. The inner surface of each prong terminates at the uppermost portion of the square-shaped end surface, thereby creating a cutting edge for the prong. The outer surface of the prong terminates at the lowermost portion of the square-shaped end surface. [0135]
  • FIG. 9B illustrates a puncture obtained from using the staple depicted in FIG. 9A. As shown, the holes formed by this staple have the appearance of being cut with a sharp edge. In addition, the material removed to create the hole is peeled back and remains well attached to the capsule; thereby preventing the capsule material from being inhaled by the user when the powder medicament is being dispensed. [0136]
  • FIG. 8 illustrates a puncture obtained from using the staple depicted in FIGS. 7A-7D. The holes formed by the staple appear to be cut with a sharp edge, and the excess material is peeled back. In testing, the effort required to puncture the capsule is lower than circular section staples, and approximately the same as a square section staple. However, during testing, no instances were noted of crushed or otherwise mispunctured capsules. These staples are extremely inexpensive to produce, approximately one-third the cost of square section staples such as those depicted in FIG. 9A. [0137]
  • In addition to improved puncturing performance, drug delivery from capsules punctured with the staple depicted in FIGS. 7A-7D is greatly improved. The Emitted Dose (ED) and Fine Particle Fraction (FPF) of a test powder was measured at both 20 and 60 Liters per minute (LPM). In all cases, the aerosol emitted from capsules punctured with the diamond section staple of FIGS. 7A-7D was improved over a conventional circular stock staple. Most significantly, the FPF of powder delivered at 20 liters per minute was improved almost to the level of the FPF at 60 liters per minute. [0138]
  • FIGS. 16A through 16D illustrate yet another preferred embodiment of a means for puncturing suitable for use in the present invention, in the form of [0139] puncturing device 1600. Puncturing device 1600 comprises two substantially longitudinal prongs 1620 coupled to a base 1610 coupled to form a U-shape. Base 1610 is configured to be coupled to inhalation device 100. Although two prongs are illustrated in the figures, it should be understood that any number of prongs 1620 could be coupled to base 1610, depending on the number of holes desired to be made in the receptacle. For ease of discussion, only one of prongs 1620 is described in detail below.
  • [0140] Prong 1620 has a proximal end coupled to the base 1610 and a distal end having a puncturing surface 1630 for making an initial puncture hole in the receptacle. In the embodiment shown, puncturing surface 1630 is a sharp point, although it should be understood that puncturing surface 1630 may also have a different shape, such as a sharp edge.
  • The periphery of [0141] prong 1620 further comprises a primary cutting edge 1640 running from the proximal end to the distal end of prong 1620 and terminating at puncturing surface 1630. In a preferred embodiment, primary cutting edge 1640 is sharp and may have additional features to enhance its cutting ability, such as being serrated or jagged. The periphery also comprises substantially planar face 1650 running from the proximal end to the distal end of prong 1620. In a preferred embodiment substantially planar face 1650 is substantially flat, although it may also be another suitable shape, such as slightly concave.
  • [0142] Prong 1620 further comprises a plurality of longitudinal edges 1645 and a plurality of longitudinal faces 1655 disposed around the periphery and running from the proximal end to the distal end of the prong. In a preferred embodiment, each of the longitudinal faces 1655 is substantially planar, although it should be understood that they may be other suitable shapes, such as concave. In a preferred embodiment, each of the longitudinal edges 1645 is sharp, although it should be understood that they may also have other suitable shapes, such as being serrated, jagged, blunt, or rounded.
  • In the embodiment shown in FIG. 16D, there are four [0143] longitudinal edges 1645 and four longitudinal faces 1655, in addition to primary cutting edge 1640 and substantially planar face 1650, so that prong 1620 has a cross section substantially in the shape of a pentagon. However, it should be understood that there may be any number and arrangement of longitudinal faces 1655 and longitudinal edges 1645 so that prong 1620 may have other suitable cross sectional shapes, so long as substantially planar face 1650 is opposite to primary cutting edge 1640. For example, width W (see FIG. 16D) of substantially planar face 1650 may be very small and the four longitudinal faces 1655 may be substantially at right angles to each other so that prong 1620 has substantially a diamond shaped cross section. In yet another embodiment, prong 1620 may have two longitudinal edges 1645 and two longitudinal faces 1655, in addition to primary cutting edge 1640 and substantially planar face 1650, so that prong 1620 has a triangular cross section.
  • The distal end of [0144] prong 1620 preferably further comprises an angled face 1660 terminating in puncturing surface 1630 at its distal end and at substantially planar face 1650 at its proximal end, as best seen in FIG. 16C. It should be understood that angled face 1660 may be at any angle, or may be comprised of a plurality of angled faces at various angles, so long as puncturing surface 1630 is located distal to the distal end of substantially planar face 1650.
  • Also, as shown in FIG. 16B, [0145] prong 1620 is slightly tapered so that the distal end is smaller than the proximal end. This tapering facilitates removing prong 1620 from the wall to be punctured without sticking and without detaching the chad formed in the wall. In a preferred embodiment, the angle of the taper is approximately 0.116 degrees with respect to a longitudinal axis of the prong.
  • In a preferred embodiment, [0146] puncturing device 1600 is made by injection molding of a suitable metal, such as stainless steel or titanium. Injection molding facilitates making larger prongs than could be achieved in conventional piercing devices. As discussed above, larger prongs facilitate making larger holes in the receptacle in order to optimize the emitted dose and the volume mean geometric diameter. It should be understood that puncturing device 1600 may be made of another material, such as ceramic or plastic, or by another manufacturing process, such as casting or forging. Moreover, it should be understood that the other embodiments of means for puncturing 230 depicted in FIGS. 7A-D and 9A-B could be made by any of these manufacturing processes or materials. It should also be understood that these other embodiments of means for puncturing 230 could be coupled to a base similar to base 1610 in FIGS. 16A-D.
  • FIGS. 17A through 17D schematically illustrate the use of [0147] prong 1620 to puncture and create a hanging chad in the wall 1710 of receptacle 1700. Although receptacle 1700 is illustrated in the shape of a capsule, it should be understood that the receptacle may have any other suitable shape, such as a tablet or a blister pack. Receptacle 1700 has a longitudinal axis 1770 substantially parallel to prong 1620 and a minor axis 1780 substantially perpendicular to longitudinal axis 1770.
  • As shown in FIG. 17A, puncturing [0148] surface 1630 of prong 1620 initially punctures a small opening 1740 in wall 1710. Next, as shown in FIG. 17B, prong 1620 is inserted into receptacle 1700 to a depth D, increasing the size of opening 1740 and forming chad 1750 having free end 1755. Substantially planar face 1650 forms a hinge 1760 between chad 1750 and wall 1710 so that chad 1750 is a hanging chad. Finally, as shown in FIG. 17C, prong 1620 is withdrawn from wall 1710, leaving handing chad 1750 inside of receptacle 1700. Preferably, the angle A between chad 1750 and minor axis 1780, after prong 1600 has been removed from receptacle 1700, is at least 30 to 45 degrees in order to facilitate efficient emptying of the receptacle and a high emitted dose.
  • Several experiments were performed to evaluate the emitted doses achieved using [0149] puncturing device 1630. The tests were done with size 00 capsules containing approximately 20 mg per capsule and using a flow rate of approximately 20 L/min for 1.5 seconds.
  • In the first experiment, two prototype staples similar in shape to the U-shaped staple shown in FIGS. 7A-7D but with larger prongs (referred herein as Staple #[0150] 1 and Staple #2 ) were used to puncture ten capsules. For Staple #1, the mean emitted dose from the punctured capsules was approximately 81.0%, with a standard deviation of approximately 13.3%. For Staple # 2, the mean emitted dose was approximately 51.0%, with a standard deviation of approximately 25.3%.
  • Next, the same experiments were run with Staple #[0151] 1 and Staple # 2, only this time the chads were manually opened to an angle of at least 45 degrees with respect to the receptacle after removal of the puncturing device, by using a blunt instrument. In that case, the mean emitted dose for Staple #1 was approximately 93.6%, with a standard deviation of approximately 2.4%. For Staple # 2, the mean emitted dose was approximately 93.0%, with a standard deviation of approximately 2.0%.
