US20120085345A1 - Nasal spray device - Google Patents

Nasal spray device Download PDF

Info

Publication number
US20120085345A1
US20120085345A1 US13/271,940 US201113271940A US2012085345A1 US 20120085345 A1 US20120085345 A1 US 20120085345A1 US 201113271940 A US201113271940 A US 201113271940A US 2012085345 A1 US2012085345 A1 US 2012085345A1
Authority
US
United States
Prior art keywords
nasal spray
spray device
discharge orifice
pharmaceutical formulation
aerosol canister
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US13/271,940
Other languages
English (en)
Inventor
Xian-Ming Zeng
Declan Walsh
Jade Ching-Ying Ly
Armando Morales
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ivax Pharmaceuticals Ireland
Teva Branded Pharmaceutical Products R&D Inc
Original Assignee
Ivax Pharmaceuticals Ireland
Teva Branded Pharmaceutical Products R&D Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=44907783&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20120085345(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Ivax Pharmaceuticals Ireland, Teva Branded Pharmaceutical Products R&D Inc filed Critical Ivax Pharmaceuticals Ireland
Priority to US13/271,940 priority Critical patent/US20120085345A1/en
Publication of US20120085345A1 publication Critical patent/US20120085345A1/en
Assigned to TEVA BRANDED PHARMACEUTICAL PRODUCTS R&D, INC. reassignment TEVA BRANDED PHARMACEUTICAL PRODUCTS R&D, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ZENG, XIAN-MING, LY, JADE, MORALES, ARMANDO
Assigned to IVAX PHARMACEUTICALS IRELAND (A TRADING NAME OF NORTON (WATERFORD) LIMITED) reassignment IVAX PHARMACEUTICALS IRELAND (A TRADING NAME OF NORTON (WATERFORD) LIMITED) ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: WALSH, DECLAN
Priority to US14/865,823 priority patent/US10188811B2/en
Abandoned legal-status Critical Current

Links

Images

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
    • A61M15/00—Inhalators
    • A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • 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
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • 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
    • A61M15/08—Inhaling devices inserted into the nose
    • 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
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D83/00—Containers or packages with special means for dispensing contents
    • B65D83/14—Containers or packages with special means for dispensing contents for delivery of liquid or semi-liquid contents by internal gaseous pressure, i.e. aerosol containers comprising propellant for a product delivered by a propellant
    • B65D83/44—Valves specially adapted therefor; Regulating devices
    • B65D83/52—Valves specially adapted therefor; Regulating devices for metering
    • B65D83/54—Metering valves ; Metering valve assemblies

