CA2078683C - Atomising devices and methods - Google Patents
Atomising devices and methodsInfo
- Publication number
- CA2078683C CA2078683C CA002078683A CA2078683A CA2078683C CA 2078683 C CA2078683 C CA 2078683C CA 002078683 A CA002078683 A CA 002078683A CA 2078683 A CA2078683 A CA 2078683A CA 2078683 C CA2078683 C CA 2078683C
- Authority
- CA
- Canada
- Prior art keywords
- fluid
- chamber
- pressure
- atomising
- metered quantity
- 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.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims description 23
- 239000007921 spray Substances 0.000 claims abstract description 76
- 229940071648 metered dose inhaler Drugs 0.000 claims abstract description 44
- 239000003814 drug Substances 0.000 claims abstract description 42
- 239000012530 fluid Substances 0.000 claims description 246
- 238000004146 energy storage Methods 0.000 claims description 52
- 230000007246 mechanism Effects 0.000 claims description 46
- 238000007599 discharging Methods 0.000 claims description 24
- 210000004072 lung Anatomy 0.000 claims description 21
- 238000004891 communication Methods 0.000 claims description 19
- 230000015572 biosynthetic process Effects 0.000 claims description 14
- 230000001105 regulatory effect Effects 0.000 claims description 7
- 206010038776 Retching Diseases 0.000 claims 1
- 239000007788 liquid Substances 0.000 abstract description 43
- 229940079593 drug Drugs 0.000 abstract description 17
- 239000002245 particle Substances 0.000 abstract description 12
- 239000007864 aqueous solution Substances 0.000 abstract description 5
- 230000000881 depressing effect Effects 0.000 abstract description 5
- 239000012263 liquid product Substances 0.000 description 23
- 239000000047 product Substances 0.000 description 19
- 239000007789 gas Substances 0.000 description 18
- 239000003380 propellant Substances 0.000 description 15
- 238000007906 compression Methods 0.000 description 10
- 230000006835 compression Effects 0.000 description 10
- 230000008901 benefit Effects 0.000 description 9
- 230000009471 action Effects 0.000 description 8
- 238000000889 atomisation Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000004033 plastic Substances 0.000 description 7
- 229920003023 plastic Polymers 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000000994 depressogenic effect Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000004810 polytetrafluoroethylene Substances 0.000 description 5
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 5
- 238000007789 sealing Methods 0.000 description 5
- 239000004677 Nylon Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229920001778 nylon Polymers 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000010304 firing Methods 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- -1 polypropylene Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000005060 rubber Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241000269627 Amphiuma means Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000002664 inhalation therapy Methods 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000010338 mechanical breakdown Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- UONOETXJSWQNOL-UHFFFAOYSA-N tungsten carbide Chemical compound [W+]#[C-] UONOETXJSWQNOL-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES 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
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
- A61M11/001—Particle size control
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES 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
- A61M15/00—Inhalators
- A61M15/0065—Inhalators with dosage or measuring devices
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B1/00—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means
- B05B1/26—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means with means for mechanically breaking-up or deflecting the jet after discharge, e.g. with fixed deflectors; Breaking-up the discharged liquid or other fluent material by impinging jets
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B1/00—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means
- B05B1/26—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means with means for mechanically breaking-up or deflecting the jet after discharge, e.g. with fixed deflectors; Breaking-up the discharged liquid or other fluent material by impinging jets
- B05B1/262—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means with means for mechanically breaking-up or deflecting the jet after discharge, e.g. with fixed deflectors; Breaking-up the discharged liquid or other fluent material by impinging jets with fixed deflectors
- B05B1/265—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means with means for mechanically breaking-up or deflecting the jet after discharge, e.g. with fixed deflectors; Breaking-up the discharged liquid or other fluent material by impinging jets with fixed deflectors the liquid or other fluent material being symmetrically deflected about the axis of the nozzle
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/0005—Components or details
- B05B11/0037—Containers
- B05B11/0039—Containers associated with means for compensating the pressure difference between the ambient pressure and the pressure inside the container, e.g. pressure relief means
- B05B11/0041—Containers associated with means for compensating the pressure difference between the ambient pressure and the pressure inside the container, e.g. pressure relief means compensating underpressure without contact of the fluid remaining in the container with the atmospheric air
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
- B05B11/02—Membranes or pistons acting on the contents inside the container, e.g. follower pistons
- B05B11/026—Membranes separating the content remaining in the container from the atmospheric air to compensate underpressure inside the container
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
- B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
- B05B11/1001—Piston pumps
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
- B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
- B05B11/1042—Components or details
- B05B11/1073—Springs
- B05B11/1074—Springs located outside pump chambers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
- B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
- B05B11/109—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle the dispensing stroke being affected by the stored energy of a spring
- B05B11/1091—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle the dispensing stroke being affected by the stored energy of a spring being first hold in a loaded state by locking means or the like, then released
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B15/00—Details of spraying plant or spraying apparatus not otherwise provided for; Accessories
- B05B15/40—Filters located upstream of the spraying outlets
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B9/00—Spraying apparatus for discharge of liquids or other fluent material, without essentially mixing with gas or vapour
- B05B9/03—Spraying apparatus for discharge of liquids or other fluent material, without essentially mixing with gas or vapour characterised by means for supplying liquid or other fluent material
- B05B9/04—Spraying apparatus for discharge of liquids or other fluent material, without essentially mixing with gas or vapour characterised by means for supplying liquid or other fluent material with pressurised or compressible container; with pump
- B05B9/08—Apparatus to be carried on or by a person, e.g. of knapsack type
- B05B9/085—Apparatus to be carried on or by a person, e.g. of knapsack type with a liquid pump
- B05B9/0877—Apparatus to be carried on or by a person, e.g. of knapsack type with a liquid pump the pump being of pressure-accumulation type or being connected to a pressure accumulation chamber
- B05B9/0883—Apparatus to be carried on or by a person, e.g. of knapsack type with a liquid pump the pump being of pressure-accumulation type or being connected to a pressure accumulation chamber having a discharge device fixed to the container
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
- G01F11/00—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it
- G01F11/02—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement
- G01F11/021—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement of the piston type
- G01F11/025—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement of the piston type with manually operated pistons
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B1/00—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means
- B05B1/34—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl
- B05B1/3405—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl to produce swirl
- B05B1/341—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl to produce swirl before discharging the liquid or other fluent material, e.g. in a swirl chamber upstream the spray outlet
- B05B1/3421—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl to produce swirl before discharging the liquid or other fluent material, e.g. in a swirl chamber upstream the spray outlet with channels emerging substantially tangentially in the swirl chamber
- B05B1/3431—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl to produce swirl before discharging the liquid or other fluent material, e.g. in a swirl chamber upstream the spray outlet with channels emerging substantially tangentially in the swirl chamber the channels being formed at the interface of cooperating elements, e.g. by means of grooves
- B05B1/3436—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl to produce swirl before discharging the liquid or other fluent material, e.g. in a swirl chamber upstream the spray outlet with channels emerging substantially tangentially in the swirl chamber the channels being formed at the interface of cooperating elements, e.g. by means of grooves the interface being a plane perpendicular to the outlet axis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Anesthesiology (AREA)
- Fluid Mechanics (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nozzles (AREA)
- Medicinal Preparation (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Saccharide Compounds (AREA)
- Application Of Or Painting With Fluid Materials (AREA)
- Massaging Devices (AREA)
- Disintegrating Or Milling (AREA)
- Crushing And Grinding (AREA)
- Pinball Game Machines (AREA)
- External Artificial Organs (AREA)
- Input Circuits Of Receivers And Coupling Of Receivers And Audio Equipment (AREA)
- Special Spraying Apparatus (AREA)
- Lift-Guide Devices, And Elevator Ropes And Cables (AREA)
- Electrostatic Spraying Apparatus (AREA)
- Steroid Compounds (AREA)
- Detail Structures Of Washing Machines And Dryers (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Colloid Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Manufacture, Treatment Of Glass Fibers (AREA)
- Developing Agents For Electrophotography (AREA)
Abstract
A metered dose inhaler comprises a piston (3) which is mounted in a cavity 12) within a body (1), and is urged by a pre-loaded spring (6) into a reduced cross-section pressure chamber (4). The piston (3) may be loaded by means of an actuating rod (31) having a handle (32), and may be latched in a loaded position by a latching means (33). A liquid drug (e.g. in aqueous solution) is contained in a collapsible bag (10). Metered quantities of the drug are successively presented in the pressure chamber (4), and then subjected to a sudden and great increase in pressure, to eject the liquid drug through an atomising head (22), to reduce it to a fine atomised spray of small mean particle size - for example, less than 30 micrometres. Non-return valves (13 and 23) control the flow of liquid through the device. The sudden pressure pulse is caused by releasing the spring loaded piston (3), upon depressing an actuating button (35) connected to the latching means (33).
Description
WO91/14U~ PCT/GB9l/~33 '3,~ 20~78683 TITLE: ATOMISING DEVICES AND METHODS
The present invention relates to atomising devices and methods, notably to self contained hand held devices for dispensing a fluid medicament as droplets of a mean size less than about 10 to 12 micrometres without the use of pressurised gas or liquefied propellants, and to methods for administering fluid droplets to a locus, notably medicaments to the nasal passages or lungs.
BACKGROUND TO THE INVENTION:
It is known to apply medicaments a sprays through the nose or mouth so that they are absorbed through the walls of the nasal passages or through the lungs. In order for the medicament to penetrate deep into the lung, for example into the alveolar sacs, it is considered necessary that the medicament particles or droplets have a mean size of less than 12 micrometres, for example from 1 to 5 micrometres.
Whilst solid particles can be prepared with a mean size of less than 5 micrometres, problems are encountered in achieving such small sized droplets in a fluid spray.
Typically, such medicaments can be dispensed by means of bursts of large volumes of compressed air which entrain small amounts of the particulate to form a dust cloud or atomise some of a fluid to form a spray of fine droplets.
However, this method results in losses of medicament and requires that the user have a source of large volumes of compressed air available and this is impractical except in a hospital environment.
For self contained hand held devices, it has been the common practice to dispense the medicament as-droplets or solid particles using a liquefied propellant medium to dispense the droplets or particles from a pressurised WO91/14~8 PCT/GB91/00433 '~7~8~ -2-container through a mechanical breakdown device, for example a swirl chamber and spray nozzle orifice. Whilst such a system enables a self contained and readily portable device to be constructed, the use of liquefied propellants is increasingly unacceptable from environmental and other grounds.
Thus, the use of chlorofluorocarbon type propellants (CFCs) is to be phased out for most uses under the Montreal Protocol of 1987 due to their alleged effect on the ozone layer of the atmosphere. However, despite this, it was considered that there was no viable alternative to the use of CFC propellants for medicaments, and their use in this field has been permitted to continue.
Furthermore, whilst it would be desirable to put up the medicament in the form of a solution to aid absorption of the active ingredient into the blood stream, many medicaments are insoluble in CFCs. In order to achieve a solution it is necessary to use co-solvents and surface-active agents which may introduce undesirable secondary components into the medicament formulation. Moreover, when such solutions are sprayed, the resultant droplets lose their CFC component through rapid evaporation. As a result, the user inhales droplets of varying sizes travelling at different speeds as their size changes. The rapid evaporation of CFCs also gives the disadvantage that the user experiencing an uncomfortable chilling effect as he inhales the spray. On the other hand, it is the very rapid evaporation of liquefied propellants which enables them to generate the high pressures within the dispenser required to discharge material from the dispenser.
Despite these problems with the use of CFCs, they are still considered by the pharmaceutical industry to be the only practicable method for administering many forms of WO91/1~68 PCT/GB91/00433 medicament. As recently as March 1990 a conference of leading experts in this field, the "Respiratory Drug Delivery II" Conference at Keystone, Colorado, USA, did not contemplate that there was any other viable method of delivery for such drugs except the use of CFCs or their close analogues, such as the HFC and HCFC propellants.
In an attempt to overcome the problems associated with CFC
propellants, there have been many proposals to adapt the mechanical pump type dispensers used to spray furniture polishes, hair lacquers and the like. In such devices a manually operated piston and cylinder or flexing diaphragm type of pump is operated by depressing and axial plunger or via a trigger type mechanism to force a fluid composition through a mechanical break up device, for example a swirl chamber and fine bore nozzle orifice, to form a spray of droplets without the use of a propellant gas or airstream.
In general, the droplets formed are of a comparatively large size, typically 30 to 200 micrometres diameter; and the volume of the spray discharged at each operation of the pump is of little concern to the user.
In order for such devices to be suitable for use in dispensing a medicament, it is necessary to control both the droplet size, notably where the spray is to penetrate into the lungs of the user as stated above, and the amount of medicament dispensed so that each actuation of the pump will deliver a consistent dose of the medicament. It has therefore been proposed to incorporate some form of measured dose mechanism into the design of such pump spray devices. This is often provided in the form of the swept volume of the cylinder of the pump used to dispense the fluid, see for example US Patents Nos 4,147,476 and 4,694,977 and PCT Application No W0 87/04373. However, where the user does not for any reason operate the pump WO91/l4~ PCT/GB91/0~33 mechanism for its full stroke, the amount of fluid dispensed can vary significantly from the desired dosage.
Furthermore, it has not hitherto been considered possible to achieve the required very small droplet size consistently. A conventional hand operated pump type sprayer is typically operated by the user manually depressing the free end of the pump housing or plunger or a trigger mechanism so as to discharge fluid held in the pump, for example from the cylinder of the pump as the piston of the pump is driven up the cylinder, see for example US Patents Nos 3,838,686, 4,693,675 and 4,694,977.
However, not only is the pressure generated by the pump comparatively low, but the pressure generated will depend upon the speed at which the pump is operated and the strength of the user. As a result, the droplet size in the spray varies from operation to operation, even with the same person operating the pump.
It has been proposed to provide a spring against which the pump mechanism acts as fluid is drawn into the pump on the sucking stroke of the pump, for example into the cylinder as the piston is retracted in a piston/cylinder type of pump, see for example US Patents Nos 3,471,065, 3,790,034, 3,797,748, 4,260,082, 4,183,449 and 4,345,718. The spring then provides a consistent driving force when released to drive the fluid out of the pump. In these proposals, the pump is designed so that fluid cannot escape from the cylinder until a release or outlet valve is operated.
Therefore, the fl~id is held within the pump under the pressure exerted by the compressed spring. When the valve is operated, the fluid is discharged from the pump under the action of the spring. Although this achieves a greater uniformity of the pressure at which the fluid is discharged, the fluid may be held under pressure within the pump before the outlet valve is operated. This can result WO91/1~8 PCT/GB91/~33 ~5~ , 2078683 in a number of problems. For example, the pump mechanism and outlet valve must be designed to resist the substantial pressures generated by the compressed spring, otherwise leakage may occur or the pump cylinder walls may rupture.
s Furthermore, where the pressure is retained for any length of time, some weepage of the fluid past the seals in the pump mechanism, for example past the seals between the piston and the cylinder wall, will occur, resulting in a loss of fluid and pressure from the cylinder. This wlll affect the volume of fluid dispensed and the droplet size in the spray which is eventually produced when the outlet valve is actuated. A further problem arises in that the user may not operate the pump mechanism for its full stroke. This will not only affect the volume of fluid lS dispensed, but will also affect the peak pressure achieved and hence the droplet size, since the spring will not be fully compressed.
In an alternative form of device proposed in US Patent No 4,892,232, the fluid is held under pressure in a main container and a pre-determined quantity is transferred to a distendable rubber or similar sleeve carried by the valve actuator stem of the outlet valve to the container. The stem is provided with suitable porting so that the sleeve is connected to the remainder of the container when the stem is in the raised position. Fluid will thus flow under pressure from the container into the annular space between the sleeve and the stem wall to expand the sleeve radially.
When the valve stem is depressed, the porting to the remainder of the container is closed and a port is opened allowing the fluid to escape from the annular space to a nozzle orifice as the sleeve is stretched axially and collapsed radially. Again, this device suffers from the problems of variable dose and variable droplet size due to variations in the speed and force used by the user in the ~ ,. ..
io 2~78~8 ~
depresslon of the valve stem and the extent to which the valve stem ls moved.
We have devised a form of atomiser device which reduces the above problems and does not use a liquefled propellant or gas stream to discharge the contents of the devlce. Whllst the devlce ls of partlcular use ln the applicatlon of medlcament flulds to the nasal passages or to the lungs, it can be used to apply a wlde range of other materlals where a simple self contalned readily portable device ls required.
In a preferred embodlment of the devlce of the lnvention the user lmparts energy to an energy storage means whlch ls retalned in the "loaded" state until required to act upon a measured dose of the fluid to discharge lt through a mechanlcal break up device or other dlscharge means. The fluld need not be held under pressure ln the devlce, thus reduclng some of the problems assoclated wlth earller proposals. Slnce the "loadlng" of the energy storage means can be lnterllnked wlth the measurement of the dose of fluld, the operatlon of a latch or other means for retalnlng of the energy storage means ln lts "loaded" state can be used to ensure that the correct dose of fluid is achieved. The device of the invention thus substantially eliminates the problems encountered with prior proposals and provides a simple and effectlve means for produclng sprays of fine sized droplets wlthout the need for pressurlzed or llquefied propellant gases.
B
~ ~078$~ ~
SUMMARY OF THE INVENTION
According to a first aspect of the present invention, there is provided a device for dispensing a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising:
a chamber for containing said metered quantity of fluid at a first pressure; an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for atomising said fluid discharged from said chamber, said atomising means comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less, whereby said fluid is atomized into droplets having a mean size suitable for inhalation into the lungs.
The invention also provides a device for dispensing fluid as a spray of droplets, comprising: a chamber for containing a quantity of fluid at a first pressure; a piston configured to act directly on said chamber to pressurize the quantity of fluid; resilient biasing means permitting withdrawal of said piston away from said chamber to a cocked position, and for urging said piston to act on said chamber so that the quantity of fluid is subjected to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of the quantity of fluid from said ~ ~7~ 3 chamber at said second pressure wherein said resilient biasing means is in a loaded state when said piston is in the cocked position; latching means for holding said resilient biasing means in the loaded state; actuating means for releasing said latching means to initiate discharge of the quantity of fluid from said chamber at said second pressure; and atomising means for atomising the quantity of fluid discharged from said chamber.
The invention further provides a device for dispensing fluid as a spray of droplets, comprising: a chamber for containing a metered quantity of fluid at a first pressure; a piston configured to act directly on said chamber to pressurize the metered quantity of fluid; resilient biasing means permitting withdrawal of said piston away from said chamber to a cocked position, and for urging said piston to act on said chamber so that the metered quantity of fluid is subjected to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of the metered quantity of fluid from said chamber at said second pressure wherein the resilient biasing means is in a loaded state when said piston is in the cocked position; latching means for holding said resilient biasing means in the loaded state; a fluid reservoir in fluid communication with said chamber, wherein the metered quantity of fluid is drawn into said chamber from said fluid reservoir when said piston is withdrawn to the cocked position; and atomising means for atomising the metered quantity of fluid discharged from said chamber.
- 7a -jv ~ ~07868 3 Preferably, the device incorporates metering means for metering said quantity of fluid, and the atomising means is provided by a mechanical break up device through which the metered quantity of fluid is passed to atomise it when it is subjected to said increase in pressure.
In a preferred embodiment, the device of the invention comprises:
a. a pressure chamber provided with an inlet connection to supply liquid to said pressure chamber, and an outlet connection to receive pressurized liquid from said pressure chamber;
b. atomising means provided at or adjacent said outlet for causing said pressurized fluid to be atomised;
c. pressurising means comprising a pulse generating means for generating one or more pulses to subject fluid within said pressure chamber to at least one predetermined increase in pressure; and d. interface means which is acted upon by said pulse(s) to vary the volume of said pressure chamber in order to increase the pressure in the chamber.
The device of the invention may further comprise one or more control means for controlling fluid flow between said pressure chamber, said inlet and said outlet.
Preferably, said pressure chamber comprises a cylinder within which a piston acting as the interface means is slideably journalled.
- 7b -C
WO91/14~8 PCT/GB91/~33 ~'- i 2078683 -8-Preferably, said pulse generating means comprises an energy storage means and a releasing means for releasing energy from the energy storage means, thereby to generate at least one pulse from the energy storage means which acts on the interface means.
The device preferably also comprises loading means for loading the energy storage means; retaining means, for example a latch or other detent means, for retaining the energy storage means in a loaded state; and release means for releasing the retaining means, thereby to release the energy storage means so as to cause the metered quantity of fluid to be discharged through the atomising means as a spray of droplets.
Accordingly, from a preferred aspect, the present invention provides a device for dispensing a fluid as a spray of droplets to a locus, which device comprises:
a. means for receiving a pre-determined quantity of the fluid to be dispensed;
b. break up means in communication with said fluid receiving means and adapted to cause the fluid to be formed into a spray of droplets;
c. an energy storage means adapted to be actuated by a user of the device, preferably to store energy imparted thereto by the user during operation of the device, and to release a pre-determined amount of energy to the pre-determined quantity of fluid in said fluid receiving means so as to subject said fluid to one or more pulses of a pre-determined increase in pressure; and d. actuator means adapted to release said stored energy to act upon said pre-determined quantity of fluid and to cause said increase in pressure in said fluid so as to discharge said quantity of fluid via said break up means so as to form said spray of droplets of said fluid.
- . ~
WO91/14~8 PCT/GB91/0~33 - 9~ ~ 2-d7g'~683 Preferably, the device of the invention comprises a piston in cylinder type pump mechanism, at least part of the bore of the cylinder acting as the pressure chamber adapted to receive a pre-determined quantity of fluid from a s reservoir, preferably corresponding to the swept volume of the pressure chamber, upon actuation of the pump on its suction stroke. The piston acts as the interface means to transmit the energy pulse(s) to the fluid in the pressure chamber. It is also preferred that the operation of the pump be interlinked with the retaining of the energy storage means in the loaded state so that the user is required to operate the pump to its full or a pre-determined extent in order to cause the retaining mechanism to engage. However, it will be appreciated that the retaining of the energy storage means may be transient and that the operation of the device may pass through the fully loaded state directly to the discharge cycle at which the energy in the storage means is released to discharge the fluid in the pressure chamber of the pump through the break up means to form the desired spray.
Preferably, the energy storage means takes the form of a compression spring. However, other forms of energy storage means can be used, for example a tension spring or bellows section to the wall of the cylinder, gas bulbs, motors, solenoids or a flexible or deformable membrane or diaphragm. In some of such energy storage means, for example a gas bulb or a motor or solenoid, the energy is already stored in the means or a battery associated therewith, and the user merely releases that energy when required. In other forms, for example a spring or flexible diaphragm, the user must impart energy to the energy storage means, ie. must load the energy storage means, whiCh energy is then released during operation of the device. For convenience, the invention will be described hereinafter in terms of a compression spring which is WO91/1~8 PCT/GB91/~33 ., i ,~ .~ , ~
located substantially co-axially below the piston of a piston in cylinder type of pump so that operation of the pump on its suction stroke causes the spring to be compressed and thus store energy for the discharge stroke of the pump. If desired, more than one spring may be used.
It is particularly preferred that the spring be at least partially pre-compressed so that the force applied by the spring as it expands does not vary greatly. The design and construction of the spring can be selected in known manner to achieve the pressure required in the pressure chamber during expansion of the spring on the discharge stroke of the pump.
The device of the invention is preferably put up in the form of a unit containing the operating mechanism of the device, for example the atomising means, the energy storage means and the fluid metering and pressure chambers; which unit can be mounted upon or can contain a removable reservoir for the fluid to be dispensed. Typically, the fluid will be contained in a collapsible container removably connected to the inlet to the pressure chamber or pump cylinder. Where large volumes of fluid are to be discharged, the reservoir can take the form of a discardable can, tube or the like onto the outlet of which the operative mechanism unit of the device of the invention is a screw, push or other fit. Part of the container can be used to provide part of the operative mechanism of the device of the invention. For example, the outlet tube of the container can be used to provide the piston of the piston in cylinder pump.
In order to achieve the high pressures required to form very fine droplets, for example less than lO micrometres mean diameter, it will usually be necessary to provide some form of mechanical advantage in the energy loading mechanism and/or in the discharge mechanism of the pump.
WO91/14K8 PCT/GB9l/~33 Thus, it will usually be desired to provide a lever or cam mechanism to aid compression of the spring; and/or to step or otherwise reduce the diameter of the pressure chamber or the outlet from the pump cylinder so as to achieve an hydraulic pressure advantage at the inlet to the atomising means. Typically, the lever mechanism will take the form of a trigger type mechanism which the user operates single handedly with the spray outlet adjacent to and directed towards the locus to which the spray is to be applied. If desired, the spray outlet can incorporate a shroud or mouthpiece to aid directionality of the spray.
As indicated above, the lever or other mechanism preferably incorporates a latch or other retaining mechanism for retaining the spring or other energy storage means in the compressed or energy loaded state prior to initiation of the discharge cycle of the device. Such a retaining means can be a simple mechanical detent or latch which physically engages the spring or the pump mechanism and prevents release of the compression in the spring until some further operation is initiated. However, the retaining means may be provided by a stepped cam or over centre type of mechanism which bears against the spring so as to hold the spring transitorily in the desired state of compression during the loading cycle, but which automatically releases the spring with continued operation of the device to discharge the fluid.
As indicated above, the device of the invention is of especial use in the formation of a spray of droplets of a medicament for inhalation by a patient. For such use it is desirable that the droplets have a mean diameter less than about 12 micrometres. However, the invention can be applied to spraying of a wide range of other materials in solution, emulsion, dispersion or suspension form to produce droplets with sizes of up to 200 micrometres or WO91/14~8 PCT/GB91/~33 ~ : -12-., ~.
20786~83 more. For convenience, the invention will be described hereinafter in terms of dispensing a spray of an aqueous solution of a medicament for inhalation into the lungs of a patient via the mouth.
For such use, the droplet size is desirably less than 10 micrometres, typically 2 to 6 micrometres. Such small droplet sizes can be achieved by atomising the fluid using a wide range of atomising or mechanical break up devices, for example ultra sonic blades, impingement of two jets of fluid or impaction of a jet or spray onto a baffle or the like. However, we prefer to form the spray by passing the fluid at high pressure through a small nozzle aperture, preferably in association with a swirl chamber or other device for causing a significant secondary flow in the fluid transverse to- the main flow at the nozzle orifice.
The optimum pressure and nozzle orifice shape and size can be determined for any given case using techniques known in the art. Thus, where very high pressures can be generated in the pump cylinder or pressure chamber, for example 300 to 500 bar, comparatively large nozzle orifice diameters can be used, for example up to 100 micrometres, typically greater than 30 to 50 micrometres. However, we prefer to operate the device of the invention with pressures of from 50 to 400 bar, preferably 100 to 350 bar; and with nozzle orifice of from 1 to 12 micrometres, notably 2 to 6 micrometres. If desired, the device of the invention can incorporate means to vary the pressure generated, for example by adjusting the extent of compression of the spring, and/or the diameter of the nozzle orifice. The pressure quoted herein are the absolute pressures achieved in the pressure chamber; and the nozzle orifice diameters are the effective hydraulic diameters.