  • The same experiments were then run using a prototype of the [0152] puncturing device 1600 illustrated in FIGS. 16A-D (called Staple #4 ). In the experiment performed without manually opening the chads to an angle of at least 45 degrees, the mean emitted dose after using Staple #4 was approximately 89.5%, with a standard deviation of approximately 4.9%. In the experiment in which the hanging chads were manually opened to an angle of at least 45 degrees, the mean emitted dose was approximately 93.9%, with a standard deviation of approximately 1.8%. By itself, Staple #4 opens the hanging chad to an angle of at least 30 to 45 degrees. Thus, the embodiment of puncturing device 1600 illustrated in FIGS. 16A-D has significant advantages over other puncturing means, including those previously described in this application, because it yields a consistent emitted dose of at least 85% and opens the chads to an angle of at least 30 to 45 degrees.
  • Other experiments were performed to determine the puncturing depth that could be achieved using [0153] puncturing device 1630. First, Staple # 3, another prototype having almost the same structure as Staples #1 and #2, was used to puncture capsules to varying depths. It was determined that the capsules could consistently be punctured to a depth of 0.1495 inches without causing chads to become removed. Next, Staple #5, another prototype of puncturing device 1600 illustrated in FIGS. 16A-D, was used to puncture capsules to varying depths. It was determined that the prongs could be inserted to a depth of at least ¾ of the length L (see FIG. 16B) of the prongs, or approximately 0.2442 inches, without causing the chads to become removed. Accordingly, puncturing device 1600 illustrated in FIGS. 16A-D has significant advantages over other puncturing means because it allows greater depth of puncturing, which allows for greater optimization of the inhaler.
  • The present invention also relates to a method for dispensing powder medicaments to a user through the various embodiments of the disclosed inhalation device. In such a method, a receptacle containing the powder medicament, e.g., a [0154] capsule 219, is placed or formed into cylindrical chamber 210. When the user compresses the inhalation device, staple 230 is moved toward capsule 219 thereby puncturing capsule 219 to cause the release of powder into chamber 210. After release into the chamber, the powder is then inhaled by the user through apertures 224 and inhalation piece 226. As noted, inhalation piece 226, can be configured as either a mouth piece or a nose piece. For subsequent uses, the user merely replaces emptied capsule 219 with another capsule 219 that contains a new supply of power medicament. Alternatively, powder medicament is injected into a permanent receptacle that is formed into chamber 210.
  • As shown in FIGS. 18 and 19A-[0155] 19C, in another embodiment of the present invention, device 100 comprises a means for indicating readiness of the device for emitting powder 1800. The means for indicating readiness 1800 comprises a body 1820 coupled to inner casing 124 and disposed in outer casing 126. Body 1820 is reversibly moveable between a first position, as shown in FIGS. 18, 19A and 19C, and a second position, as shown in FIG. 19B. Body 1820 preferably is coupled to compression spring 244 so that it is biased in the first position. In a preferred embodiment, body 1820 comprises a hollow tube of oblong cross section, although it should be understood that body 1820 may have any other suitable shape, such as a round cylinder or rod.
  • Means for indicating [0156] readiness 1800 further comprises an indicator 1810 disposed in outer casing 126. Indicator 1810 is reversibly moveable between a rest position, as shown in FIGS. 18, 19A and 19B, and an indicating position, as shown in FIG. 19C. Indicator 1810 preferably comprises a hollow ring of oblong cross section, although it should be understood that indicator may have any other suitable shape, such as a round cylinder, a rod, or a plate.
  • Means for indicating [0157] readiness 1800 further comprises a means 1830 for coupling body 1820 and indicator 1810. In a preferred embodiment, coupling means 1830 comprises at least one lip 1836 coupled to indicator 1810 and a corresponding at least one flange 1832 coupled to indicator 1810. Each flange 1832 preferably comprises a ratchet surface 1834 to facilitate coupling and to prevent inadvertent decoupling of each lip 1836 and each flange 1832. In addition, each flange 1832 preferable also comprises a stop 1838 to prevent indicator 1810 from riding up body 1820 beyond each flange 1832. Although a preferred embodiment is illustrated, coupling means 1830 may comprise any other suitable structure for coupling body 1820 and indicator 1810, such as, for example, a friction fit engagement, a plurality of corresponding tangs and grooves, a clip, or a hook and loop fastener.
  • In a preferred embodiment, as shown in FIG. 19A, before [0158] device 100 is actuated, body 1820 is biased in the first position and indicator 1810 is in the rest position and is substantially within outer casing 126, so as to not be visible to the user. When device 100 is actuated to puncture a receptacle, body 1820 moves from the first position to the second position and further into outer casing 126, as shown in FIG. 19B. When in the second position, coupling means 1830 causes body 1820 to become coupled to indicator 1810. In the preferred embodiment illustrated in FIG. 19B, lip 1836 rides over ratchet surface 1834 of flange 1832 and becomes locked between flange 1832 and stop 1838. Preferably, indicator 1810 makes an audible click when it becomes coupled to flange 1832, which informs the user that the device has been actuated properly.
  • After [0159] device 100 is actuated, body 1820 is released and allowed to return to the first position, as shown in FIG. 19C. Because body 1820 is coupled to indicator 1810, the movement of body 1820 to the first position causes indicator 1810 to move from the rest position to the indicating position. In the indicating position, indicator 1810 is at least partially outside of outer casing 126 so that indicator 1810 is visible to the user to indicate that device 100 is ready for inhalation. Indicator 1810 preferably has a bright color, such as, for example, green, to be easily visible.
  • Upon subsequent actuations of [0160] device 100, indicator 1810 remains coupled to body 1820 and moves between the indicating position and the rest position as body 1820 moves between the first position and the second position, respectively, as shown in FIGS. 19B and 19C. In a preferred embodiment, indicator 1810 is equipped with a means 1840 for decoupling indicator 1810 from body 1820, in order to return indicator 1810 to the rest position while body 1820 remains in the first position, as shown in FIG. 19A. The decoupling means 1840 is configured so that applying an axial force to indicator 1810 decouples indicator 1810 from body 1820. In a preferred embodiment illustrated in the figures, decoupling means 1840 comprises at least one knob 1845 coupled to indicator 1810 to facilitate the user returning indicator 1810 to the rest position. It should be understood that decoupling means 1840 may have any other suitable structure, including a plurality of grooves or knobs or another type of easily graspable surface.
  • In the embodiment shown in FIGS. 19A-19C, [0161] indicator 1810 is disposed almost completely within outer casing 126 while in the rest position and is disposed partially within outer casing 126 when in the indicating position. However, it should be understood that a wide variety of other configurations are within the scope of the present invention. For example, indicator 1810 may be disposed substantially within outer casing 126 at both the rest position and the indicating position and may be viewable in one or both of these positions through a window in outer casing 126. In another alternative embodiment, indicator 1810 may be disposed in upper casing portion 130. In yet another alternative embodiment, indicator 1810 may be interchanged with body 1820 such that, for example, the body comprises a ring surrounding the indicator and the indicator is viewable through a window in the body and/or in the outer casing. In yet another alternative embodiment, indicator 1810 may be disposed in the indicating position before device 100 is ready for inhalation and in the rest position when device 100 is ready for inhalation, particularly in an embodiment in which indicator 1810 is viewable through a window in outer casing 126.
  • Means for indicating [0162] 1800 may be used with any type of inhaler, or any another type of device that utilizes a body to which is applied an axial force. For example, in an alternative embodiment, means for indicating 1800 may be used to indicate that an epinephrine injection pen, used for treating allergies, has been used or is ready for use. In another alternative embodiment, means for indicating 1800 may be used to indicate that an aerosol canister inhaler has been used or is ready for use. Means for indicating 1800 may be used with both single-use and multiple-use devices. In addition, a device containing a plurality of inhalation chambers and a plurality of receptacles may comprise a plurality means for indicating 800.