Definitions

  • This invention relates to a nasal spray device and particularly to a nasal spray device for the delivery of a pharmaceutical formulation to the nasal cavity in metered doses.
  • Nasal spray devices for the delivery of medicament to the nasal cavity can be useful for the prophylaxis and/or treatment of certain diseases and disorders of the nasal cavity.
  • Such devices are also capable of delivering medicament to the systemic circulation via the turbinates and lymphoid tissues located at the back of the nasal cavity and to the central nervous system via the olfactory region at the top of the nasal cavity.
  • Nasal spray devices include unit-dose (single use) devices having syringe-like mechanisms and metered-dose devices intended for multiple usage cycles. Unit dose devices are appropriate for delivering certain medicaments such as vaccines, whereas metered-dose devices are more suited to long-term dosage regimes, for example for the treatment of rhinitis.
  • a known metered-dose device comprises a vial containing an aqueous suspension of a suitable medicament. The vial is provided with a manually operated pump adapted to atomise metered doses of the medicament formulation for delivery to the nasal cavity.
  • nasal spray device examples include Flixonase® (fluticasone propionate, GSK), Nasacort AQ® (triamcinolone acetoinide, Sanofi-Aventis) and Nasonex® (momethasone furoate monohydrate, Schering-Plough).
  • Flixonase® fluticasone propionate, GSK
  • Nasacort AQ® triamcinolone acetoinide, Sanofi-Aventis
  • Nasonex® mithasone furoate monohydrate, Schering-Plough
  • nasal spray devices having manually operated pumps have achieved some success in the marketplace, they have a number of drawbacks.
  • manually operated pumps have a relatively large actuation force which may, for some users, such as the very young and the elderly, be difficult to achieve on a repeatable basis.
  • variations in the applied actuation force can lead to some users receiving medicament doses with less than optimal spray characteristics.
  • a typical aerosol canister comprises a cylindrical vial containing the medicament.
  • the medicament is typically an active ingredient together with a suitable propellant.
  • the medicament may be in the form of a solution or a suspension in the propellant and excipients may be added to facilitate dissolution of the active ingredient (e.g. co-solvents) or to stabilise the suspension (e.g. surfactants).
  • the vial is provided with a metering valve having an axially extending valve stem. Displacement of the valve stem relative to the vial causes the dispensation of a metered dose of the medicament formulation as an aerosol.
  • pressurised aerosol canisters require low actuation forces and provide consistent aerosol characteristics.
  • WO 92/06675 describes a medicament formulation for a pMDI comprising beclomethasone dipropionate, a co-solvent and an HFA propellant.
  • the disclosure is principally directed to administration of the formulation by inhalation into the lungs via the mouth.
  • the formulation may be administered nasally; however, there is no disclosure of how this method of administration can be achieved and there is no consideration of the problem of poor patient tolerability for nasal applications.
  • the present invention provides a nasal spray device for the delivery of a pharmaceutical formulation to the nasal cavity in metered doses, the device comprising: a pressurised aerosol canister including a vial containing a pharmaceutical formulation comprising an active ingredient, a propellant and, optionally, a co-solvent, the aerosol canister further including a metering valve having a valve stem; and
  • an actuator for the aerosol canister including a stem block having a receptacle into which the valve stem of metering valve of the aerosol canister is received and axially located and being displaceable relative to the vial of the aerosol canister to actuate the metering valve of the aerosol canister, a sump extending below the receptacle, the stem block further defining a discharge orifice for the pharmaceutical formulation and a transfer channel through which a dispensed dose of the pharmaceutical formulation is able to pass from the sump to the discharge orifice,
  • the actuator further comprises a delivery outlet for the aerosol plume, the discharge orifice being arranged to direct the aerosol plume through the delivery outlet, and wherein the device is adapted to produce an aerosol plume for a dispensed dose having a spray force value no greater than 40 mN measured at a distance of 30 mm from the discharge orifice.
  • the formulation is a solution formulation.
  • the formulation is a suspension formulation. Accordingly, use of the term formulation encompasses both solution and suspension formulations.
  • the present invention also provides the use of the nasal spray device for the delivery of a pharmaceutical formulation (solution or suspension) to the nasal cavity in metered doses.
  • nasal spray device used to deliver the formulation to the nasal cavity is adapted to provide a so-called “soft spray”.
  • the nasal spray device having the propellant-based formulation described hereinbelow provides the advantages of a metered dose pressurised aerosol canister without suffering from the disadvantage of poor patient tolerability.
  • FIG. 1 shows a cut-away perspective schematic view of a nasal spray device according to the present invention
  • FIG. 2 shows a conventional valve for a pMDI
