EP2794964A1 - Générateurs d'aérosol - Google Patents

Générateurs d'aérosol

Info

Publication number
EP2794964A1
EP2794964A1 EP12812228.0A EP12812228A EP2794964A1 EP 2794964 A1 EP2794964 A1 EP 2794964A1 EP 12812228 A EP12812228 A EP 12812228A EP 2794964 A1 EP2794964 A1 EP 2794964A1
Authority
EP
European Patent Office
Prior art keywords
aperture plate
aperture
plate
μιη
mandrel
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.)
Granted
Application number
EP12812228.0A
Other languages
German (de)
English (en)
Other versions
EP2794964B1 (fr
Inventor
Brendan Hogan
Daniela Butan
Seamus Clifford
Michael Pomeroy
Mark Southern
David SHEIL
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.)
Stamford Devices Ltd
Original Assignee
Stamford Devices Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Stamford Devices Ltd filed Critical Stamford Devices Ltd
Priority to EP16156955.3A priority Critical patent/EP3042982A1/fr
Publication of EP2794964A1 publication Critical patent/EP2794964A1/fr
Application granted granted Critical
Publication of EP2794964B1 publication Critical patent/EP2794964B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B05B17/06—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
    • B05B17/0607—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
    • B05B17/0638—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers spray being produced by discharging the liquid or other fluent material through a plate comprising a plurality of orifices
    • B05B17/0646—Vibrating plates, i.e. plates being directly subjected to the vibrations, e.g. having a piezoelectric transducer attached thereto
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B05B17/06—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
    • B05B17/0607—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
    • B05B17/0653—Details
    • B05B17/0669—Excitation frequencies
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C5/00—Alloys based on noble metals
    • C22C5/04—Alloys based on a platinum group metal
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D1/00—Electroforming
    • C25D1/10—Moulds; Masks; Masterforms
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D3/00—Electroplating: Baths therefor
    • C25D3/02—Electroplating: Baths therefor from solutions
    • C25D3/56—Electroplating: Baths therefor from solutions of alloys
    • C25D3/567—Electroplating: Baths therefor from solutions of alloys containing more than 50% by weight of platinum group metals