  • Conclusion
  • While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not limitation. For example, the present invention is not limited to the physical arrangements or dimensions illustrated or described. Nor is the present invention limited to any particular design or materials of construction. As such, the breadth and scope of the present invention should not be limited to any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents. [0163]

Claims (36)

What is claimed is:
1. An indicating device comprising:
a casing;
a body disposed within the casing and reversibly moveable between a first position and a second position;
an indicator reversibly moveable between a rest position and an indicating position; and
a means for coupling the body and the indicator;
wherein upon a first movement of the body from the first position to the second position the means for coupling couples the body and the indicator, and upon a second movement of the body from the second position to the first position the indicator moves from the rest position to the indicating position.
2. The indicating device of claim 1, wherein upon a subsequent movement of the body from the first position to the second position the body and the indicator remain coupled and the indicator moves from the indicating position to the rest position, and upon a subsequent movement of the body from the second position to the first position the body and the indicator remain coupled and the indicator moves from the rest position to the indicating position.
3. The indicating device of claim 1, wherein the indicator makes an audible click when the means for coupling couples the body and the indicator.
4. The indicating device of claim 1, wherein the indicator is disposed in the casing.
5. The indicating device of claim 1, wherein a portion of the indicator is outside of the casing when the indicator is in the indicating position.
6. The indicating device of claim 1, wherein the indicator comprises a ring disposed between the casing and the body.
7. The indicating device of claim 1, wherein the means for coupling comprises a lip coupled to the indicator and a flange coupled to the body for engaging the lip.
8. The indicating device of claim 7, wherein the flange comprises a ratchet surface so that the lip remains locked with the flange once the flange engages the lip.
9. The indicating device of claim 7, wherein the means for coupling further comprises a stop coupled to the body for coupling the lip between the stop and the flange.
10. The indicating device of claim 1, further comprising a means for decoupling the body and the indicator.
11. The indicating device of claim 10, wherein the means for decoupling is configured so that applying an axial force to the indicator disengages the flange from the lip.
12. The indicating device of claim 10, wherein the means for decoupling comprises a knob coupled to the indicator.
13. A device for emitting powder comprising an indicating device of claim 1.
14. The device for emitting powder of claim 13, wherein the indicating device indicates the device is ready for use when the indicator is in the indicating position.
15. An indicating device comprising:
a casing;
a body disposed within the casing and reversibly moveable between a first position and a second position;
an indicator reversibly moveable between a rest position and an indicating position;
a lip coupled to the indicator; and
a flange coupled to the body for engaging the lip;
wherein the flange engages the lip upon a first movement of the body from the first position to the second position, and wherein the engagement of the flange to the lip causes the indicator to move from the rest position to the indicating position upon a second movement of the body from the second position to the first position.
16. A device for emitting powder, comprising:
a casing, said casing comprising at least one aperture configured to emit powder therethrough;
a cylindrical chamber, defined by a straight wall of circular cross-section, disposed in said casing, said chamber having a proximal end and a distal end, said chamber comprising a ring circumferentially coupled to an inner surface of said chamber;
a body disposed within the casing and reversibly moveable between a first position and a second position;
an indicator reversibly moveable between a rest position and an indicating position; and
a means for coupling the body and the indicator;
wherein upon a first movement of the body from the first position to the second position the means for coupling couples the body and the indicator, and upon a second movement of the body from the second position to the first position the indicator moves from the rest position to the indicating position.
17. The device of claim 16, wherein the casing further comprises a hemispheric region defining said at least one aperture.
18. The device of claim 16, further comprising a second casing, the body being disposed in the second casing.
19. The device of claim 16, wherein upon a subsequent movement of the body from the first position to the second position the body and the indicator remain coupled and the indicator moves from the indicating position to the rest position, and upon a subsequent movement of the body from the second position to the first position the body and the indicator remain coupled and the indicator moves from the rest position to the indicating position.
20. The device of claim 16, wherein the indicator makes an audible click when the means for coupling couples the body and the indicator.
21. The device of claim 16, wherein a portion of the indicator is outside of the casing when the indicator is in the indicating position.
22. The device of claim 16, wherein the indicator comprises a ring disposed between the casing and the body.
23. The device of claim 16, wherein the means for coupling comprises a lip coupled to the indicator and a flange coupled to the body for engaging the lip.
24. The device of claim 23, wherein the flange comprises a ratchet surface so that the lip remains locked with the flange once the flange engages the lip.
25. The device of claim 23, wherein the means for coupling further comprises a stop coupled to the body for coupling the lip between the stop and the flange
26. The device of claim 16, further comprising a means for decoupling the body and the indicator.
27. The device of claim 26, wherein the means for decoupling is configured so that applying an axial force to the indicator disengages the flange from the lip.
28. The device of claim 26, wherein the means for decoupling comprises a knob coupled to the indicator.
29. A device for emitting powder, comprising:
a casing, said casing comprising at least one aperture configured to emit powder therethrough;
a cylindrical chamber, defined by a straight wall of circular cross-section, disposed in said casing, said chamber having a proximal end and a distal end, said chamber comprising a ring circumferentially coupled to an inner surface of said chamber;
a body disposed within the casing and reversibly moveable between a first position and a second position;
an indicator reversibly moveable between a rest position and an indicating position;
a lip coupled to the indicator; and
a flange coupled to the body for engaging the lip;
wherein the flange engages the lip upon a first movement of the body from the first position to the second position while the indicator remains in the rest position, and wherein the engagement of the flange to the lip causes the indicator to move from the rest position to the indicating position upon a second movement of the body from the second position to the first position.
30. The device for emitting powder of claim 29, wherein the casing further comprises a hemispheric region defining said at least one aperture.
31. The device for emitting powder of claim 29, further comprising a second casing, the body being disposed in the second casing.
32. A device for emitting powder, comprising:
a casing, said casing comprising at least one aperture configured to emit powder therethrough;
a cylindrical chamber, defined by a straight wall of circular cross-section, disposed in said casing, said chamber having a proximal end and a distal end, said chamber comprising a ring circumferentially coupled to an inner surface of said chamber;
a means for indicating readiness of the device for emitting powder.
33. A method for indicating the readiness of a device for dispensing a medicament, comprising:
providing a device for dispensing a medicament, the device comprising
a casing comprising at least one aperture configured to emit powder therethrough,
a body coupled to said casing and reversibly moveable between a first position and a second position, and
an indicator coupled to said casing and reversibly moveable between a rest position and an indicating position;
applying an axial force to said body to move said body from said first position to said second position, which readies the powder for dispensing and couples said body to said indicator; and
releasing said axial force from said body to allow said body to move from said second position to said first position, which moves said indicator to said indicating position.
34. The method of claim 33, further comprising
decoupling said indicator from said body; and
moving said indicator to said rest position.
35. A method of indicating that a device for dispensing a medicament has been used, comprising:
providing a device for dispensing a medicament, the device comprising
a casing comprising at least one aperture configured to emit a medicament therethrough,
a body coupled to said casing and reversibly moveable between a first position and a second position, and
an indicator coupled to said casing and reversibly moveable between a rest position and an indicating position;
applying an axial force to said body to move said body from said first position to said second position, which couples said body to said indicator;
dispensing the medicament from the device;
releasing said axial force from said body to allow said body to move from said second position to said first position, which moves said indicator to said indicating position to indicate that the device has been used.
36. The method of claim 35, further comprising
decoupling said indicator from said body; and
moving said indicator to said rest position.