  • FIG. 3 shows another cut-away view showing a portion of the nasal spray device of FIG. 1 in greater detail
  • FIG. 4 is a cross-sectional view showing a component for the nasal spray device shown in FIGS. 1 and 3 ;
  • FIG. 5 is a chart showing the effect of actuation variables on the spray force values for four different nasal spray devices.
  • the nasal spray device of the present invention contains an active ingredient.
  • the pharmaceutical formulation of the present invention comprises an active ingredient and a propellant.
  • any pharmaceutically active ingredient which is soluble or suspended in the formulation and acts via the cavity, such as the nasal mucosa, may be used in the present invention.
  • the active ingredient is generally present in the formulation of the invention in a therapeutically effective amount, i.e. an amount such that metered volumes of the medicament administered to the patient contains an amount of drug effective to exert the intended therapeutic action.
  • a therapeutically effective amount i.e. an amount such that metered volumes of the medicament administered to the patient contains an amount of drug effective to exert the intended therapeutic action.
  • Non-limiting examples of the active ingredient which may be used in the formulation of the present invention are as follows:
  • Steroids such as alcometasone, beclomethasone, betamethasone, budesonide, ciclesonide, clobetasol, deflazacort, diflucortolone, desoxymethasone, dexamethasone, fludrocortisone, flunisolide, fluocinolone, fluometholone, fluticasone, hydrocortisone, mometasone furoate, nandrolone decanoate, neomycin sulfate, rimexolone, methylprednisolone, prednisolone and triamcinolone acetonide.
  • Steroids such as alcometasone, beclomethasone, betamethasone, budesonide, ciclesonide, clobetasol, deflazacort, diflucortolone, desoxymethasone, dexamethasone, fludrocortisone, flunisolid
  • the steroid is preferably beclomethasone dipropionate, budesonide, fluticasone propionate or mometasone furoate.
  • Beclomethasone dipropionate also termed beclometasone dipropionate (INN) or (8S,9R,10S,11S,13S,14S, 16S,17R)-9-chloro-11-hydroxy-10,13,16-trimethyl-3-oxo-17-[2-(propionyloxy)acetyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phen-anthren-17-yl propionate (IUPAC)) is particularly preferred.
  • Short- and long-acting ⁇ 2 -adrenergic agonists include formoterol, salmeterol and salts thereof, such as formoterol fumarate and salmeterol xinafoate.
  • Short-acting ⁇ 2 -agonists include salbutamol, terbutaline and salts thereof such as salbutamol sulfate.
  • Anticholinergics such as muscarinic receptor antagonists, e.g. dexpyrronium bromide, glycopyrronium bromide, ipratropium bromide, oxitropium bromide and tiotropium bromide.
  • muscarinic receptor antagonists e.g. dexpyrronium bromide, glycopyrronium bromide, ipratropium bromide, oxitropium bromide and tiotropium bromide.
  • ACE inhibitors e.g. opioids, angiotension II receptor blockers, antiarrhythmics, antibiotics, anti-cancer agents, anti-clotting agents, antidepressants, anti-emetics, antihistamines, anti-fungal drugs, anti-inflammatory agents, antipsychotics, anti-viral agents, bisphosphonates, calcium channel blockers, diuretics, dopamine agonists, hormonal drugs, hypoglycaemics, immunoglobulins, leukotriene receptor antagonists, local anaesthetics, mucolytic agents, narcotic agonists and opiate antidotes, nitrates, NMDA receptor antagonists, nucleic acids, phosphodiesterase 4 (PDE4) inhibitors, polypeptides, potassium channel modulators, serotonin agonists, serotonin antagonists, smoking cessation drugs and sympathom
  • the nasal aerosol device of the present invention provides a delivered dose of the active ingredient of at least 50 ⁇ g, more preferably at least 60 ⁇ g and most preferably at least 70 ⁇ g, while at the same time providing the desirable “soft spray”.
  • the propellant of the pharmaceutical formulation of the present invention is preferably a hydrofluoroalkane (HFA) propellant, more preferably P134a (1,1,1,2-tetrafluoroethane), P227 (1,1,1,2,3,3,3-heptafluoropropane) or mixtures thereof.
  • HFA hydrofluoroalkane
  • P134a 1,1,1,2-tetrafluoroethane
  • P227 1,1,1,2,3,3,3-heptafluoropropane
  • Other hydrofluorocarbons, hydrocarbons or aliphatic gases e.g. butane or dimethylether
  • P134a and/or P227 are the sole propellants present.
  • the propellant preferably constitutes 80% to 99% w/w, more preferably 90 to 98% w/w, based on the total weight of the formulation.
  • the present invention is applicable to nasal spray devices for delivering all types of pharmaceutical formulations, but is particularly effective for delivering pharmaceutical formulations which include a co-solvent for the active ingredient.
  • the co-solvent is generally present in order to solubilise the active ingredient and the precise nature of the co-solvent will therefore depend on the nature of the active ingredient.
  • the co-solvent is preferably a C 2-6 aliphatic alcohol, such as ethanol or propylene glycol, and preferably ethanol.
  • the co-solvent is present in an amount sufficient to dissolve substantially all of the medicament present in the formulation and to maintain the medicament dissolved over the time period and conditions experienced by commercial aerosol products.
  • the solvent is present in an amount to prevent precipitation of the active ingredient even at temperatures down to ⁇ 20° C.
  • the solvent is preferably anhydrous, although trace amounts of water absorbed by the ingredients, for example during manufacture of the medicament, may be tolerated.