Preferably, the atomising means comprises an outlet orifice mounted in or on a body, and ~he device of the invention WO91/14~ PCT/GB91/0~33 -13- 20~78683 further comprises a member which is moveable with respect to said body to initiate operation of said atomising or break up means, the arrangement ~eing such that such movement of said member does not cause movement of said s orifice. It is thus possible for a user to operate the device without moving the outlet nozzle, which is of benefit when applying a medicament through the mouth or nose. It is also preferred that, where the device of the invention is to be used as a Metered Dose Inhaler (MDI) for the application of a medicament to the lung, the device is provided with a shroud or mouthpiece surrounding the atomising nozzle so as to assist in containing and direction of the spray into the nose or mouth. The shroud or mouthpiece may also assist the user in inhaling the spray.
The device of the invention preferably incorporates one or more valve means or other control means for regulating the flow into and out of the pressure chamber or the pump cylinder. Thus, it will usually be necessary to provide a non-return valve on the inlet and outlet to the cylinder or pressure chamber so that fluid flows into the cylinder or pressure chamber only during the suction stroke of the pump; and fluid flows to the atomising means only when the pressure is applied to the fluid in the pressure chamber or pump cylinder. In order to reduce the risk of premature escape of fluid from the device, it may be preferred that the outlet be provided with a pressure release valve, typically set to open when a pressure in excess of 50 bar is achieved in the pressure chamber or the pump cylinder.
Alternatively, the flow to and from the pressure chamber or the pump cylinder can be controlled by a rotary or other valve mechanism which is interlinked with the operation of the trigger or other lever mechanism which is used to operate the pump and to load the energy storage means.
" .~ , , ~ ~78~83 Thus, the operatlng trlgger can be pivotally mounted on a shaft which incorporates a rotary valve so that as the trigger ls progressively depressed it not only operates the pump to suck fluid lnto the pump cyllnder through the valve, but also compresses the spring to store energy, and rotates the valve so that the connection between the cylinder and the reservoir ls shut off and the connection to the nozzle outlet opened prior to release of the spring, for example as a cam carried on the shaft goes over centre.
It is also preferred that the device of the invention incorporate one or more separation members upstream of the nozzle orlflce to reduce the risk of blockage of the fine nozzle orifice by particulate material in aqueous or other solutions of medicaments to be applied to the lung. Thus, a flne mesh fllter, a ceramlc or fritted dlsc or the llke can be incorporated into the nozzle chamber or in the outlet to the pressure chamber. Typically, the filter will have an effective aperture or mesh size which is about half the nozzle orifice diameter.
The devlce of the invention is operated by charging the pressure chamber with the required quantity of fluid; loading the energy storage means with the required amount of energy where this has not already been done as when a bulb of pressurized gas or a motor is used to drive the piston of the pump; and then releasing the energy to apply one or more pressure pulses to the fluid in the pressure chamber so as to e~ect lt through the atomising means to form the desired spray B
~ ~7~8 3 ' of fluid.
In a yet another aspect, the lnvention therefore provides a method of dlscharglng a metered quantlty of fluid as a spray of droplets by discharglng the metered quantity of fluld under pressure through an atomlslng means, comprlslng the steps of:
provlding sald metered quantlty of fluid in a chamber at whlch sald fluld ls held at a flrst pressure; applylng a predetermlned amount of energy to an energy storage means;
releaslng sald predetermlned amount of energy from sald energy storage means to sald chamber so as to sub~ect sald fluld to a predetermlned lncrease ln pressure to a second pressure and to lnltlate dlscharge of sald fluld from sald chamber; and dlscharglng sald metered quantlty of pressurlzed fluld from sald chamber as a single dlscharge from sald chamber through an outlet aperture ln the atomlslng means, sald outlet aperture havlng a hydraullc dlameter of 100 micrometers or less, thereby atomlslng sald fluld lnto droplets havlng a mean slze sultable for lnhalatlon lnto the lungs.
DESCRIPTION OF THE DRAWINGS:
For a better understandlng of the lnventlon, and to show how the same may be carrled lnto effect, lt wlll now be descrlbed, by way of lllustratlon only, wlth reference to the accompanylng dlagrammatlc drawlngs, in whlch:
Flgure 1 ls a sectlonal view of a Metered Dose Inhaler (MDI) accordlng to the lnventlon, wlth the fluld to be dlspensed carrled ln a collapslble bag removably mounted ln the devlce;
Flgure 2 ls a vlew slmllar to Flgure 1, but wlth a product to t ~78~ 3 ' be dlspensed ln a pressurlsed contalner; Flgure 3 ls a sectlonal vlew of part of an alternatlve Metered Dose Inhaler, ln whlch a product to be dlspensed ls contalned ln a collapslble tube havlng a nozzle whlch serves as a plston;
Flgure 4 ls a vlew slmllar to Flgure 3, showlng an alternatlve pressurlslng arrangement; Flgure 5 ls an enlarged detall vlew of one example of an atomlslng orlflce assembly; Flgure 6 ls an enlarged detall vlew of one example of a mechanlcal break-up orlflce; Flgure 7 lllustrates, dlagrammatlcally, an alternatlve atomlslng means; and Flgure 8 lllustrates, dlagrammatlcally, another alternatlve atomlslng means. In the Flgures, llke reference numerals denote llke or correspondlng parts.
DESCRIPTION OF THE ~ ~K~ EMBODIMENTS:
The MDI shown ln Flgure 1 comprlses a body ln whlch there ls deflned a cyllnder 2 of clrcular cross-sectlon, ln whlch a plston 3 ls mounted for reclprocatlng movement. The cyllnder 2 communlcates wlth a pressure chamber 4 of reduced cross-sectlon. The plston 3 has a reduced dlameter portlon 5 whlch seallngly engages wlthln the pressure chamber 4, by means of a plastlc [e.g. PTFE or Nylon]
- 15a -B
WO91/1~8 PCT/GB91/00433 : 2û78683 sealing cap or ring provided on the piston portion 5. The seal may be formed integrally with the reduced diameter portion 5 of the piston - for example, as a cap, rib or bead.
A pre-loaded compression spring 6 is located in the cylinder 2, between the enlarged head of the piston 3 and an opposite end wall of the cylinder 2. An operating rod 31 is connected to the piston 3, and passes through the spring 6 and through a passageway 34 in the body 1, to protrude from the body 1. At or adjacent an end of the rod 31 there is provided a handle means 32 for moving the rod 31 and the piston 3. If desired, the end of rod 31 can be connected to a trigger mechanism or lever mechanism incorporating a mechanical advantage so that the user can readily operate the device against the compressive force of spring 6. A latching means 33 provided on the body 1 engages with the rod 31, to latch the rod 31 in a loaded position, as illustrated in Figure 1. An actuating button 35 is provided, for releasing the latching means 33.
Also defined within the body 1 is a cavity 15 in which there is located a collapsible bag 10 containing the product to be dispensed [e.g. a liquid drug]. A door 16 on the side of the body 1 may be opened, in order to exchange the collapsible bag 10. By means of a connector 12, the interior of the bag 10 communicates with an inlet passage 11 which, in turn, communicates with the pressure chamber 4 via a non-return valve 13.
Also connected to the pressure chamber 4 is an outlet passage 21 which extends from the pressure chamber 4 to an atomising head 22, via a non-return valve 23 and a pressure release valve 25.
. .
~ $ . -~
WO91/14~8 PCT/GB91/~33 -17- ~
-- : 2078683 7 ,~ ' .
Optionally, the body 1 is provided with a mouthpiece 40, which affords an atomization chamber around the atomislng head 22.
In use of the MDI of Figure 1, when the piston 3 is in the s loaded position as illustrated in Figure 1, the pressure chamber 4 is full of liquid which has been supplied from the bag 10, via the passage 11 and non-return valve 13.
The compression spring 6, as mentioned above, is already pre-loaded when fitted in the cylinder 2. The loading of the spring is increased further by withdrawing the rod 31 and thereby the piston 3 to the loaded position that is illustrated in Figure 1.
The rod 31 is latched in its loaded position as illustrated in Figure 1, by the latching means 33. Upon depressing the actuating button 35, the latching means 33 is released, thereby allowing the piston 3 to move suddenly forward under the force of the compression spring 6, to impart a sudden pressure pulse to the liquid in the pressure chamber 4.
The pressure in the liquid in the pressure chamber 4 therefore quickly builds up to exceed the limit value of the pressure release valve 25, and the liquid is then ejected under high pressure through the outlet passage 21 to the atomising head 22, via the one-way valve 23. During the forward travel of the piston 3, the non-return valve 13 prevents liquid from being returned to the bag 10, via the inlet passage 11. As the liquid is ejected through the atomising head 22, it is atomised into a fine spray, which can then be inhaled. The optional mouthpiece 40 provides an atomization chamber within which the fine spray is enclosed, and facilitates the inhalation of the spray.
WO91/14~8 PCT/GB91/0~33 .. .
2o78683 To reload the MDI, the rod 31 is pulled back by means of the handle 32 against the resilient bias of the spring 6 and, at the end of its travel, the latching means 33 automatically latches the rod 31 into a latched end position. During this travel of the piston 3, liquid is sucked out of the collapsible bag 10 into the pressure chamber 4, via the inlet passage 11 and one-way valve 13.
At this time, the one-way valve 23 prevents air being sucked into the pressure chamber 4 via the outlet passage 21. Due to the latching of rod 31, the fluid in pressure chamber 4 is held at ambient pressure and there is little or no risk of loss of fluid from the chamber. The operation of latching means 33 provides the user with a clear indication when piston 3 has completed the desired travel within cylinder 2 and that the required dose of fluid has been taken-up. If the user fails to withdraw rod 31 to a sufficient extent, the latching means 33 will not engage and the user will detect the spring bias from spring 6 and will know to withdraw rod 31 further. The latching means 33 thus provides both the means for holding fluid in chamber 4 under ambient pressure and a means for alerting the user to incomplete operation of the device, hence reducing the risk of variable operation of the device.
Thus, the MDI is again in a loaded position, as illustrated in Figure 1, ready for firing.
It will be appreciated that, in use of the MDI illustrated in Figure 1, a metered dose of liquid product is pressurised and atomised in a highly accurate and repeatable manner. When the rod 31 and piston 3 are withdrawn to their loaded position, an exact metered quantity of liquid product is drawn into the pressure chamber 4. Upon releasing the latching means 33, the piston 3 is urged forwardly to impart a predetermined amount of energy to the liquid, and thereby increase its WO91/14~ PCT/GB9l/00433 2078~83 ,., ~ .
pressure by a predetermined amount. Thus, as the pressurised liquid is then ejected through the atomising head 22 of predetermined atomising characteristics, the liquid is atomised to a fine spray of predetermined mean particle size without the use of liquefied propellant or other gases.
In order to atomise the liquid to a very fine spray - for example, having a mean particle size in the range 1 to 12 micrometres - a very high pressure has to be applied to the lo liquid in the pressure chamber 4. By way of example, the capacity of the pressure chamber 4 may be 20 microlltres;
the diameter of the small end 5 of the piston 3 may be 2 mm; the diameter of the cylinder 2 may be 15 mm; the force of the spring 6 may be 100 Newtons; and the atomising head 22 may have an exit orifice of a diameter or the order of 3 to 15 micrometres. In such an arrangement, a pressure of the order of 400 bar may be generated in the liquid in the pressure chamber 4.
The cavity 15 may be open to atmosphere and at atmospheric pressure. In an alternative embodiment, the cavity 15 may be pressurised above atmospheric pressure, which helps to force the contents of the collapsible bag 10 into the pressure chamber 4, without the need to create sub-atmospheric pressures in the pressure chamber 4. This can help to avoid the formation of gas bubbles in liquid sucked into the pressure chamber 4.
The pressure release valve 25 may be optional; it may be omitted if desired. The pressure release valve 25 and non-return valve 23 may be combined as a single unit (not shown). It will be appreciated that the illustration of Figure 1 is essentially diagrammatic in nature. A
practical embodiment may be of different construction. for example, a lever or other gearing mechanism may be employed WO91/14K8 PCT/GB91/~33 ~ -20-' ~ ZU78683 to assist loading of the piston 3 against the force of the spring 6. In one example, the MDI may be provided with a cover which, when opened, automatically loads the piston 3 and latches the latching means 33, so that the MDI is then s ready for firing. The MDI would be fired by actuating the button 35, when the cover was open. In an alternative arrangement, the piston 3 may be loaded against the spring 6 and the latching means 33 latched, whilst a cover of the MDI is being closed. Thus, the device would be pre-loaded and may be fired straight away, upon opening the cover. In another variation, opening of a cover of the device may automatically load the piston 3 against the force of the spring 6, latch the latching means 33, and then automatically released the latching means 33 at the end of lS the action of the opening cover so that the latching is only transient.
The MDI of Figure l is preferably of small, pocket slze.
Since, in contrast to known MDIs, it does not have to provide an appreciable volume to contain a liquified gas propellent under pressure it can readily be made of small dimensions. Despite this, the product container, in the form of the collapsible bag lO, can contain much more medicament than conventional MDIs. For example, whereas conventional MDIs might be limited to 200 to 400 doses, an MDI constructed along the lines illustrated in Figure l may readily contain l,000 or more doses, in the collapsible bag lO. As will be appreciated, the contents of the bag lO are protected from contamination by the atmosphere and the operation of the device of the invention is by way of atomization of the fluid in chamber 4 without the use of an air blast, ie. the device of the invention operates as an airless sprayer.
When the bag lO is empty, it may simply be removed from the cavity lS and replaced with a fresh bag. Preferably, the WO91/14U~ PCT/GB91/00433 ~ ~'78'S~68 3 bag 10 includes a seal to prevent the escape of product from the bag 10, unless the bag 10 is connected to a connector such as 12.
In alternative embodiments, part of the piston and/or valve arrangement may be made disposable, together with the product container such as the collapsible bag 10.
It is to be appreciated that, in use of the illustrated MDI, there is nothing [short of catastrophic failure of the apparatus] to stop the discharge of the contents of the pressure chamber 4 as an atomised spray, once the actuating button 35 has been depressed to release the latching means 33 and thereby release the spring 6. Thus, the amount of energy applied by the spring 6 to the metered quantity of liquid in the pressure chamber 4 is absolutely predetermined, so that the increase in pressure to which the metered quantity of liquid is subjected is likewise absolutely predetermined. This objective is to be realised in all other illustrated embodiments of the invention described below.
Another feature of the MDI of Figure 1 is that the metered quantity of liquid in the pressure chamber 4 is subjected to an increase in pressure only when the actuating button 35 has been depressed to release the latching means 33 and thereby release the spring 6. This has the advantage that no seals or other means are required to constrain the highly pressurised liquid, prior to the atomization stroke.
The increase in pressure applied by spring 6 and piston 3 to the metered quantity of liquid in the pressure chamber 4 causes the pressurised liquid to pass through the atomising head 22, to be atomised thereby. This objective is to be realised in all other illustrated embodiments on the invention described below.
WO91/14~8 PCT/GB91/0~33 20-78~83 Another important advantage of the MDI of Figure 1 is that, upon depressing the actuatlng button 35 to release the latching means 33 and spring 6, the atomising head 22 does not move within the body 1 - only the button 35 moves.
This facilitates accurate direction of the atomised spray, and contrasts with a conventional vertical-axis finger pump arrangement, in which the atomising nozzle itself is depressed to initiate atomization. This would be inconvenient in a medical inhaler, since it would be difficult to direct the spray accurately. Again, this objective is to be realised in all other illustrated embodiments of the invention described below.
The MDI illustrated in Figure 2 is generally similar to that of Figure 1. However, in Figure 2, the pressure release valve 25 is not provided. Also, the product container comprises a long tube 16 in which liquid product 17 is stored under pressure, which is created by a reservoir of gas 18 stored behind the liquid 17. As the piston 3 is pulled back to a loaded position, liquid product 17 is forced into the pressure chamber 4 via the inlet passage 11 and non-return valve 13, under the pressure of the gas 18. As the liquid product 17 is used, the gas 18 expands into the tube 16, pushing the liquid product 17 ahead and losing some pressure. The initial pressure of the gas 18 should be sufficient to maintain a pressure above atmospheric, until all of the liquid product 17 is used up.
The pressure tube 16 may be made as a replaceable item, for exchange in the MDI when the liquid product 17 is used up.
Alternatively, the whole MDI may be manufactured quite cheaply of principally plastics parts, such that it may be a throw-away item. If the tube 16 is at least partly visible from the outside of the MDI, a visual check may be provided, as to the level of product remaining.
WO91/14~8 PCT/GB91/00433 In the embodiments of Flgures l and 2, the spray action is initiated by actuating of the button 35. In an alternative - arrangement, the latching mechanism 33 may be released automatically in response to a user inhaling adjacent the atomising head 22. For example, a mouthpiece such as 40 may be connected to a vane that is caused to move by pressure difference across it when a user inhales, and thereby release the latching mechanism 33 to initiate the spray. Such automatic actuating mechanisms are known in themselves, in existing MDIs.
In the embodiments of Figures 1 and 2, the stroke of the piston 3 is fixed. If desired, means may be provided for varying the stroke of the piston. Preferably, such means is calibrated, so that a user may optionally adjust the MDI
to dispense differing quantities of spray. However, it will be appreciated that, in every case, once the adjustment means has been set to a particular value, the MDI will then provide a metered dose of spray in a highly repeatable manner, just as if the stroke of the piston were fixed.
It will be appreciated that the devices of Figures l and 2 have been described above in terms of a device in which the cylinder of the pump mechanism is static and the piston moves axially therein. However, it is within the scope of the present invention to carry the cylinder upon the rod 3l and to have the piston fixed.
In the embodiment illustrated in Figure 3, a liquid product 50 is contained within a collapsible tube 5l which is formed integrally with an extended nozzle 52 which serves as a piston. The nozzle/piston 52 is located for reciprocating movement within a cylinder 53. At the end of the nozzle/piston 52 there is incorporated a simple non-return valve 54. A pressure chamber 55 is defined at the WO91/14~8 PCT/GB91/~33 ~ -24-207~683 end of the cylinder 53, and communicates via a simple non-return valve 56 with an atomising head 57.
The cylinder 53, non-return valve 56 and atomising head s7 are all contained within a casing 58, which is formed with annular ribs 59, which serve to locate the casing 58 in a first main body part 60.
The top of the product tube Sl is formed with an annular rib 6l, which serves to locate the tube 5l in a second main body part 62. Resilient bias means is provided for urging the two main body parts 60 and 62 towards one another. A
latching means is provided for latching the two main body parts 60, 62 at a predetermined distance apart, in a loaded condition, and actuating means is provided for releasing the latching means. In the interests of clarity, the resilient bias means, latching means and actuating means have not been shown in Figure 3, but, of course, examples of these have already been shown in Figures l and 2.
The embodiment of Figure 3 operates as follows: as illustrated in Figure 3, the MDI is in an unloaded or "fired" condition. By means of a suitable mechanism, the main body parts 60 and 62 are moved away from one another, to cause the nozzle/piston 52 to withdraw relative to the cylinder 53. The depressurisation in the pressure chamber 55 thereby causes the liquid product 50 to be sucked out of the tube 51, via the non-return valve 54, to fill the pressure chamber 55. During this action, the non-return valve 56 serves to prevent air from entering the pressure chamber 55 from the atomising assembly 57.
At the end of the loading stroke, the latching means operates to hold the main body parts 60, 62 apart at predetermined relative positions. Upon releasing the latching means by the actuating means, the nozzle/piston 52 WO91/l4K8 PCT/GB91/~433 ,. ,~
is suddenly urged under the action of the resilient bias means into the cylinder 53, to apply sudden pressure to the liquid product 50 in the pressure chamber 55, in a manner generally similar to that in the embodiments of Figures 1 and 2. The pressurised liquid product is then ejected under pressure into the atomising assembly 57, via the non-return valve 56, and is then atomised into a fine spray by the atomising assembly 57.
The MDI is then reloaded by the respective lever mechanism to move apart again the two main body parts 60, 62, against the force of the resilient bias means.
Thus, it will be appreciated that the embodiment of Figure 3 operates in a generally similar manner to the embodiments of Figures 1 and 2. However, in Figure 3, the product 50 is provided in a particularly convenient manner in the product tube 51 which, together with the nozzle/piston 52 and the built in simple non-return valve 54, may be exchanged as a complete throw-away unit. It will be appreciated that the product tube 51 and its integral nozzle 52 and non-return valve 54 may readily be manufactured in a relatively economical manner out of plastics materials. The user is protected from contact with the liquid product 50, except when the MDI is properly actuated. Features of the embodiments of Figures 1 and 2, including variations as discussed above, may be provided, where appropriate, in combination with features of the embodiment of Figure 3.
In the embodiment of Figure 3, either of the parts 60, 62 may be fixed in relation to a main body of the MDI, the other of the parts 60, 62 then being moveable with respect to the fixed part. Alternatively, both parts 60, 62 may be moveable with respect to a main body of the MDI.
WO91/14~8 PCT/GB91/0~33 ~ -26-In the embodiment of Figure 4, liquid product 70 is contained within a collapsible tube 7l. A nozzle 72 of the tube 71 connects with an inlet passage 73 which contains a non-return valve 74. The non-return valve 74 communicates with a flexible tube 75, which may flex between a "full"
position [illustrated in solid lines] and an "empty"
position 75a [illustrated in broken lines]. The flexible tube 75 communicates with another non-return valve 76 which, in turn, communicates with an atomising head [not shown]. The flexible tube 75 is contained within a pressure chamber 77 which is filled with a secondary liquid 78. The secondary liquid 78 communicates with a pressure pulse generator [not shown] via a passage 79.
The embodiment of Figure 4 operates as follows: when a flexible tube 75 is in its "full" position, it is full of liquid product 70 sucked from the collapsible tube 7l.
Upon applying a pressure pulse to the secondary liquid 78, the pressure in the pressure chamber 77 suddenly increases, and this causes the flexible tube 75 to be urged into its "empty" position 75a, during which action the liquid product within the tube 75 is expelled out of the non-return valve 76 to the atomising head [not shown] under high pressure, such that the atomising head atomises the liquid product into a fine spray, generally as in the preceding embodiment.
At the end of the pressure pulse, the flexible tube 75 resumes its initial "full" position and, during this action, liquid product 70 is sucked up from the collapsible tube 7l, via the non-return valve 74, into the space within the flexible tube 75. The flexible tube 75 may return to its "full" position under its own natural resilience.
Alternatively or additionally, it may be assisted in this by the application of a negative or reduced pressure pulse to the secondary liquid 78 in the pressure chamber 77.
WO91/14~8 PCT/GB91/0~33 -27- 2078~83 The pressure pulses in the secondary liquid 78 may be generated by any suitable means. However, it is important that the pressure pulses are of a predetermined amplitude and duration to ensure that a metered dose of liquid is repeatedly sucked into the flexible tube 75 and subsequently expelled therefrom under a predetermined pressure increase, to produce a repeatable spray through the atomising head.
By way of example, the pressure pulse generator may include a piston and cylinder arrangement, together with latching and actuation means, of a type generally similar to that illustrated in Figures l and 2.
Typically,, the pressure pulses may be of substantially square wave form. However, if desired, the pressure pulses may be of any predetermined shape - for example, if a time-varying spray spectrum were deliberately chosen. The important factor is that whatever the shape of the pulses, they are accurately repeatable. Thus may apply to all embodiments.
Figure 5 shows, in enlarged detail, one example of an atomising head assembly 80. An inlet passage 8l formed in a body 82 leads to an inlet chamber 83. Interposed between successive sections of the inlet chamber 83 is a filter 84.
The final section of the inlet chamber 83 leads to swirl chamber 85 which, in turn, leads to a nozzle 86.
The purpose of the filter 84 is to prevent particles from blocking the final orifice. For example, the filter 84 may be made of stainless steel mesh, having a mesh size in the range l to lO micrometres - preferably, 3 micrometres.
Figure 6 shows one example of an atomising orifice 90, which is formed in a plate 9l which may be positioned, for WO91/1~8 PCT/GB91/0~33 . .
.. . .
2~-78683 examp e, downstream of the atomising nozzle 86 in the assembly of Figure 5, as shown by chain-dot lines in that Flgure.
As may be seen in Figure 6, the final exit orifice 90 has a diameter of 6 micrometres, and an overall length of 30 micrometres, to include an inwardly tapering throat 92 at an angle of 30~ to normal and an outwardly flared mouth 93.
The orifice plate 91 has a thickness of the order of 1 mm, and a tapering inlet passage has a length of about 1 mm, tapering at an angle of 20~ from an initial entry orifice size of 70 micrometres. We have found that, surprisingly, using a final atomising orifice of the order of 6 micrometres, together with a high pressure applied to the liquid to be atomised [by means of the energy store such as the compression spring 6, etc], can lead to a very effective and uniform mean particle size of the eventual spray. Tests with an exit orifice of the order of 6 micrometres, as illustrated in Figure 6, together with a liquid pressure of the order of 300 bars, has produced a uniform spray of mean particle size of the order 5-8 micrometres. Preferably, the diameter of the exit orifice 90 is less than 100 micrometres. The preferred range for its diameter is 1 - 20 micrometres and the most preferred range is 3 - 10 micrometres.
The exit orifice 90 may be formed by piercing the plate 91 - for example, by means of a tungsten carbide needle [e.g.
similar to those used in forming spinarettes in the textile industry] or by any other suitable method.
Although it is preferred to use a small bore nozzle orifice to achieve atomization of the fluid, it is possible to use alternative atomising means. For example, as shown in Figure 7, a liquid jet 102 may be produced through an exit orifice 104 to impinge at high velocity upon an object such WO9l/1~8 PCT/GB9l/0~33 ~-2û~ 683 as a metal ball 106, which then causes the liquid to atomise. Another alternative arrangement is shown in Figure 8, where two liquid jets 110 at high velocity and pressure are caused to meet, such that the liquid becomes atomised at their meeting point.
Initial experiments with MDIs having constructions along the lines of at least some of the embodiments illustrated herein have proved to be surprisingly effective, readily providing repeatable spray doses of drugs having a mean particle size less that 30 micrometres and typically of the order of 3-10 micrometres. Mean particle sizes in the range 2 - 8 micrometres or less than 5 micrometres may be preferred. A particularly important aspect of such embodiments of the invention is that the drug can be used immediately in its water soluble form. Many drugs used at present have two formulations - one for use in an MDI, and the other for use in nebulizers usually used in hospitals.
The latter formulation is almost always an aqueous solution of the drug, so such formulations are immediately available for use with embodiments of the present invention.
By enabling application of drugs in aqueous solution with MDIs embodying the invention, new drug development may be accelerated. This is because much of the present long term testing is to ensure that the propellant (typically CFC) does not degrade or affect the drug and its effect and, of course, in the illustrated embodiments, no additional propellant agent is required.
Many of the drugs presently administered by MDIs are concerned with bronchodilators and similar drugs for treating asthma, allergies and congestive disorders.
However, it is becoming increasingly important to be able to treat other conditions (such as pneumonocystes carinii) by inhalation therapy. The reason for this is that drugs WO9l/1~68 PCT/GB91/00433 -2~078~68'~
taken via the stomach are often destroyed by stomach secretions, or that whlch does get lnto the blood stream is taken out by the liver ("first pass metabollsm"). In other cases, slde effects can be severe. Some of these new drugs are difficult to mlcronlse and, untll now, they have been admlnistered only be nebulization in hospitals, because a portable delivery method has not previously been available.