US10/771,525 2001-04-16 2004-02-05 Inhalation device and method Abandoned US20040216738A1 (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050155601A1 (en) * 2004-01-16 2005-07-21 Biodel Inc. Sublingual drug delivery device
USD752204S1 (en) 2014-03-10 2016-03-22 Civitas Therapeutics, Inc. Indicator for an inhaler
USD752734S1 (en) 2014-03-10 2016-03-29 Civitas Therapeutics, Inc. Inhaler grip
USD755367S1 (en) 2014-03-10 2016-05-03 Civitas Therapeutics, Inc. Indicator for an inhaler

Families Citing this family (139)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4423457B2 (en) 1998-01-16 2010-03-03 トルーデル メディカル インターナショナル Dispenser and administration device display device
US6082358A (en) 1998-05-05 2000-07-04 1263152 Ontario Inc. Indicating device for aerosol container
US9006175B2 (en) 1999-06-29 2015-04-14 Mannkind Corporation Potentiation of glucose elimination
WO2002013897A2 (en) * 2000-08-14 2002-02-21 Advanced Inhalation Research, Inc. Inhalation device and method
GB0023654D0 (en) * 2000-09-27 2000-11-08 Cambridge Consultants Device for administering doses of particulate material
US6766799B2 (en) * 2001-04-16 2004-07-27 Advanced Inhalation Research, Inc. Inhalation device
ITMI20010357U1 (en) * 2001-06-28 2002-12-30 Plastiape Spa INHALER DEVICE
JP4437040B2 (en) * 2001-11-14 2010-03-24 ネクター セラピューティクス Aerosolization device with connectable body and end piece
ES2425392T3 (en) 2002-03-20 2013-10-15 Mannkind Corporation Cartridge for an inhalation device
WO2003079885A2 (en) 2002-03-20 2003-10-02 Advanced Inhalation Research, Inc. Inhalable sustained therapeutic formulations
PT1485154E (en) * 2002-03-20 2008-06-17 Alkermes Inc Powder inhalation device
US7004164B2 (en) * 2002-03-21 2006-02-28 Trudell Medical International Indicating device for aerosol container
SI1531794T1 (en) 2002-06-28 2017-12-29 Civitas Therapeteutics, Inc. Inhalable epinephrine
EP2065066A3 (en) * 2002-10-11 2009-07-08 Otsuka Pharmaceutical Co., Ltd. Powder inhalator
DE10258360A1 (en) 2002-12-12 2004-06-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg Chamber for accommodation of disposable capsules for powder inhalers has an inner surface with protruding elements serving as distance pieces between the capsules
US7284553B2 (en) 2002-12-12 2007-10-23 Boehringer Ingelheim Pharma Gmbh & Co. Kg Powder inhaler comprising a chamber for a capsule for taking up a non-returnable capsule being filled with an active ingredient
US20040206350A1 (en) * 2002-12-19 2004-10-21 Nektar Therapeutics Aerosolization apparatus with non-circular aerosolization chamber
EP1615689B1 (en) 2003-04-09 2016-02-03 Novartis AG Aerosolization apparatus with capsule puncture alignment guide
WO2004091705A1 (en) 2003-04-09 2004-10-28 Nektar Therapeutics Aerosolization apparatus with air inlet shield
US8869794B1 (en) 2003-04-09 2014-10-28 Novartis Pharma Ag Aerosolization apparatus with capsule puncturing member
EP1635762B1 (en) * 2003-06-13 2021-03-03 Civitas Therapeutics, Inc. Low dose pharmaceutical powders for inhalation
US7621273B2 (en) 2003-10-28 2009-11-24 Trudell Medical International Indicating device with warning dosage indicator
US7100530B2 (en) 2003-12-15 2006-09-05 Trudell Medical International, Inc. Dose indicating device
EP1755732A4 (en) * 2004-04-23 2008-01-16 Mystic Pharmaceuticals Inc Multiple unit dose drug delivery system
SE528190C2 (en) * 2004-06-07 2006-09-19 Mederio Ag Inhaler
EP1773301A2 (en) 2004-06-21 2007-04-18 Nektar Therapeutics Compositions comprising amphotericinb methods and systems
US8513204B2 (en) 2004-06-21 2013-08-20 Novartis Ag Compositions comprising amphotericin B, mehods and systems
ES2385934T3 (en) 2004-08-20 2012-08-03 Mannkind Corporation CATALYSIS OF THE SYNTHESIS OF DICETOPIPERAZINA.
WO2006023943A1 (en) 2004-08-23 2006-03-02 Mannkind Corporation Diketopiperazine salts, diketomorpholine salts or diketodioxane salts for drug delivery
US7543582B2 (en) 2004-09-20 2009-06-09 Trudell Medical International Dose indicating device with display elements attached to container
CN101090711A (en) * 2004-10-29 2007-12-19 哈佛学院校长同事会 Particles for treatment of pulmonary infection
US20060105051A1 (en) * 2004-11-18 2006-05-18 Blair Jackson Manufacture of particles for pulmonary drug delivery by carbon dioxide assisted nebulization
US20060129460A1 (en) * 2004-12-09 2006-06-15 Innerfund, Ltd. Internet service provider branded facades
US20060134009A1 (en) * 2004-12-16 2006-06-22 Daniel Deaver Low dose corticosteroid powders for inhalation
EP1838371B1 (en) 2005-01-20 2020-09-09 Trudell Medical International Dispensing device
GB0507711D0 (en) 2005-04-15 2005-05-25 Vectura Group Plc Improved blister piercing
ES2640282T3 (en) 2005-09-14 2017-11-02 Mannkind Corporation Drug formulation method based on increasing the affinity of crystalline microparticle surfaces for active agents
US20070123449A1 (en) * 2005-11-01 2007-05-31 Advanced Inhalation Research, Inc. High load particles for inhalation having rapid release properties
US8039431B2 (en) 2006-02-22 2011-10-18 Mannkind Corporation Method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and an active agent
DE102006010089A1 (en) * 2006-02-24 2007-10-18 Aha-Kunststofftechnik Gmbh The dry powder inhaler
US7832399B2 (en) * 2006-03-10 2010-11-16 One Dose, Llc Medication inhaler
US8464712B2 (en) * 2006-03-10 2013-06-18 Dose One, Llc Medication inhaler
US8360057B2 (en) * 2006-03-10 2013-01-29 Dose One, Llc Medication inhaler for dispensing multiple capsules
US8141550B2 (en) 2006-08-01 2012-03-27 Trudell Medical International Dispensing device
US20080063722A1 (en) * 2006-09-08 2008-03-13 Advanced Inhalation Research, Inc. Composition of a Spray-Dried Powder for Pulmonary Delivery of a Long Acting Neuraminidase Inhibitor (LANI)
NL1033047C2 (en) 2006-12-13 2008-06-16 Pharmachemie Bv Capsule filled with a medicine, in particular an inhalable medicine.