  • Anhydrous ethanol is particularly preferred.
  • the co-solvent, preferably ethanol, is typically present at 1-20% w/w, more preferably 6-15% w/w and most preferably about 8% w/w, based on the total weight of the formulation.
  • the pharmaceutical formulation comprises beclomethasone dipropionate, ethanol and a propellant selected from 1,1,1,2-tetrafluoroethane (P134a), 1,1,1,2,3,3,3-heptafluoropropane (P227) and a mixture thereof.
  • This formulation is typically used for the prophylaxis and/or treatment of seasonal allergic rhinitis (including hay fever) and perennial rhinitis.
  • the active ingredient beclomethasone dipropionate is generally present in a formulation of the present invention in a therapeutically effective amount, i.e. an amount such that metered volumes of the medicament administered to the patient contains an amount of drug effective to exert the intended therapeutic action.
  • the aerosol formulation preferably contains 0.02% to 0.6% w/w, more preferably 0.05% to 0.5% w/w of beclomethasone dipropionate, based on the total weight of the formulation.
  • a preferred formulation according to the present invention comprises 0.02% to 0.6% w/w beclomethasone dipropionate, 1% to 20% w/w ethanol and 80 to 99% w/w of propellant, wherein the percentages by weight are based on the total weight of the aerosol.
  • a particularly preferred formulation consists essentially of beclomethasone dipropionate, ethanol and a propellant selected from 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane and a mixture thereof; more preferably the formulation consists of these components.
  • the pharmaceutical formulation of the present invention is preferably substantially free of surfactant.
  • Surfactants are often added to suspensions to stabilise the suspension.
  • a surfactant is not required. Nevertheless, small quantities can be tolerated without adversely affecting the formulation.
  • the formulation contains no more than 0.0005% w/w of a surfactant based on the total weight of the formulation.
  • Preferred formulations contain no surfactant.
  • the presence of a significant amount of a surfactant is believed to be undesirable for solution formulations of beclomethasone dipropionate because surfactants such as oleic acid and lecithin are believed to promote chemical degradation of the active ingredient when the latter is dissolved in the mixture of the propellant and ethanol.
  • the pharmaceutical formulation of the present invention may be prepared by dissolving the desired amount of active ingredient in the desired amount of co-solvent accompanied by stirring or sonication.
  • the aerosol canister may then be filled using conventional cold-fill or pressure-fill methods.
  • the present invention provides a nasal spray device for the delivery of a pharmaceutical formulation to the nasal cavity in metered doses.
  • the device comprises a pressurised aerosol canister.
  • Such canisters are known in the art and are commercially available.
  • the aerosol canister 3 is typically composed of aluminium or an aluminium alloy.
  • the internal surfaces of the aerosol canister 3 may be coated with a fluorocarbon polymer, such as PTFE or FEP, optionally together with non-fluorinated polymer to promote adhesion, such as PES.
  • the canister includes a vial containing a pharmaceutical formulation comprising an active ingredient and a propellant.
  • the aerosol canister further includes a metering valve having a valve stem axially displaceable relative to the vial to cause the dispensation of a metered dose of the pharmaceutical formulation through the valve stem.
  • the device also comprises an actuator for the aerosol canister including a stem block having a receptacle into which the valve stem of the aerosol canister is received and axially located, and being displaceable relative to the vial of the aerosol canister to actuate the metering valve of the aerosol canister.
  • the stem block further defines a discharge nozzle for the pharmaceutical formulation and a transfer channel through which a dispensed dose of the pharmaceutical formulation is able to pass from the valve stem to the discharge orifice.
  • the actuator further comprises a delivery outlet, such as a nose piece, for the aerosol plume, the discharge orifice being arranged to direct the aerosol plume through the delivery outlet.
  • the device is adapted to produce an aerosol plume for a dispensed dose of a formulation composition preferably having a spray force value no greater than 40 mN measured at a distance of 30 mm from the discharge orifice.
  • a nasal spray device 1 is based on a conventional pressurised metered dose inhaler (pMDI), but modified for nasal use rather than for inhalation via the mouth.
  • the device 1 comprises an actuator 2 accommodating an aerosol canister 3 containing a pharmaceutical formulation for delivery to the nasal cavity of a user.
  • the aerosol canister 3 is constructed to a standard design and specification and comprises a substantially cylindrical vial body 4 which contains the pharmaceutical formulation.
  • the aerosol canister 3 is charged with a pharmaceutical formulation as described hereinabove.
  • the vial body 4 is provided with a ferrule 5 which is crimped over a lip of the body to hermetically seal the pharmaceutical formulation under pressure.
  • the ferrule 5 of the aerosol canister 3 is provided with a metering valve 6 designed to deliver a metered amount of the pharmaceutical formulation to the user for each actuation of the valve 6 .