Hospital nebulizers typically comprise gas blast devices in which small quantities of liquid product are added to large quantitles of gas blasted under hlgh pressure. Large gas cylinders are required for such apparatus, which is therefore distinctly non-portable. (Certainly in the sense of a pocket-sized device, or the like). Embodiments of the present invention may readily apply such drugs to readily portable devices and an important advantage is that such embodiments may be-used immediately to administer drugs that are already tested and available for nebulizer application.
Another particularly useful advantage of the illustrated embodiments is that they may be used quite satisfactorily in an orlentation. In contrast to this, existing sprayers, both the propellant type (eg CFC) and pump action type will work only in one (usually upright) orientation. It will be appreciated that patients can not always be relied upon to be in an upright position.
As suggested above in the foregoing description, embodiments of the present invention may include product container which are a least partially transparent, so that the level of the contents may be visually checked.
A further advantage of illustrated embodiments of the invention is that they may be constructed quite satisfactorily without the use of any elastomeric sealing members. This is in contrast to all known MDIs of which we WO91/14~ PCT/GB91/~33 2 d 7 8 6 8 3 are aware, which use resilient sealing members which may possible degrade in contact with products to be dispensed, and/or in which extractable from the elastomers (eg rubbers) may leach into the products to be dispensed.
One reason why preferred embodiments of the invention can function well without the need for elastomeric seals is that the products are not stored under high pressure. High pressure exists only for a very short time! during the atomization cycle, Therefore, in the embodiments of Figures 1 and 2, for example, only a sealing cap or ring on the piston end portion 5 is required and, as mentioned above, this can be of PTFE or Nylon. In fact, it is both possible and desirable to manufacture the embodiments of Figures 1 and 2 entirely from stainless steel and approved lS plastics materials (eg polypropylene, PTFE, Nylon) which are entirely safe and non-reactive with the products to be dispensed.
If there is need for a seal at the connectors 12, this can be provided by a sealing ring or gasket of approved plastics (eg PTFE). Alternatively or additionally, the connectors such as 12 may include parts which screwthreadly engage, and at least one of which is of an approved plastic.
In the embodiment of Figure 4, it is possible if desired, to employ elastomeric seals in the pressure pulse generator (not shown). This is because the product 70 is completely isolated from such seals by the flexible tube 75 and secondary liquid 78. The flexible tube 75 is of an approved plastics (eg polypropylene, PTFE, Nylon).
In the embodiment of Figures 1 and 2, a mechanical piston, urged by a strong spring, is used to create a pressure pulse which is applied to the liquid in the pressure WO91/1~K8 PCT/GB91/0~33 2 0 7:8 6.83~ ~
chamber 4. Alternative means may be employed to produce such pressure pulses. For example, gas spring 5, electric motors, solenoids or other means may be employed.
Although above described embodiments of the invention utilize a liquid product which may typically comprise an aqueous solution of a drug, alternative fluid products may be used, For example, a fluid which is a suspension, emulsion or solution in water, alcohol or other liquid may be used.
As mentioned above, the illustrated embodiments of the invention may emit a spray at much less velocity than conventional MDIs. For example in a conventional CFC
repellant MDI, the cloud or bolus of spray that is emitted may travel at a speed of the order of 30 metres per second.
Preferred embodiments of the present invention may release an équivalent amount of spray at a quarter of this speed.
In fact it is possible to design embodiments of the present invention to match the optimum inhalation rate of the user at a figure of the order of 60 litres per minute.
The illustrated embodiments of the invention include means for metering a quantity of fluid to be atomised. In alternative embodiments atomising devices may be provided with pre-metered quantities of fluid to be atomised. For example a strip of foil or plastics material (or other material) may contain individual pre-metered doses of liquid product and the strip could be punctured locally prior to or as part of a pressurising operation, following which the liquid is atomised to a fine spray. To this end, the strip may be pre-weakened at pre-determined locations, to promote correct rupturing of the strip material when required. Alternatively pre-metered doses of liquid product may be contained in individual capsules which are fed successively to a pressure chamber or other WO91/1~68 PCT/GB91/0~33 ;'~ 0~78~83 pressurizing location where the capsules are then ruptured.
The strip mate~-al or capsules may be designed to rupture at a pre-determined pressure applied by the atomising device, such that a pressure release effect is created in the liquid product upon rupture.
The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification and which are open to public inspection with this specification, and the contents of all such lo papers and documents are incorporated herein by reference.
All of the features disclosed in this specification (including any accompanying claims, abstract and drawings) and/or all of the steps of any method or process so disclosed, may be -combined in any combination, except combinations where at lease some of such features and/or steps are mutually exclusive.
Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, useless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.
The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in the specification (including any accompanying claims, abstract and drawings), or to any one novel one, or any novel combination, of the steps of any method or process so disclosed.
. ~
The present invention relates to atomising devices and methods, notably to self contained hand held devices for dispensing a fluid medicament as droplets of a mean size less than about 10 to 12 micrometres without the use of pressurised gas or liquefied propellants, and to methods for administering fluid droplets to a locus, notably medicaments to the nasal passages or lungs.
BACKGROUND TO THE INVENTION:
It is known to apply medicaments a sprays through the nose or mouth so that they are absorbed through the walls of the nasal passages or through the lungs. In order for the medicament to penetrate deep into the lung, for example into the alveolar sacs, it is considered necessary that the medicament particles or droplets have a mean size of less than 12 micrometres, for example from 1 to 5 micrometres.
Whilst solid particles can be prepared with a mean size of less than 5 micrometres, problems are encountered in achieving such small sized droplets in a fluid spray.
Typically, such medicaments can be dispensed by means of bursts of large volumes of compressed air which entrain small amounts of the particulate to form a dust cloud or atomise some of a fluid to form a spray of fine droplets.
However, this method results in losses of medicament and requires that the user have a source of large volumes of compressed air available and this is impractical except in a hospital environment.
For self contained hand held devices, it has been the common practice to dispense the medicament as-droplets or solid particles using a liquefied propellant medium to dispense the droplets or particles from a pressurised WO91/14~8 PCT/GB91/00433 '~7~8~ -2-container through a mechanical breakdown device, for example a swirl chamber and spray nozzle orifice. Whilst such a system enables a self contained and readily portable device to be constructed, the use of liquefied propellants is increasingly unacceptable from environmental and other grounds.
Thus, the use of chlorofluorocarbon type propellants (CFCs) is to be phased out for most uses under the Montreal Protocol of 1987 due to their alleged effect on the ozone layer of the atmosphere. However, despite this, it was considered that there was no viable alternative to the use of CFC propellants for medicaments, and their use in this field has been permitted to continue.
Furthermore, whilst it would be desirable to put up the medicament in the form of a solution to aid absorption of the active ingredient into the blood stream, many medicaments are insoluble in CFCs. In order to achieve a solution it is necessary to use co-solvents and surface-active agents which may introduce undesirable secondary components into the medicament formulation. Moreover, when such solutions are sprayed, the resultant droplets lose their CFC component through rapid evaporation. As a result, the user inhales droplets of varying sizes travelling at different speeds as their size changes. The rapid evaporation of CFCs also gives the disadvantage that the user experiencing an uncomfortable chilling effect as he inhales the spray. On the other hand, it is the very rapid evaporation of liquefied propellants which enables them to generate the high pressures within the dispenser required to discharge material from the dispenser.
Despite these problems with the use of CFCs, they are still considered by the pharmaceutical industry to be the only practicable method for administering many forms of WO91/1~68 PCT/GB91/00433 medicament. As recently as March 1990 a conference of leading experts in this field, the "Respiratory Drug Delivery II" Conference at Keystone, Colorado, USA, did not contemplate that there was any other viable method of delivery for such drugs except the use of CFCs or their close analogues, such as the HFC and HCFC propellants.
In an attempt to overcome the problems associated with CFC
propellants, there have been many proposals to adapt the mechanical pump type dispensers used to spray furniture polishes, hair lacquers and the like. In such devices a manually operated piston and cylinder or flexing diaphragm type of pump is operated by depressing and axial plunger or via a trigger type mechanism to force a fluid composition through a mechanical break up device, for example a swirl chamber and fine bore nozzle orifice, to form a spray of droplets without the use of a propellant gas or airstream.
In general, the droplets formed are of a comparatively large size, typically 30 to 200 micrometres diameter; and the volume of the spray discharged at each operation of the pump is of little concern to the user.
In order for such devices to be suitable for use in dispensing a medicament, it is necessary to control both the droplet size, notably where the spray is to penetrate into the lungs of the user as stated above, and the amount of medicament dispensed so that each actuation of the pump will deliver a consistent dose of the medicament. It has therefore been proposed to incorporate some form of measured dose mechanism into the design of such pump spray devices. This is often provided in the form of the swept volume of the cylinder of the pump used to dispense the fluid, see for example US Patents Nos 4,147,476 and 4,694,977 and PCT Application No W0 87/04373. However, where the user does not for any reason operate the pump WO91/l4~ PCT/GB91/0~33 mechanism for its full stroke, the amount of fluid dispensed can vary significantly from the desired dosage.
Furthermore, it has not hitherto been considered possible to achieve the required very small droplet size consistently. A conventional hand operated pump type sprayer is typically operated by the user manually depressing the free end of the pump housing or plunger or a trigger mechanism so as to discharge fluid held in the pump, for example from the cylinder of the pump as the piston of the pump is driven up the cylinder, see for example US Patents Nos 3,838,686, 4,693,675 and 4,694,977.
However, not only is the pressure generated by the pump comparatively low, but the pressure generated will depend upon the speed at which the pump is operated and the strength of the user. As a result, the droplet size in the spray varies from operation to operation, even with the same person operating the pump.
It has been proposed to provide a spring against which the pump mechanism acts as fluid is drawn into the pump on the sucking stroke of the pump, for example into the cylinder as the piston is retracted in a piston/cylinder type of pump, see for example US Patents Nos 3,471,065, 3,790,034, 3,797,748, 4,260,082, 4,183,449 and 4,345,718. The spring then provides a consistent driving force when released to drive the fluid out of the pump. In these proposals, the pump is designed so that fluid cannot escape from the cylinder until a release or outlet valve is operated.
Therefore, the fl~id is held within the pump under the pressure exerted by the compressed spring. When the valve is operated, the fluid is discharged from the pump under the action of the spring. Although this achieves a greater uniformity of the pressure at which the fluid is discharged, the fluid may be held under pressure within the pump before the outlet valve is operated. This can result WO91/1~8 PCT/GB91/~33 ~5~ , 2078683 in a number of problems. For example, the pump mechanism and outlet valve must be designed to resist the substantial pressures generated by the compressed spring, otherwise leakage may occur or the pump cylinder walls may rupture.
s Furthermore, where the pressure is retained for any length of time, some weepage of the fluid past the seals in the pump mechanism, for example past the seals between the piston and the cylinder wall, will occur, resulting in a loss of fluid and pressure from the cylinder. This wlll affect the volume of fluid dispensed and the droplet size in the spray which is eventually produced when the outlet valve is actuated. A further problem arises in that the user may not operate the pump mechanism for its full stroke. This will not only affect the volume of fluid lS dispensed, but will also affect the peak pressure achieved and hence the droplet size, since the spring will not be fully compressed.
In an alternative form of device proposed in US Patent No 4,892,232, the fluid is held under pressure in a main container and a pre-determined quantity is transferred to a distendable rubber or similar sleeve carried by the valve actuator stem of the outlet valve to the container. The stem is provided with suitable porting so that the sleeve is connected to the remainder of the container when the stem is in the raised position. Fluid will thus flow under pressure from the container into the annular space between the sleeve and the stem wall to expand the sleeve radially.
When the valve stem is depressed, the porting to the remainder of the container is closed and a port is opened allowing the fluid to escape from the annular space to a nozzle orifice as the sleeve is stretched axially and collapsed radially. Again, this device suffers from the problems of variable dose and variable droplet size due to variations in the speed and force used by the user in the ~ ,. ..
io 2~78~8 ~
depresslon of the valve stem and the extent to which the valve stem ls moved.
We have devised a form of atomiser device which reduces the above problems and does not use a liquefled propellant or gas stream to discharge the contents of the devlce. Whllst the devlce ls of partlcular use ln the applicatlon of medlcament flulds to the nasal passages or to the lungs, it can be used to apply a wlde range of other materlals where a simple self contalned readily portable device ls required.
In a preferred embodlment of the devlce of the lnvention the user lmparts energy to an energy storage means whlch ls retalned in the "loaded" state until required to act upon a measured dose of the fluid to discharge lt through a mechanlcal break up device or other dlscharge means. The fluld need not be held under pressure ln the devlce, thus reduclng some of the problems assoclated wlth earller proposals. Slnce the "loadlng" of the energy storage means can be lnterllnked wlth the measurement of the dose of fluld, the operatlon of a latch or other means for retalnlng of the energy storage means ln lts "loaded" state can be used to ensure that the correct dose of fluid is achieved. The device of the invention thus substantially eliminates the problems encountered with prior proposals and provides a simple and effectlve means for produclng sprays of fine sized droplets wlthout the need for pressurlzed or llquefied propellant gases.
B
~ ~078$~ ~
SUMMARY OF THE INVENTION
According to a first aspect of the present invention, there is provided a device for dispensing a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising:
a chamber for containing said metered quantity of fluid at a first pressure; an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for atomising said fluid discharged from said chamber, said atomising means comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less, whereby said fluid is atomized into droplets having a mean size suitable for inhalation into the lungs.
The invention also provides a device for dispensing fluid as a spray of droplets, comprising: a chamber for containing a quantity of fluid at a first pressure; a piston configured to act directly on said chamber to pressurize the quantity of fluid; resilient biasing means permitting withdrawal of said piston away from said chamber to a cocked position, and for urging said piston to act on said chamber so that the quantity of fluid is subjected to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of the quantity of fluid from said ~ ~7~ 3 chamber at said second pressure wherein said resilient biasing means is in a loaded state when said piston is in the cocked position; latching means for holding said resilient biasing means in the loaded state; actuating means for releasing said latching means to initiate discharge of the quantity of fluid from said chamber at said second pressure; and atomising means for atomising the quantity of fluid discharged from said chamber.
The invention further provides a device for dispensing fluid as a spray of droplets, comprising: a chamber for containing a metered quantity of fluid at a first pressure; a piston configured to act directly on said chamber to pressurize the metered quantity of fluid; resilient biasing means permitting withdrawal of said piston away from said chamber to a cocked position, and for urging said piston to act on said chamber so that the metered quantity of fluid is subjected to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of the metered quantity of fluid from said chamber at said second pressure wherein the resilient biasing means is in a loaded state when said piston is in the cocked position; latching means for holding said resilient biasing means in the loaded state; a fluid reservoir in fluid communication with said chamber, wherein the metered quantity of fluid is drawn into said chamber from said fluid reservoir when said piston is withdrawn to the cocked position; and atomising means for atomising the metered quantity of fluid discharged from said chamber.
- 7a -jv ~ ~07868 3 Preferably, the device incorporates metering means for metering said quantity of fluid, and the atomising means is provided by a mechanical break up device through which the metered quantity of fluid is passed to atomise it when it is subjected to said increase in pressure.
In a preferred embodiment, the device of the invention comprises:
a. a pressure chamber provided with an inlet connection to supply liquid to said pressure chamber, and an outlet connection to receive pressurized liquid from said pressure chamber;
b. atomising means provided at or adjacent said outlet for causing said pressurized fluid to be atomised;
c. pressurising means comprising a pulse generating means for generating one or more pulses to subject fluid within said pressure chamber to at least one predetermined increase in pressure; and d. interface means which is acted upon by said pulse(s) to vary the volume of said pressure chamber in order to increase the pressure in the chamber.
The device of the invention may further comprise one or more control means for controlling fluid flow between said pressure chamber, said inlet and said outlet.
Preferably, said pressure chamber comprises a cylinder within which a piston acting as the interface means is slideably journalled.
- 7b -C
WO91/14~8 PCT/GB91/~33 ~'- i 2078683 -8-Preferably, said pulse generating means comprises an energy storage means and a releasing means for releasing energy from the energy storage means, thereby to generate at least one pulse from the energy storage means which acts on the interface means.
The device preferably also comprises loading means for loading the energy storage means; retaining means, for example a latch or other detent means, for retaining the energy storage means in a loaded state; and release means for releasing the retaining means, thereby to release the energy storage means so as to cause the metered quantity of fluid to be discharged through the atomising means as a spray of droplets.
Accordingly, from a preferred aspect, the present invention provides a device for dispensing a fluid as a spray of droplets to a locus, which device comprises:
a. means for receiving a pre-determined quantity of the fluid to be dispensed;
b. break up means in communication with said fluid receiving means and adapted to cause the fluid to be formed into a spray of droplets;
c. an energy storage means adapted to be actuated by a user of the device, preferably to store energy imparted thereto by the user during operation of the device, and to release a pre-determined amount of energy to the pre-determined quantity of fluid in said fluid receiving means so as to subject said fluid to one or more pulses of a pre-determined increase in pressure; and d. actuator means adapted to release said stored energy to act upon said pre-determined quantity of fluid and to cause said increase in pressure in said fluid so as to discharge said quantity of fluid via said break up means so as to form said spray of droplets of said fluid.
- . ~
WO91/14~8 PCT/GB91/0~33 - 9~ ~ 2-d7g'~683 Preferably, the device of the invention comprises a piston in cylinder type pump mechanism, at least part of the bore of the cylinder acting as the pressure chamber adapted to receive a pre-determined quantity of fluid from a s reservoir, preferably corresponding to the swept volume of the pressure chamber, upon actuation of the pump on its suction stroke. The piston acts as the interface means to transmit the energy pulse(s) to the fluid in the pressure chamber. It is also preferred that the operation of the pump be interlinked with the retaining of the energy storage means in the loaded state so that the user is required to operate the pump to its full or a pre-determined extent in order to cause the retaining mechanism to engage. However, it will be appreciated that the retaining of the energy storage means may be transient and that the operation of the device may pass through the fully loaded state directly to the discharge cycle at which the energy in the storage means is released to discharge the fluid in the pressure chamber of the pump through the break up means to form the desired spray.
Preferably, the energy storage means takes the form of a compression spring. However, other forms of energy storage means can be used, for example a tension spring or bellows section to the wall of the cylinder, gas bulbs, motors, solenoids or a flexible or deformable membrane or diaphragm. In some of such energy storage means, for example a gas bulb or a motor or solenoid, the energy is already stored in the means or a battery associated therewith, and the user merely releases that energy when required. In other forms, for example a spring or flexible diaphragm, the user must impart energy to the energy storage means, ie. must load the energy storage means, whiCh energy is then released during operation of the device. For convenience, the invention will be described hereinafter in terms of a compression spring which is WO91/1~8 PCT/GB91/~33 ., i ,~ .~ , ~
located substantially co-axially below the piston of a piston in cylinder type of pump so that operation of the pump on its suction stroke causes the spring to be compressed and thus store energy for the discharge stroke of the pump. If desired, more than one spring may be used.
It is particularly preferred that the spring be at least partially pre-compressed so that the force applied by the spring as it expands does not vary greatly. The design and construction of the spring can be selected in known manner to achieve the pressure required in the pressure chamber during expansion of the spring on the discharge stroke of the pump.
The device of the invention is preferably put up in the form of a unit containing the operating mechanism of the device, for example the atomising means, the energy storage means and the fluid metering and pressure chambers; which unit can be mounted upon or can contain a removable reservoir for the fluid to be dispensed. Typically, the fluid will be contained in a collapsible container removably connected to the inlet to the pressure chamber or pump cylinder. Where large volumes of fluid are to be discharged, the reservoir can take the form of a discardable can, tube or the like onto the outlet of which the operative mechanism unit of the device of the invention is a screw, push or other fit. Part of the container can be used to provide part of the operative mechanism of the device of the invention. For example, the outlet tube of the container can be used to provide the piston of the piston in cylinder pump.
In order to achieve the high pressures required to form very fine droplets, for example less than lO micrometres mean diameter, it will usually be necessary to provide some form of mechanical advantage in the energy loading mechanism and/or in the discharge mechanism of the pump.
WO91/14K8 PCT/GB9l/~33 Thus, it will usually be desired to provide a lever or cam mechanism to aid compression of the spring; and/or to step or otherwise reduce the diameter of the pressure chamber or the outlet from the pump cylinder so as to achieve an hydraulic pressure advantage at the inlet to the atomising means. Typically, the lever mechanism will take the form of a trigger type mechanism which the user operates single handedly with the spray outlet adjacent to and directed towards the locus to which the spray is to be applied. If desired, the spray outlet can incorporate a shroud or mouthpiece to aid directionality of the spray.
As indicated above, the lever or other mechanism preferably incorporates a latch or other retaining mechanism for retaining the spring or other energy storage means in the compressed or energy loaded state prior to initiation of the discharge cycle of the device. Such a retaining means can be a simple mechanical detent or latch which physically engages the spring or the pump mechanism and prevents release of the compression in the spring until some further operation is initiated. However, the retaining means may be provided by a stepped cam or over centre type of mechanism which bears against the spring so as to hold the spring transitorily in the desired state of compression during the loading cycle, but which automatically releases the spring with continued operation of the device to discharge the fluid.
As indicated above, the device of the invention is of especial use in the formation of a spray of droplets of a medicament for inhalation by a patient. For such use it is desirable that the droplets have a mean diameter less than about 12 micrometres. However, the invention can be applied to spraying of a wide range of other materials in solution, emulsion, dispersion or suspension form to produce droplets with sizes of up to 200 micrometres or WO91/14~8 PCT/GB91/~33 ~ : -12-., ~.
20786~83 more. For convenience, the invention will be described hereinafter in terms of dispensing a spray of an aqueous solution of a medicament for inhalation into the lungs of a patient via the mouth.
For such use, the droplet size is desirably less than 10 micrometres, typically 2 to 6 micrometres. Such small droplet sizes can be achieved by atomising the fluid using a wide range of atomising or mechanical break up devices, for example ultra sonic blades, impingement of two jets of fluid or impaction of a jet or spray onto a baffle or the like. However, we prefer to form the spray by passing the fluid at high pressure through a small nozzle aperture, preferably in association with a swirl chamber or other device for causing a significant secondary flow in the fluid transverse to- the main flow at the nozzle orifice.
The optimum pressure and nozzle orifice shape and size can be determined for any given case using techniques known in the art. Thus, where very high pressures can be generated in the pump cylinder or pressure chamber, for example 300 to 500 bar, comparatively large nozzle orifice diameters can be used, for example up to 100 micrometres, typically greater than 30 to 50 micrometres. However, we prefer to operate the device of the invention with pressures of from 50 to 400 bar, preferably 100 to 350 bar; and with nozzle orifice of from 1 to 12 micrometres, notably 2 to 6 micrometres. If desired, the device of the invention can incorporate means to vary the pressure generated, for example by adjusting the extent of compression of the spring, and/or the diameter of the nozzle orifice. The pressure quoted herein are the absolute pressures achieved in the pressure chamber; and the nozzle orifice diameters are the effective hydraulic diameters.
Preferably, the atomising means comprises an outlet orifice mounted in or on a body, and ~he device of the invention WO91/14~ PCT/GB91/0~33 -13- 20~78683 further comprises a member which is moveable with respect to said body to initiate operation of said atomising or break up means, the arrangement ~eing such that such movement of said member does not cause movement of said s orifice. It is thus possible for a user to operate the device without moving the outlet nozzle, which is of benefit when applying a medicament through the mouth or nose. It is also preferred that, where the device of the invention is to be used as a Metered Dose Inhaler (MDI) for the application of a medicament to the lung, the device is provided with a shroud or mouthpiece surrounding the atomising nozzle so as to assist in containing and direction of the spray into the nose or mouth. The shroud or mouthpiece may also assist the user in inhaling the spray.
The device of the invention preferably incorporates one or more valve means or other control means for regulating the flow into and out of the pressure chamber or the pump cylinder. Thus, it will usually be necessary to provide a non-return valve on the inlet and outlet to the cylinder or pressure chamber so that fluid flows into the cylinder or pressure chamber only during the suction stroke of the pump; and fluid flows to the atomising means only when the pressure is applied to the fluid in the pressure chamber or pump cylinder. In order to reduce the risk of premature escape of fluid from the device, it may be preferred that the outlet be provided with a pressure release valve, typically set to open when a pressure in excess of 50 bar is achieved in the pressure chamber or the pump cylinder.
Alternatively, the flow to and from the pressure chamber or the pump cylinder can be controlled by a rotary or other valve mechanism which is interlinked with the operation of the trigger or other lever mechanism which is used to operate the pump and to load the energy storage means.
" .~ , , ~ ~78~83 Thus, the operatlng trlgger can be pivotally mounted on a shaft which incorporates a rotary valve so that as the trigger ls progressively depressed it not only operates the pump to suck fluid lnto the pump cyllnder through the valve, but also compresses the spring to store energy, and rotates the valve so that the connection between the cylinder and the reservoir ls shut off and the connection to the nozzle outlet opened prior to release of the spring, for example as a cam carried on the shaft goes over centre.
It is also preferred that the device of the invention incorporate one or more separation members upstream of the nozzle orlflce to reduce the risk of blockage of the fine nozzle orifice by particulate material in aqueous or other solutions of medicaments to be applied to the lung. Thus, a flne mesh fllter, a ceramlc or fritted dlsc or the llke can be incorporated into the nozzle chamber or in the outlet to the pressure chamber. Typically, the filter will have an effective aperture or mesh size which is about half the nozzle orifice diameter.
The devlce of the invention is operated by charging the pressure chamber with the required quantity of fluid; loading the energy storage means with the required amount of energy where this has not already been done as when a bulb of pressurized gas or a motor is used to drive the piston of the pump; and then releasing the energy to apply one or more pressure pulses to the fluid in the pressure chamber so as to e~ect lt through the atomising means to form the desired spray B
~ ~7~8 3 ' of fluid.
In a yet another aspect, the lnvention therefore provides a method of dlscharglng a metered quantlty of fluid as a spray of droplets by discharglng the metered quantity of fluld under pressure through an atomlslng means, comprlslng the steps of:
provlding sald metered quantlty of fluid in a chamber at whlch sald fluld ls held at a flrst pressure; applylng a predetermlned amount of energy to an energy storage means;
releaslng sald predetermlned amount of energy from sald energy storage means to sald chamber so as to sub~ect sald fluld to a predetermlned lncrease ln pressure to a second pressure and to lnltlate dlscharge of sald fluld from sald chamber; and dlscharglng sald metered quantlty of pressurlzed fluld from sald chamber as a single dlscharge from sald chamber through an outlet aperture ln the atomlslng means, sald outlet aperture havlng a hydraullc dlameter of 100 micrometers or less, thereby atomlslng sald fluld lnto droplets havlng a mean slze sultable for lnhalatlon lnto the lungs.