Definitions

  • This invention relates to aerosol generators.
  • Aerosol generators comprising a vibratable member and a plate body operably coupled to the vibratable member are known.
  • the plate body has a top surface, a bottom surface, and a plurality of apertures extending from the top surface to the bottom surface.
  • the apertures may be tapered such that when a liquid is supplied to one surface and the aperture plate is vibrated using the vibratable member, liquid droplets are ejected from the opposite surface. Details of such known systems are described for example in US6,235,177, US2007/0023547A, and US7066398, the entire contents of which are herein incorporated by reference.
  • the aperture plate is subjected to a dynamic cyclic stress, flexing inwards and downwards with liquid passing through the upper portion and ejected through the lower portion of the aperture plate, through the action of a member comprising a piezoelectric transducer that is configured to vibrate upon application of an electric signal as described in Patent US 7,066,398.
  • Such aperture plates are usually vibrated between 100 to 200 kHz, over extended periods of time. These periods can vary as some nebulizers are reused intermittently for up to 1 year, (which might equate to approximately 800 x 15 minute nebulisation periods) and others are used continuously over short periods of up to 1 week.
  • an aperture plate body having a plurality of apertures extending between a first surface and a second surface, the plate being formed from a palladium nickel alloy comprising about 89% of palladium and about 11% nickel and having a fine randomly oriented equiaxed grain microstructure throughout the thickness of the aperture plate.
  • the average grain width may be from 0.2 ⁇ to 2.0 ⁇ , in some cases from 0.2 ⁇ to 1.0 ⁇ . In one embodiment the average grain width is approximately 0.5 ⁇ .
  • the grain width may be up to 5 ⁇ and may even be as high as 8 ⁇ .
  • One typical process which requires such high temperatures is brazing.
  • the average grain width may be from 0.2 ⁇ to 8.0 ⁇ , in some cases from 0.2 ⁇ to 5.0 ⁇ . In some embodiments the average grain width may be from 1.0 ⁇ to 4.0 ⁇
  • the aperture plate may be of any suitable thickness. In one case the aperture plate has a thickness of from 59 to 63 microns.
  • the aperture plate may have a domed - shaped geometry and the aerosol exits on the convex side of the dome-shaped plate.
  • the invention also provides an aerosol generator comprising an aperture plate of the invention and means for vibrating the aperture plate.
  • the means for vibrating the aperture plate is preferably configured to vibrate the plate at a frequency of from 125 to 155 kHz.
  • the plate may be vibrated at from 128 to 148 kHz.
  • the invention provides an aperture plate in which fatigue life is preserved and extended to ensure aersolisation over extended periods.
  • the aperture plate comprises a plate body having a top surface, a bottom surface, and a plurality of apertures that taper in a direction from the top surface to the bottom surface. Liquid is supplied to the top (rear) surface of the aperture plate, and the aperture plate is vibrated to eject liquid droplets from the bottom (front) surface. Further, the apertures have an exit angle that is in the range from about 30° to about 60°, more preferably about 41° to about 49°, and more preferably at about 45°. The apertures also have a diameter that is in the range from about 1 micron to about 10 microns at the narrowest portion of the taper.
  • Such an aperture plate is advantageous in that it may produce liquid droplets having a size that are in the range from about 2 ⁇ to about ⁇ , at a rate in the range from about 2 ⁇ 1 to about 25 ⁇ 1 per 1000 apertures per second.
  • the aperture plate may be employed to aerosolise a sufficient amount of a liquid medicament so that a capture chamber that may otherwise be employed to capture the aerosolised medicament will not be needed.
  • the aperture plate body is constructed from a palladium nickel alloy.
  • a palladium nickel alloy is corrosion resistant to many corrosive materials particularly solutions for treating respiratory diseases by inhalation therapy, such as an albuterol sulfate and ipratropium solution, which is used in many medical applications.
  • the palladium nickel alloy has a low modulus of elasticity and therefore a lower stress for a given oscillation amplitude.
  • an aperture plate that comprises a plate body having a top surface, a bottom surface, and a plurality of apertures that taper in a direction from the top surface to the bottom surface.
  • the apertures have an exit angle that is in the range from about 30° to about 60°, preferably in the range from about 41° to about 49°, more preferably at about 45°.
  • the apertures also have a diameter that is in the range from about 1 micron to about 10 microns at the narrowest portion of the taper.
  • a liquid is supplied to the top (rear) surface of the aperture plate, and the aperture plate is vibrated to eject liquid droplets from the bottom (front) surface.
  • the droplets have a size in the range from about 2 ⁇ to about ⁇ .
  • the aperture plate may be provided with as many apertures as possible, typically at least about 1,000 apertures so that a volume of liquid in the range from about 2 ⁇ 1 to about 25 ⁇ 1 may be produced within a time of less than about one second. In this way, a sufficient dosage may be aerosolized so that a patient may inhale the aerosolized medicament without the need for a capture chamber to capture and hold the prescribed amount of medicament.