  • the metering valve 6 is of a known type available from manufacturers such as Consort Medical plc and 3M Drug Delivery Systems. See WO 99/47195 for further details of the metering valve suitable for use in the device of the present invention.
  • the valve 6 generally comprises a metering chamber 7 (not visible in FIG. 1 , but shown in FIG. 2 reproduced from WO 99/47195) and a valve stem 8 in the form of a narrow tube protruding outwardly from ferrule 5 .
  • the metering valve 6 is actuated by displacing the valve stem 8 into the valve body against the action of a valve spring 9 to allow the metered amount of the pharmaceutical formulation to vent from the metering chamber through the stem 8 .
  • the propellant component of the pharmaceutical formulation causes atomisation of the active ingredient by vaporising on release to the atmosphere.
  • the metering chamber 7 is then recharged with the pharmaceutical formulation as the valve stem 8 is allowed to return to its starting position under the action of the valve spring 9 .
  • the aerosol canister 3 is received into the open end of a body 10 of the actuator 2 , with the valve stem 8 being received into and axially located by a stem block 11 of the actuator 2 .
  • the actuator body 10 is a moulded plastics component and the stem block 11 is formed as a protrusion which stands from the closed end of the actuator body 10 .
  • the stem block 11 includes a cylindrical receptacle configured for an interference fit with the valve stem 8 of the aerosol canister 3 .
  • the actuator body 10 generally defines a sleeve-like portion having a substantially circular cross-section, within which sleeve-like portion the aerosol canister 3 is axially displaceable relative to the stem block 11 and valve stem 8 to actuate the metering valve 6 .
  • a portion of the aerosol canister 3 at its non-valve end remains exposed in use so that the user is able to apply a manual pressure to displace the aerosol canister relative to the valve stem.
  • the nasal spray device 1 according to the present invention differs from conventional pMDIs in two important respects.
  • the actuator body 10 defines a delivery outlet in the form of a nose piece 12 (rather than a mouth piece) for delivering the atomised pharmaceutical formulation to the nasal cavity.
  • the delivery outlet may be a tubular nose piece adapted for insertion into the nostril, and a circular end of the nose piece may have an inner diameter of 5 to 7.5 mm, preferably about 7.2 mm.
  • the delivery outlet, the delivery orifice and the transfer channel may be aligned with each other, that is to say they may have substantially identical axes.
  • the axis of the delivery outlet may be substantially perpendicular, or at an angle of up to 20° to the perpendicular, to the aerosol canister and the receptacle of the stem block.
  • an axis of the nose piece 12 defines an angle of about 80° with the sleeve-like portion of the actuator body 10 .
  • the nose piece 12 directly faces the stem block 11 so that an aerosol plume produced at the valve stem can be delivered through the nose piece 12 into the nasal cavity.
  • the nasal spray device 1 according to the present invention differs from conventional pMDIs in relation to the design of the stem block 11 .
  • a stem block of a conventional pMDI is moulded with a discharge orifice facing the delivery outlet, and the discharge orifice is fluidly connected to the receptacle of the stem block so that the pharmaceutical formulation is able to pass from the aerosol canister out through the delivery outlet.
  • the nasal spray device 1 according to the present invention has a stem block 11 that is provided with a transfer channel 13 (not shown fully in FIG. 1 ) through which the pharmaceutical formulation is able to pass from the aerosol canister 3 , through the nose piece 12 , and into the nasal cavity of a user.
  • a transfer channel 13 not shown fully in FIG. 1
  • the stem block 11 is shown having a first part 14 of the transfer channel 13 extending from a sump 15 underneath the receptacle of the stem block 11 into an opening defining a socket 16 .
  • the sump 15 is preferably rounded to help to prevent blockages.
  • the socket 16 is adapted to receive a moulded plastic insert 17 which defines a second part 18 of the transfer channel 13 and the discharge orifice 19 , as described hereinbelow in more detail (note that the insert 17 is not cut-away in FIG. 1 ).
  • the first 14 and second 18 (in FIG. 3 ) parts together define a transfer channel 13 through which the pharmaceutical formulation is able to pass from the aerosol canister 3 , through the nose piece 12 , and into the nasal cavity of a user.
  • the transfer channel 13 has a first part 14 in fluid communication with the sump 15 of the stem block 11 and a second part 18 in fluid communication with the discharge orifice 19 , the second part 18 and the discharge orifice 19 being defined by a separate insert received into an opening formed in the stem block of the actuator.
  • FIG. 3 is a view similar to that of FIG. 1 , but with the insert 17 cut-away to show the second part 18 of the transfer channel and the discharge orifice 19 . It will also be seen more clearly that the sump 15 is narrower than the receptacle of the stem block 11 in order to locate axially the valve stem 8 of the aerosol canister (not shown in FIG. 3 ).
  • An end of the insert 17 is provided with a radial flange from which a resilient sleeve 20 extends in a coaxial relationship with the second part 18 of the transfer channel 13 and discharge orifice 19 .