DESCRIPTION OF THE DRAWINGS:
For a better understandlng of the lnventlon, and to show how the same may be carrled lnto effect, lt wlll now be descrlbed, by way of lllustratlon only, wlth reference to the accompanylng dlagrammatlc drawlngs, in whlch:
Flgure 1 ls a sectlonal view of a Metered Dose Inhaler (MDI) accordlng to the lnventlon, wlth the fluld to be dlspensed carrled ln a collapslble bag removably mounted ln the devlce;
Flgure 2 ls a vlew slmllar to Flgure 1, but wlth a product to t ~78~ 3 ' be dlspensed ln a pressurlsed contalner; Flgure 3 ls a sectlonal vlew of part of an alternatlve Metered Dose Inhaler, ln whlch a product to be dlspensed ls contalned ln a collapslble tube havlng a nozzle whlch serves as a plston;
Flgure 4 ls a vlew slmllar to Flgure 3, showlng an alternatlve pressurlslng arrangement; Flgure 5 ls an enlarged detall vlew of one example of an atomlslng orlflce assembly; Flgure 6 ls an enlarged detall vlew of one example of a mechanlcal break-up orlflce; Flgure 7 lllustrates, dlagrammatlcally, an alternatlve atomlslng means; and Flgure 8 lllustrates, dlagrammatlcally, another alternatlve atomlslng means. In the Flgures, llke reference numerals denote llke or correspondlng parts.
DESCRIPTION OF THE ~ ~K~ EMBODIMENTS:
The MDI shown ln Flgure 1 comprlses a body ln whlch there ls deflned a cyllnder 2 of clrcular cross-sectlon, ln whlch a plston 3 ls mounted for reclprocatlng movement. The cyllnder 2 communlcates wlth a pressure chamber 4 of reduced cross-sectlon. The plston 3 has a reduced dlameter portlon 5 whlch seallngly engages wlthln the pressure chamber 4, by means of a plastlc [e.g. PTFE or Nylon]
- 15a -B
WO91/1~8 PCT/GB91/00433 : 2û78683 sealing cap or ring provided on the piston portion 5. The seal may be formed integrally with the reduced diameter portion 5 of the piston - for example, as a cap, rib or bead.
A pre-loaded compression spring 6 is located in the cylinder 2, between the enlarged head of the piston 3 and an opposite end wall of the cylinder 2. An operating rod 31 is connected to the piston 3, and passes through the spring 6 and through a passageway 34 in the body 1, to protrude from the body 1. At or adjacent an end of the rod 31 there is provided a handle means 32 for moving the rod 31 and the piston 3. If desired, the end of rod 31 can be connected to a trigger mechanism or lever mechanism incorporating a mechanical advantage so that the user can readily operate the device against the compressive force of spring 6. A latching means 33 provided on the body 1 engages with the rod 31, to latch the rod 31 in a loaded position, as illustrated in Figure 1. An actuating button 35 is provided, for releasing the latching means 33.
Also defined within the body 1 is a cavity 15 in which there is located a collapsible bag 10 containing the product to be dispensed [e.g. a liquid drug]. A door 16 on the side of the body 1 may be opened, in order to exchange the collapsible bag 10. By means of a connector 12, the interior of the bag 10 communicates with an inlet passage 11 which, in turn, communicates with the pressure chamber 4 via a non-return valve 13.
Also connected to the pressure chamber 4 is an outlet passage 21 which extends from the pressure chamber 4 to an atomising head 22, via a non-return valve 23 and a pressure release valve 25.
. .
~ $ . -~
WO91/14~8 PCT/GB91/~33 -17- ~
-- : 2078683 7 ,~ ' .
Optionally, the body 1 is provided with a mouthpiece 40, which affords an atomization chamber around the atomislng head 22.
In use of the MDI of Figure 1, when the piston 3 is in the s loaded position as illustrated in Figure 1, the pressure chamber 4 is full of liquid which has been supplied from the bag 10, via the passage 11 and non-return valve 13.
The compression spring 6, as mentioned above, is already pre-loaded when fitted in the cylinder 2. The loading of the spring is increased further by withdrawing the rod 31 and thereby the piston 3 to the loaded position that is illustrated in Figure 1.
The rod 31 is latched in its loaded position as illustrated in Figure 1, by the latching means 33. Upon depressing the actuating button 35, the latching means 33 is released, thereby allowing the piston 3 to move suddenly forward under the force of the compression spring 6, to impart a sudden pressure pulse to the liquid in the pressure chamber 4.
The pressure in the liquid in the pressure chamber 4 therefore quickly builds up to exceed the limit value of the pressure release valve 25, and the liquid is then ejected under high pressure through the outlet passage 21 to the atomising head 22, via the one-way valve 23. During the forward travel of the piston 3, the non-return valve 13 prevents liquid from being returned to the bag 10, via the inlet passage 11. As the liquid is ejected through the atomising head 22, it is atomised into a fine spray, which can then be inhaled. The optional mouthpiece 40 provides an atomization chamber within which the fine spray is enclosed, and facilitates the inhalation of the spray.
WO91/14~8 PCT/GB91/0~33 .. .
2o78683 To reload the MDI, the rod 31 is pulled back by means of the handle 32 against the resilient bias of the spring 6 and, at the end of its travel, the latching means 33 automatically latches the rod 31 into a latched end position. During this travel of the piston 3, liquid is sucked out of the collapsible bag 10 into the pressure chamber 4, via the inlet passage 11 and one-way valve 13.
At this time, the one-way valve 23 prevents air being sucked into the pressure chamber 4 via the outlet passage 21. Due to the latching of rod 31, the fluid in pressure chamber 4 is held at ambient pressure and there is little or no risk of loss of fluid from the chamber. The operation of latching means 33 provides the user with a clear indication when piston 3 has completed the desired travel within cylinder 2 and that the required dose of fluid has been taken-up. If the user fails to withdraw rod 31 to a sufficient extent, the latching means 33 will not engage and the user will detect the spring bias from spring 6 and will know to withdraw rod 31 further. The latching means 33 thus provides both the means for holding fluid in chamber 4 under ambient pressure and a means for alerting the user to incomplete operation of the device, hence reducing the risk of variable operation of the device.
Thus, the MDI is again in a loaded position, as illustrated in Figure 1, ready for firing.
It will be appreciated that, in use of the MDI illustrated in Figure 1, a metered dose of liquid product is pressurised and atomised in a highly accurate and repeatable manner. When the rod 31 and piston 3 are withdrawn to their loaded position, an exact metered quantity of liquid product is drawn into the pressure chamber 4. Upon releasing the latching means 33, the piston 3 is urged forwardly to impart a predetermined amount of energy to the liquid, and thereby increase its WO91/14~ PCT/GB9l/00433 2078~83 ,., ~ .
pressure by a predetermined amount. Thus, as the pressurised liquid is then ejected through the atomising head 22 of predetermined atomising characteristics, the liquid is atomised to a fine spray of predetermined mean particle size without the use of liquefied propellant or other gases.
In order to atomise the liquid to a very fine spray - for example, having a mean particle size in the range 1 to 12 micrometres - a very high pressure has to be applied to the lo liquid in the pressure chamber 4. By way of example, the capacity of the pressure chamber 4 may be 20 microlltres;
the diameter of the small end 5 of the piston 3 may be 2 mm; the diameter of the cylinder 2 may be 15 mm; the force of the spring 6 may be 100 Newtons; and the atomising head 22 may have an exit orifice of a diameter or the order of 3 to 15 micrometres. In such an arrangement, a pressure of the order of 400 bar may be generated in the liquid in the pressure chamber 4.
The cavity 15 may be open to atmosphere and at atmospheric pressure. In an alternative embodiment, the cavity 15 may be pressurised above atmospheric pressure, which helps to force the contents of the collapsible bag 10 into the pressure chamber 4, without the need to create sub-atmospheric pressures in the pressure chamber 4. This can help to avoid the formation of gas bubbles in liquid sucked into the pressure chamber 4.
The pressure release valve 25 may be optional; it may be omitted if desired. The pressure release valve 25 and non-return valve 23 may be combined as a single unit (not shown). It will be appreciated that the illustration of Figure 1 is essentially diagrammatic in nature. A
practical embodiment may be of different construction. for example, a lever or other gearing mechanism may be employed WO91/14K8 PCT/GB91/~33 ~ -20-' ~ ZU78683 to assist loading of the piston 3 against the force of the spring 6. In one example, the MDI may be provided with a cover which, when opened, automatically loads the piston 3 and latches the latching means 33, so that the MDI is then s ready for firing. The MDI would be fired by actuating the button 35, when the cover was open. In an alternative arrangement, the piston 3 may be loaded against the spring 6 and the latching means 33 latched, whilst a cover of the MDI is being closed. Thus, the device would be pre-loaded and may be fired straight away, upon opening the cover. In another variation, opening of a cover of the device may automatically load the piston 3 against the force of the spring 6, latch the latching means 33, and then automatically released the latching means 33 at the end of lS the action of the opening cover so that the latching is only transient.
The MDI of Figure l is preferably of small, pocket slze.
Since, in contrast to known MDIs, it does not have to provide an appreciable volume to contain a liquified gas propellent under pressure it can readily be made of small dimensions. Despite this, the product container, in the form of the collapsible bag lO, can contain much more medicament than conventional MDIs. For example, whereas conventional MDIs might be limited to 200 to 400 doses, an MDI constructed along the lines illustrated in Figure l may readily contain l,000 or more doses, in the collapsible bag lO. As will be appreciated, the contents of the bag lO are protected from contamination by the atmosphere and the operation of the device of the invention is by way of atomization of the fluid in chamber 4 without the use of an air blast, ie. the device of the invention operates as an airless sprayer.
When the bag lO is empty, it may simply be removed from the cavity lS and replaced with a fresh bag. Preferably, the WO91/14U~ PCT/GB91/00433 ~ ~'78'S~68 3 bag 10 includes a seal to prevent the escape of product from the bag 10, unless the bag 10 is connected to a connector such as 12.
In alternative embodiments, part of the piston and/or valve arrangement may be made disposable, together with the product container such as the collapsible bag 10.
It is to be appreciated that, in use of the illustrated MDI, there is nothing [short of catastrophic failure of the apparatus] to stop the discharge of the contents of the pressure chamber 4 as an atomised spray, once the actuating button 35 has been depressed to release the latching means 33 and thereby release the spring 6. Thus, the amount of energy applied by the spring 6 to the metered quantity of liquid in the pressure chamber 4 is absolutely predetermined, so that the increase in pressure to which the metered quantity of liquid is subjected is likewise absolutely predetermined. This objective is to be realised in all other illustrated embodiments of the invention described below.
Another feature of the MDI of Figure 1 is that the metered quantity of liquid in the pressure chamber 4 is subjected to an increase in pressure only when the actuating button 35 has been depressed to release the latching means 33 and thereby release the spring 6. This has the advantage that no seals or other means are required to constrain the highly pressurised liquid, prior to the atomization stroke.
The increase in pressure applied by spring 6 and piston 3 to the metered quantity of liquid in the pressure chamber 4 causes the pressurised liquid to pass through the atomising head 22, to be atomised thereby. This objective is to be realised in all other illustrated embodiments on the invention described below.
WO91/14~8 PCT/GB91/0~33 20-78~83 Another important advantage of the MDI of Figure 1 is that, upon depressing the actuatlng button 35 to release the latching means 33 and spring 6, the atomising head 22 does not move within the body 1 - only the button 35 moves.
This facilitates accurate direction of the atomised spray, and contrasts with a conventional vertical-axis finger pump arrangement, in which the atomising nozzle itself is depressed to initiate atomization. This would be inconvenient in a medical inhaler, since it would be difficult to direct the spray accurately. Again, this objective is to be realised in all other illustrated embodiments of the invention described below.
The MDI illustrated in Figure 2 is generally similar to that of Figure 1. However, in Figure 2, the pressure release valve 25 is not provided. Also, the product container comprises a long tube 16 in which liquid product 17 is stored under pressure, which is created by a reservoir of gas 18 stored behind the liquid 17. As the piston 3 is pulled back to a loaded position, liquid product 17 is forced into the pressure chamber 4 via the inlet passage 11 and non-return valve 13, under the pressure of the gas 18. As the liquid product 17 is used, the gas 18 expands into the tube 16, pushing the liquid product 17 ahead and losing some pressure. The initial pressure of the gas 18 should be sufficient to maintain a pressure above atmospheric, until all of the liquid product 17 is used up.
The pressure tube 16 may be made as a replaceable item, for exchange in the MDI when the liquid product 17 is used up.
Alternatively, the whole MDI may be manufactured quite cheaply of principally plastics parts, such that it may be a throw-away item. If the tube 16 is at least partly visible from the outside of the MDI, a visual check may be provided, as to the level of product remaining.
WO91/14~8 PCT/GB91/00433 In the embodiments of Flgures l and 2, the spray action is initiated by actuating of the button 35. In an alternative - arrangement, the latching mechanism 33 may be released automatically in response to a user inhaling adjacent the atomising head 22. For example, a mouthpiece such as 40 may be connected to a vane that is caused to move by pressure difference across it when a user inhales, and thereby release the latching mechanism 33 to initiate the spray. Such automatic actuating mechanisms are known in themselves, in existing MDIs.
In the embodiments of Figures 1 and 2, the stroke of the piston 3 is fixed. If desired, means may be provided for varying the stroke of the piston. Preferably, such means is calibrated, so that a user may optionally adjust the MDI
to dispense differing quantities of spray. However, it will be appreciated that, in every case, once the adjustment means has been set to a particular value, the MDI will then provide a metered dose of spray in a highly repeatable manner, just as if the stroke of the piston were fixed.
It will be appreciated that the devices of Figures l and 2 have been described above in terms of a device in which the cylinder of the pump mechanism is static and the piston moves axially therein. However, it is within the scope of the present invention to carry the cylinder upon the rod 3l and to have the piston fixed.
In the embodiment illustrated in Figure 3, a liquid product 50 is contained within a collapsible tube 5l which is formed integrally with an extended nozzle 52 which serves as a piston. The nozzle/piston 52 is located for reciprocating movement within a cylinder 53. At the end of the nozzle/piston 52 there is incorporated a simple non-return valve 54. A pressure chamber 55 is defined at the WO91/14~8 PCT/GB91/~33 ~ -24-207~683 end of the cylinder 53, and communicates via a simple non-return valve 56 with an atomising head 57.
The cylinder 53, non-return valve 56 and atomising head s7 are all contained within a casing 58, which is formed with annular ribs 59, which serve to locate the casing 58 in a first main body part 60.
The top of the product tube Sl is formed with an annular rib 6l, which serves to locate the tube 5l in a second main body part 62. Resilient bias means is provided for urging the two main body parts 60 and 62 towards one another. A
latching means is provided for latching the two main body parts 60, 62 at a predetermined distance apart, in a loaded condition, and actuating means is provided for releasing the latching means. In the interests of clarity, the resilient bias means, latching means and actuating means have not been shown in Figure 3, but, of course, examples of these have already been shown in Figures l and 2.
The embodiment of Figure 3 operates as follows: as illustrated in Figure 3, the MDI is in an unloaded or "fired" condition. By means of a suitable mechanism, the main body parts 60 and 62 are moved away from one another, to cause the nozzle/piston 52 to withdraw relative to the cylinder 53. The depressurisation in the pressure chamber 55 thereby causes the liquid product 50 to be sucked out of the tube 51, via the non-return valve 54, to fill the pressure chamber 55. During this action, the non-return valve 56 serves to prevent air from entering the pressure chamber 55 from the atomising assembly 57.
At the end of the loading stroke, the latching means operates to hold the main body parts 60, 62 apart at predetermined relative positions. Upon releasing the latching means by the actuating means, the nozzle/piston 52 WO91/l4K8 PCT/GB91/~433 ,. ,~
is suddenly urged under the action of the resilient bias means into the cylinder 53, to apply sudden pressure to the liquid product 50 in the pressure chamber 55, in a manner generally similar to that in the embodiments of Figures 1 and 2. The pressurised liquid product is then ejected under pressure into the atomising assembly 57, via the non-return valve 56, and is then atomised into a fine spray by the atomising assembly 57.
The MDI is then reloaded by the respective lever mechanism to move apart again the two main body parts 60, 62, against the force of the resilient bias means.
Thus, it will be appreciated that the embodiment of Figure 3 operates in a generally similar manner to the embodiments of Figures 1 and 2. However, in Figure 3, the product 50 is provided in a particularly convenient manner in the product tube 51 which, together with the nozzle/piston 52 and the built in simple non-return valve 54, may be exchanged as a complete throw-away unit. It will be appreciated that the product tube 51 and its integral nozzle 52 and non-return valve 54 may readily be manufactured in a relatively economical manner out of plastics materials. The user is protected from contact with the liquid product 50, except when the MDI is properly actuated. Features of the embodiments of Figures 1 and 2, including variations as discussed above, may be provided, where appropriate, in combination with features of the embodiment of Figure 3.
In the embodiment of Figure 3, either of the parts 60, 62 may be fixed in relation to a main body of the MDI, the other of the parts 60, 62 then being moveable with respect to the fixed part. Alternatively, both parts 60, 62 may be moveable with respect to a main body of the MDI.
WO91/14~8 PCT/GB91/0~33 ~ -26-In the embodiment of Figure 4, liquid product 70 is contained within a collapsible tube 7l. A nozzle 72 of the tube 71 connects with an inlet passage 73 which contains a non-return valve 74. The non-return valve 74 communicates with a flexible tube 75, which may flex between a "full"
position [illustrated in solid lines] and an "empty"
position 75a [illustrated in broken lines]. The flexible tube 75 communicates with another non-return valve 76 which, in turn, communicates with an atomising head [not shown]. The flexible tube 75 is contained within a pressure chamber 77 which is filled with a secondary liquid 78. The secondary liquid 78 communicates with a pressure pulse generator [not shown] via a passage 79.
The embodiment of Figure 4 operates as follows: when a flexible tube 75 is in its "full" position, it is full of liquid product 70 sucked from the collapsible tube 7l.
Upon applying a pressure pulse to the secondary liquid 78, the pressure in the pressure chamber 77 suddenly increases, and this causes the flexible tube 75 to be urged into its "empty" position 75a, during which action the liquid product within the tube 75 is expelled out of the non-return valve 76 to the atomising head [not shown] under high pressure, such that the atomising head atomises the liquid product into a fine spray, generally as in the preceding embodiment.
At the end of the pressure pulse, the flexible tube 75 resumes its initial "full" position and, during this action, liquid product 70 is sucked up from the collapsible tube 7l, via the non-return valve 74, into the space within the flexible tube 75. The flexible tube 75 may return to its "full" position under its own natural resilience.
Alternatively or additionally, it may be assisted in this by the application of a negative or reduced pressure pulse to the secondary liquid 78 in the pressure chamber 77.
WO91/14~8 PCT/GB91/0~33 -27- 2078~83 The pressure pulses in the secondary liquid 78 may be generated by any suitable means. However, it is important that the pressure pulses are of a predetermined amplitude and duration to ensure that a metered dose of liquid is repeatedly sucked into the flexible tube 75 and subsequently expelled therefrom under a predetermined pressure increase, to produce a repeatable spray through the atomising head.
By way of example, the pressure pulse generator may include a piston and cylinder arrangement, together with latching and actuation means, of a type generally similar to that illustrated in Figures l and 2.
Typically,, the pressure pulses may be of substantially square wave form. However, if desired, the pressure pulses may be of any predetermined shape - for example, if a time-varying spray spectrum were deliberately chosen. The important factor is that whatever the shape of the pulses, they are accurately repeatable. Thus may apply to all embodiments.
Figure 5 shows, in enlarged detail, one example of an atomising head assembly 80. An inlet passage 8l formed in a body 82 leads to an inlet chamber 83. Interposed between successive sections of the inlet chamber 83 is a filter 84.
The final section of the inlet chamber 83 leads to swirl chamber 85 which, in turn, leads to a nozzle 86.
The purpose of the filter 84 is to prevent particles from blocking the final orifice. For example, the filter 84 may be made of stainless steel mesh, having a mesh size in the range l to lO micrometres - preferably, 3 micrometres.
Figure 6 shows one example of an atomising orifice 90, which is formed in a plate 9l which may be positioned, for WO91/1~8 PCT/GB91/0~33 . .
.. . .
2~-78683 examp e, downstream of the atomising nozzle 86 in the assembly of Figure 5, as shown by chain-dot lines in that Flgure.
As may be seen in Figure 6, the final exit orifice 90 has a diameter of 6 micrometres, and an overall length of 30 micrometres, to include an inwardly tapering throat 92 at an angle of 30~ to normal and an outwardly flared mouth 93.
The orifice plate 91 has a thickness of the order of 1 mm, and a tapering inlet passage has a length of about 1 mm, tapering at an angle of 20~ from an initial entry orifice size of 70 micrometres. We have found that, surprisingly, using a final atomising orifice of the order of 6 micrometres, together with a high pressure applied to the liquid to be atomised [by means of the energy store such as the compression spring 6, etc], can lead to a very effective and uniform mean particle size of the eventual spray. Tests with an exit orifice of the order of 6 micrometres, as illustrated in Figure 6, together with a liquid pressure of the order of 300 bars, has produced a uniform spray of mean particle size of the order 5-8 micrometres. Preferably, the diameter of the exit orifice 90 is less than 100 micrometres. The preferred range for its diameter is 1 - 20 micrometres and the most preferred range is 3 - 10 micrometres.
The exit orifice 90 may be formed by piercing the plate 91 - for example, by means of a tungsten carbide needle [e.g.
similar to those used in forming spinarettes in the textile industry] or by any other suitable method.
Although it is preferred to use a small bore nozzle orifice to achieve atomization of the fluid, it is possible to use alternative atomising means. For example, as shown in Figure 7, a liquid jet 102 may be produced through an exit orifice 104 to impinge at high velocity upon an object such WO9l/1~8 PCT/GB9l/0~33 ~-2û~ 683 as a metal ball 106, which then causes the liquid to atomise. Another alternative arrangement is shown in Figure 8, where two liquid jets 110 at high velocity and pressure are caused to meet, such that the liquid becomes atomised at their meeting point.
Initial experiments with MDIs having constructions along the lines of at least some of the embodiments illustrated herein have proved to be surprisingly effective, readily providing repeatable spray doses of drugs having a mean particle size less that 30 micrometres and typically of the order of 3-10 micrometres. Mean particle sizes in the range 2 - 8 micrometres or less than 5 micrometres may be preferred. A particularly important aspect of such embodiments of the invention is that the drug can be used immediately in its water soluble form. Many drugs used at present have two formulations - one for use in an MDI, and the other for use in nebulizers usually used in hospitals.
The latter formulation is almost always an aqueous solution of the drug, so such formulations are immediately available for use with embodiments of the present invention.
By enabling application of drugs in aqueous solution with MDIs embodying the invention, new drug development may be accelerated. This is because much of the present long term testing is to ensure that the propellant (typically CFC) does not degrade or affect the drug and its effect and, of course, in the illustrated embodiments, no additional propellant agent is required.
Many of the drugs presently administered by MDIs are concerned with bronchodilators and similar drugs for treating asthma, allergies and congestive disorders.
However, it is becoming increasingly important to be able to treat other conditions (such as pneumonocystes carinii) by inhalation therapy. The reason for this is that drugs WO9l/1~68 PCT/GB91/00433 -2~078~68'~
taken via the stomach are often destroyed by stomach secretions, or that whlch does get lnto the blood stream is taken out by the liver ("first pass metabollsm"). In other cases, slde effects can be severe. Some of these new drugs are difficult to mlcronlse and, untll now, they have been admlnistered only be nebulization in hospitals, because a portable delivery method has not previously been available.
Hospital nebulizers typically comprise gas blast devices in which small quantities of liquid product are added to large quantitles of gas blasted under hlgh pressure. Large gas cylinders are required for such apparatus, which is therefore distinctly non-portable. (Certainly in the sense of a pocket-sized device, or the like). Embodiments of the present invention may readily apply such drugs to readily portable devices and an important advantage is that such embodiments may be-used immediately to administer drugs that are already tested and available for nebulizer application.
Another particularly useful advantage of the illustrated embodiments is that they may be used quite satisfactorily in an orlentation. In contrast to this, existing sprayers, both the propellant type (eg CFC) and pump action type will work only in one (usually upright) orientation. It will be appreciated that patients can not always be relied upon to be in an upright position.
As suggested above in the foregoing description, embodiments of the present invention may include product container which are a least partially transparent, so that the level of the contents may be visually checked.
A further advantage of illustrated embodiments of the invention is that they may be constructed quite satisfactorily without the use of any elastomeric sealing members. This is in contrast to all known MDIs of which we WO91/14~ PCT/GB91/~33 2 d 7 8 6 8 3 are aware, which use resilient sealing members which may possible degrade in contact with products to be dispensed, and/or in which extractable from the elastomers (eg rubbers) may leach into the products to be dispensed.
One reason why preferred embodiments of the invention can function well without the need for elastomeric seals is that the products are not stored under high pressure. High pressure exists only for a very short time! during the atomization cycle, Therefore, in the embodiments of Figures 1 and 2, for example, only a sealing cap or ring on the piston end portion 5 is required and, as mentioned above, this can be of PTFE or Nylon. In fact, it is both possible and desirable to manufacture the embodiments of Figures 1 and 2 entirely from stainless steel and approved lS plastics materials (eg polypropylene, PTFE, Nylon) which are entirely safe and non-reactive with the products to be dispensed.
If there is need for a seal at the connectors 12, this can be provided by a sealing ring or gasket of approved plastics (eg PTFE). Alternatively or additionally, the connectors such as 12 may include parts which screwthreadly engage, and at least one of which is of an approved plastic.
In the embodiment of Figure 4, it is possible if desired, to employ elastomeric seals in the pressure pulse generator (not shown). This is because the product 70 is completely isolated from such seals by the flexible tube 75 and secondary liquid 78. The flexible tube 75 is of an approved plastics (eg polypropylene, PTFE, Nylon).
In the embodiment of Figures 1 and 2, a mechanical piston, urged by a strong spring, is used to create a pressure pulse which is applied to the liquid in the pressure WO91/1~K8 PCT/GB91/0~33 2 0 7:8 6.83~ ~
chamber 4. Alternative means may be employed to produce such pressure pulses. For example, gas spring 5, electric motors, solenoids or other means may be employed.
Although above described embodiments of the invention utilize a liquid product which may typically comprise an aqueous solution of a drug, alternative fluid products may be used, For example, a fluid which is a suspension, emulsion or solution in water, alcohol or other liquid may be used.
As mentioned above, the illustrated embodiments of the invention may emit a spray at much less velocity than conventional MDIs. For example in a conventional CFC
repellant MDI, the cloud or bolus of spray that is emitted may travel at a speed of the order of 30 metres per second.
Preferred embodiments of the present invention may release an équivalent amount of spray at a quarter of this speed.
In fact it is possible to design embodiments of the present invention to match the optimum inhalation rate of the user at a figure of the order of 60 litres per minute.
The illustrated embodiments of the invention include means for metering a quantity of fluid to be atomised. In alternative embodiments atomising devices may be provided with pre-metered quantities of fluid to be atomised. For example a strip of foil or plastics material (or other material) may contain individual pre-metered doses of liquid product and the strip could be punctured locally prior to or as part of a pressurising operation, following which the liquid is atomised to a fine spray. To this end, the strip may be pre-weakened at pre-determined locations, to promote correct rupturing of the strip material when required. Alternatively pre-metered doses of liquid product may be contained in individual capsules which are fed successively to a pressure chamber or other WO91/1~68 PCT/GB91/0~33 ;'~ 0~78~83 pressurizing location where the capsules are then ruptured.
The strip mate~-al or capsules may be designed to rupture at a pre-determined pressure applied by the atomising device, such that a pressure release effect is created in the liquid product upon rupture.
The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification and which are open to public inspection with this specification, and the contents of all such lo papers and documents are incorporated herein by reference.