  • the liquid that is supplied to the top surface is held to the top surface by surface tension forces until the liquid droplets are ejected from the bottom surface.
  • Fig. 1(a) is a micrograph of an aperture plate according to the invention with a fracture free, fine equiaxed microstructure (with a trench milled out);
  • Fig. 1(b) is a micrograph taken from the milled out trench showing a fracture free, fine equiaxed microstructure
  • Fig. 1(c) is a micrograph of an aperture plate according to the invention showing a microstructure which is somewhat larger than that of Figs la and lb, and caused by higher temperatures used in the process to assemble the aperture plate into a functioning nebuliser;
  • Fig. 2 is an FEA model of a vibrating aperture plate of the invention
  • Fig. 3 illustrates a direct relationship between the thickness of the plate and natural frequency
  • Fig. 4 illustrates an inverse relationship between the dome diameter of the plate and natural frequency
  • Fig. 5 is a side view of an aperture plate
  • Fig. 6 is a cross-sectional side view of a portion of the aperture plate of Fig. 5;
  • Fig. 7 is a more detailed view of one of the apertures of the aperture plate of Fig 6;.
  • Fig. 8 is a graph illustrating the flow rate of liquid through an aperture as the exit angle of the aperture is varied;
  • Fig. 9 is a top perspective view of a mandrel having nonconductive islands to produce an aperture plate in an electroforming process;
  • Fig. 10 is a side view of a portion of the mandrel of Fig. 9 showing one of the
  • Fig. 11 is a flow chart illustrating one method for producing an electroforming mandrel
  • Fig. 12 is a cross-sectional side view of the mandrel of Fig. 11 when used to produce an aperture plate using an electroforming process;
  • Fig. 13 is flow chart illustrating one method for producing an aperture plate
  • Fig. 14 is a cross-sectional side view of a portion of an alternative aperture plate
  • Fig. 15 is a side view of a portion of an alternative electroforming mandrel when used to form the aperture plate of Fig. 14;
  • Fig. 16 illustrates the aperture plate of Fig. 5 when used in an aerosol generator to aerosolize a liquid.
  • an aperture plate is formed from a palladium nickel alloy comprising about 89% palladium and about 11% nickel.
  • the grain width was obtained from SEM (Scanning Electron Microscope) pictures using the line intercept method for calculating the average grain size:
  • D is the average grain size
  • C is the total length of the test line used
  • N is the number of grain boundary intercepts on the line
  • M magnification of the micrograph
  • the grain structure was investigated with a Focused Ion Beam Microscope (FIB) and a FIB FEI 200 machine.
  • FIB Focused Ion Beam Microscope
  • a gallium source Ga +
  • a primary ion beam of +30keV a trench was milled ⁇ in width X 20 ⁇ length X 6 ⁇ depth.
  • the sample was then tilted at 45° and imaged at a magnification of 20,000X and the grain size, shape, and distribution observed.
  • the aperture plate also has a generally equiaxed, randomly oriented grain microstructure with an average grain width approximately 0.5 ⁇ in size - Fig. 1, through the whole thickness of the aperture plate.
  • the plate has a metallurgical configuration that is highly resistant to fatigue crack initiation and crack propagation.
  • FIB Focused Ion Beam Microscope
  • the total number of vibrational cycles and the aperture plate geometrical characteristics are optimised to ensure a fracture free vibrating plate and a prolonged fatigue life for the nebuliser.
  • NF natural frequency
  • an aperture plate undergoes an approximately 810 nebulisation periods with each nebulisation period of 15 minutes duration.
  • the total number of the aperture plate's vibrational cycles per life of a nebuliser is:
  • J n is the Bessel function
  • G0(m,n) is the natural frequency
  • R- is the radius of the membrane
  • h is the thickness of the membrane
  • the natural frequencies of the vibrating plate can be determined.
  • the first natural fre uency denoted ⁇ , ⁇ will have the formula:
  • the natural frequency is dependent on the vibrational plate's geometrical characteristics, ie thickness and plate radius (or diameter).
  • FEA Finite Element Analysis
  • the thickness of the aperture plate can be reduced or the dome diameter can be increased.
  • decreasing the plate thickness by 3 ⁇ will decrease the natural frequency up to 9 kHz and that will contribute to an increase in the fatigue life of the vibrational plate as described above.
  • an aperture plate with a generally equiaxed microstructure The fatigue life may be further enhanced using a lower specification of the thickness and natural frequency range.
  • An increase in the fatigue life of the vibrating aperture plate provides suitable aersolisation over extended periods of time.
  • the invention provides an improved aperture plate that:- extends the life of nebulisers;
  • the aperture plates of the invention are constructed of a relatively thin plate that may be formed into a desired shape and includes a plurality of apertures that are employed to produce fine liquid droplets when the aperture plate is vibrated. Techniques for vibrating such aperture plates are described generally in U.S. Pat. Nos. 5,164,740; 5,586,550; and 5,758,637, which are incorporated herein by reference.