  • the resilient sleeve 20 provides an interference fit in the socket 16 .
  • the insert 17 may be provided with a mechanical locking means for engagement with a corresponding means formed in the stem block, such as an annular flange (see flange 21 in FIG. 4 ) arranged to lock into a corresponding annular groove formed in the side wall of the socket 16 .
  • a mechanical locking means for engagement with a corresponding means formed in the stem block, such as an annular flange (see flange 21 in FIG. 4 ) arranged to lock into a corresponding annular groove formed in the side wall of the socket 16 .
  • the second part 18 of the transfer channel 13 and the discharge orifice 19 are shown as defined by a separate insert 17 received into an opening formed in the stem block 11 of the actuator 2 .
  • a nasal spray device can then be configured simply by altering the design of the insert.
  • the insert may be manufactured with smaller tolerances than those of other components of the nasal spray device. In this way, it may be possible to reduce unit-to-unit variation in the delivered dose and spray force value of the device.
  • the device of the present invention is not limited to a separate insert and the first 14 and second parts 18 of the transfer channel 13 may be integrally formed into a unitary structure. Such a unitary structure may be produced by injection moulding.
  • the transfer channel 13 preferably has circular cross-section. It also preferably tapers down towards the discharge orifice 19 .
  • the transfer channel 13 may taper down towards the discharge orifice end, for example such that a side wall of the chamber defines an angle of 0.5 to 3°, preferably about 1°. It is believed that the risk of blockages may be reduced by tapering the chamber in this way. The risk of blockages may also be reduced by avoiding sharp corners in the fluid path.
  • a further preferred feature is a maximum transverse dimension of 1.0 to 3.0 mm, preferably from 1.2 to 2 mm and most preferably about 1.5 mm.
  • the transfer channel 13 has a length of 3 to 20 mm, more preferably 4 mm to 15 mm, more preferably 4 to 10 mm and most preferably about 7 mm.
  • the transfer channel 13 serves as an expansion chamber for modifying the spray characteristics of the aerosol plume, in particular by reducing the spray force value for the plume, as compared to the plume generated using a device with no expansion chamber.
  • the discharge orifice 19 has a diameter of 0.15 to 0.65 mm, preferably 0.20 to 0.50 mm and most preferably about 0.4 mm. It is believed that discharge orifices smaller than 0.15 mm may be prone to blockages.
  • a length of the outlet orifice, measured between the outlet end of the transfer channel 13 and the opening of the outlet orifice, (also known as the “land length”) is 0.5 to 1.0 mm, preferably 0.6 to 0.9 mm and most preferably about 0.65 mm.
  • the length of the outlet orifice is believed to be significant because it may strongly influence the shape (spread) of the aerosol plume.
  • a focused plume is important in ensuring that a large proportion of the dose is delivered to the nasal cavity of the user and not retained on the surfaces of the actuator 2 .
  • FIG. 4 is a cross-sectional view showing an insert 17 suitable for use with the nasal spray device shown in FIGS. 1 and 3 .
  • Like reference numerals indicate the same or corresponding elements.
  • the length of the insert 17 not only affects the volume of the transfer channel 13 , but also modifies the distance of the delivery outlet 12 from the discharge orifice 19 . It is believed that a greater proportion of the dose is delivered to the nasal cavity of the user when this distance is reduced (for example, by employing a longer insert).
  • the user shakes the device 1 several times, as is normal practice for pMDIs.
  • the user inserts the nose piece 12 into a nostril and depresses the exposed end of the aerosol canister 3 .
  • Displacement of the canister 3 relative to the valve stem 8 causes actuation of the metering valve 6 and a metered amount of the pharmaceutical formulation is vented from the metering chamber in the aerosol canister 3 .
  • the formulation passes through the sump 15 and into the transfer channel 13 where it undergoes controlled expansion, before finally being discharged through the discharge orifice 19 and the nose piece 12 .
  • the present invention provides a nasal spray device in which the conventionally unpleasant effects of using a propellant-based formulations are avoided by providing the device with soft spray characteristics; by which is meant a spray force value of no greater than 40 mN measured at 30 mm from the discharge orifice 19 .
  • the minimum spray force is less critical and may be any positive non-zero value.
  • the spray force is 10 to 40 mN measured at 30 mm from the discharge orifice 19 . It has been found that such soft sprays are well tolerated by users and allows pMDI technology to be applied to the nasal delivery of medicaments, thereby avoiding the disadvantages associated with pump-action devices.
  • the desired spray force value may be achieved by appropriate combination of the orifice diameter, land length and the geometry of the transfer channel as described hereinabove.
  • a lower spray force value is favoured by a smaller orifice diameter.
  • a longer land length and a geometry of the transfer channel such that the transverse dimension tapers down towards the discharge orifice is also preferred.