All of the features disclosed in this specification (including any accompanying claims, abstract and drawings) and/or all of the steps of any method or process so disclosed, may be -combined in any combination, except combinations where at lease some of such features and/or steps are mutually exclusive.
Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, useless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.
The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in the specification (including any accompanying claims, abstract and drawings), or to any one novel one, or any novel combination, of the steps of any method or process so disclosed.
. ~
Claims (100)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A device for dispensing a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising:
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for atomising said fluid discharged from said chamber, said atomising means comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less, whereby said fluid is atomized into droplets having a mean size suitable for inhalation into the lungs.
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for atomising said fluid discharged from said chamber, said atomising means comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less, whereby said fluid is atomized into droplets having a mean size suitable for inhalation into the lungs.
2. A device according to claim 1, further comprising:
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
3. A device according to claim 2 wherein said hydraulic diameter is of suitable size for formation of droplets having a mean size of less than 10 micrometers.
4. A device according to claim 2, wherein said valve mechanism comprises a pressure release valve.
5. A device according to claim 1, further comprising:
latching means to retain said energy storage means in a state retaining said predetermined amount of energy; and actuation means for releasing said predetermined amount of energy from said energy storage means.
latching means to retain said energy storage means in a state retaining said predetermined amount of energy; and actuation means for releasing said predetermined amount of energy from said energy storage means.
6. A device according to claim 1, wherein said first pressure is substantially ambient pressure.
7. A device according to claim 1, wherein said outlet aperture has a hydraulic diameter of up to 50 micrometers.
8. A device according to claim 1, wherein said second pressure is in the range of approximately 100 bar to approximately 350 bar.
9. A device according to claim 8, wherein said hydraulic diameter is in the range of 1 to 12 micrometers.
10. A device according to claim 9, wherein said hydraulic diameter is in the range of 2 to 6 micrometers.
11. A device according to claim 1, wherein said energy storage means comprises a piston adapted to act directly on said chamber to pressurize said metered quantity of fluid.
12. A device according to claim 11, wherein said piston comprises a hollow channel in fluid communication with said chamber.
13. A device according to claim 12, further comprising:
a non-return inlet valve for said chamber disposed within said channel.
a non-return inlet valve for said chamber disposed within said channel.
14. A device according to claim 12, further comprising a fluid reservoir in fluid communication with said channel, wherein said piston extends from said fluid reservoir.
15. A device according to claim 1, wherein said hydraulic diameter is of suitable size for formation of droplets having a mean size of less than 10 micrometers.
16. A device according to claim 15, wherein said hydraulic diameter is of suitable size for formation of droplets having a mean size in the range of 2 to 6 micrometers.
17. A device according to claim 1, wherein said energy storage means comprises a pump having a piston and a spring, said chamber defined by a cylinder space in said pump beyond said piston.
18. A device according to claim 17, wherein said pump is provided with a latching mechanism whereby said pump can be held in a cocked state prior to release of the energy from said spring.
19. A device according to claim 1, further comprising:
a non-return inlet valve in fluid communication with said chamber; and a non-return outlet valve in fluid communication with said chamber to permit repeated charge of fluid into said chamber and discharge of fluid from said chamber.
a non-return inlet valve in fluid communication with said chamber; and a non-return outlet valve in fluid communication with said chamber to permit repeated charge of fluid into said chamber and discharge of fluid from said chamber.
20. A device according to claim 1, further comprising:
a fluid reservoir in fluid communication with said chamber from which said chamber can be charged with fluid.
a fluid reservoir in fluid communication with said chamber from which said chamber can be charged with fluid.
21. A device according to claim 20, wherein said fluid reservoir is removable.
22. A device according to claim 20, wherein said reservoir is collapsible.
23. A device according to claim 1, wherein said second pressure is in the range of approximately 300 bar to approximately 500 bar.
24. A device for dispensing a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising:
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of 50 bar or more to permit discharge of said metered quantity of fluid from said chamber at said second pressure;
and atomising means for atomising said fluid from said chamber comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less and configured so that said fluid forms a jet of fluid, and an impingement body located in the line of trajectory of said jet, said impingement body adapted to cause break up of said jet into a spray of droplets, said droplets having a mean size suitable for inhalation into the lungs.
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of 50 bar or more to permit discharge of said metered quantity of fluid from said chamber at said second pressure;
and atomising means for atomising said fluid from said chamber comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less and configured so that said fluid forms a jet of fluid, and an impingement body located in the line of trajectory of said jet, said impingement body adapted to cause break up of said jet into a spray of droplets, said droplets having a mean size suitable for inhalation into the lungs.
25. A device according to claim 24, wherein said second pressure is in the range of approximately 100 bar to approximately 350 bar and wherein said hydraulic diameter is in the range of 1 to 12 micrometers.
26. A device according to claim 25, wherein said hydraulic diameter is in the range of 2 to 6 micrometers.
27. A device for dispensing a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising:
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of 50 bar or more to permit discharge of said metered quantity of fluid from said chamber at said second pressure;
and atomising means for atomising said fluid from said chamber comprising a plurality of outlet apertures, each of said plurality of outlet apertures having a hydraulic diameter of 100 micrometers or less and configured so that said fluid forms a plurality of jets of fluid, said plurality of jets of fluid impinging upon one another to form a spray of droplets, said droplets having a mean size suitable for inhalation into the lungs.
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of 50 bar or more to permit discharge of said metered quantity of fluid from said chamber at said second pressure;
and atomising means for atomising said fluid from said chamber comprising a plurality of outlet apertures, each of said plurality of outlet apertures having a hydraulic diameter of 100 micrometers or less and configured so that said fluid forms a plurality of jets of fluid, said plurality of jets of fluid impinging upon one another to form a spray of droplets, said droplets having a mean size suitable for inhalation into the lungs.
28. A device according to claim 27, wherein said second pressure is in the range of approximately 100 bar to approximately 350 bar and wherein each of said plurality of outlet apertures has a hydraulic diameter in the range of 1 to 12 micrometers.
29. A device according to claim 28, wherein each of said plurality of outlet apertures has a hydraulic diameter in the range of 2 to 6 micrometers.
30. A device for dispensing a metered quantity of fluid as a spray of fine droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising:
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retching and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least about 100 bar to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for atomising said fluid discharged from said chamber, said atomising means comprising an outlet aperture having a hydraulic diameter suitable for formation of atomized droplets having a mean size of less than 10 micrometers for inhalation into the lungs.
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retching and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least about 100 bar to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for atomising said fluid discharged from said chamber, said atomising means comprising an outlet aperture having a hydraulic diameter suitable for formation of atomized droplets having a mean size of less than 10 micrometers for inhalation into the lungs.
31. A device according to claim 30, wherein said hydraulic diameter is suitable for formation of atomised droplets having a mean size in the range of 2 to 6 micrometers.
32. A device for discharging a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means;
means for applying a predetermined amount of energy to said energy storage means;
means for releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure to a second pressure and to initiate discharge of said fluid from said chamber; and atomising means for receiving said metered quantity of pressurized fluid from said chamber as a single discharge from said chamber, and for atomising said metered quantity of fluid, said atomising means comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less whereby said fluid is atomised into droplets having a mean size suitable for inhalation into the lungs.
an energy storage means;
means for applying a predetermined amount of energy to said energy storage means;
means for releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure to a second pressure and to initiate discharge of said fluid from said chamber; and atomising means for receiving said metered quantity of pressurized fluid from said chamber as a single discharge from said chamber, and for atomising said metered quantity of fluid, said atomising means comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less whereby said fluid is atomised into droplets having a mean size suitable for inhalation into the lungs.
33. A device according to claim 32, wherein said second pressure is 50 bar or greater.
34. A device according to claim 33, wherein said hydraulic diameter is of suitable size for formation of droplets having a mean size of less than 10 micrometers.
35. A device according to claim 34, wherein said hydraulic diameter of said outlet aperture is 50 micrometers or less.
36. A device according to claim 34, wherein said hydraulic diameter is of suitable size for formation of droplets having a mean size in the range of 2 to 6 micrometers.
37. A device according to claim 31, wherein said second pressure is 100 bar or greater.
38. A device according to claim 37, wherein said hydraulic diameter is of suitable size for formation of droplets having a mean size of less than 10 micrometers.
39. A device according to claim 32, wherein said hydraulic diameter is of suitable size for formation of droplets having a mean size of less than 10 micrometers.
40. A device according to claim 39, wherein said hydraulic diameter is of suitable size for formation of droplets having a mean size in the range of 2 to 6 micrometers.
41. A device according to claim 32, further comprising:
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
42. A device according to claim 41, wherein said valve mechanism comprises a pressure release valve.
43. A device according to claim 32, further comprising a non-return inlet valve in fluid communication with said chamber; and a non-return outlet valve in fluid communication with said chamber to permit repeated charge of fluid into said chamber and discharge of fluid from said chamber.
44. A device according to claim 24, further comprising:
a fluid reservoir in fluid communication with said chamber from which said chamber can be charged with fluid.
a fluid reservoir in fluid communication with said chamber from which said chamber can be charged with fluid.
45. A device according to claim 44, wherein said fluid reservoir is removable.
46. A device according to claim 44, wherein said reservoir is collapsible.
47. A method of discharging a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising the steps of:
providing said metered quantity of fluid in a chamber at which said fluid is held at a first pressure;
applying a predetermined amount of energy to an energy storage means;
releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure to a second pressure and to initiate discharge of said fluid from said chamber; and discharging said metered quantity of pressurized fluid from said chamber as a single discharge from said chamber through an outlet aperture in the atomising means, said outlet aperture having a hydraulic diameter of 100 micrometers or less, thereby atomising said fluid into droplets having a mean size suitable for inhalation into the lungs.
providing said metered quantity of fluid in a chamber at which said fluid is held at a first pressure;
applying a predetermined amount of energy to an energy storage means;
releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure to a second pressure and to initiate discharge of said fluid from said chamber; and discharging said metered quantity of pressurized fluid from said chamber as a single discharge from said chamber through an outlet aperture in the atomising means, said outlet aperture having a hydraulic diameter of 100 micrometers or less, thereby atomising said fluid into droplets having a mean size suitable for inhalation into the lungs.
48. A method according to claim 47, wherein said second pressure is from 50 to 500 bar and wherein said discharging step produces droplets having a mean size of less than 10 micrometers.
49. A method according to claim 47, wherein said energy storage means comprises a pump having a piston and a spring, said chamber defined by a cylinder space in said pump beyond said piston.
50. A method according to claim 49, wherein said pump is provided with a latching mechanism whereby said pump can be held in a cocked state prior to release of the energy from said spring.
51. A method according to claim 47, wherein said droplets have a mean size in the range of 1 to 12 micrometers.
52. A method according to claim 51, wherein said droplets have a mean size in the range of 2 to 6 micrometers.
53. A method of discharging a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising the steps of:
providing said metered quantity of fluid in a chamber at which said fluid is held at a first pressure;
applying a predetermined amount of energy to an energy storage means;
releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar; and discharging said fluid from said chamber through an outlet aperture in the atomising means, said outlet aperture having a hydraulic diameter of 100 micrometers or less, thereby atomising said fluid into droplets having a mean size suitable for inhalation into the lungs.
providing said metered quantity of fluid in a chamber at which said fluid is held at a first pressure;
applying a predetermined amount of energy to an energy storage means;
releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar; and discharging said fluid from said chamber through an outlet aperture in the atomising means, said outlet aperture having a hydraulic diameter of 100 micrometers or less, thereby atomising said fluid into droplets having a mean size suitable for inhalation into the lungs.
54. A method according to claim 53, wherein said droplets have a mean size in the range of 1 to 12 micrometers.
55. A metered dose inhaler for supplying fluid medicament to the lungs, comprising:
a chamber for containing a metered quantity of fluid medicament at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of said metered quantity from said chamber at said second pressure, said energy storage means comprising a piston adapted to act directly on said chamber to pressurize said metered quantity, a spring, and a latching mechanism whereby said energy storage means can be held in a cocked state prior to release of the energy from said spring; and atomising means for atomising said metered quantity discharged from said chamber, said atomising means comprising a first outlet aperture having a hydraulic diameter of 100 micrometers or less.
a chamber for containing a metered quantity of fluid medicament at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of said metered quantity from said chamber at said second pressure, said energy storage means comprising a piston adapted to act directly on said chamber to pressurize said metered quantity, a spring, and a latching mechanism whereby said energy storage means can be held in a cocked state prior to release of the energy from said spring; and atomising means for atomising said metered quantity discharged from said chamber, said atomising means comprising a first outlet aperture having a hydraulic diameter of 100 micrometers or less.
56. A metered dose inhaler according to claim 55, further comprising:
a non-return inlet valve, wherein said piston comprises a hollow channel in fluid communication with said chamber, said non-return inlet valve disposed within said channel; and a fluid reservoir in fluid communication with said channel, wherein said piston extends from said fluid reservoir.
a non-return inlet valve, wherein said piston comprises a hollow channel in fluid communication with said chamber, said non-return inlet valve disposed within said channel; and a fluid reservoir in fluid communication with said channel, wherein said piston extends from said fluid reservoir.
57. A metered dose inhaler according to claim 56, wherein said latching mechanism is released to initiate discharge of said metered quantity from said chamber at said second pressure, wherein said second pressure is in excess of 100 bar.
58. A metered dose inhaler according to claim 57, wherein said atomising means further comprises:
a second outlet aperture, wherein a first jet of said metered quantity is discharged through said first outlet aperture and a second jet of said metered quantity is discharged through said second outlet aperture, said first jet and said second jet impinging upon one another to form a spray of droplets.
a second outlet aperture, wherein a first jet of said metered quantity is discharged through said first outlet aperture and a second jet of said metered quantity is discharged through said second outlet aperture, said first jet and said second jet impinging upon one another to form a spray of droplets.
59. A metered dose inhaler according to claim 56, wherein said second pressure is in excess of 100 bar.
60. A metered dose inhaler according to claim 55, wherein said latching mechanism is released to initiate discharge of said metered quantity from said chamber at said second pressure.
61. A metered dose inhaler according to claim 60, wherein the second pressure is in excess of 100 bar.
62. A metered dose inhaler according to claim 60, wherein said atomising means further comprises:
a second outlet aperture, wherein a first jet of said metered quantity is discharged through said first outlet aperture and a second jet of said metered quantity is discharged through said second outlet aperture, said first jet and said second jet impinging upon one another to form a spray of droplets.
a second outlet aperture, wherein a first jet of said metered quantity is discharged through said first outlet aperture and a second jet of said metered quantity is discharged through said second outlet aperture, said first jet and said second jet impinging upon one another to form a spray of droplets.
63. A metered dose inhaler according to claim 55, wherein said second pressure is in excess of 100 bar.
64. A metered dose inhaler according to claim 55, wherein said atomising means further comprises:
a second outlet aperture, wherein a first jet of said metered quantity is discharged through said first outlet aperture and a second jet of said metered quantity is discharged through said second outlet aperture, said first jet and said second jet impinging upon one another to form a spray of droplets.
a second outlet aperture, wherein a first jet of said metered quantity is discharged through said first outlet aperture and a second jet of said metered quantity is discharged through said second outlet aperture, said first jet and said second jet impinging upon one another to form a spray of droplets.
65. A device for dispensing a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising:
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for atomising said fluid discharged from said chamber, said atomising means comprising an outlet aperture having a hydraulic diameter of suitable size for formation of droplets having a mean size of less than 10 micrometers for inhalation into the lungs.
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means for retaining and applying a predetermined amount of energy to said chamber so as to subject said metered quantity of fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for atomising said fluid discharged from said chamber, said atomising means comprising an outlet aperture having a hydraulic diameter of suitable size for formation of droplets having a mean size of less than 10 micrometers for inhalation into the lungs.
66. A device according to claim 65, further comprising:
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
67. A device according to claim 65, further comprising:
latching means to retain said energy storage means in a state retaining said predetermined amount of energy; and actuation means for releasing said predetermined amount of energy from said energy storage means.
latching means to retain said energy storage means in a state retaining said predetermined amount of energy; and actuation means for releasing said predetermined amount of energy from said energy storage means.
68. A device according to claim 65, wherein said first pressure is substantially ambient pressure.
69. A device according to claim 65, wherein said second pressure is in the range of approximately 100 bar to approximately 350 bar.
70. A device according to claim 65, wherein said energy storage means comprises a piston adapted to act directly on said chamber to pressurize said metered quantity of fluid.
71. A device according to claim 70, wherein said piston comprises a hollow channel in fluid communication with said chamber.
72. A device according to claim 71, further comprising:
a non-return inlet valve for said chamber disposed within said channel.
a non-return inlet valve for said chamber disposed within said channel.
73. A device according to claim 71, further comprising:
a fluid reservoir in fluid communication with said channel, wherein said piston extends from said fluid reservoir.
a fluid reservoir in fluid communication with said channel, wherein said piston extends from said fluid reservoir.
74. A device according to claim 65, wherein said second pressure is in the range of approximately 300 bar to approximately 500 bar.
75. A method of discharging a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising the steps of:
providing said metered quantity of fluid in a chamber at which said fluid is held at a first pressure;
applying a predetermined amount of energy to an energy storage means;
releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar; and discharging said fluid from said chamber through an outlet aperture in the atomising means, said outlet aperture having a hydraulic diameter of suitable size for formation of droplets having a mean size of less than 10 micrometers, thereby atomising said fluid into droplets having a mean size suitable for inhalation into the lungs.
providing said metered quantity of fluid in a chamber at which said fluid is held at a first pressure;
applying a predetermined amount of energy to an energy storage means;
releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar; and discharging said fluid from said chamber through an outlet aperture in the atomising means, said outlet aperture having a hydraulic diameter of suitable size for formation of droplets having a mean size of less than 10 micrometers, thereby atomising said fluid into droplets having a mean size suitable for inhalation into the lungs.
76. A device for discharging a metered quantity of fluid as a spray of droplets by discharging the metered quantity of fluid under pressure through an atomising means, comprising:
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means;
means for applying a predetermined amount of energy to said energy storage means;
means for releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure to a second pressure to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for receiving said metered quantity of pressurized fluid from said chamber, and for atomising said metered quantity of fluid, said atomising means comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less whereby said fluid is atomized into droplets having a mean size suitable for inhalation into the lungs.
a chamber for containing said metered quantity of fluid at a first pressure;
an energy storage means;
means for applying a predetermined amount of energy to said energy storage means;
means for releasing said predetermined amount of energy from said energy storage means to said chamber so as to subject said fluid to a predetermined increase in pressure to a second pressure to permit discharge of said metered quantity of fluid from said chamber at said second pressure; and atomising means for receiving said metered quantity of pressurized fluid from said chamber, and for atomising said metered quantity of fluid, said atomising means comprising an outlet aperture having a hydraulic diameter of 100 micrometers or less whereby said fluid is atomized into droplets having a mean size suitable for inhalation into the lungs.
77. A device for dispensing fluid as a spray of droplets, comprising:
a chamber for containing a quantity of fluid at a first pressure;
a piston configured to act directly on said chamber to pressurize the quantity of fluid;
resilient biasing means permitting withdrawal of said piston away from said chamber to a cocked position, and for urging said piston to act on said chamber so that the quantity of fluid is subjected to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of the quantity of fluid from said chamber at said second pressure wherein said resilient biasing means is in a loaded state when said piston is in the cocked position;
latching means for holding said resilient biasing means in the loaded state;
actuating means for releasing said latching means to initiate discharge of the quantity of fluid from said chamber at said second pressure; and atomising means for atomising the quantity of fluid discharged from said chamber.
a chamber for containing a quantity of fluid at a first pressure;
a piston configured to act directly on said chamber to pressurize the quantity of fluid;
resilient biasing means permitting withdrawal of said piston away from said chamber to a cocked position, and for urging said piston to act on said chamber so that the quantity of fluid is subjected to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of the quantity of fluid from said chamber at said second pressure wherein said resilient biasing means is in a loaded state when said piston is in the cocked position;
latching means for holding said resilient biasing means in the loaded state;
actuating means for releasing said latching means to initiate discharge of the quantity of fluid from said chamber at said second pressure; and atomising means for atomising the quantity of fluid discharged from said chamber.
78. A device according to claim 77, wherein said piston comprises a channel in fluid communication with said chamber.
79. A device according to claim 78, further comprising:
a non-return inlet valve for said chamber disposed within said channel.
a non-return inlet valve for said chamber disposed within said channel.
80. A device according to claim 78, further comprising:
a fluid reservoir in fluid communication with said channel, wherein said piston extends from said fluid reservoir.
a fluid reservoir in fluid communication with said channel, wherein said piston extends from said fluid reservoir.
81. A device according to claim 78, further comprising:
a fluid reservoir in fluid communication with said channel, wherein said piston is integrally formed with said fluid reservoir.
a fluid reservoir in fluid communication with said channel, wherein said piston is integrally formed with said fluid reservoir.
82. A device according to claim 81, wherein said fluid reservoir is collapsible.
83. A device according to claim 77, further comprising:
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
84. A device according to claim 79, further comprising:
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
85. A device according to claim 77, wherein said second pressure is in the range of approximately 300 bar to approximately 500 bar.
86. A device according to claim 77, wherein said piston is configured to have a variable stroke.
87. A device according to claim 80, wherein a metered quantity of fluid is drawn into said chamber from said fluid reservoir when said piston is withdrawn to the cocked position.
88. A device according to claim 81, wherein a metered quantity of fluid is drawn into said chamber from said fluid reservoir when said piston is withdrawn to the cocked position.
89. A device according to claim 77, wherein said resilient biasing means comprises a spring.
90. A device for dispensing fluid as a spray of droplets, comprising:
a chamber for containing a metered quantity of fluid at a first pressure;
a piston configured to act directly on said chamber to pressurize the metered quantity of fluid;
resilient biasing means permitting withdrawal of said piston away from said chamber to a cocked position, and for urging said piston to act on said chamber so that the metered quantity of fluid is subjected to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of the metered quantity of fluid from said chamber at said second pressure wherein the resilient biasing means is in a loaded state when said piston is in the cocked position;
latching means for holding said resilient biasing means in the loaded state;
a fluid reservoir in fluid communication with said chamber, wherein the metered quantity of fluid is drawn into said chamber from said fluid reservoir when said piston is withdrawn to the cocked position; and atomising means for atomising the metered quantity of fluid discharged from said chamber.
a chamber for containing a metered quantity of fluid at a first pressure;
a piston configured to act directly on said chamber to pressurize the metered quantity of fluid;
resilient biasing means permitting withdrawal of said piston away from said chamber to a cocked position, and for urging said piston to act on said chamber so that the metered quantity of fluid is subjected to a predetermined increase in pressure from said first pressure to a second pressure of at least 50 bar to permit discharge of the metered quantity of fluid from said chamber at said second pressure wherein the resilient biasing means is in a loaded state when said piston is in the cocked position;
latching means for holding said resilient biasing means in the loaded state;
a fluid reservoir in fluid communication with said chamber, wherein the metered quantity of fluid is drawn into said chamber from said fluid reservoir when said piston is withdrawn to the cocked position; and atomising means for atomising the metered quantity of fluid discharged from said chamber.
91. A device according to claim 90, further comprising:
actuating means for releasing said latching means to initiate discharge of the metered quantity of fluid from said chamber at said second pressure.
actuating means for releasing said latching means to initiate discharge of the metered quantity of fluid from said chamber at said second pressure.
92. A device according to claim 90, wherein said piston comprises a channel in fluid communication with said chamber.
93. A device according to claim 90, wherein said piston extends from said fluid reservoir.
94. A device according to claim 90, wherein said piston is integrally formed with said fluid reservoir.
95. A device according to claim 92, further comprising:
a non-return inlet valve for said chamber disposed within said channel.
a non-return inlet valve for said chamber disposed within said channel.
96. A device according to claim 92, further comprising:
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
a conduit connecting said chamber and said atomising means; and a valve mechanism for regulating the flow of fluid between said chamber and said atomising means.
97. A device according to claim 90, wherein said resilient biasing means comprises a spring.
98. A device according to claim 77, wherein said atomising means comprises:
a first outlet aperture for discharging a first jet of fluid; and a second outlet aperture for discharging a second jet of fluid, said first jet and said second jet impinging upon one another to form a spray of droplets.
a first outlet aperture for discharging a first jet of fluid; and a second outlet aperture for discharging a second jet of fluid, said first jet and said second jet impinging upon one another to form a spray of droplets.
99. A device according to claim 90, wherein said atomising means comprises:
a first outlet aperture for discharging a first jet of fluid; and a second outlet aperture for discharging a second jet of fluid, said first jet and said second jet impinging upon one another to form a spray of droplets.
a first outlet aperture for discharging a first jet of fluid; and a second outlet aperture for discharging a second jet of fluid, said first jet and said second jet impinging upon one another to form a spray of droplets.