  • the aperture plates are constructed to permit the production of relatively small liquid droplets at a relatively fast rate.
  • the aperture plates of the invention may be employed to produce liquid droplets having a size in the range from about 2 microns to about 10 microns, and more typically between about 2 microns to about 5 microns.
  • the aperture plates may be employed to produce a spray that is useful in pulmonary drug delivery procedures.
  • the sprays produced by the aperture plates may have a respirable fraction that is greater than about 70%, preferably more than about 80%, and most preferably more than about 90%> as described in U.S. Pat. No. 5,758,637.
  • such fine liquid droplets may be produced at a rate in the range from about 2 microliters per second to about 25 microliters per second per 1000 apertures.
  • aperture plates may be constructed to have multiple apertures that are sufficient to produce aerosolized volumes that are in the range from about 2 microliters to about 25 microliters, within a time that is less than about one second.
  • a rate of production is particularly useful for pulmonary drug delivery applications where a desired dosage is aerosolized at a rate sufficient to permit the aerosolised medicament to be directly inhaled. In this way, a capture chamber is not needed to capture the liquid droplets until the specified dosage has been produced.
  • the aperture plates may be included within aerosolisers, nebulizers, or inhalers that do not utilise elaborate capture chambers.
  • the aperture plate may be employed to deliver a wide variety of drugs to the respiratory system.
  • the aperture plate may be utilized to deliver drugs having potent therapeutic agents, such as hormones, peptides, and other drugs requiring precise dosing including drugs for local treatment of the respiratory system.
  • liquid drugs that may be aerosolized include drugs in solution form, e.g., aqueous solutions, ethanol solutions, aqueous/ethanol mixture solutions, and the like, in colloidal suspension form, and the like.
  • the invention may also find use in aerosolizing a variety of other types of liquids, such as insulin.
  • the palladium nickel alloy aperture plates of the invention may be used with a variety of liquids without significantly corroding the aperture plate.
  • liquids that may be used and which will not significantly corrode such an aperture plate include albuterol, chromatin, and other inhalation solutions that are normally delivered by jet nebulizers, and the like.
  • the palladium nickel alloy has a low modulus of elasticity.
  • the stress for a given oscillation amplitude is proportional to the amount of elongation and the modulus of elasticity.
  • the apertures may be constructed to have a certain shape. More specifically, the apertures are preferably tapered such that the aperture is narrower in cross section where the droplet exits the aperture.
  • the angle of the aperture at the exit opening is in the range from about 30° to about 60°, more preferably from about 41° to about 49°, and more preferably at about 45°. Such an exit angle provides for an increased flow rate while minimizing droplet size. In this way, the aperture plate may find particular use with inhalation drug delivery applications.
  • the apertures of the aperture plates will typically have an exit opening having a diameter in the range from about 1 micron to about 10 microns, to produce droplets that are about 2 microns to about 10 microns in size.
  • the taper at the exit angle is preferably within the desired angle range for at least about the first 15 microns of the aperture plate.
  • the shape of the aperture is less critical.
  • the angle of taper may increase toward the opposite surface of the aperture plate.
  • the aperture plates of the invention may be formed in the shape of a dome as described generally in U.S. Pat. No. 5,758,637.
  • the aperture plate is vibrated at a frequency in the range from about 125 kHz to about 155 kHz when aerosolising a liquid.
  • the liquid may be placed onto a rear surface of the aperture plate where the liquid adheres to the rear surface by surface tension forces.
  • liquid droplets are ejected from the front surface as described generally in U.S. Pat. Nos. 5,164,740, 5,586,550 and 5,758,637.
  • the aperture plates of the invention may be constructed using an electro-deposition process where a metal is deposited from a solution onto a conductive mandrel by an electrolytic process.
  • the aperture plates are formed using an electroforming process where the metal is electroplated onto an accurately made mandrel that has the inverse contour, dimensions, and surface finish desired on the finished aperture plate. When the desired thickness of deposited metal has been attained, the aperture plate is separated from the mandrel. Electroforming techniques are described generally in E. Paul DeGarmo, "Materials and Processes in Manufacturing” McMillan Publishing Co., Inc., New York, 5.sup.th Edition, 1979, the complete disclosure of which is herein incorporated by reference.
  • the mandrels that may be utilised to produce the aperture plates may comprise a conductive surface having a plurality of spaced apart nonconductive islands. In this way, when the mandrel is placed into the solution and current is applied to the mandrel, the metal material in the solution is deposited onto the mandrel.