  • a balance must be obtained in order to prevent deposition of the active ingredient on the internal surfaces of the device which in turn can lead to reduced dose uniformity and even clogging of the device.
  • the discharge orifice has a diameter of 0.15 to 0.65 mm and a length of 0.5 to 1.0 mm
  • the transfer channel has a transverse dimension which tapers down towards the discharge orifice end.
  • the proportion of the dose of active ingredient that is retained by the device described herein may be no greater than 40%, preferably no greater than 30% and more preferably no greater than 20%. It has been found that the delivered dose uniformity of the device may be acceptable, with a relative standard deviation (RSD) no greater than 20%, preferably no greater than 10%.
  • RSD relative standard deviation
  • the spray force value is given as the value measured at a predetermined distance, typically 30 mm, from the discharge orifice 19 .
  • Spray force values may be measured using conventional techniques, such as with an impaction plate coupled to a digital load cell, e.g. a Copley SFT 1000 spray force tester available from Copley Scientific Limited, Nottingham, United Kingdom.
  • This device comprises a circular impaction plate coupled to a digital load cell for measuring forces acting on the impaction plate.
  • the device includes a movable carriage to which a spray device is mounted so that its spray outlet is centred on and faces the impaction plate. The spray device is then actuated and the load cell measures the spray force value of the spray.
  • Spray force values are measured under controlled conditions of temperature of 25° C., pressure of 101 kPa and relative humidity of 50%.
  • the impaction plate is mounted in a vertical orientation.
  • the spray device is mounted in the movable carriage so that the discharge orifice of the device is positioned 30 mm from the impaction plate.
  • the spray device is then actuated and the maximum compression force of the impaction plate recorded.
  • Six actuations are measured for each device to be tested. The mean of these six values is recorded as the spray force value for the device.
  • the measurements are preferably taken using an actuation velocity of 70 mm/s and an acceleration of 7,000 mm/s 2 , although this is not critical as the spray force is not significantly affected by these variables.
  • Spray force values for a nasal spray device according to the present invention were measured using a variety of actuation velocities and accelerations.
  • the device tested was of the type shown in FIGS. 1 and 3 and configured with a nose piece having an inner diameter of 8.2 mm.
  • the stem block insert had the shape generally shown in FIG. 4 .
  • the orifice size is 0.4 mm and insert length is 10 mm.
  • the device was loaded with a HFA aerosol canister configured to provide an 80 ⁇ g dose (ex-valve) of beclomethasone dipropionate.
  • the solution formulation consisted of the beclomethasone dipropionate as the active ingredient, together with ethanol 4.8 mg per actuation as a co-solvent and P134a 55.1 mg per actuation as a propellant.
  • Spray force values for three commercially available manual pump-type nasal spray devices were also measured using the same variety of actuation velocities and accelerations for comparison purposes. Details of the devices tested are summarised in Table 1.
  • the nasal spray device according to the present invention (Example 1) was actuated for the tests using a SprayVIEW® Vereo MDx Automated Actuation System available from Proveris Scientific Corporation, Marlborough, Mass., USA.
  • the manual pump-type nasal spray devices (Comparative Examples 1 to 3) were actuated using a SprayVIEW® Vereo NSx Automated Actuation System available from Proveris Scientific Corporation, Marlborough, Mass., USA.
  • FIG. 5 is a chart plotting spray force values (vertical axis) against actuation settings. It will be seen from the chart that spray force values for the manual pump-type nasal spray devices vary significantly with the actuation parameters, but this is not the case for the nasal spray device according to the invention (NQVAR 80 ⁇ g in FIG. 5 ).
  • the nasal spray device according to the present invention provides the advantage of consistent spray force values, regardless of the velocity and/or acceleration of actuation. This advantage is particularly important in relation to use by the very young and the elderly, who may find it difficult to actuate the device repeatedly with a consistent velocity.
  • the devices were each configured with a nose piece having an inner diameter of 7.2 mm.
  • the stem block insert of each device had the shape generally shown in FIG. 4 , with the dimensions provided in Table 6.
  • the orifice size is 0.4 mm, the insert length of 10 mm, a land length of 0.65 mm, and a tip diameter of 6.4 mm.
  • the device was loaded with an HFA aerosol canister configured to provide a 100 ⁇ g dose (ex-valve) of beclomethasone dipropionate.
  • the solution formulation consisted of the beclomethasone dipropionate as the active ingredient, together with ethanol 4.8 mg per actuation as a co-solvent and P134a 55.1 mg per actuation as a propellant.
  • the nasal spray devices were tested for spray force values using the test procedure set out hereinabove.
  • the results of the testing are set out in Table 7.
  • the nasal spray devices were also tested for spray content uniformity (SCU) to measure variation in delivered doses of the active ingredient.
  • SCU spray content uniformity