100. A metered dose inhaler according to claim 58, which includes manually operable means for withdrawing the piston from the chamber such that fluid medicament enters the chamber through the channel, and for simultaneously loading the spring, means also being provided to prevent air being drawn in through the atomising means during such withdrawal and the reservoir being collapsible.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002206753A CA2206753C (en) | 1990-03-21 | 1991-03-21 | Atomising devices and methods |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB909006340A GB9006340D0 (en) | 1990-03-21 | 1990-03-21 | Metered dose aerosol delivery system |
GB9006340.5 | 1990-11-01 | ||
GB909023767A GB9023767D0 (en) | 1990-11-01 | 1990-11-01 | Atomising devices and methods |
GB9023767.8 | 1990-11-01 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002206753A Division CA2206753C (en) | 1990-03-21 | 1991-03-21 | Atomising devices and methods |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2078683A1 CA2078683A1 (en) | 1991-09-22 |
CA2078683C true CA2078683C (en) | 1997-10-07 |
Family
ID=26296818
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002206753A Expired - Lifetime CA2206753C (en) | 1990-03-21 | 1991-03-21 | Atomising devices and methods |
CA002078683A Expired - Lifetime CA2078683C (en) | 1990-03-21 | 1991-03-21 | Atomising devices and methods |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002206753A Expired - Lifetime CA2206753C (en) | 1990-03-21 | 1991-03-21 | Atomising devices and methods |
Country Status (37)
Country | Link |
---|---|
US (2) | US5497944A (en) |
EP (2) | EP0521061B1 (en) |
JP (1) | JP2630347B2 (en) |
KR (1) | KR0139652B1 (en) |
CN (2) | CN1042203C (en) |
AT (2) | ATE160947T1 (en) |
AU (1) | AU650870B2 (en) |
BR (1) | BR9106249A (en) |
CA (2) | CA2206753C (en) |
CZ (1) | CZ283820B6 (en) |
DE (2) | DE69131966T2 (en) |
DK (2) | DK0521061T3 (en) |
ES (2) | ES2109943T3 (en) |
FI (1) | FI104311B (en) |
GB (1) | GB2256805B (en) |
GR (2) | GR3026065T3 (en) |
HK (1) | HK1005059A1 (en) |
HR (1) | HRP921357B1 (en) |
HU (1) | HU216121B (en) |
IE (1) | IE62626B1 (en) |
IL (1) | IL97619A (en) |
IN (1) | IN177383B (en) |
MY (1) | MY110310A (en) |
NO (1) | NO303206B1 (en) |
NZ (1) | NZ237502A (en) |
PH (1) | PH30833A (en) |
PL (1) | PL165926B1 (en) |
PT (1) | PT97098B (en) |
RS (1) | RS49548B (en) |
RU (1) | RU2104048C1 (en) |
SG (1) | SG45171A1 (en) |
SI (1) | SI9110500B (en) |
SK (1) | SK280225B6 (en) |
TW (1) | TW253846B (en) |
UA (1) | UA27777C2 (en) |
WO (1) | WO1991014468A1 (en) |
YU (1) | YU48710B (en) |
Families Citing this family (406)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL100224A (en) * | 1990-12-04 | 1994-10-21 | Dmw Tech Ltd | Atomising nozzles |
US6540154B1 (en) * | 1991-04-24 | 2003-04-01 | Aerogen, Inc. | Systems and methods for controlling fluid feed to an aerosol generator |
GB9114080D0 (en) * | 1991-06-28 | 1991-08-14 | Weston Terence E | Atomising valve |
ES2099266T5 (en) * | 1991-07-01 | 2004-01-01 | Alexander George Brian O'neil | INFUSION DEVICE CONTROLLED BY THE PATIENT. |
EP0632734B1 (en) * | 1992-03-25 | 1998-06-10 | Tebro S.A. | Powder jet dispenser for medicament inhalation therapies |
IL107120A (en) * | 1992-09-29 | 1997-09-30 | Boehringer Ingelheim Int | Atomising nozzle and filter and spray generating device |
US6007676A (en) * | 1992-09-29 | 1999-12-28 | Boehringer Ingelheim International Gmbh | Atomizing nozzle and filter and spray generating device |
US7448375B2 (en) * | 1993-01-29 | 2008-11-11 | Aradigm Corporation | Method of treating diabetes mellitus in a patient |
US5873358A (en) * | 1993-01-29 | 1999-02-23 | Aradigm Corporation | Method of maintaining a diabetic patient's blood glucose level in a desired range |
US6098620A (en) * | 1993-01-29 | 2000-08-08 | Aradigm Corporation | Device for aerosolizing narcotics |
US5915378A (en) * | 1993-01-29 | 1999-06-29 | Aradigm Corporation | Creating an aerosolized formulation of insulin |
US5934272A (en) * | 1993-01-29 | 1999-08-10 | Aradigm Corporation | Device and method of creating aerosolized mist of respiratory drug |
US5507277A (en) * | 1993-01-29 | 1996-04-16 | Aradigm Corporation | Lockout device for controlled release of drug from patient-activateddispenser |
US5724957A (en) * | 1993-01-29 | 1998-03-10 | Aradigm Corporation | Intrapulmonary delivery of narcotics |
US5970973A (en) * | 1993-01-29 | 1999-10-26 | Aradigm Corporation | Method of delivering insulin lispro |
US5672581A (en) * | 1993-01-29 | 1997-09-30 | Aradigm Corporation | Method of administration of insulin |
US5743250A (en) * | 1993-01-29 | 1998-04-28 | Aradigm Corporation | Insulin delivery enhanced by coached breathing |
US5558085A (en) * | 1993-01-29 | 1996-09-24 | Aradigm Corporation | Intrapulmonary delivery of peptide drugs |
US6024090A (en) * | 1993-01-29 | 2000-02-15 | Aradigm Corporation | Method of treating a diabetic patient by aerosolized administration of insulin lispro |
US6012450A (en) * | 1993-01-29 | 2000-01-11 | Aradigm Corporation | Intrapulmonary delivery of hematopoietic drug |
US5694919A (en) * | 1993-01-29 | 1997-12-09 | Aradigm Corporation | Lockout device for controlled release of drug from patient-activated dispenser |
US6131567A (en) * | 1993-01-29 | 2000-10-17 | Aradigm Corporation | Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin |
US5819726A (en) * | 1993-01-29 | 1998-10-13 | Aradigm Corporation | Method for the delivery of aerosolized drugs to the lung for the treatment of respiratory disease |
US5888477A (en) * | 1993-01-29 | 1999-03-30 | Aradigm Corporation | Use of monomeric insulin as a means for improving the bioavailability of inhaled insulin |
DK48993D0 (en) * | 1993-04-30 | 1993-04-30 | Steen Erik Holm | NON-TREATMENT FOR WATERABLE LUNG MEDICINE |
US5709202A (en) * | 1993-05-21 | 1998-01-20 | Aradigm Corporation | Intrapulmonary delivery of aerosolized formulations |
US5497763A (en) * | 1993-05-21 | 1996-03-12 | Aradigm Corporation | Disposable package for intrapulmonary delivery of aerosolized formulations |
US5792057A (en) * | 1993-05-21 | 1998-08-11 | Aradigm Corporation | Ventilation imaging using a fine particle aerosol generator |
FR2705911B1 (en) * | 1993-06-02 | 1995-08-11 | Oreal | Piezoelectric nebulization device. |
DE69523301T2 (en) * | 1994-05-13 | 2002-07-04 | Aradigm Corp | A NARCOTIC AEROSOL FORMULATION |
DE4428434A1 (en) * | 1994-08-11 | 1996-02-15 | Boehringer Ingelheim Kg | Sealing cap and method for filling gas-free containers |
US5522385A (en) * | 1994-09-27 | 1996-06-04 | Aradigm Corporation | Dynamic particle size control for aerosolized drug delivery |
US6782886B2 (en) * | 1995-04-05 | 2004-08-31 | Aerogen, Inc. | Metering pumps for an aerosolizer |
US5758637A (en) | 1995-08-31 | 1998-06-02 | Aerogen, Inc. | Liquid dispensing apparatus and methods |
EP0840630B1 (en) | 1995-06-07 | 2009-05-06 | O'NEIL, Christine | Patient controlled drug delivery device |
AU710177B2 (en) * | 1995-06-07 | 1999-09-16 | Alexander George Brian O'neil | Patient controlled drug delivery device |
SE9503141D0 (en) * | 1995-09-12 | 1995-09-12 | Siemens Elema Ab | Anesthesia apparatus |
DE19536902A1 (en) | 1995-10-04 | 1997-04-10 | Boehringer Ingelheim Int | Miniature fluid pressure generating device |
DE19545226C1 (en) | 1995-12-05 | 1997-06-19 | Boehringer Ingelheim Int | Locking mechanism for a spring-operated output |
US5829436A (en) * | 1996-02-05 | 1998-11-03 | Aradigm Corporation | Ventilation imaging using a fine particle aerosol generator |
AUPN814496A0 (en) | 1996-02-19 | 1996-03-14 | Monash University | Dermal penetration enhancer |
FR2745551B1 (en) * | 1996-02-29 | 1998-05-07 | Kerplas Snc | PUSH CAP FOR A PRODUCT DISPENSING BOTTLE, AND CORRESPONDING BOTTLE |
DE19615422A1 (en) * | 1996-04-19 | 1997-11-20 | Boehringer Ingelheim Kg | Two-chamber cartridge for propellant-free MDIs |
AUPO418696A0 (en) | 1996-12-12 | 1997-01-16 | Resmed Limited | A substance delivery apparatus |
US20030215396A1 (en) | 1999-09-15 | 2003-11-20 | Boehringer Ingelheim Pharma Kg | Method for the production of propellant gas-free aerosols from aqueous medicament preparations |
DE19653969A1 (en) * | 1996-12-20 | 1998-06-25 | Boehringer Ingelheim Kg | New aqueous pharmaceutical preparation for the production of propellant-free aerosols |
US5829435A (en) * | 1997-02-24 | 1998-11-03 | Aradigm Corporation | Prefilter for prevention of clogging of a nozzle in the generation of an aerosol and prevention of administration of undesirable particles |
GB9818111D0 (en) | 1998-08-19 | 1998-10-14 | Weston Medical Ltd | Device for metered fluid delivery |
US5810211A (en) * | 1997-03-06 | 1998-09-22 | Hayes Products, Llc | Pump assembly with sliding plug |
US6089414A (en) | 1997-03-06 | 2000-07-18 | Hayes Products, Llc | Pump assembly with one piece piston |
US5918782A (en) * | 1997-03-06 | 1999-07-06 | Hayes Products, Llc | Pump assembly with sprayer |
US5816447A (en) * | 1997-03-06 | 1998-10-06 | Hayes Products, Llc | Non-aerosol pump spray apparatus |
DE19715893C2 (en) * | 1997-04-16 | 1999-04-29 | Boehringer Ingelheim Int | Device for removing a liquid from a closed container |
US20060239930A1 (en) * | 1997-08-04 | 2006-10-26 | Herbert Lamche | Process for nebulizing aqueous compositions containing highly concentrated insulin |
DE19733651A1 (en) * | 1997-08-04 | 1999-02-18 | Boehringer Ingelheim Pharma | Aqueous aerosol preparations containing biologically active marrow molecules and processes for producing corresponding aerosols |
USD418201S (en) * | 1997-08-27 | 1999-12-28 | Hayes Products, Llc | Bottle, pump and sprayer assembly |
USD417618S (en) * | 1997-08-28 | 1999-12-14 | Hayes Products, Llc | Pump assembly |
DE19742439C1 (en) | 1997-09-26 | 1998-10-22 | Boehringer Ingelheim Int | Fluid micro-filter |
US6016800A (en) * | 1997-10-24 | 2000-01-25 | Century; Theodore J. | Intrapulmonary aerosolizer |
GB9724223D0 (en) * | 1997-11-18 | 1998-01-14 | Pa Consulting Services | Drug delivery device |
US6223746B1 (en) * | 1998-02-12 | 2001-05-01 | Iep Pharmaceutical Devices Inc. | Metered dose inhaler pump |
US7963955B2 (en) * | 1998-02-27 | 2011-06-21 | Boehringer Ingelheim International Gmbh | Container for a medicinal liquid |
US7335186B2 (en) | 1998-03-13 | 2008-02-26 | Alexander George Brian O'Neil | Patient controlled drug delivery device |
US6234167B1 (en) | 1998-10-14 | 2001-05-22 | Chrysalis Technologies, Incorporated | Aerosol generator and methods of making and using an aerosol generator |
DE19847968A1 (en) | 1998-10-17 | 2000-04-20 | Boehringer Ingelheim Pharma | Separate storage of an active material and a solvent comprises a closure cap and a container, with a chamber attached to the unit. |
US6745763B2 (en) * | 1998-10-27 | 2004-06-08 | Garth T. Webb | Vaporizing device for administering sterile medication |
DE19851404A1 (en) | 1998-11-07 | 2000-05-11 | Boehringer Ingelheim Int | Pressure compensation device for a double tank |
WO2000029167A1 (en) | 1998-11-16 | 2000-05-25 | Aradigm Corporation | Method of fabricating porous membrane with unique pore structure for aerosolized delivery of drugs |
US6070575A (en) * | 1998-11-16 | 2000-06-06 | Aradigm Corporation | Aerosol-forming porous membrane with certain pore structure |
US6354516B1 (en) | 1999-11-02 | 2002-03-12 | Aradigm Corporation | Pore structures for reduced pressure aerosolization |
US6322008B1 (en) * | 1999-01-11 | 2001-11-27 | Graves Spray Supply, Inc | Liquid impingement nozzle with paired openings |
DE19940713A1 (en) * | 1999-02-23 | 2001-03-01 | Boehringer Ingelheim Int | Diffusion resistant cartridge for storing and dosing liquids, especially for producing drug-containing inhalable aerosols, has three-shell structure with collapsible bag, container and rigid housing |
DE19921693A1 (en) | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Pharmaceutical composition for treating respiratory disorders, e.g. asthma, comprises combination of anticholinergic and beta-mimetic agents having synergistic bronchospasmolytic activity and reduced side-effects |
US6360922B1 (en) | 1999-04-27 | 2002-03-26 | Hayes Products, Llc | Pump assembly with pressure release capability |
US6606992B1 (en) * | 1999-06-30 | 2003-08-19 | Nektar Therapeutics | Systems and methods for aerosolizing pharmaceutical formulations |
ES2165768B1 (en) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | NEW DERIVATIVES OF QUINUCLIDINE AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM. |
US6235177B1 (en) | 1999-09-09 | 2001-05-22 | Aerogen, Inc. | Method for the construction of an aperture plate for dispensing liquid droplets |
AU781452B2 (en) | 1999-09-15 | 2005-05-26 | Aradigm Corporation | Pore structures for reduced pressure aerosolization |
EP1747816A3 (en) * | 1999-09-15 | 2007-02-14 | Aradigm Corporation | Pore structures for reduced pressure aerosolization |
SE9903990D0 (en) * | 1999-11-02 | 1999-11-02 | Shl Medical Ab | Inhaler with aerosolizing unit |
GB0002798D0 (en) * | 2000-02-09 | 2000-03-29 | Glaxo Group Ltd | Actuator nozzle for metered dose inhaler |
US8336545B2 (en) * | 2000-05-05 | 2012-12-25 | Novartis Pharma Ag | Methods and systems for operating an aerosol generator |
US6948491B2 (en) * | 2001-03-20 | 2005-09-27 | Aerogen, Inc. | Convertible fluid feed system with comformable reservoir and methods |
US7971588B2 (en) * | 2000-05-05 | 2011-07-05 | Novartis Ag | Methods and systems for operating an aerosol generator |
US7600511B2 (en) * | 2001-11-01 | 2009-10-13 | Novartis Pharma Ag | Apparatus and methods for delivery of medicament to a respiratory system |
MXPA02010884A (en) * | 2000-05-05 | 2003-03-27 | Aerogen Ireland Ltd | Apparatus and methods for the delivery of medicaments to the respiratory system. |
GB0012356D0 (en) | 2000-05-22 | 2000-07-12 | Textron Automotive Company Lim | Fluid spray nozzle |
US6325248B1 (en) | 2000-07-05 | 2001-12-04 | Robert E. Corba | Container assembly |
US6299024B1 (en) | 2000-07-05 | 2001-10-09 | Robert E. Corba | Valve assembly for dispensing container |
CN1302823C (en) * | 2000-10-05 | 2007-03-07 | 欧姆龙健康医疗事业株式会社 | Liquid atomizer |
RS50859B (en) * | 2000-10-31 | 2010-08-31 | Boehringer Ingelheim Pharma Gmbh. & Co.Kg. | Inhalative solution formulation containing a tiotropium salt |
US20020084290A1 (en) * | 2000-11-10 | 2002-07-04 | Therics, Inc. | Method and apparatus for dispensing small volume of liquid, such as with a weting-resistant nozzle |
AU2002216489A1 (en) * | 2000-12-11 | 2002-06-24 | Fenton, Colleen Mary | An inflation device |
DE10062630A1 (en) * | 2000-12-15 | 2002-08-29 | Bartels Mikrotechnik Gmbh | Beduftungsverfahren |
US6799572B2 (en) | 2000-12-22 | 2004-10-05 | Chrysalis Technologies Incorporated | Disposable aerosol generator system and methods for administering the aerosol |
US6491233B2 (en) | 2000-12-22 | 2002-12-10 | Chrysalis Technologies Incorporated | Vapor driven aerosol generator and method of use thereof |
US6501052B2 (en) | 2000-12-22 | 2002-12-31 | Chrysalis Technologies Incorporated | Aerosol generator having multiple heating zones and methods of use thereof |
US6701921B2 (en) | 2000-12-22 | 2004-03-09 | Chrysalis Technologies Incorporated | Aerosol generator having heater in multilayered composite and method of use thereof |
US6681998B2 (en) | 2000-12-22 | 2004-01-27 | Chrysalis Technologies Incorporated | Aerosol generator having inductive heater and method of use thereof |
US20110301569A1 (en) | 2001-01-20 | 2011-12-08 | Gordon Wayne Dyer | Methods and apparatus for the CVCS |
US6550472B2 (en) * | 2001-03-16 | 2003-04-22 | Aerogen, Inc. | Devices and methods for nebulizing fluids using flow directors |
US6732944B2 (en) * | 2001-05-02 | 2004-05-11 | Aerogen, Inc. | Base isolated nebulizing device and methods |
GB0111336D0 (en) * | 2001-05-10 | 2001-07-04 | Innovata Biomed Ltd | Device |
DE10125564A1 (en) | 2001-05-25 | 2002-11-28 | Transmit Technologietransfer | Inhalation mask for horses is made of a flexible, preferably transparent material, and incorporates inhalation/exhalation air channels, an inhalate source and exhalation air filters |
FR2826344B1 (en) * | 2001-06-22 | 2003-09-05 | Oreal | DEVICE FOR SPRAYING A PRODUCT, PARTICULARLY IN THE FORM OF A SAMPLE DOSE |
DE10131178A1 (en) | 2001-06-29 | 2003-01-16 | Boehringer Ingelheim Pharma | Nebulizer for applying liquids to the eyes |
DE10136555A1 (en) | 2001-07-27 | 2003-02-13 | Boehringer Ingelheim Int | Method for determining the size distribution of particles in an aerosol, especially particles of a medicament involves mixing of a carrier medium with the medicament to produce an appropriately conditioned aerosol |
US6640050B2 (en) | 2001-09-21 | 2003-10-28 | Chrysalis Technologies Incorporated | Fluid vaporizing device having controlled temperature profile heater/capillary tube |
US6568390B2 (en) | 2001-09-21 | 2003-05-27 | Chrysalis Technologies Incorporated | Dual capillary fluid vaporizing device |
JP4795637B2 (en) * | 2001-09-28 | 2011-10-19 | カーブ テクノロジー,インコーポレイティド | Nose nebulizer |
DE10154237A1 (en) * | 2001-11-07 | 2003-05-15 | Steag Microparts Gmbh | Manual sputterer, to spray liquid droplets on to a surface, has a spring acting on a piston with a manual release, to spray a portion of the stored liquid with a controlled droplet size |
US6681769B2 (en) | 2001-12-06 | 2004-01-27 | Crysalis Technologies Incorporated | Aerosol generator having a multiple path heater arrangement and method of use thereof |
US6804458B2 (en) | 2001-12-06 | 2004-10-12 | Chrysalis Technologies Incorporated | Aerosol generator having heater arranged to vaporize fluid in fluid passage between bonded layers of laminate |
US6701922B2 (en) | 2001-12-20 | 2004-03-09 | Chrysalis Technologies Incorporated | Mouthpiece entrainment airflow control for aerosol generators |
US20030178022A1 (en) * | 2001-12-21 | 2003-09-25 | Chiesi Farmaceutici S.P.A. | Pressurized metered dose inhaler (PMDI) actuators and medicinal aerosol solution formulation products comprising therse actuators |
DE10163500A1 (en) * | 2001-12-21 | 2002-12-19 | Wella Ag | Sprayable hair gel giving good setting and gloss comprises a combination of a hair-setting polymer and a polymeric (meth)acrylamidoalkyl sulfonic acid-based gel-former |
US7677467B2 (en) * | 2002-01-07 | 2010-03-16 | Novartis Pharma Ag | Methods and devices for aerosolizing medicament |
US20050205089A1 (en) * | 2002-01-07 | 2005-09-22 | Aerogen, Inc. | Methods and devices for aerosolizing medicament |
WO2003057291A1 (en) * | 2002-01-07 | 2003-07-17 | Aerogen, Inc. | Devices and methods for nebulizing fluids for inhalation |
WO2003059424A1 (en) | 2002-01-15 | 2003-07-24 | Aerogen, Inc. | Methods and systems for operating an aerosol generator |
US6868851B2 (en) * | 2002-01-31 | 2005-03-22 | Instrumentarium Corp. | Liquid reservoir for nebulizer |
US6953133B2 (en) * | 2002-04-02 | 2005-10-11 | Hayes Products, Inc. | Pump assembly with continuous tube |
DE10216036A1 (en) | 2002-04-11 | 2003-10-23 | Boehringer Ingelheim Pharma | Aerosol formulation for inhalation containing a tiotropium salt |
DE10216429A1 (en) | 2002-04-12 | 2003-10-23 | Boehringer Ingelheim Pharma | Synergistic medicaments for treating inflammatory or obstructive respiratory tract diseases, containing quaternized scopine ester anticholinergic agent and steroid, e.g. budesonide |
US8122881B2 (en) * | 2002-05-09 | 2012-02-28 | Kurve Technology, Inc. | Particle dispersion device for nasal delivery |
US6915962B2 (en) * | 2002-05-20 | 2005-07-12 | Aerogen, Inc. | Apparatus for providing aerosol for medical treatment and methods |
US20070044792A1 (en) * | 2005-08-30 | 2007-03-01 | Aerogen, Inc. | Aerosol generators with enhanced corrosion resistance |
DE20221948U1 (en) | 2002-06-08 | 2009-09-24 | Boehringer Ingelheim International Gmbh | Nebulizer with reminder for the therapy regiment |
EP1534282B1 (en) | 2002-07-09 | 2006-12-27 | Boehringer Ingelheim Pharma GmbH & Co.KG | Pharmaceutical compositions of anticholinergics and p38 kinase inhibitors in the treatment of respiratory diseases |
DE10230751A1 (en) | 2002-07-09 | 2004-01-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | New drug compositions based on new anticholinergics and EGFR kinase inhibitors |
GB0217866D0 (en) * | 2002-08-01 | 2002-09-11 | Steag Microparts Gmbh | Low dose spray pump |
GB2391862C (en) * | 2002-08-13 | 2007-01-11 | Shield Medicare Ltd | Spray dispenser assembly and vessel therefor |
US20040166065A1 (en) | 2002-08-14 | 2004-08-26 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Aerosol formulation for inhalation comprising an anticholinergic |
CN1674887A (en) * | 2002-08-14 | 2005-09-28 | 贝林格尔英格海姆法玛两合公司 | Aerosol formulation for inhalation comprising an anticholinergic |
US7699052B2 (en) | 2002-09-05 | 2010-04-20 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Apparatus for the dispensing of liquids, container cartridge suitable for this, and system comprising the apparatus for the dispensing of liquids, and the container cartridge |
DE10243255A1 (en) | 2002-09-17 | 2004-03-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Leak testing for pharmaceutical package, e.g. blister pack, involves exposing it to test gas, opening the package and analyzing for the gas |
US20040055595A1 (en) * | 2002-09-19 | 2004-03-25 | Noymer Peter D. | Aerosol drug delivery system employing formulation pre-heating |
SE0202800D0 (en) * | 2002-09-23 | 2002-09-23 | Pharmacia Ab | Dispensing apparatus and method for liquid products, particularly medicinal products |
EP1567217A2 (en) * | 2002-10-30 | 2005-08-31 | Nektar Therapeutics | Increased dosage metered dose inhaler |
US7056916B2 (en) * | 2002-11-15 | 2006-06-06 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Medicaments for the treatment of chronic obstructive pulmonary disease |
US7037535B2 (en) * | 2002-11-19 | 2006-05-02 | Kimberly-Clark Worldwide, Inc. | Method and composition for neutralizing house dust mite feces |
US7621266B2 (en) | 2003-01-14 | 2009-11-24 | Boehringer Ingelheim International Gmbh | Nozzle-system for a dispenser for fluids consisting of a nozzle and a nozzle-holder and/or screw cap |
DE10300983A1 (en) | 2003-01-14 | 2004-07-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Jet system for an inhaler, to deliver a mist of fluid droplets, has inner surfaces with micro- or nano-structures on the surfaces in contact with the aerosol flow to reduce precipitation |
GB0300939D0 (en) * | 2003-01-16 | 2003-02-12 | Unilever Plc | Method of creating a cosmetic spray |
US7883031B2 (en) | 2003-05-20 | 2011-02-08 | James F. Collins, Jr. | Ophthalmic drug delivery system |
PL1644129T3 (en) | 2003-07-16 | 2007-04-30 | Boehringer Ingelheim Pharma | A process for producing microfluidic arrangements from a plate-shaped composite structure |
US8616195B2 (en) * | 2003-07-18 | 2013-12-31 | Novartis Ag | Nebuliser for the production of aerosolized medication |
US20050017089A1 (en) * | 2003-07-21 | 2005-01-27 | Marc Rohrschneider | Finger operated spray pump |
KR20060052911A (en) | 2003-07-29 | 2006-05-19 | 베링거 인겔하임 인터내셔날 게엠베하 | Medicaments for inhalation comprising betamimetics and an anticholinergic |
JP5144070B2 (en) * | 2003-09-05 | 2013-02-13 | カーブ テクノロジー,インコーポレイティド | Integrated nebulizer and particle dispersion chamber for nasal delivery of drugs into the deep nasal cavity and sinuses |
WO2005023334A2 (en) * | 2003-09-05 | 2005-03-17 | Kurve Technology, Inc. | Nasal adapter for the base of the nose |
US7427004B2 (en) * | 2003-10-20 | 2008-09-23 | Meadwestvaco Calmar, Inc. | Hand held pressurized sprayer |
DE102004001451A1 (en) | 2004-01-08 | 2005-08-11 | Boehringer Ingelheim International Gmbh | Device for holding a fluidic component |