  • a variety of other techniques may be employed to place a pattern of nonconductive material onto the electroforming mandrel. Examples of techniques that may be employed to produce the desired pattern include exposure, silk screening, and the like. This pattern is then employed to control where plating of the material initiates and continues throughout the plating process.
  • a variety of nonconductive materials may be employed to prevent plating on the conductive surface, such as a photoresist, plastic, and the like.
  • treatments include baking, curing, heat cycling, carving, cutting, molding or the like. Such processes may be employed to produce a curved or angled surface on the nonconducting pattern which may then be employed to modify the angle of the exit opening in the aperture plate.
  • Aperture plate 10 comprises a plate body 12 into which are formed a plurality of tapered apertures 14.
  • Plate body 12 is constructed of a palladium nickel alloy as described above.
  • the plate body 12 may be configured to have a dome shape as described generally in U.S. Pat. No. 5,758,637, previously incorporated by reference.
  • Plate body 12 includes a top or front surface 16 and a bottom or rear surface 18. In operation, liquid is supplied to rear surface 18 and liquid droplets are ejected from front surface 16.
  • apertures 14 are configured to taper from rear surface 18 to front surface 16.
  • Each aperture 14 has an entrance opening 20 and an exit opening 22.
  • liquid supplied to rear surface 18 proceeds through entrance opening 20 and exits through exit opening 22.
  • plate body 12 further includes a flared portion 24 adjacent exit opening 22. As described in greater detail hereinafter, flared portion 24 is created from the manufacturing process employed to produce aperture plate 10.
  • the angle of taper of apertures 14 as they approach exit openings 22 may be defined by an exit angle ⁇ .
  • the exit angle is selected to maximize the ejection of liquid droplets through exit opening 20 while maintaining the droplets within a desired size range.
  • Exit angle ⁇ may be constructed to be in the range from about 30° to about 60° more preferably from about 41° to about 49°, and most preferably around 45°.
  • exit opening 22 may have a diameter in the range from about 1 micron to about 10 microns.
  • the exit angle ⁇ preferably extends over a vertical distance of at least about 15 microns, i.e., exit angel ⁇ is within the above recited ranges at any point within this vertical distance . As shown, beyond this vertical distance, apertures 14 may flare outward beyond the range of the exit angle ⁇ .
  • Fig. 8 is a graph containing aerosolisation simulation data when vibrating an aperture plate similar to aperture plate 10 of Fig. 1.
  • the aperture plate was vibrated at about 180 kHz when a volume of water was applied to the rear surface.
  • Each aperture had an exit diameter of 5 microns.
  • the exit angle was varied from about 10° to about 70°. (noting that the exit angle in Fig. 8 is from the center line to the wall of the aperture).
  • the maximum flow rate per aperture occurred at about 45°.
  • Relatively high flow rates were also achieved in the range from about 41° to about 49°. Exit angles in the range from about 30° to about 60° also produced high flow rates.
  • a single aperture is capable of ejecting about 0.08 microliters of water per second when ejecting water.
  • an aperture plate containing about 1000 apertures that each have an exit angle of about 45° may be used to produce a dosage in the range from about 30 microliters to about 50 microliters within about one second. Because of such a rapid rate of production, the aerosolized medicament may be inhaled by the patient within a few inhalation manoeuvres without first being captured within a capture chamber.
  • Mandrel 26 comprises a mandrel body 28 having a conductive surface 30.
  • the mandrel body 28 may be constructed of a metal, such as stainless steel.
  • conductive surface 30 is flat in geometry. However, in some cases it will be appreciated that conductive surface 30 may be shaped depending on the desired shape of the resulting aperture plate. Disposed on conductive surface 30 are a plurality of nonconductive islands 32.
  • Islands 32 are configured to extend above conductive surface 30 so that they may be employed in electroforming apertures within the aperture plate as described in greater detail hereinafter. Islands 32 may be spaced apart by a distance corresponding to the desired spacing of the resulting apertures in the aperture plate. Similarly, the number of islands 32 may be varied depending on the particular need.
  • island 32 is generally conical or dome shaped in geometry.
  • island 32 may be defined in terms of a height h and a diameter D.
  • each island 32 may be said to include an average angle of incline or slope that is defined by the inverse tangent of 1/2 (D)/h. The average angle of incline may be varied to produce the desired exit angle in the aperture plate as previously described.
  • island 32 is constructed of a bottom layer 34 and a top layer 36. As described in greater detail hereinafter, use of such layers assists in obtaining the desired conical or domed shape. However, it will be appreciated that islands 32 may in some cases be constructed from only a single layer or multiple layers.
  • a photoresist film is then applied to the mandrel.
  • a photoresist film may comprise a thick film photoresist having a thickness in the range from about 7 to about 9 microns.
  • a thick film photoresist may comprise a Hoechst Celanese AZ P4620 positive photoresist.