CA2675030C (en) 2007-01-09 2015-06-09 Mystic Pharmaceuticals, Inc. Intranasal cartridge devices
US20080210228A1 (en) * 2007-03-02 2008-09-04 Corbco, Inc. Monodose nasal sprayer
AU2008231093A1 (en) * 2007-03-22 2008-10-02 Alkermes, Inc. Coacervation process
US8683995B2 (en) 2007-05-16 2014-04-01 Mystic Pharmaceuticals, Inc. Dose dispensing containers
EP2164799B1 (en) 2007-05-16 2018-12-26 Mystic Pharmaceuticals, Inc. Combination unit dose dispensing containers
US9248076B2 (en) 2007-05-16 2016-02-02 Mystic Pharmaceuticals, Inc. Dose dispensing containers
WO2008156586A2 (en) * 2007-06-12 2008-12-24 Alkermes, Inc. Inhalation device for powdered substances
EP2200909B1 (en) * 2007-09-14 2014-12-17 Mystic Pharmaceuticals, Inc. Deep draw container forming method and device
DK2230934T3 (en) 2007-12-14 2012-11-26 Aerodesigns Inc Release of aerosolizable food products
WO2009091780A2 (en) * 2008-01-14 2009-07-23 Dr. Reddy's Laboratories Ltd. Device for inhaling powdered medicaments
US8082873B2 (en) 2008-05-05 2011-12-27 Trudell Medical International Drive mechanism for an indicating device
WO2009140587A1 (en) 2008-05-15 2009-11-19 Novartis Ag Pulmonary delivery of a fluoroquinolone
US8181591B1 (en) 2008-05-23 2012-05-22 Trudell Medical International Domed actuator for indicating device
CN104689432B (en) 2008-06-13 2018-07-06 曼金德公司 Diskus and the system for drug conveying
US8485180B2 (en) 2008-06-13 2013-07-16 Mannkind Corporation Dry powder drug delivery system
CN102065942B (en) 2008-06-20 2013-12-11 曼金德公司 An interactive apparatus and method for real-time profiling of inhalation efforts
TWI532497B (en) 2008-08-11 2016-05-11 曼凱公司 Use of ultrarapid acting insulin
EP2179760B1 (en) 2008-10-22 2013-02-27 Trudell Medical International Modular Aerosol Delivery System
US8314106B2 (en) 2008-12-29 2012-11-20 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
CA2754595C (en) 2009-03-11 2017-06-27 Mannkind Corporation Apparatus, system and method for measuring resistance of an inhaler
AU2010226613B2 (en) 2009-03-18 2013-07-25 Incarda Therapeutics, Inc. Unit doses, aerosols, kits, and methods for treating heart conditions by pulmonary administration
US20120064126A1 (en) 2009-03-26 2012-03-15 Pulmatrix, Inc. Dry powder formulations and methods for treating pulmonary diseases
WO2010144789A2 (en) 2009-06-12 2010-12-16 Mannkind Corporation Diketopiperazine microparticles with defined specific surface areas
US10166338B2 (en) 2009-09-21 2019-01-01 Novo Nordisk A/S Drug delivery system and device with cap function
CA2778698A1 (en) 2009-11-03 2011-05-12 Mannkind Corporation An apparatus and method for simulating inhalation efforts
WO2011060334A2 (en) 2009-11-12 2011-05-19 Stc.Unm Dry powder inhaler with flutter dispersion member
PT105065B (en) * 2010-04-26 2012-07-31 Hovione Farmaciencia S A A SIMPLE INHALER OF CAPSULES
EP2582421A1 (en) 2010-06-21 2013-04-24 MannKind Corporation Dry powder drug delivery system and methods
CA2809666C (en) 2010-08-30 2020-09-22 Michael M. Lipp Dry powder formulations and methods for treating pulmonary diseases
EP2448571B1 (en) 2010-08-30 2013-06-12 Pulmatrix, Inc. Respirably dry powder comprising calcium lactate, sodium chloride and leucine
CA2812414C (en) 2010-09-29 2020-09-22 Pulmatrix, Inc. Monovalent metal cation dry powders for inhalation
ES2899621T3 (en) 2010-09-29 2022-03-14 Pulmatrix Operating Co Inc Cationic dry powders comprising magnesium salt
TR201109804A2 (en) * 2010-10-07 2012-05-21 Bi̇lgi̇ç Mahmut Single dose inhalation device.
JP6050758B2 (en) 2010-12-07 2016-12-21 レスピラ セラピューティクス インコーポレイテッドRespira Therapeutics,Inc. Dry powder inhaler and method of operating the same
CA3078334C (en) 2011-04-01 2022-08-09 Mannkind Corporation Blister package for pharmaceutical cartridges
RO127873A2 (en) * 2011-04-04 2012-10-30 Salt Pharma S.R.L. Bifunctional inhalation device
WO2012174472A1 (en) 2011-06-17 2012-12-20 Mannkind Corporation High capacity diketopiperazine microparticles
MX2014004983A (en) 2011-10-24 2014-09-22 Mannkid Corp Methods and compositions for treating pain.
US10463815B2 (en) 2012-02-21 2019-11-05 Respira Therapeutics, Inc. Inhaler to deliver substances for prophylaxis or prevention of disease or injury caused by the inhalation of biological or chemical agents
WO2013130767A1 (en) 2012-02-29 2013-09-06 Pulmatrix, Inc. Inhalable dry powders
CA3098386C (en) 2012-07-12 2022-11-29 Mannkind Corporation Dry powder drug delivery systems and methods
WO2014066856A1 (en) 2012-10-26 2014-05-01 Mannkind Corporation Inhalable influenza vaccine compositions and methods
WO2014074797A1 (en) 2012-11-09 2014-05-15 Civitas Therapeutics, Inc. Ultra low density pulmonary powders
US20140150787A1 (en) 2012-12-04 2014-06-05 Civitas Therapeutics, Inc. Devices and methods for puncturing a capsule to release a powdered medicament therefrom
US9757395B2 (en) 2012-12-20 2017-09-12 Otitopic Inc. Dry powder inhaler and methods of use
US9757529B2 (en) 2012-12-20 2017-09-12 Otitopic Inc. Dry powder inhaler and methods of use
GB201301192D0 (en) 2013-01-23 2013-03-06 Vectura Delivery Devices Ltd A blister piercing element for a dry powder inhaler
WO2014144895A1 (en) 2013-03-15 2014-09-18 Mannkind Corporation Microcrystalline diketopiperazine compositions and methods
MX355658B (en) * 2013-03-28 2018-04-26 Halliburton Energy Services Inc Calibration method for multi-component induction tools.
CN105324106A (en) 2013-04-01 2016-02-10 普马特里克斯营业公司 Tiotropium dry powders
AU2013388034B2 (en) 2013-04-30 2019-08-15 Vectura Inc. Dry powder formulations and methods of use
AU2014290438B2 (en) 2013-07-18 2019-11-07 Mannkind Corporation Heat-stable dry powder pharmaceutical compositions and methods
JP2016530930A (en) 2013-08-05 2016-10-06 マンカインド コーポレイション Ventilation device and method
JP6667440B2 (en) 2013-09-21 2020-03-18 インスピリックス, インコーポレーテッドInspirx, Inc. Breath activated nebulizer
EP3086829B1 (en) * 2013-12-23 2020-03-25 Glenmark Pharmaceuticals Limited A dry powder inhaler
US11491288B2 (en) 2014-01-08 2022-11-08 Seroton, Inc. Dispenser for dry-powder inhalation devices
US10238820B2 (en) * 2014-01-08 2019-03-26 Seroton, Inc. Dry-powder inhalation device
CN112656780A (en) 2014-02-20 2021-04-16 奥迪托皮克股份有限公司 Dry powder formulations for inhalation
WO2015148905A1 (en) 2014-03-28 2015-10-01 Mannkind Corporation Use of ultrarapid acting insulin
US10561806B2 (en) 2014-10-02 2020-02-18 Mannkind Corporation Mouthpiece cover for an inhaler
MA40910A (en) 2014-11-07 2017-09-12 Civitas Therapeutics Inc RAPAMYCIN POWDERS FOR PULMONARY ADMINISTRATION
MX2017009112A (en) 2015-01-14 2018-06-15 Respira Therapeutics Inc Powder dispersion methods and devices.
AU2016257729A1 (en) 2015-05-01 2017-11-09 Civitas Therapeutics, Inc. Zolmitriptan powders for pulmonary delivery
CA2991108A1 (en) 2015-07-02 2017-01-05 Civitas Therapeutics, Inc. Triptan powders for pulmonary delivery
CN104984451A (en) * 2015-07-30 2015-10-21 中山市美捷时包装制品有限公司 Pen-shaped capsule dry powder inhaler
MX2018009248A (en) 2016-02-01 2019-01-21 Incarda Therapeutics Inc Combining electronic monitoring with inhaled pharmacological therapy to manage cardiac arrhythmias including atrial fibrillation.