DE102004009434A1 (en) | 2004-02-24 | 2005-12-15 | Boehringer Ingelheim International Gmbh | atomizer |
WO2005079997A1 (en) | 2004-02-24 | 2005-09-01 | Boehringer Ingelheim International Gmbh | Atomiser |
DE102004009436A1 (en) | 2004-02-24 | 2005-10-13 | Boehringer Ingelheim International Gmbh | atomizer |
DE102004009435A1 (en) | 2004-02-24 | 2005-12-08 | Boehringer Ingelheim International Gmbh | atomizer |
DE102004011381A1 (en) * | 2004-03-05 | 2005-09-15 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Cartridge with a gas-driven aerosol preparation incorporates a valve or a valve system provided with at least two outer channels oriented to one another at a specified angle |
DE102004012093A1 (en) * | 2004-03-05 | 2005-09-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Powder inhaler with Merkanaldüse |
BE1015973A3 (en) * | 2004-04-09 | 2005-12-06 | Oultremont Aurian D | Liquid freshener spraying device for refreshing user during extreme heat, has spritzer fixed, by screw thread, on flexible bag having freshener, where bag has suspension unit which, using twine, permits to suspend it around user`s neck |
US7946291B2 (en) | 2004-04-20 | 2011-05-24 | Novartis Ag | Ventilation systems and methods employing aerosol generators |
CA2561403C (en) * | 2004-04-20 | 2015-12-01 | Aerogen, Inc. | Aerosol delivery apparatus for pressure assisted breathing |
US7267121B2 (en) * | 2004-04-20 | 2007-09-11 | Aerogen, Inc. | Aerosol delivery apparatus and method for pressure-assisted breathing systems |
US7290541B2 (en) * | 2004-04-20 | 2007-11-06 | Aerogen, Inc. | Aerosol delivery apparatus and method for pressure-assisted breathing systems |
EP2422786B1 (en) | 2004-04-22 | 2014-08-13 | Boehringer Ingelheim Pharma GmbH & Co. KG | New medicine combinations for treating respiratory diseases |
US20050272726A1 (en) * | 2004-04-22 | 2005-12-08 | Boehringer Ingelheim International Gmbh | Novel medicaments for the treatment of respiratory diseases |
HUE026152T2 (en) | 2004-04-23 | 2016-05-30 | Philip Morris Products Sa | Aerosol generators and methods for producing aerosols |
DE102004021789A1 (en) * | 2004-05-03 | 2006-04-27 | Boehringer Ingelheim International Gmbh | Atomizers for dispensing liquids for medical purposes |
US7723306B2 (en) | 2004-05-10 | 2010-05-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Spray-dried powder comprising at least one 1,4 O-linked saccharose-derivative and methods for their preparation |
US7727962B2 (en) | 2004-05-10 | 2010-06-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Powder comprising new compositions of oligosaccharides and methods for their preparation |
US7611709B2 (en) | 2004-05-10 | 2009-11-03 | Boehringer Ingelheim Pharma Gmbh And Co. Kg | 1,4 O-linked saccharose derivatives for stabilization of antibodies or antibody derivatives |
US20050255050A1 (en) * | 2004-05-14 | 2005-11-17 | Boehringer Ingelheim International Gmbh | Powder formulations for inhalation, comprising enantiomerically pure beta agonists |
US20050256115A1 (en) * | 2004-05-14 | 2005-11-17 | Boehringer Ingelheim International Gmbh | Aerosol formulation for the inhalation of beta-agonists |
US7220742B2 (en) | 2004-05-14 | 2007-05-22 | Boehringer Ingelheim International Gmbh | Enantiomerically pure beta agonists, process for the manufacture thereof and use thereof as medicaments |
ES2257152B1 (en) | 2004-05-31 | 2007-07-01 | Laboratorios Almirall S.A. | COMBINATIONS THAT INCLUDE ANTIMUSCARINIC AGENTS AND BETA-ADRENERGIC AGONISTS. |
PL1905451T3 (en) | 2004-05-31 | 2010-05-31 | Almirall Sa | Combinations comprising antimuscarinic agents and corticosteroids |
US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
US7299950B2 (en) * | 2004-09-03 | 2007-11-27 | Rieke Corporation | Dispensing apparatus |
US7152813B2 (en) * | 2004-09-13 | 2006-12-26 | Ding Hwa Co., Ltd. | Cap with a suction type spray head |
WO2006037636A2 (en) * | 2004-10-06 | 2006-04-13 | Boehringer Ingelheim International Gmbh | Dispensing device, storage device and method for dispensing powder |
JP2008515606A (en) * | 2004-10-12 | 2008-05-15 | アラダイム コーポレーション | Apparatus and method for generating an aerosol from a liquid formulation and ensuring its sterility |
PT2522365T (en) | 2004-11-24 | 2017-02-08 | Meda Pharmaceuticals Inc | Compositions comprising azelastine and methods of use thereof |
US20070020330A1 (en) | 2004-11-24 | 2007-01-25 | Medpointe Healthcare Inc. | Compositions comprising azelastine and methods of use thereof |
US8758816B2 (en) * | 2004-11-24 | 2014-06-24 | Meda Pharmaceuticals Inc. | Compositions comprising azelastine and methods of use thereof |
JP4715254B2 (en) * | 2005-03-18 | 2011-07-06 | オムロンヘルスケア株式会社 | Inhaler |
CN100366347C (en) * | 2005-04-15 | 2008-02-06 | 池龙岩 | Full automatic sprayer |
EP1893273B1 (en) | 2005-05-18 | 2014-06-25 | Nektar Therapeutics | Adapter for use with aerosolization device for endobronchial therapy |
ES2265276B1 (en) | 2005-05-20 | 2008-02-01 | Laboratorios Almirall S.A. | DERIVATIVES OF 4- (2-AMINO-1-HYDROXYETHYL) Phenol as agonists of the BETA2 ADRENERGIC RECEIVER. |
DE102005024439A1 (en) | 2005-05-24 | 2006-12-07 | Boehringer Ingelheim International Gmbh | atomizer |
EA012656B1 (en) * | 2005-05-25 | 2009-12-30 | Аэроджен, Инк. | Vibration systems and use thereof |
TWI366460B (en) | 2005-06-16 | 2012-06-21 | Euro Celtique Sa | Cannabinoid active pharmaceutical ingredient for improved dosage forms |
JP2008543806A (en) * | 2005-06-17 | 2008-12-04 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | MRPIV inhibitors for the treatment of respiratory diseases |
DE102005029746B4 (en) * | 2005-06-24 | 2017-10-26 | Boehringer Ingelheim International Gmbh | atomizer |
DE102005063657B3 (en) | 2005-06-24 | 2022-11-03 | Boehringer Ingelheim International Gmbh | atomizers and containers |
JP2008544784A (en) | 2005-06-29 | 2008-12-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Method and apparatus for atomizing a liquid |
DE102005030733A1 (en) | 2005-07-01 | 2007-01-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | New drug combinations for the treatment of respiratory diseases containing long-acting beta-2 agonists and at least one other active ingredient |
DE102005035715A1 (en) | 2005-07-27 | 2007-02-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Method for checking the permeability rate of a closed container |
PL1917253T3 (en) * | 2005-08-15 | 2015-06-30 | Boehringer Ingelheim Int | Method for producing betamimetics |
MX2008002090A (en) | 2005-08-24 | 2008-04-19 | Boehringer Ingelheim Int | Atomiser comprising a counter and an end of operation lock. |
US20070086957A1 (en) | 2005-10-10 | 2007-04-19 | Thierry Bouyssou | Combination of medicaments for the treatment of respiratory diseases |
DE102005052898A1 (en) * | 2005-11-03 | 2007-05-10 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Method and device for dosing medicaments |
US7423146B2 (en) | 2005-11-09 | 2008-09-09 | Boehringer Ingelheim International Gmbh | Process for the manufacturing of pharmaceutically active 3,1-benzoxazine-2-ones |
EP1792660A1 (en) | 2005-12-02 | 2007-06-06 | Boehringer Ingelheim Pharma GmbH & Co. KG | Dispensing device |
JP4731304B2 (en) * | 2005-12-14 | 2011-07-20 | Hoya株式会社 | Endoscope liquid applicator |
JP4774290B2 (en) * | 2005-12-19 | 2011-09-14 | Hoya株式会社 | Endoscope liquid sprayer |
JP4674541B2 (en) * | 2005-12-22 | 2011-04-20 | パナソニック電工株式会社 | Electrostatic atomization device and food storage equipped with electrostatic atomization device |
US7958887B2 (en) | 2006-03-10 | 2011-06-14 | Aradigm Corporation | Nozzle pore configuration for intrapulmonary delivery of aerosolized formulations |
TWM297751U (en) * | 2006-03-21 | 2006-09-21 | Taidoc Technology Corp | Liquid nebulizer |
DE102006016901A1 (en) * | 2006-04-11 | 2007-10-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Mouthpiece for an inhaler |
DE102006016904A1 (en) * | 2006-04-11 | 2007-10-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | inhaler |
DE102006022002A1 (en) * | 2006-05-10 | 2007-11-15 | Boehringer Ingelheim International Gmbh | Atomizers and methods for atomizing fluid |
EP2026785A1 (en) | 2006-05-19 | 2009-02-25 | Boehringer Ingelheim International GmbH | Propellant-free inhalation aerosol formulation containing ipratropium bromide and salbutamol sulfate |
DE102006025871A1 (en) * | 2006-06-02 | 2007-12-06 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | atomizer |
US8061350B2 (en) * | 2006-06-02 | 2011-11-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Process and device for dosing pharmaceutical agents |
US20090324510A1 (en) | 2006-08-07 | 2009-12-31 | Boehringer Ingelheim International Gmbh | Drug combinations for the treatment of respiratory tract diseases |
UY30550A1 (en) | 2006-08-22 | 2008-03-31 | Boehringer Ingelheim Int | NEW BETA-AGANISTAS ENANTIOMÉRICAMENTE PUROS, PROCEDURES FOR ITS PREPARATION AND ITS USE AS MEDICATIONS |
WO2008028092A2 (en) | 2006-08-30 | 2008-03-06 | Kurve Technology, Inc. | Aerosol generating and delivery device |
NL1033149C2 (en) * | 2006-12-29 | 2008-07-01 | Afa Polytek Bv | Dosing device consisting of a holder with a neck and a dosing head connected thereto by a snap coupling. |
ES2306595B1 (en) | 2007-02-09 | 2009-09-11 | Laboratorios Almirall S.A. | NAPADISYLATE SALT OF 5- (2 - ((6- (2,2-DIFLUORO-2-PHENYLETOXI) HEXIL) AMINO) -1-HYDROXYETHYL) -8-HYDROXYCHINOLIN-2 (1H) -ONE AS ADRENERGIC RECEIVER AGONIST BETA2 . |
CN101636232A (en) * | 2007-02-28 | 2010-01-27 | 艾博特呼吸有限责任公司 | Atomization system based on nozzle |
ES2320955B1 (en) | 2007-03-02 | 2010-03-16 | Laboratorios Almirall S.A. | NEW DERIVATIVES OF 3 - ((1,2,4) TRIAZOLO (4,3-A) PIRIDIN-7-IL) BENZAMIDA. |
DE102007020578A1 (en) | 2007-05-02 | 2008-11-06 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Aqueous aerosol preparations containing therapeutically active microorganisms or parts of microorganisms and processes for producing corresponding aerosols |
DE102007023012A1 (en) | 2007-05-15 | 2008-11-20 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Atomizer and filter |
TW200911311A (en) | 2007-06-15 | 2009-03-16 | Boehringer Ingelheim Int | Inhaler |
EP2044967A1 (en) * | 2007-10-01 | 2009-04-08 | Boehringer Ingelheim Pharma GmbH & Co. KG | Atomiser |
ES2320961B1 (en) | 2007-11-28 | 2010-03-17 | Laboratorios Almirall, S.A. | DERIVATIVES OF 4- (2-AMINO-1-HYDROXYETHYL) PHENOL AS BETA2 ADRENERGIC RECEIVER AGONISTS. |
EP2077132A1 (en) | 2008-01-02 | 2009-07-08 | Boehringer Ingelheim Pharma GmbH & Co. KG | Dispensing device, storage device and method for dispensing a formulation |
GB0800709D0 (en) * | 2008-01-16 | 2008-02-20 | Dunne Stephen T | Double jet impinging nozzle |
US9364841B2 (en) * | 2008-02-19 | 2016-06-14 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Cartridge system |
EP2093219A1 (en) | 2008-02-22 | 2009-08-26 | Boehringer Ingelheim International Gmbh | Crystalline enantiomer free salt form of a betamimetic and its use as medicine |
EP2096105A1 (en) | 2008-02-28 | 2009-09-02 | Laboratorios Almirall, S.A. | Derivatives of 4-(2-amino-1-hydroxyethyl)phenol as agonists of the b2 adrenergic receptor |
US20090218412A1 (en) * | 2008-02-29 | 2009-09-03 | Sge Analytical Science Pty Ltd. | Non-contact dispensing of liquid droplets |
EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
EP2108641A1 (en) | 2008-04-11 | 2009-10-14 | Laboratorios Almirall, S.A. | New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors |
ES2459198T3 (en) | 2008-04-20 | 2014-05-08 | D2 Bioscience Group Ltd | Use of deuterium oxide as an elastase inhibitor |
EP2113503A1 (en) | 2008-04-28 | 2009-11-04 | Laboratorios Almirall, S.A. | New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors |
EP2135632A1 (en) | 2008-06-20 | 2009-12-23 | Boehringer Ingelheim International Gmbh | Inhalator |
EP2350118B1 (en) | 2008-09-19 | 2016-03-30 | Nektar Therapeutics | Carbohydrate-based drug delivery polymers and conjugates thereof |
US7984567B2 (en) * | 2008-10-07 | 2011-07-26 | Christ Bill Bertakis | Apparatus for cleaning simulated hair articles |
DE202008015493U1 (en) | 2008-11-21 | 2009-02-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | folding |
EP2189224A1 (en) | 2008-11-22 | 2010-05-26 | Grundfos Management A/S | Jet |
UY32297A (en) | 2008-12-22 | 2010-05-31 | Almirall Sa | MESILATE SALT OF 5- (2 - {[6- (2,2-DIFLUORO-2-PHENYLITOXI) HEXIL] AMINO} -1-HYDROXYETHYL) -8-HYDROXYCHINOLIN-2 (1H) -ONA AS A RECEIVER AGONIST B (BETA ) 2 ACRENERGIC |
EP2393492A1 (en) | 2009-02-09 | 2011-12-14 | Boehringer Ingelheim International GmbH | New pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
EP2221055A1 (en) | 2009-02-18 | 2010-08-25 | Almirall, S.A. | 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one for the treatment of lung function |
EP2221297A1 (en) | 2009-02-18 | 2010-08-25 | Almirall, S.A. | 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one and its use in the treatment of pulmonary diseases |
EP2226323A1 (en) | 2009-02-27 | 2010-09-08 | Almirall, S.A. | New tetrahydropyrazolo[3,4-c]isoquinolin-5-amine derivatives |
EP2228368A1 (en) | 2009-03-12 | 2010-09-15 | Almirall, S.A. | Process for manufacturing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy) hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one |
EP2236227B1 (en) | 2009-03-30 | 2013-12-18 | Boehringer Ingelheim International GmbH | Forming tool with a rotatable base body |
EP2236224B1 (en) | 2009-03-30 | 2013-03-06 | Boehringer Ingelheim International GmbH | Forming tool with a rotatable basis body for forming an inhalator cartridge and use of such a tool |
US10011906B2 (en) | 2009-03-31 | 2018-07-03 | Beohringer Ingelheim International Gmbh | Method for coating a surface of a component |
WO2010124795A1 (en) | 2009-04-28 | 2010-11-04 | Boehringer Ingelheim International Gmbh | Inhalation device |
EP3508239B1 (en) | 2009-05-18 | 2020-12-23 | Boehringer Ingelheim International GmbH | Adapter, inhalant apparatus and atomizer |
US8815258B2 (en) | 2009-05-29 | 2014-08-26 | Pearl Therapeutics, Inc. | Compositions, methods and systems for respiratory delivery of two or more active agents |
CN107412212B (en) | 2009-05-29 | 2021-01-22 | 珍珠治疗公司 | Pulmonary delivery of long-acting muscarinic antagonists and long-acting beta2Compositions of adrenergic receptor agonists and related methods and systems |
RU2452585C2 (en) * | 2009-06-03 | 2012-06-10 | Макнейл Аб | Pocket distributor |
KR101792696B1 (en) * | 2009-06-18 | 2017-11-02 | 알레간 인코포레이티드 | Safe desmopressin administration |
WO2011005645A1 (en) | 2009-07-06 | 2011-01-13 | Boehringer Ingelheim International Gmbh | Polymorph of [4,6-bis(dimethylamino)-2-(4-{[4-(trifluoromethyl)benzoyl]amino}benzyl)pyrimidin-5-yl] |
JP2012532729A (en) * | 2009-07-16 | 2012-12-20 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | Single motion control mechanism for pressurized gas oral cleaning device |
CA2768379C (en) * | 2009-07-17 | 2017-10-10 | David Mark Blakey | Negatively biased sealed nebulizers systems and methods |
EP2322176A1 (en) | 2009-11-11 | 2011-05-18 | Almirall, S.A. | New 7-phenyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives |
KR20120101399A (en) | 2009-11-24 | 2012-09-13 | 베링거 인겔하임 인터내셔날 게엠베하 | Process for preparing a polymorph of the choline salt of a pyrimidin-5-yl acetic acid derivative |
JP2013512239A (en) | 2009-11-24 | 2013-04-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Novel salt forms of pyrimidin-5-ylacetic acid derivatives |
US10016568B2 (en) | 2009-11-25 | 2018-07-10 | Boehringer Ingelheim International Gmbh | Nebulizer |
WO2011064163A1 (en) | 2009-11-25 | 2011-06-03 | Boehringer Ingelheim International Gmbh | Nebulizer |
UA107097C2 (en) | 2009-11-25 | 2014-11-25 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | Dispenser |
US8464742B2 (en) * | 2010-02-11 | 2013-06-18 | Honeywell International Inc. | Injection or other system with anti-thermal lockdown mechanism and related method |
US8974771B2 (en) * | 2010-03-09 | 2015-03-10 | Penn-Century, Inc. | Apparatus and method for aerosol delivery to the lungs or other locations of the body |
EP2380890A1 (en) | 2010-04-23 | 2011-10-26 | Almirall, S.A. | New 7,8-dihydro-1,6-naphthyridin-5(6h)-one-derivatives as PDE4 inhibitors |
EP2386555A1 (en) | 2010-05-13 | 2011-11-16 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and m3 muscarinic antagonist activities |
EP2394998A1 (en) | 2010-05-31 | 2011-12-14 | Almirall, S.A. | 3-(5-Amino-6-oxo-1,6-dihydropyridazin-3-yl)-biphenyl derivatives as PDE4 inhibitors |
WO2011154295A2 (en) | 2010-06-08 | 2011-12-15 | Boehringer Ingelheim International Gmbh | Medical device having a counter having a preset counting range, device having counter variation |
EP2585151B1 (en) | 2010-06-24 | 2018-04-04 | Boehringer Ingelheim International GmbH | Nebulizer |
AU2011278924B2 (en) | 2010-07-15 | 2015-06-18 | Eyenovia, Inc. | Ophthalmic drug delivery |
EA201390121A8 (en) | 2010-07-15 | 2014-02-28 | Коринтиан Офтэлмик, Инк. | METHOD AND SYSTEM FOR PERFORMING REMOTE TREATMENT AND CONTROL |
KR101545413B1 (en) | 2010-07-15 | 2015-08-18 | 아이노비아 인코포레이티드 | Drop generating device |
US10154923B2 (en) | 2010-07-15 | 2018-12-18 | Eyenovia, Inc. | Drop generating device |
US9283333B2 (en) | 2010-07-16 | 2016-03-15 | Boehringer Ingelheim International Gmbh | Filter system for use in medical devices |
BR112013005283A2 (en) * | 2010-09-06 | 2019-09-24 | Chiesi Farm Spa | metered dose inhaler actuator, metered dose inhaler actuator and use of an actuator |
EP2441755A1 (en) | 2010-09-30 | 2012-04-18 | Almirall, S.A. | Pyridine- and isoquinoline-derivatives as Syk and JAK kinase inhibitors |
EP2457900A1 (en) | 2010-11-25 | 2012-05-30 | Almirall, S.A. | New pyrazole derivatives having CRTh2 antagonistic behaviour |
EP2463289A1 (en) | 2010-11-26 | 2012-06-13 | Almirall, S.A. | Imidazo[1,2-b]pyridazine derivatives as JAK inhibitors |
EP2489663A1 (en) | 2011-02-16 | 2012-08-22 | Almirall, S.A. | Compounds as syk kinase inhibitors |
AU2012223160B2 (en) | 2011-03-03 | 2016-08-18 | Impel Pharmaceuticals Inc. | Nasal drug delivery device |
GB2489216B (en) * | 2011-03-16 | 2013-08-07 | Consort Medical Plc | Fluid delivery device |
WO2012130757A1 (en) | 2011-04-01 | 2012-10-04 | Boehringer Ingelheim International Gmbh | Medical device comprising a container |
EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
EP2518071A1 (en) | 2011-04-29 | 2012-10-31 | Almirall, S.A. | Imidazopyridine derivatives as PI3K inhibitors |
EP2518070A1 (en) | 2011-04-29 | 2012-10-31 | Almirall, S.A. | Pyrrolotriazinone derivatives as PI3K inhibitors |
CA2834171C (en) | 2011-05-13 | 2019-07-30 | Unilever Plc | Spraying device |
US9827384B2 (en) | 2011-05-23 | 2017-11-28 | Boehringer Ingelheim International Gmbh | Nebulizer |
EP2526945A1 (en) | 2011-05-25 | 2012-11-28 | Almirall, S.A. | New CRTH2 Antagonists |
EP2527344A1 (en) | 2011-05-25 | 2012-11-28 | Almirall, S.A. | Pyridin-2(1H)-one derivatives useful as medicaments for the treatment of myeloproliferative disorders, transplant rejection, immune-mediated and inflammatory diseases |
CA3010658C (en) | 2011-06-06 | 2020-12-01 | Trudell Medical International | Oscillating positive expiratory pressure device |
EP2548863A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists. |
EP2548876A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists |
EP2554544A1 (en) | 2011-08-01 | 2013-02-06 | Almirall, S.A. | Pyridin-2(1h)-one derivatives as jak inhibitors |
WO2013017393A1 (en) * | 2011-08-03 | 2013-02-07 | Unilever N.V. | Spraying device |
EP2578570A1 (en) | 2011-10-07 | 2013-04-10 | Almirall, S.A. | Novel process for preparing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(r)-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one via novel intermediates of synthesis. |
WO2013064690A1 (en) * | 2011-11-04 | 2013-05-10 | Chv Pharma Gmbh & Co. Kg | Inhaler and method for producing an aerosol |
EP2592078A1 (en) | 2011-11-11 | 2013-05-15 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and M3 muscarinic antagonist activities |
EP2592077A1 (en) | 2011-11-11 | 2013-05-15 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and M3 muscarinic antagonist activities |
WO2013090459A1 (en) | 2011-12-12 | 2013-06-20 | Corinthian Ophthalmic, Inc. | Ejector mechanism, ejector device, and methods of use |
US8816305B2 (en) | 2011-12-20 | 2014-08-26 | Asml Netherlands B.V. | Filter for material supply apparatus |
US8771799B2 (en) | 2011-12-27 | 2014-07-08 | JM Harwood LLC | Liquid delivery system |
JP6335798B2 (en) * | 2012-02-28 | 2018-05-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | New propellant-containing tiotropium formulation |
EP2641900A1 (en) | 2012-03-20 | 2013-09-25 | Almirall, S.A. | Novel polymorphic Crystal forms of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy) hexyl]amino}-1-(R)-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one, heminapadisylate as agonist of the ß2 adrenergic receptor. |
US9220852B2 (en) | 2012-04-10 | 2015-12-29 | Boehringer Ingelheim Microparts Gmbh | Method for producing trench-like depressions in the surface of a wafer |
WO2013152894A1 (en) | 2012-04-13 | 2013-10-17 | Boehringer Ingelheim International Gmbh | Atomiser with coding means |
US9562523B2 (en) | 2012-10-01 | 2017-02-07 | JM Harwood LLC | Wobble drive mechanism |
WO2014060431A1 (en) | 2012-10-16 | 2014-04-24 | Almirall, S.A. | Pyrrolotriazinone derivatives as pi3k inhibitors |
EP2738172A1 (en) | 2012-11-28 | 2014-06-04 | Almirall, S.A. | New bicyclic compounds as crac channel modulators |
US9517315B2 (en) | 2012-11-30 | 2016-12-13 | Trudell Medical International | Oscillating positive expiratory pressure device |
CN102963603A (en) * | 2012-12-08 | 2013-03-13 | 胡成佐 | Packaging box |
SG11201504452WA (en) | 2012-12-18 | 2015-07-30 | Almirall Sa | New cyclohexyl and quinuclidinyl carbamate derivatives having beta2 adrenergic agonist and m3 muscarinic antagonist activity |
TW201446767A (en) | 2013-02-15 | 2014-12-16 | Almirall Sa | Pyrrolotriazine derivatives as PI3K inhibitors |
RU2696582C2 (en) | 2013-03-15 | 2019-08-05 | Перл Терапьютикс, Инк. | Methods and systems for conditioning disperse crystalline materials |
EP2848615A1 (en) | 2013-07-03 | 2015-03-18 | Almirall, S.A. | New pyrazole derivatives as CRAC channel modulators |
ES2836977T3 (en) | 2013-08-09 | 2021-06-28 | Boehringer Ingelheim Int | Nebulizer |
WO2015018904A1 (en) | 2013-08-09 | 2015-02-12 | Boehringer Ingelheim International Gmbh | Nebulizer |
FI20135903L (en) | 2013-09-09 | 2015-03-10 | Beneq Oy | Device and method for producing aerosol and focusing lot |
US10292424B2 (en) * | 2013-10-31 | 2019-05-21 | Rai Strategic Holdings, Inc. | Aerosol delivery device including a pressure-based aerosol delivery mechanism |
US10195374B2 (en) | 2014-05-07 | 2019-02-05 | Boehringer Ingelheim International Gmbh | Container, nebulizer and use |
DE202014103984U1 (en) * | 2014-03-10 | 2015-06-12 | Rpc Bramlage Gmbh | donor |
KR102492824B1 (en) | 2014-05-07 | 2023-01-30 | 베링거 인겔하임 인터내셔날 게엠베하 | Nebulizer, indicator device and container |
WO2015169430A1 (en) | 2014-05-07 | 2015-11-12 | Boehringer Ingelheim International Gmbh | Nebulizer |
GB201408561D0 (en) * | 2014-05-14 | 2014-06-25 | The Technology Partnership Plc | Aerosolisation engine for liquid drug delivery |
US11273271B2 (en) * | 2014-07-01 | 2022-03-15 | Aerami Therapeutics, Inc. | Aerosolization system with flow restrictor and feedback device |
GB201413181D0 (en) | 2014-07-25 | 2014-09-10 | Dunne Consultancy Services Ltd | Inhaler cartridge system |
US10300228B2 (en) * | 2014-08-26 | 2019-05-28 | Innovosciences, Llc | Thermal modulation of an inhalable medicament |