  • such a resist may be pre-baked in a convection oven in air or other environment for about 30 minutes at about 100°C.
  • a mask having a pattern of circular regions is placed over the photoresist film.
  • the photoresist film is then developed to form an arrangement of nonconductive islands.
  • the resist may be developed in a basic developer, such as a Hoechst Celanese AZ 400 K developer.
  • a negative photoresist may also be used as is known in the art.
  • the islands are then treated to form the desired shape by heating the mandrel to permit the islands to flow and cure in the desired shape.
  • the conditions of the heating cycle of step 46 may be controlled to determine the extent of flow (or doming) and the extent of curing that takes place, thereby affecting the durability and permanence of the pattern.
  • the mandrel is slowly heated to an elevated temperature to obtain the desired amount of flow and curing.
  • the mandrel and the resist may be heated at a rate of about 2° C per minute from room temperature to an elevated temperature of about 240° C. The mandrel and resist are then held at the elevated temperature for about 30 minutes.
  • steps 40-46 may be repeated to place additional photoresist layers onto the islands.
  • the mask will contain circular regions that are smaller in diameter so that the added layers will be smaller in diameter to assist in producing the domed shape of the islands.
  • step 50 once the desired shape has been attained, the process ends.
  • a mandrel having a pattern of nonconductive islands is provided.
  • a mandrel may be mandrel 26 of Fig. 9 as illustrated in Fig. 12.
  • the process then proceeds to step 54 where the mandrel is placed in a solution containing a material that is to be deposited on the mandrel.
  • the solution may be a Pallatech PdNi plating solution, commercially available from Lucent Technologies, containing a palladium nickel that is to be deposited on mandrel 26.
  • electric current is supplied to the mandrel to electro deposit the material onto mandrel 26 and to form aperture plate 10.
  • the aperture plate may be peeled off from mandrel 26.
  • the time during which electric current is supplied to the mandrel may be varied.
  • the type of solution into which the mandrel is immersed may also be varied.
  • the shape and angle of islands 32 may be varied to vary the exit angle of the apertures as previously described.
  • one mandrel that may be used to produce exit angles of about 45° is made by depositing a first photoresist island having a diameter of 100 microns and a height of 10 microns.
  • the second photoresist island may have a diameter of 10 microns and a thickness of 6 microns and is deposited on a center of the first island.
  • the mandrel is then heated to a temperature of 200° C for 2 hours.
  • Aperture plate 60 comprises a plate body 62 having a plurality of tapered apertures 64 (only one being shown for convenience of illustration).
  • Plate body 62 has a rear surface 66 and a front surface 68.
  • Apertures 64 are configured to taper from rear surface 66 to front surface 68.
  • aperture 64 has a constant angle of taper.
  • the angle of taper is in the range from about 30° to about 60°, more preferably about 41° to about 49°, and most preferably at about 45°.
  • Aperture 64 further includes an exit opening 70 that may have a diameter in the range from about 2 microns to about 10 microns. Referring to Fig.
  • aperture plate 62 one method that may be employed to construct aperture plate 62 will be described.
  • the process employs the use of an electroforming mandrel 72 having a plurality of non-conductive islands 74.
  • island 74 may be constructed to be generally conical or domed-shaped in geometry and may be constructed using any of the processes previously described herein.
  • mandrel 72 is placed within a solution and electrical current is applied to mandrel 72.
  • the electroplating time is controlled so that front surface 68 of aperture plate 60 does not extend above the top of island 74.
  • the amount of electroplating time may be controlled to control the height of aperture plate 60.
  • the size of exit openings 72 may be controlled by varying the electroplating time.
  • aperture plate 10 is coupled to a cupped shaped member 78 having a central opening 80.
  • Aperture plate 10 is placed over opening 80, with rear surface 18 being adjacent liquid 76.
  • a piezoelectric transducer 82 is coupled to cupped shaped member 78.
  • An interface 84 may also be provided as a convenient way to couple the aerosol generator to other components of a device.
  • electrical current is applied to transducer 82 to vibrate aperture plate 10.
  • Liquid 76 may be held to rear surface 18 of aperture plate 10 by surface tension forces. As aperture plate 10 is vibrated, liquid droplets are ejected from the front surface as shown.
  • aperture plate 10 may be constructed so that a volume of liquid in the range from about 4 microliters to about 30 microliters may be aerosolized within a time that is less than about one second per about 1000 apertures. Further, each of the droplets may be produced such that they have a respirable fraction that is greater than about 90 percent. In this way, a medicament may be aerosolized and then directly inhaled by a patient.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Metallurgy (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Mechanical Engineering (AREA)
  • Special Spraying Apparatus (AREA)
  • Nozzles (AREA)