WO2018002044A1 (en) 2016-06-29 2018-01-04 Novo Nordisk A/S Drug delivery device with drug differentiation feature
SG11201811250TA (en) * 2016-07-07 2019-01-30 Philip Morris Products Sa Nicotine inhaler system
TWI778052B (en) 2017-04-24 2022-09-21 美商共結晶製藥公司 Inhibitors of influenza virus replication
JP2020519628A (en) 2017-05-10 2020-07-02 インカーダ セラピューティクス, インコーポレイテッド Unit doses, aerosols, kits and methods for treating cardiac conditions by pulmonary administration
US20200275709A1 (en) * 2017-10-25 2020-09-03 Philip Morris Products S.A. Inhaler with boundary element
US11878023B2 (en) 2017-10-25 2024-01-23 Arizona Board Of Regents On Behalf Of The University Of Arizona Compositions and methods for delivering pharmaceutical agents
US11667612B2 (en) 2017-10-25 2023-06-06 Arizona Board Of Regents On Behalf Of The University Of Arizona Compositions and methods for delivering pharmaceutical agents
US11904054B2 (en) 2018-01-19 2024-02-20 Arizona Board Of Regents On Behalf Of The University Of Arizona Compositions and methods for delivering pharmaceutical agents
WO2019183470A2 (en) 2018-03-22 2019-09-26 Incarda Therapeutics, Inc. A novel method to slow ventricular rate
EP3829719A1 (en) 2018-07-27 2021-06-09 Cocrystal Pharma, Inc. Pyrrolo[2,3-b]pyridin derivatives as inhibitors of influenza virus replication
US20220056024A1 (en) 2018-09-10 2022-02-24 Cocrystal Pharma, Inc. Pyridopyrazine and pyridotriazine inhibitors of influenza virus replication
MX2021004215A (en) 2018-10-17 2021-07-15 Cocrystal Pharma Inc Combinations of inhibitors of influenza virus replication.
EP3887355A1 (en) 2018-11-26 2021-10-06 Cocrystal Pharma, Inc. Inhibitors of influenza virus replication
CN113490522B (en) * 2019-03-05 2023-10-17 菲利普莫里斯生产公司 Holder for an inhaler product
BR112021021775A2 (en) 2019-04-29 2022-01-04 Insmed Inc Dry powder compositions of treprostinil prodrugs and methods of use thereof
US20220233555A1 (en) 2019-05-24 2022-07-28 Stichting Radboud Universitair Medisch Centrum Improved administration of glycylcyclines by inhalation
US10828432B1 (en) * 2019-06-24 2020-11-10 De Motu Cordis Pty Ltd Respiratory delivery device and method
US11717621B2 (en) 2019-06-24 2023-08-08 De Motu Cordis Pty Ltd Automatic dispenser for respiratory delivery device
US11793951B2 (en) 2019-06-24 2023-10-24 De Motu Cordis Pty Ltd Automatic dispenser for respiratory delivery device and method
US11020384B2 (en) 2019-08-01 2021-06-01 Incarda Therapeutics, Inc. Antiarrhythmic formulation
WO2021188620A1 (en) 2020-03-17 2021-09-23 Cocrystal Pharma Inc. Peptidomimetic n5-methyl-n2-(nonanoyl-l-leucyl)-l-glutaminate derivatives, triazaspiro[4.14]nonadecane derivatives and similar compounds as inhibitors of norovirus and coronavirus replication
BR112022019557A2 (en) 2020-04-10 2022-12-06 Cocrystal Pharma Inc NOROVIRUS AND CORONAVIRUS REPLICATION INHIBITORS
TW202228792A (en) 2020-10-09 2022-08-01 殷漢生技股份有限公司 Nanocarrier formulations for inhalation
FR3116440A1 (en) * 2020-11-20 2022-05-27 Nemera La Verpilliere Tip for product dispensing device
WO2022189662A1 (en) 2021-03-12 2022-09-15 Alvarius Pharmaceuticals Ltd. Compositions and methods for treating addictions comprising 5-meo-dmt
AU2022322889A1 (en) 2021-08-03 2024-02-22 Cocrystal Pharma, Inc. Inhibitors for coronaviruses
WO2023150747A1 (en) 2022-02-07 2023-08-10 Insmed Incorporated Dry powder compositions of bedaquiline and salts and methods of use thereof

Citations (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3635219A (en) * 1968-06-07 1972-01-18 Fisons Pharmaceuticals Ltd Inhalation device
US3669113A (en) * 1966-03-07 1972-06-13 Fisons Ltd Inhalation device
US3795244A (en) * 1973-02-02 1974-03-05 Syntex Corp Inhalation device
US3837341A (en) * 1972-08-23 1974-09-24 Fisons Ltd Medicament inhalation device with audible indicating means
US3888253A (en) * 1972-08-04 1975-06-10 Beecham Group Ltd Device for administration of medicines
US3906950A (en) * 1973-04-04 1975-09-23 Isf Spa Inhaling device for powdered medicaments
US4013075A (en) * 1974-07-15 1977-03-22 I.S.F. S.P.A. Inhalers and insufflators having a cutting means
US4069228A (en) * 1975-06-27 1978-01-17 Bayer Aktiengesellschaft Coumarins containing sulphonylamino groups
US4069819A (en) * 1973-04-13 1978-01-24 Societa Farmaceutici S.P.A. Inhalation device
US4105027A (en) * 1975-06-13 1978-08-08 Syntex Puerto Rico, Inc. Inhalation device
US4192309A (en) * 1978-09-05 1980-03-11 Syntex Puerto Rico, Inc. Inhalation device with capsule opener
US4240418A (en) * 1974-08-22 1980-12-23 Schering Aktiengesellschaft Apparatus for the inhalation of medicinal agents
US4860740A (en) * 1980-10-30 1989-08-29 Riker Laboratories, Inc. Powder inhalation device
US4889114A (en) * 1983-12-17 1989-12-26 Boehringer Ingelheim Kg Powdered pharmaceutical inhaler
US4955285A (en) * 1984-10-08 1990-09-11 Geilinger Ag System for covering the energy requirement of a room
US5152284A (en) * 1989-02-23 1992-10-06 Phidea S.P.A. Disposable inhaler with pre-pierced capsule
US5239992A (en) * 1991-05-30 1993-08-31 Societe Francaise D'aerosols Et De Bouchage Loose powder inhaler with inhalation-actuated dosing piston
US5301666A (en) * 1991-12-14 1994-04-12 Asta Medica Aktiengesellschaft Powder inhaler
US5349947A (en) * 1993-07-15 1994-09-27 Newhouse Michael T Dry powder inhaler and process that explosively discharges a dose of powder and gas from a soft plastic pillow
US5421482A (en) * 1989-02-03 1995-06-06 Senetics, Inc. Indicator device responsive to axial force
US5595175A (en) * 1991-08-16 1997-01-21 Sandoz Ltd. Inhaler for administration of powdery substances
US5647349A (en) * 1995-06-01 1997-07-15 Unisia Jecs Corporation Medicine administering inhaling device
US5651359A (en) * 1994-10-18 1997-07-29 Sofab Device for inhaling powder
US5673686A (en) * 1994-02-02 1997-10-07 Plurichemie Anstalt Medicament inhaler and method
US5727546A (en) * 1993-08-18 1998-03-17 Fisons Plc Powder inhaler with breath flow regulation valve
US5740794A (en) * 1994-09-21 1998-04-21 Inhale Therapeutic Systems Apparatus and methods for dispersing dry powder medicaments
US5797391A (en) * 1991-03-28 1998-08-25 Rhone-Poulenc Rorer Limited Inhaler