US10737042B2 (en) | 2014-08-26 | 2020-08-11 | Michael Edward Breede | Thermal modulation of an inhalable medicament |
US9743999B2 (en) * | 2014-08-29 | 2017-08-29 | Piero A. Policicchio | Dental prophylaxis device and air appliance |
EP3061501A1 (en) | 2015-02-27 | 2016-08-31 | Rottapharm Ltd. | Composition for the treatment of acne |
JP6480598B2 (en) | 2015-04-02 | 2019-03-13 | ヒル−ロム サービシーズ プライヴェート リミテッド | Respirator manifold |
IL238387B (en) * | 2015-04-20 | 2019-01-31 | Paz Ilan | Medication dispenser depilling mechanism |
WO2016170009A1 (en) | 2015-04-21 | 2016-10-27 | Almirall, S.A. | Amino-substituted heterocyclic derivatives as sodium channel inhibitors |
WO2016180975A1 (en) * | 2015-05-14 | 2016-11-17 | Medical Graphics Italia S.R.L. | Kit for performing a bronchial challenge test with methacholine and device containing methacholine |
CN108310560A (en) * | 2015-05-16 | 2018-07-24 | 苏州汉方医药有限公司 | A kind of medicine box for treating sex hypofunction that medicine instrument is combined into |
EP3103498B2 (en) * | 2015-06-12 | 2023-06-14 | AP Pharma Systems Atomizadores e Dispensadores Ltda | Spray dispenser for nasal drugs |
WO2016202800A1 (en) | 2015-06-16 | 2016-12-22 | Almirall, S.A. | Pyrrolotriazinone derivatives as pi3k inhibitors |
EP3117825A1 (en) | 2015-07-16 | 2017-01-18 | Rottapharm S.p.A. | Oral formulation comprising berberine and morus alba extract |
MX2018001321A (en) | 2015-07-30 | 2018-08-15 | Trudell Medical Int | Combined respiratory muscle training and oscillating positive expiratory pressure device. |
DE102016105998A1 (en) * | 2015-09-23 | 2017-03-23 | Rpc Bramlage Gmbh | Dispensers for liquid to pasty masses |
WO2017060386A1 (en) | 2015-10-09 | 2017-04-13 | Boehringer Ingelheim International Gmbh | Method for coating microstructured components |
RU2636522C1 (en) * | 2016-06-09 | 2017-11-23 | федеральное государственное автономное образовательное учреждение высшего образования "Казанский (Приволжский) федеральный университет" (ФГАОУ ВО КФУ) | Method and device for producing fine aerosols with prevention of atomizer clogging |
CN106215291A (en) * | 2016-08-17 | 2016-12-14 | 岑溪市东正动力科技开发有限公司 | A kind of medical vaporizer |
CN106390252B (en) * | 2016-08-30 | 2019-07-30 | 苏州涵轩信息科技有限公司 | A kind of medicinal liquid atomizer |
CN115355347A (en) | 2016-09-15 | 2022-11-18 | 索芙特海尔公司 | Valve, in particular for a device for administering a liquid drug, and corresponding device for administering a liquid drug |
WO2018059390A1 (en) * | 2016-09-29 | 2018-04-05 | 广东东阳光药业有限公司 | Pharmaceutical composition |
DK3519024T3 (en) * | 2016-09-30 | 2021-07-05 | Softhale Nv | Atomizer, in particular inhaler, for atomizing a liquid drug substance into an aerosol and a similar method |
CN110582316B (en) | 2017-04-28 | 2023-12-26 | 索芙特海尔公司 | Inhalation device and method |
JP7227163B2 (en) | 2017-06-10 | 2023-02-21 | アイノビア,インコーポレイティド | Methods and apparatus for handling and delivering fluids to the eye |
CN110869134B (en) * | 2017-06-22 | 2023-12-22 | 索芙特海尔公司 | Inhalation device, reservoir and delivery method for pirfenidone aerosols |
WO2018234527A1 (en) | 2017-06-22 | 2018-12-27 | Softhale Nv | Aerosol delivery of pirfenidone |
WO2018234524A1 (en) | 2017-06-22 | 2018-12-27 | Softhale Nv | Multiliquid-nozzle |
CA3067134A1 (en) * | 2017-06-22 | 2018-12-27 | Softhale Nv | Inhalation device with multiliquid-nozzle and method |
DK179667B1 (en) * | 2017-06-30 | 2019-03-14 | Mbh-International A/S | An enema device and a method of refilling said device with an enema |
TW201919682A (en) | 2017-08-08 | 2019-06-01 | 西班牙商阿爾米雷爾有限公司 | Novel compounds activating the Nrf2 pathway |
DE202017005165U1 (en) * | 2017-10-06 | 2017-10-18 | WERRTA GmbH Düsen- und Zerstäubungstechnik | nozzle body |
EP3697541B1 (en) | 2017-10-18 | 2023-04-26 | Softhale NV | Seal for an inhalation device |
US10617832B2 (en) | 2017-11-22 | 2020-04-14 | Southwest Research Institute | High precision, low dose atomizer |
ES2906600T3 (en) | 2017-11-27 | 2022-04-19 | Softhale Nv | Mouthpiece fixing device for an inhalation device |
CN109894907A (en) * | 2017-12-07 | 2019-06-18 | 上海铼钠克数控科技股份有限公司 | Brake apparatus |
EP3723836A4 (en) * | 2017-12-11 | 2021-11-24 | Target Point Technologies Ltd. | Intranasal administration device |
EP3501582B1 (en) * | 2017-12-21 | 2022-04-27 | Boehringer Ingelheim International GmbH | Nebulizer and cartridge |
CN111491682B (en) * | 2017-12-22 | 2024-02-13 | 索芙特海尔公司 | Flexible pump chamber |
EP3727533B1 (en) | 2017-12-22 | 2022-11-16 | Softhale NV | Blocking device |
CA3093176A1 (en) | 2018-03-21 | 2019-09-26 | Softhale Nv | Spray nozzle for an inhalation device |
CN110388467A (en) * | 2018-04-20 | 2019-10-29 | 梅特勒-托利多(常州)测量技术有限公司 | Imbibition handle control valve |
EP3563894B1 (en) * | 2018-05-04 | 2021-12-22 | Boehringer Ingelheim International GmbH | Nebulizer and container |
WO2019229042A1 (en) | 2018-05-30 | 2019-12-05 | Softhale Nv | Inhalation device with a pumping unit |
CN108499769B (en) * | 2018-06-12 | 2023-05-19 | 湖南科道尔生物科技有限公司 | High atomizer with automatic hydrojet of time delay |
CN108704779A (en) * | 2018-06-20 | 2018-10-26 | 浙江普莱得电器有限公司 | A kind of spray gun |
GB201810546D0 (en) * | 2018-06-27 | 2018-08-15 | Ttp Plc | Droplet Dispenser |
DK3823763T3 (en) | 2018-07-16 | 2023-11-27 | Invox Belgium Nv | IMPROVED INHALATION DEVICE |
CN112533656A (en) * | 2018-08-10 | 2021-03-19 | 索芙特海尔公司 | High pressure suction device |
CN111345948A (en) * | 2018-09-30 | 2020-06-30 | 潘爱平 | Can breathe wheelchair of dosing |
BR112021008861A2 (en) * | 2018-11-09 | 2021-08-31 | Softhale Nv | RESERVOIR FOR AN INHALATION DEVICE |
EP3906119A1 (en) * | 2019-01-03 | 2021-11-10 | Aptar Radolfzell GmbH | Nozzle unit, liquid dispenser comprising such a nozzle unit, and method for producing such nozzle units |
CN111450361B (en) * | 2019-01-21 | 2022-02-08 | 樊启民 | Pulmonary heart disease atomizing and breathing treatment device |
TW202100194A (en) | 2019-04-15 | 2021-01-01 | 比利時商索芙特海爾公司 | Improved valve |
MX2021012723A (en) * | 2019-04-18 | 2022-01-31 | Jon Greenfield | Positive pressure inhaler for delivery of inhalable medication and methods for use. |
FR3095968B1 (en) | 2019-05-14 | 2021-10-01 | Aptar France Sas | Fluid dispenser device |
CN110141744B (en) * | 2019-06-30 | 2021-03-23 | 河南省斯科赛斯科技发展有限公司 | Airflow atomizer |
CN110627149B (en) * | 2019-08-23 | 2021-12-07 | 江苏星鑫分离设备制造有限公司 | Landfill leachate back-spraying treatment equipment capable of treating tail gas |
CN110786345A (en) * | 2019-11-13 | 2020-02-14 | 申璐璐 | Natural plant antibacterial agent |
US20210283145A1 (en) | 2020-03-13 | 2021-09-16 | Softhale Nv | Method for the treatment of viral infections |
WO2021185912A1 (en) | 2020-03-19 | 2021-09-23 | Softhale Nv | Method for the treatment nlrp3-associated diseases |
CN111299007B (en) * | 2020-03-20 | 2021-06-25 | 浙江宝龙工贸有限公司 | A paint spraying apparatus that spraying is even for timber production |
CA3168027A1 (en) | 2020-03-31 | 2021-10-07 | Jurgen Rawert | Aerosol delivery of at least two liquid compositions |
JP2023519523A (en) | 2020-03-31 | 2023-05-11 | ソフトハレ エヌヴイ | inhaler system |
CN111544715B (en) * | 2020-04-02 | 2022-08-19 | 佛山市澳斯卡医疗器械有限公司 | Bottled atomizer |
US20210308047A1 (en) | 2020-04-03 | 2021-10-07 | Softhale Nv | Methods of treatment using niclosamide |
EP4132484A1 (en) | 2020-04-10 | 2023-02-15 | Galenus G.H. AG | Composition comprising resveratrol |
CN111532591A (en) * | 2020-04-29 | 2020-08-14 | 丁亚宁 | Disinfection spray bottle for respiratory medicine and using method thereof |
EP4153346A1 (en) * | 2020-05-20 | 2023-03-29 | Victaulic Company | Emitter and system for discharge of a decontaminating liquid-gas stream |
US11013688B1 (en) | 2020-05-28 | 2021-05-25 | Softhale Nv | Methods of treatment of viral diseases |
RU2745231C9 (en) * | 2020-06-08 | 2021-04-27 | Акционерное общество "Столетика" | Spray inhaler with preparation and storage functions |
US20230248924A1 (en) | 2020-06-26 | 2023-08-10 | Softhale Nv | Inverted nozzle fixture and method |
CN113171895B (en) * | 2021-04-20 | 2022-12-13 | 广州腾龙健康实业股份有限公司 | Multi-directional nozzle |
EP4109066A1 (en) | 2021-06-25 | 2022-12-28 | Harro Höfliger Verpackungsmaschinen GmbH | Device for leakage testing of a pump assembly for high pressure spray applicators |
TW202317217A (en) | 2021-07-20 | 2023-05-01 | 比利時商索芙特海爾公司 | Inhalation device system with a counting and blocking assembly |
DE202021002812U1 (en) | 2021-08-31 | 2021-09-15 | Harro Höfliger Verpackungsmaschinen GmbH | Device for testing high-pressure check valves attached to capillaries, in particular for use in spray applicators |
CN114392454A (en) * | 2022-02-09 | 2022-04-26 | 商丘市中心医院 | Controllable atomizer of local anesthesia for clinical anesthesia |
WO2024023231A1 (en) | 2022-07-29 | 2024-02-01 | Softhale Nv | Microfluidic devices and methods of producing |
CN115068755B (en) * | 2022-08-24 | 2023-06-06 | 中国人民解放军总医院第六医学中心 | Atomizing device for department of respiration |
Family Cites Families (96)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US460458A (en) * | 1891-09-29 | Edward t | ||
US334110A (en) * | 1886-01-12 | Edwaed j | ||
US1035261A (en) * | 1912-02-16 | 1912-08-13 | Hermann Strumpf | Atomizer. |
US1116536A (en) * | 1913-10-06 | 1914-11-10 | Charles Ballreich | Lawn-sprinkler. |
US1276245A (en) * | 1916-11-03 | 1918-08-20 | Gilmour Sharp | Spraying-nozzle. |
US1838873A (en) * | 1930-02-27 | 1931-12-29 | Lewis L Scott | Atomizer |
GB405458A (en) * | 1933-05-18 | 1934-02-08 | Harry Krantz | An improved device for disinfecting the mouthpieces of telephones |
US2024339A (en) * | 1933-11-11 | 1935-12-17 | James W Connell | Water spraying device |
US2052869A (en) * | 1934-10-08 | 1936-09-01 | Coanda Henri | Device for deflecting a stream of elastic fluid projected into an elastic fluid |
US2187779A (en) * | 1936-07-22 | 1940-01-23 | Gardner Mfg Company | Atomizing nozzle |
US2432791A (en) * | 1945-12-12 | 1947-12-16 | Osses Jacob | Defense weapon |
US2673123A (en) * | 1949-10-14 | 1954-03-23 | Atlantic Plastics Inc | Spray cap |
US2676845A (en) * | 1949-11-04 | 1954-04-27 | Gen Closure Corp | Atomizing closure device for liquid receptacles |
US2786656A (en) * | 1954-06-23 | 1957-03-26 | Ernest R Corneil | Impact spraying of slurries |
FR1072399A (en) * | 1961-01-07 | 1954-09-13 | Intra-dermal injector | |
NL296493A (en) * | 1962-08-14 | |||
US3187748A (en) * | 1963-04-29 | 1965-06-08 | Merck And Company Inc | Inhalation-actuated aerosol device |
US3330277A (en) * | 1964-08-17 | 1967-07-11 | Scherer Corp R P | Multidose hypodermic injector |
US3317002A (en) * | 1965-02-08 | 1967-05-02 | Walker Mfg Co | Fluid distributing system |
GB1131918A (en) * | 1965-05-06 | 1968-10-30 | Murray Budd Burgess | Jet injector |
DE1475174A1 (en) * | 1965-09-20 | 1969-01-16 | Afa Corp | Liquid spray device |
US3421662A (en) * | 1967-03-07 | 1969-01-14 | Ralph W Hanson | Dispersal device |
US3396874A (en) * | 1967-05-15 | 1968-08-13 | Afa Corp | Positive action dispensing valve |
DE1803541A1 (en) * | 1968-10-17 | 1970-04-23 | Wild Dr Walter J | Method and device for spraying low-viscosity media |
GB1239855A (en) * | 1969-01-30 | 1971-07-21 | Pye Ltd | Improvements in or relating to liquid injectors for medical respirators |
US3514017A (en) * | 1969-03-03 | 1970-05-26 | Afa Corp | Pressure regulating structure for piston pump |
US3575322A (en) * | 1969-03-21 | 1971-04-20 | Union Carbide Corp | Metering aerosol actuator with downstroke discharge |
US3605738A (en) * | 1969-06-20 | 1971-09-20 | Paul J Ciranna | Medicinal spray device |
US3647143A (en) * | 1970-04-06 | 1972-03-07 | Champion Spark Plug Co | Atomizer |
US3838686A (en) | 1971-10-14 | 1974-10-01 | G Szekely | Aerosol apparatus for inhalation therapy |
BE795375A (en) * | 1972-02-14 | 1973-08-13 | Thiokol Chemical Corp | ATOMIZER |
US3797748A (en) | 1972-03-30 | 1974-03-19 | T Nozawa | Liquid spraying device |
US3818908A (en) * | 1972-08-07 | 1974-06-25 | Riker Laboratories Inc | Medicament dispenser |
US3794247A (en) * | 1972-11-22 | 1974-02-26 | Corsette Douglas Frank | Spray fitment for squeeze bottles |
US3933279A (en) * | 1972-11-28 | 1976-01-20 | Ciba-Geigy Corporation | Aerosol dispenser for fluid products comprising a piston pump assembly for generating compressed air |
US3831861A (en) * | 1973-03-23 | 1974-08-27 | Par Way Mfg Co | Liquid spray head for producing rectangular spray patterns |
US3878973A (en) * | 1973-10-31 | 1975-04-22 | Ciba Geigy Corp | Metered dose dispenser |
CH588896A5 (en) * | 1973-10-31 | 1977-06-15 | Ciba Geigy Ag | |
US3921857A (en) * | 1973-11-29 | 1975-11-25 | Ciba Geigy Corp | Non-spitting liquid dispensing device |
US3923202A (en) * | 1973-11-29 | 1975-12-02 | Ciba Geigy Corp | Non-spitting liquid dispensing device with pressurized product supply |
AT343788B (en) * | 1973-11-30 | 1978-06-12 | Thomae Gmbh Dr K | LOCKING DEVICE FOR PUMP METERING VALVES |
US4017007A (en) * | 1973-12-26 | 1977-04-12 | Ciba-Geigy Corporation | Single dose air pressure operated dispenser |
CA1008825A (en) * | 1974-03-28 | 1977-04-19 | William E. Warren | Pump assembly for an atomizing piston pump |
US3893628A (en) * | 1974-04-08 | 1975-07-08 | Alsons Corp | Spray head |
JPS5824183B2 (en) * | 1974-05-17 | 1983-05-19 | コンドウ ヒロシ | Chikuatsufunmusouchi |
US3921916A (en) * | 1974-12-31 | 1975-11-25 | Ibm | Nozzles formed in monocrystalline silicon |
US4007855A (en) * | 1975-03-24 | 1977-02-15 | Joseph M. Magrath | Liquid dispenser of the metering type |
CA1099674A (en) * | 1975-12-05 | 1981-04-21 | Gerald A. Rooney | Manually operated liquid dispensing device |
IT1069354B (en) * | 1976-03-05 | 1985-03-25 | Zanasi Nigris Spa | IMPROVEMENTS IN VOLUME DOSING UNITS |
US4167941A (en) * | 1976-10-05 | 1979-09-18 | James D. Pauls, Ltd. (Limited Partnership) | Mechanically operated dispensing device for increasing discharge pressure and dispensing time |
US4174055A (en) * | 1977-04-20 | 1979-11-13 | James D. Pauls & J. Claybrook Lewis & Associates, Ltd. | Non-aerosol pressure dispenser |
US4179070A (en) * | 1977-05-09 | 1979-12-18 | Tetsuya Tada | Sprayer |
US4174056A (en) * | 1977-05-10 | 1979-11-13 | Ciba-Geigy Corporation | Pump type dispenser with continuous flow feature |
US4079865A (en) * | 1977-06-30 | 1978-03-21 | John H. Oltman | Non-pulsating, non-throttling, vented pumping system for continuously dispensing product |
US4183449A (en) | 1978-01-09 | 1980-01-15 | The Afa Corporation | Manually operated miniature atomizer |
US4245788A (en) * | 1978-03-20 | 1981-01-20 | Wright Hershel E | Dispensing device for fluid material |
US4271875A (en) * | 1978-09-21 | 1981-06-09 | Philip Meshberg | Dispenser adapted for fast pressure filling |
DE2854841C2 (en) * | 1978-12-19 | 1981-03-26 | Bosch-Siemens Hausgeräte GmbH, 7000 Stuttgart | Liquid atomizer, preferably inhalation device |
US4345718A (en) | 1979-04-23 | 1982-08-24 | William Horvath | Manually actuated trigger sprayer |
CA1156695A (en) * | 1979-10-10 | 1983-11-08 | Macmillan Bloedel Limited | Self protecting spray nozzle |
US4602726A (en) * | 1979-12-31 | 1986-07-29 | George Goda | Dispensing device |
US4402432A (en) * | 1980-02-13 | 1983-09-06 | Corsette Douglas Frank | Leak-proof dispensing pump |
DE3007512C2 (en) | 1980-02-28 | 1982-04-29 | Fa. Hermann Heye, 3063 Obernkirchen | Device for applying a lubricating or separating liquid to a glass molding machine part |
EP0045419B1 (en) * | 1980-08-04 | 1984-10-17 | FISONS plc | Inhalation device for administering medicaments |
GB2109690B (en) * | 1981-02-12 | 1985-02-20 | Robert Charles Turner | Dose metering plunger devices for use with syringes |
US4412632A (en) * | 1981-05-28 | 1983-11-01 | Berger Richard F | Self-cleaning valve |
SE438261B (en) * | 1981-07-08 | 1985-04-15 | Draco Ab | USE IN A DOSHALATOR OF A PERFORED MEMBRANE |
SU992070A1 (en) * | 1981-09-28 | 1983-01-30 | Тартуский Ордена Трудового Красного Знамени Государственный Университет | Inhalator |
US4441634A (en) * | 1982-01-13 | 1984-04-10 | Philip Meshberg | Dispenser adapted for fast pressure filling |
FR2521036A1 (en) * | 1982-02-05 | 1983-08-12 | Valois Sa | DEVICE FOR PROJECTING PRECISE DOSES OF AEROSOL |
FR2524348A1 (en) * | 1982-03-30 | 1983-10-07 | Ramis Michel | Vaporising pump made with plastics parts - has spray orifice which closes automatically after vapourisation under plastics spring action |
EP0105964A1 (en) * | 1982-10-18 | 1984-04-25 | Fischer, Jürgen L. | Process for continuous separation of polluting matter from a carrier fluid |
US4771769A (en) * | 1982-12-20 | 1988-09-20 | Schering Corporation | Hand held metered spray dispenser |
DE3303419A1 (en) * | 1983-02-02 | 1984-08-02 | W. Schlafhorst & Co, 4050 Mönchengladbach | METHOD AND DEVICE FOR DOSING AND INJECTING SMALL LIQUID AMOUNTS INTO THE SPLICE AIR OF A COMPRESSED GAS THREAD SPLICING DEVICE |
JPS59222251A (en) * | 1983-05-31 | 1984-12-13 | Matsushita Electric Works Ltd | Motor type extruder for viscous material |
DE3339180C2 (en) | 1983-10-28 | 1993-10-14 | Pfeiffer Erich Gmbh & Co Kg | Discharge device for media |
US4648393A (en) * | 1984-11-02 | 1987-03-10 | Ackrad Laboratories, Inc. | Breath activated medication spray |
DE8621135U1 (en) * | 1985-09-02 | 1987-01-29 | Callahan, George Edgar, Prof. | |
US4705034A (en) * | 1985-10-02 | 1987-11-10 | Perkins Warren E | Method and means for dispensing respirating gases by effecting a known displacement |
CA1323004C (en) * | 1985-10-15 | 1993-10-12 | Yuji Higo | Process for injecting a minute volume of a solution and an apparatus therefor |
US4693675A (en) * | 1986-01-16 | 1987-09-15 | The Pharmasol Corporation | Non-throttling discharge pump |
US4738398A (en) * | 1986-07-29 | 1988-04-19 | Corsette Douglas Frank | Sprayer having induced air assist |
US4819834A (en) * | 1986-09-09 | 1989-04-11 | Minnesota Mining And Manufacturing Company | Apparatus and methods for delivering a predetermined amount of a pressurized fluid |
GB8629982D0 (en) * | 1986-12-16 | 1987-01-28 | English Glass Co Ltd | Dispenser pump |
EP0293442A1 (en) * | 1986-12-17 | 1988-12-07 | Microvol Limited | Pressurised metering dispenser |
DE3704210A1 (en) * | 1987-02-11 | 1988-08-25 | Friedhelm Schneider | DOSING GUN FOR LIQUIDS AND PASTE |
JPS63232866A (en) * | 1987-03-20 | 1988-09-28 | Tokyo Electron Ltd | Spray nozzle |
US4896832A (en) * | 1987-09-07 | 1990-01-30 | Bespak Plc | Dispensing apparatus for metered quantities of pressurised fluid |
US4892232A (en) * | 1988-07-25 | 1990-01-09 | Martin James H | Unit dose dispenser |
US4828184A (en) * | 1988-08-12 | 1989-05-09 | Ford Motor Company | Silicon micromachined compound nozzle |
FR2641202B1 (en) * | 1989-01-03 | 1991-03-15 | Poizot Francis | FOAM PRODUCTION DEVICE |
DK0401060T3 (en) * | 1989-05-31 | 1993-10-25 | Conceptair Anstalt | Process and electrical, electronic and mechanical device for distributing, dosing or diffusing liquid or gaseous flavoring agents, drugs and other liquid or viscous products |
US5031839A (en) * | 1989-09-13 | 1991-07-16 | Dowelanco | Volume controllable applicator |
US5056511A (en) * | 1989-12-14 | 1991-10-15 | Juergen L. Fischer | Method and apparatus for compressing, atomizing, and spraying liquid substances |
GB2243880B (en) * | 1990-05-01 | 1994-03-16 | Bespak Plc | Dispensing device |
US5088649A (en) * | 1990-07-12 | 1992-02-18 | Par-Way Group | Pump sprayable dispensing system for vegetable oil based pan coatings |
-
1990
- 1990-03-21 SG SG1996000929A patent/SG45171A1/en unknown
-
1991
- 1991-03-19 NZ NZ237502A patent/NZ237502A/en unknown
- 1991-03-19 PH PH42165A patent/PH30833A/en unknown
- 1991-03-20 IE IE92991A patent/IE62626B1/en not_active IP Right Cessation
- 1991-03-20 IN IN232CA1991 patent/IN177383B/en unknown
- 1991-03-20 CZ CS91750A patent/CZ283820B6/en not_active IP Right Cessation
- 1991-03-20 IL IL9761991A patent/IL97619A/en not_active IP Right Cessation
- 1991-03-20 SK SK750-91A patent/SK280225B6/en not_active IP Right Cessation
- 1991-03-21 CN CN91102794A patent/CN1042203C/en not_active Expired - Lifetime
- 1991-03-21 EP EP91906552A patent/EP0521061B1/en not_active Expired - Lifetime
- 1991-03-21 RU SU5053235A patent/RU2104048C1/en active
- 1991-03-21 DE DE69131966T patent/DE69131966T2/en not_active Expired - Lifetime
- 1991-03-21 UA UA93004115A patent/UA27777C2/en unknown
- 1991-03-21 HU HUP9202985A patent/HU216121B/en unknown
- 1991-03-21 SI SI9110500A patent/SI9110500B/en unknown
- 1991-03-21 CA CA002206753A patent/CA2206753C/en not_active Expired - Lifetime
- 1991-03-21 CA CA002078683A patent/CA2078683C/en not_active Expired - Lifetime
- 1991-03-21 AT AT91906552T patent/ATE160947T1/en not_active IP Right Cessation
- 1991-03-21 US US07/938,174 patent/US5497944A/en not_active Expired - Lifetime
- 1991-03-21 AT AT94112017T patent/ATE189413T1/en not_active IP Right Cessation
- 1991-03-21 DE DE69128419T patent/DE69128419T2/en not_active Expired - Lifetime
- 1991-03-21 YU YU50091A patent/YU48710B/en unknown
- 1991-03-21 ES ES91906552T patent/ES2109943T3/en not_active Expired - Lifetime
- 1991-03-21 PL PL91296183A patent/PL165926B1/en unknown
- 1991-03-21 BR BR919106249A patent/BR9106249A/en not_active IP Right Cessation
- 1991-03-21 MY MYPI91000470A patent/MY110310A/en unknown
- 1991-03-21 EP EP94112017A patent/EP0627230B1/en not_active Expired - Lifetime
- 1991-03-21 WO PCT/GB1991/000433 patent/WO1991014468A1/en active IP Right Grant
- 1991-03-21 JP JP3506336A patent/JP2630347B2/en not_active Expired - Lifetime
- 1991-03-21 RS YUP-529/98A patent/RS49548B/en unknown
- 1991-03-21 DK DK91906552.4T patent/DK0521061T3/en active
- 1991-03-21 AU AU75484/91A patent/AU650870B2/en not_active Expired
- 1991-03-21 ES ES94112017T patent/ES2141786T3/en not_active Expired - Lifetime
- 1991-03-21 DK DK94112017T patent/DK0627230T3/en active
- 1991-03-21 PT PT97098A patent/PT97098B/en not_active IP Right Cessation
- 1991-06-18 TW TW082106336A patent/TW253846B/zh not_active IP Right Cessation
-
1992
- 1992-07-20 GB GB9215398A patent/GB2256805B/en not_active Expired - Lifetime
- 1992-09-18 KR KR92702249A patent/KR0139652B1/en not_active IP Right Cessation
- 1992-09-18 NO NO923647A patent/NO303206B1/en not_active IP Right Cessation
- 1992-09-21 FI FI924216A patent/FI104311B/en active
- 1992-11-25 HR HR921357A patent/HRP921357B1/en not_active IP Right Cessation
-
1995
- 1995-06-02 US US08/459,458 patent/US5662271A/en not_active Expired - Lifetime
-
1997
- 1997-11-11 CN CN97122300A patent/CN1119182C/en not_active Expired - Lifetime
-
1998
- 1998-02-04 GR GR980400233T patent/GR3026065T3/en unknown
- 1998-05-14 HK HK98104193A patent/HK1005059A1/en not_active IP Right Cessation
-
2000
- 2000-04-26 GR GR20000401001T patent/GR3033317T3/en not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2078683C (en) | Atomising devices and methods | |
US20230277784A1 (en) | Inhalation device and method | |
EP1370318B1 (en) | Systems and methods for aerosol delivery of agents | |
JP3162487B2 (en) | Spray nozzle | |
US6328035B1 (en) | Pneumatic breath actuated inhaler | |
US20100199984A1 (en) | Breath actuated nasal pump | |
US8714151B2 (en) | Atomizing device, inhaler and method for dispensing a liquid formulation | |
JP2005537834A (en) | Liquid dispensing device, container cartridge suitable therefor, and system comprising liquid dispensing device and container cartridge | |
PL185789B1 (en) | Fluid sprayer, containing miniaturized fluid compression device | |
AU2002336246A1 (en) | Nebulizer having cooling chamber | |
JP2007522902A (en) | Nebulizer | |
WO1992012799A1 (en) | Metered dose atomising and delivery device | |
CN112533656A (en) | High pressure suction device | |
RU2807165C2 (en) | Inhalation device and its use |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKEX | Expiry | ||
MKEX | Expiry |
Effective date: 20110321 |