Abstract

Une plaque d'ouverture est formée à partir d'un alliage palladium nickel comprenant environ 89 % de palladium et environ 11 % de nickel. Il y a une microstructure de grains sensiblement équiaxe, généralement fine, à travers toute l'épaisseur de la plaque d'ouverture. La largeur moyenne de grain (W) se situe dans la plage de 0,2 µm à 5,0 µm, dans certains cas de 0,2 µm à 2,0 µm. En raison du fait que la structure de grains est équiaxe (L/W = 1), la longueur de grain (L) est la même que la largeur de grain. La plaque d'ouverture perfectionnée prolonge la durée de vie de nébuliseur, élimine le risque de défaut prématuré et imprévisible d'un nébuliseur en service, élimine le risque de retours de produits en provenance d'hôpitaux et de patients, et élimine le risque possible de fragments de la plaque d'ouverture libérés par cassure à partir du nébuliseur.
EP12812228.0A 2011-12-21 2012-12-19 Générateurs d'aérosol Active EP2794964B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP16156955.3A EP3042982A1 (fr) 2011-12-21 2012-12-19 Générateurs d'aérosol

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161578645P 2011-12-21 2011-12-21
IE20110562 2011-12-21
PCT/EP2012/076135 WO2013092701A1 (fr) 2011-12-21 2012-12-19 Générateurs d'aérosol

Related Child Applications (1)

Application Number Title Priority Date Filing Date
EP16156955.3A Division EP3042982A1 (fr) 2011-12-21 2012-12-19 Générateurs d'aérosol

Publications (2)

Publication Number Publication Date
EP2794964A1 true EP2794964A1 (fr) 2014-10-29
EP2794964B1 EP2794964B1 (fr) 2016-03-02

Family

ID=48667754

Family Applications (2)

Application Number Title Priority Date Filing Date
EP16156955.3A Withdrawn EP3042982A1 (fr) 2011-12-21 2012-12-19 Générateurs d'aérosol
EP12812228.0A Active EP2794964B1 (fr) 2011-12-21 2012-12-19 Générateurs d'aérosol

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP16156955.3A Withdrawn EP3042982A1 (fr) 2011-12-21 2012-12-19 Générateurs d'aérosol

Country Status (5)

Country Link
EP (2) EP3042982A1 (fr)
JP (1) JP6368247B2 (fr)
CN (1) CN104302813B (fr)
RU (1) RU2014121781A (fr)
WO (1) WO2013092701A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3042982A1 (fr) * 2011-12-21 2016-07-13 Stamford Devices Limited Générateurs d'aérosol

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101953970B1 (ko) * 2016-06-29 2019-03-05 동국대학교 경주캠퍼스 산학협력단 미세분무용 다공성 필터의 제조방법 및 이를 이용하여 제조된 다공성 필터