US5810004A (en) * 1995-10-09 1998-09-22 Unisia Jecs Corporation Medicator for a capsule filled with a powdered drug
US5860419A (en) * 1990-03-02 1999-01-19 Glaxo Group Limited Inhalation device
US5896855A (en) * 1992-12-24 1999-04-27 Rhone-Poulenc Rorer Limited Multi dose inhaler apparatus
US5921237A (en) * 1995-04-24 1999-07-13 Dura Pharmaceuticals, Inc. Dry powder inhaler
US6076521A (en) * 1994-11-29 2000-06-20 Astra Aktiebolag Dose indicating device
US6089228A (en) * 1994-09-21 2000-07-18 Inhale Therapeutic Systems Apparatus and methods for dispersing dry powder medicaments
US6092522A (en) * 1990-06-14 2000-07-25 Rhone-Poulenc Rorer Limited Powder inhaler having capsule holding structure and anti-static walls
US6102035A (en) * 1995-08-10 2000-08-15 Astra Aktiebolag Inhaler
US6116237A (en) * 1996-04-29 2000-09-12 Dura Pharmaceuticals, Inc. Methods of dry powder inhalation
US6116238A (en) * 1997-12-02 2000-09-12 Dura Pharmaceuticals, Inc. Dry powder inhaler
US6142145A (en) * 1997-03-14 2000-11-07 Astra Aktiebolag Inhalation device
US6240918B1 (en) * 1996-02-21 2001-06-05 Schering Corporation Powdered medication inhaler
US6328037B1 (en) * 1998-05-05 2001-12-11 1263152 Ontario Inc. Indicating device for aerosol container
US6336453B1 (en) * 1999-04-30 2002-01-08 Trudell Medical International Indicating device for aerosol container
US6685294B2 (en) * 2001-04-30 2004-02-03 Hewlett-Packard Development Company, L.P. Method for controlling media ejection
US6729330B2 (en) * 1998-05-05 2004-05-04 Trudell Medical International Indicating device for aerosol container
US6732732B2 (en) * 2001-04-16 2004-05-11 Advanced Inhalation Research, Inc. Inhalation device and method

Family Cites Families (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3425414A (en) * 1965-05-28 1969-02-04 William J La Roche Inhalant dispenser
GB1182779A (en) * 1966-09-17 1970-03-04 Fisons Pharmaceuticals Ltd Inhalation Device
US3752027A (en) * 1970-02-09 1973-08-14 Gerber Garment Technology Inc Cutting tool for notching sheet material
IT1116047B (en) * 1979-04-27 1986-02-10 Sigma Tau Ind Farmaceuti DEVICE FOR THE QUICK INHALATION OF POWDER DRUGS BY PERSONS SUFFERING FROM ASTHMA
GB8316640D0 (en) * 1983-06-18 1983-07-20 Gill S S Introducing drainage tubing scopes/instruments into cavities
AT384552B (en) * 1985-08-01 1987-12-10 Hurka Wilhelm INHALATION DEVICE FOR DOSING AND DISTRIBUTING SOLID BODIES INTO THE BREATHING AIR
JPS63143081A (en) * 1986-12-05 1988-06-15 メクト株式会社 Inhalator
US5267965A (en) * 1988-07-06 1993-12-07 Ethicon, Inc. Safety trocar
JPH02102965A (en) 1988-10-06 1990-04-16 Aisin Aw Co Ltd Hydraulic control device in automatic transmission
IT1228459B (en) 1989-02-23 1991-06-19 Phidea S R L INHALER WITH REGULAR AND COMPLETE EMPTYING OF THE CAPSULE.
US5239991A (en) * 1989-06-21 1993-08-31 Fisons Plc Disposable powder medicament inhalation device with peel-off cover
FR2649323B1 (en) 1989-07-04 1995-06-30 Valois DEVICE FOR SPRAYING AND SPRAYING A DOSE OF A DIVIDABLE PRODUCT
DE3927170A1 (en) 1989-08-17 1991-02-21 Boehringer Ingelheim Kg INHALATOR
US5507281A (en) * 1990-08-30 1996-04-16 Boehringer Ingelheim Kg Device for initiating a mechanical switching operation in synchronism with the breathing
DE4027391A1 (en) * 1990-08-30 1992-03-12 Boehringer Ingelheim Kg GAS-FREE INHALATION DEVICE
SE9002895D0 (en) * 1990-09-12 1990-09-12 Astra Ab INHALATION DEVICES FOR DISPENSING POWDERS I
US5042472A (en) * 1990-10-15 1991-08-27 Merck & Co., Inc. Powder inhaler device
GB9026025D0 (en) * 1990-11-29 1991-01-16 Boehringer Ingelheim Kg Inhalation device
US5350393A (en) * 1992-01-06 1994-09-27 Inbae Yoon Safety trocar penetrating instrument
GB9106649D0 (en) 1991-03-28 1991-05-15 Rhone Poulenc Rorer Ltd Novel inhaler
ATE359842T1 (en) * 1991-07-02 2007-05-15 Nektar Therapeutics DISPENSING DEVICE FOR MIST-FORMED MEDICATIONS
EP0558879B1 (en) * 1992-03-04 1997-05-14 Astra Aktiebolag Disposable inhaler
GB9216038D0 (en) * 1992-07-28 1992-09-09 Bespak Plc Dispensing apparatus for powdered medicaments
PL172758B1 (en) 1992-10-19 1997-11-28 Dura Pharma Inc Dry powder inhaler
CZ287848B6 (en) * 1992-12-18 2001-02-14 Schering Corp Inhalator of powder substances
US5314417A (en) * 1992-12-22 1994-05-24 Ethicon, Inc. Safety trocar
IL108780A (en) * 1993-02-27 1999-06-20 Fisons Plc Inhalation device
DE69413528T2 (en) * 1993-04-06 1999-05-06 Minnesota Mining & Mfg DEAGGLOMERING DEVICE FOR DRY POWDER INHALERS
US5524613A (en) * 1993-08-25 1996-06-11 Habley Medical Technology Corporation Controlled multi-pharmaceutical inhaler
FI942196A (en) * 1994-05-11 1995-11-12 Orion Yhtymae Oy powder inhaler
JP3308425B2 (en) * 1995-03-10 2002-07-29 株式会社ユニシアジェックス Nasal administration device
GB9505425D0 (en) * 1995-03-17 1995-05-03 Unilever Plc Assay devices
SE9502799D0 (en) * 1995-08-10 1995-08-10 Astra Ab Device in inhalers
EP0883414B1 (en) * 1996-01-03 2001-11-21 Glaxo Group Limited Inhalation device
US5699789A (en) * 1996-03-11 1997-12-23 Hendricks; Mark R. Dry powder inhaler
DE69829139T2 (en) * 1997-01-30 2006-04-06 Hitachi, Ltd. MEDICATOR OF INTAKE TYPE
SE9700422D0 (en) * 1997-02-07 1997-02-07 Astra Ab Single dose inhaler II
SE9700421D0 (en) * 1997-02-07 1997-02-07 Astra Ab Single dose inhalation I
DE19704849B4 (en) * 1997-02-08 2011-02-17 Ing. Erich Pfeiffer Gmbh Discharge device for media
US6006747A (en) * 1997-03-20 1999-12-28 Dura Pharmaceuticals, Inc. Dry powder inhaler
CA2212430A1 (en) * 1997-08-07 1999-02-07 George Volgyesi Inhalation device
US6237590B1 (en) * 1997-09-18 2001-05-29 Delsys Pharmaceutical Corporation Dry powder delivery system apparatus
GB9810126D0 (en) * 1998-05-13 1998-07-08 Glaxo Group Ltd
US6119853A (en) * 1998-12-18 2000-09-19 Glaxo Wellcome Inc. Method and package for storing a pressurized container containing a drug
US6390291B1 (en) * 1998-12-18 2002-05-21 Smithkline Beecham Corporation Method and package for storing a pressurized container containing a drug
US6615826B1 (en) * 1999-02-26 2003-09-09 3M Innovative Properties Company Slow spray metered dose inhaler
FI108518B (en) 1999-04-23 2002-02-15 Orion Yhtymae Oyj Powder inhaler for combination medicine
ES2275544T3 (en) 1999-07-23 2007-06-16 Mannkind Corporation DRY POWDER INHALER.