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS493369B1 (fr) * 1963-10-01 1974-01-25
US4628165A (en) * 1985-09-11 1986-12-09 Learonal, Inc. Electrical contacts and methods of making contacts by electrodeposition
US5164740A (en) 1991-04-24 1992-11-17 Yehuda Ivri High frequency printing mechanism
US5586550A (en) 1995-08-31 1996-12-24 Fluid Propulsion Technologies, Inc. Apparatus and methods for the delivery of therapeutic liquids to the respiratory system
US5758637A (en) 1995-08-31 1998-06-02 Aerogen, Inc. Liquid dispensing apparatus and methods
US6205999B1 (en) * 1995-04-05 2001-03-27 Aerogen, Inc. Methods and apparatus for storing chemical compounds in a portable inhaler
CN1042654C (zh) * 1995-06-28 1999-03-24 太原化学工业集团公司化肥厂 钯合金吸附网
US6235177B1 (en) 1999-09-09 2001-05-22 Aerogen, Inc. Method for the construction of an aperture plate for dispensing liquid droplets
US6533394B1 (en) * 2001-08-29 2003-03-18 Hewlett-Packard Company Orifice plate with break tabs and method of manufacturing
US20070097176A1 (en) * 2005-10-31 2007-05-03 Kenneth Hickey Orifice plate coated with palladium nickel alloy
JP2010540526A (ja) * 2007-09-25 2010-12-24 ノバルティス アーゲー エアロゾル化されたバンコマイシンのような薬剤での肺障害の処置
CN101637637B (zh) * 2009-06-08 2011-12-07 陕西坚瑞消防股份有限公司 一种热气溶胶灭火装置
CN101891253B (zh) * 2010-07-16 2012-08-22 中国原子能科学研究院 单分散微米级铀氧化物微粒的制备方法
CN102244976B (zh) * 2011-04-22 2013-07-31 杭州威利广光电科技股份有限公司 适于金线键合的bt线路板合金镀层
WO2013092701A1 (fr) * 2011-12-21 2013-06-27 Stamford Devices Limited Générateurs d'aérosol
EP2607524B1 (fr) * 2011-12-21 2014-09-10 Stamford Devices Limited Générateurs d'aérosol
US9522409B2 (en) * 2011-12-21 2016-12-20 Stamford Devices Limited Aerosol generators

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2013092701A1 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3042982A1 (fr) * 2011-12-21 2016-07-13 Stamford Devices Limited Générateurs d'aérosol

Also Published As

Publication number Publication date
RU2014121781A (ru) 2016-02-10
CN104302813A (zh) 2015-01-21
WO2013092701A1 (fr) 2013-06-27
EP3042982A1 (fr) 2016-07-13
JP6368247B2 (ja) 2018-08-01
EP2794964B1 (fr) 2016-03-02
JP2015511988A (ja) 2015-04-23
CN104302813B (zh) 2017-07-21

Similar Documents

Publication Publication Date Title
US20170136485A1 (en) Aerosol generators
JP4500477B2 (ja) 改良されたアパーチャプレートならびにその構築および使用のための方法
JP6235905B2 (ja) 光画成有孔プレートおよびそれを生産する方法
RU2637737C2 (ru) Способ изготовления дырчатой пластины для распылителя
US20230032517A1 (en) Method for producing an aperture plate
EP2886185A1 (fr) Membrane perforée et son procédé de préparation
EP2794964B1 (fr) Générateurs d'aérosol
EP2607524B1 (fr) Générateurs d'aérosol
WO2015011608A1 (fr) Maille destinée à être utilisée dans un nébuliseur, et procédé de fabrication de cette dernière
US9889261B2 (en) Nebulizer mesh and production method thereof
BR112014014247B1 (pt) Placa de orifícios e produtor de aerossol compreendendo a referida placa
EP2947181A1 (fr) Procédé de production d'une plaque d'ouverture

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20140616

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAX Request for extension of the european patent (deleted)
GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

INTG Intention to grant announced

Effective date: 20150812

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 778124

Country of ref document: AT

Kind code of ref document: T

Effective date: 20160315

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602012015299

Country of ref document: DE

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20160302

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 778124

Country of ref document: AT

Kind code of ref document: T

Effective date: 20160302

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160602

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160603

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 5

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160702

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160704

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602012015299

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

26N No opposition filed

Effective date: 20161205

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160602

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20161231

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20161231

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20161219

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 6

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20121219

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20161219

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 7

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160302

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230427

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20231003

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IE

Payment date: 20231002

Year of fee payment: 12

Ref country code: FR

Payment date: 20231027

Year of fee payment: 12

Ref country code: DE

Payment date: 20231030

Year of fee payment: 12