EP1268139B1 (en) * 2000-04-04 2004-10-13 Wenco LLC Multi-blade cutting device
US6948494B1 (en) * 2000-05-10 2005-09-27 Innovative Devices, Llc. Medicament container with same side airflow inlet and outlet and method of use
US6443152B1 (en) * 2001-01-12 2002-09-03 Becton Dickinson And Company Medicament respiratory delivery device
WO2003041777A1 (en) 2001-11-14 2003-05-22 Nektar Therapeutics Aerosolization device with improved endpiece connection
ITMI20020078A1 (en) * 2002-01-16 2003-07-16 Fabrizio Niccolai DEVICE USABLE IN THE TREATMENT OF RESPIRATORY TRACT AFFECTIONS
US7516741B2 (en) * 2002-12-06 2009-04-14 Novartis Ag Aerosolization apparatus with feedback mechanism
EP1635762B1 (en) * 2003-06-13 2021-03-03 Civitas Therapeutics, Inc. Low dose pharmaceutical powders for inhalation

Patent Citations (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3669113A (en) * 1966-03-07 1972-06-13 Fisons Ltd Inhalation device
US3635219A (en) * 1968-06-07 1972-01-18 Fisons Pharmaceuticals Ltd Inhalation device
US3888253A (en) * 1972-08-04 1975-06-10 Beecham Group Ltd Device for administration of medicines
US3837341A (en) * 1972-08-23 1974-09-24 Fisons Ltd Medicament inhalation device with audible indicating means
US3795244A (en) * 1973-02-02 1974-03-05 Syntex Corp Inhalation device
US3906950A (en) * 1973-04-04 1975-09-23 Isf Spa Inhaling device for powdered medicaments
US4069819A (en) * 1973-04-13 1978-01-24 Societa Farmaceutici S.P.A. Inhalation device
US4013075A (en) * 1974-07-15 1977-03-22 I.S.F. S.P.A. Inhalers and insufflators having a cutting means
US4240418A (en) * 1974-08-22 1980-12-23 Schering Aktiengesellschaft Apparatus for the inhalation of medicinal agents
US4105027A (en) * 1975-06-13 1978-08-08 Syntex Puerto Rico, Inc. Inhalation device
US4069228A (en) * 1975-06-27 1978-01-17 Bayer Aktiengesellschaft Coumarins containing sulphonylamino groups
US4192309A (en) * 1978-09-05 1980-03-11 Syntex Puerto Rico, Inc. Inhalation device with capsule opener
US4860740A (en) * 1980-10-30 1989-08-29 Riker Laboratories, Inc. Powder inhalation device
US4889114A (en) * 1983-12-17 1989-12-26 Boehringer Ingelheim Kg Powdered pharmaceutical inhaler
US4955285A (en) * 1984-10-08 1990-09-11 Geilinger Ag System for covering the energy requirement of a room
US5421482A (en) * 1989-02-03 1995-06-06 Senetics, Inc. Indicator device responsive to axial force
US5152284A (en) * 1989-02-23 1992-10-06 Phidea S.P.A. Disposable inhaler with pre-pierced capsule
US5860419A (en) * 1990-03-02 1999-01-19 Glaxo Group Limited Inhalation device
US6092522A (en) * 1990-06-14 2000-07-25 Rhone-Poulenc Rorer Limited Powder inhaler having capsule holding structure and anti-static walls
US5797391A (en) * 1991-03-28 1998-08-25 Rhone-Poulenc Rorer Limited Inhaler
US5239992A (en) * 1991-05-30 1993-08-31 Societe Francaise D'aerosols Et De Bouchage Loose powder inhaler with inhalation-actuated dosing piston
US5595175A (en) * 1991-08-16 1997-01-21 Sandoz Ltd. Inhaler for administration of powdery substances
US5301666A (en) * 1991-12-14 1994-04-12 Asta Medica Aktiengesellschaft Powder inhaler
US5896855A (en) * 1992-12-24 1999-04-27 Rhone-Poulenc Rorer Limited Multi dose inhaler apparatus
US5349947A (en) * 1993-07-15 1994-09-27 Newhouse Michael T Dry powder inhaler and process that explosively discharges a dose of powder and gas from a soft plastic pillow
US5727546A (en) * 1993-08-18 1998-03-17 Fisons Plc Powder inhaler with breath flow regulation valve
US5673686A (en) * 1994-02-02 1997-10-07 Plurichemie Anstalt Medicament inhaler and method
US6089228A (en) * 1994-09-21 2000-07-18 Inhale Therapeutic Systems Apparatus and methods for dispersing dry powder medicaments
US5785049A (en) * 1994-09-21 1998-07-28 Inhale Therapeutic Systems Method and apparatus for dispersion of dry powder medicaments
US5740794A (en) * 1994-09-21 1998-04-21 Inhale Therapeutic Systems Apparatus and methods for dispersing dry powder medicaments
US5651359A (en) * 1994-10-18 1997-07-29 Sofab Device for inhaling powder
US6076521A (en) * 1994-11-29 2000-06-20 Astra Aktiebolag Dose indicating device
US5921237A (en) * 1995-04-24 1999-07-13 Dura Pharmaceuticals, Inc. Dry powder inhaler
US5647349A (en) * 1995-06-01 1997-07-15 Unisia Jecs Corporation Medicine administering inhaling device
US6102035A (en) * 1995-08-10 2000-08-15 Astra Aktiebolag Inhaler
US5810004A (en) * 1995-10-09 1998-09-22 Unisia Jecs Corporation Medicator for a capsule filled with a powdered drug
US6240918B1 (en) * 1996-02-21 2001-06-05 Schering Corporation Powdered medication inhaler
US6116237A (en) * 1996-04-29 2000-09-12 Dura Pharmaceuticals, Inc. Methods of dry powder inhalation
US6142145A (en) * 1997-03-14 2000-11-07 Astra Aktiebolag Inhalation device
US6116238A (en) * 1997-12-02 2000-09-12 Dura Pharmaceuticals, Inc. Dry powder inhaler
US6328037B1 (en) * 1998-05-05 2001-12-11 1263152 Ontario Inc. Indicating device for aerosol container
US6729330B2 (en) * 1998-05-05 2004-05-04 Trudell Medical International Indicating device for aerosol container
US6761161B2 (en) * 1998-05-05 2004-07-13 Trudell Medical International Indicating device
US6336453B1 (en) * 1999-04-30 2002-01-08 Trudell Medical International Indicating device for aerosol container
US6732732B2 (en) * 2001-04-16 2004-05-11 Advanced Inhalation Research, Inc. Inhalation device and method
US6766799B2 (en) * 2001-04-16 2004-07-27 Advanced Inhalation Research, Inc. Inhalation device
US6685294B2 (en) * 2001-04-30 2004-02-03 Hewlett-Packard Development Company, L.P. Method for controlling media ejection

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050155601A1 (en) * 2004-01-16 2005-07-21 Biodel Inc. Sublingual drug delivery device
US20080047550A2 (en) * 2004-01-16 2008-02-28 Biodel, Inc. Sublingual drug delivery device
US7658721B2 (en) * 2004-01-16 2010-02-09 Biodel Inc. Sublingual drug delivery device
USD752204S1 (en) 2014-03-10 2016-03-22 Civitas Therapeutics, Inc. Indicator for an inhaler
USD752734S1 (en) 2014-03-10 2016-03-29 Civitas Therapeutics, Inc. Inhaler grip
USD755367S1 (en) 2014-03-10 2016-05-03 Civitas Therapeutics, Inc. Indicator for an inhaler

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US20060283448A1 (en) 2006-12-21
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AU2002255808B2 (en) 2007-08-02
EP1381416A2 (en) 2004-01-21
ES2256467T3 (en) 2006-07-16
CY1108214T1 (en) 2014-02-12
WO2002083220A8 (en) 2003-03-06
US7278425B2 (en) 2007-10-09
WO2002083220A2 (en) 2002-10-24
DE60208891D1 (en) 2006-04-13
HK1061658A1 (en) 2004-09-30
CA2444129C (en) 2008-01-08
JP2004526523A (en) 2004-09-02
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US7146978B2 (en) 2006-12-12
US6766799B2 (en) 2004-07-27
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US20040154618A1 (en) 2004-08-12
EP1381416B1 (en) 2006-01-25
MXPA03009412A (en) 2005-03-07
IL158357A0 (en) 2004-05-12
ATE316397T1 (en) 2006-02-15
IL158357A (en) 2013-02-28
US20040154619A1 (en) 2004-08-12
US20040011360A1 (en) 2004-01-22
US20030150453A1 (en) 2003-08-14
CA2444129A1 (en) 2002-10-24
US6732732B2 (en) 2004-05-11
NZ528682A (en) 2005-02-25

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