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Anesthesiology (AREA)
  • Pulmonology (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Otolaryngology (AREA)
  • Epidemiology (AREA)
  • Dispersion Chemistry (AREA)
  • Mechanical Engineering (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Massaging Devices (AREA)
US13/271,940 2010-10-12 2011-10-12 Nasal spray device Abandoned US20120085345A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US13/271,940 US20120085345A1 (en) 2010-10-12 2011-10-12 Nasal spray device
US14/865,823 US10188811B2 (en) 2010-10-12 2015-09-25 Nasal spray device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US39222310P 2010-10-12 2010-10-12
US13/271,940 US20120085345A1 (en) 2010-10-12 2011-10-12 Nasal spray device

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US14/865,823 Continuation US10188811B2 (en) 2010-10-12 2015-09-25 Nasal spray device

Publications (1)

Publication Number Publication Date
US20120085345A1 true US20120085345A1 (en) 2012-04-12

Family

ID=44907783

Family Applications (2)

Application Number Title Priority Date Filing Date
US13/271,940 Abandoned US20120085345A1 (en) 2010-10-12 2011-10-12 Nasal spray device
US14/865,823 Active US10188811B2 (en) 2010-10-12 2015-09-25 Nasal spray device

Family Applications After (1)

Application Number Title Priority Date Filing Date
US14/865,823 Active US10188811B2 (en) 2010-10-12 2015-09-25 Nasal spray device

Country Status (30)

Country Link
US (2) US20120085345A1 (fr)
EP (2) EP2627386B1 (fr)
JP (2) JP6050236B2 (fr)
KR (1) KR101559639B1 (fr)
CN (3) CN106178206A (fr)
AU (1) AU2011316124B2 (fr)
BR (1) BR112013008824A2 (fr)
CA (1) CA2814212C (fr)
CL (1) CL2013000958A1 (fr)
CY (1) CY1121719T1 (fr)
DK (2) DK2627386T3 (fr)
EA (1) EA023795B1 (fr)
ES (2) ES2536969T3 (fr)
HK (1) HK1214990A1 (fr)
HR (2) HRP20150452T1 (fr)
HU (1) HUE043276T2 (fr)
IL (1) IL225712A (fr)
LT (1) LT2926855T (fr)
MX (1) MX336164B (fr)
NZ (1) NZ608218A (fr)
PE (1) PE20131492A1 (fr)
PL (2) PL2926855T3 (fr)
PT (2) PT2926855T (fr)
RS (2) RS54037B1 (fr)
SG (1) SG189892A1 (fr)
SI (2) SI2627386T1 (fr)
SM (1) SMT201500114B (fr)
TR (1) TR201902415T4 (fr)
WO (1) WO2012048867A1 (fr)
ZA (1) ZA201301938B (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014033057A1 (fr) * 2012-08-29 2014-03-06 Chiesi Farmaceutici S.P.A. Dispositif d'inhalation d'aérosol
WO2015095341A1 (fr) * 2013-12-20 2015-06-25 3M Innovative Properties Company Actionneur d'inhalateur
WO2015169974A1 (fr) * 2014-05-09 2015-11-12 Norton (Waterford) Limited Dispositif d'aérosol
CN105246534A (zh) * 2013-05-14 2016-01-13 3M创新有限公司 用于吸入器的致动器
WO2017008127A1 (fr) * 2015-07-16 2017-01-19 Gd Pharma Pty Ltd Dispositif de pulvérisation et cartouche de dosage
CN106376976A (zh) * 2016-10-13 2017-02-08 深圳市新宜康科技有限公司 一种单侧气道油气分离电子烟雾化器
US9655969B2 (en) 2011-12-19 2017-05-23 Teva Branded Pharmaceutical Products R&D, Inc. Inhalable medicament comprising tiotropium
US10034866B2 (en) 2014-06-19 2018-07-31 Teva Branded Pharmaceutical Products R&D, Inc. Inhalable medicament comprising tiotropium
WO2022189742A1 (fr) * 2021-03-09 2022-09-15 Aptar France Sas Dispositif de distribution nasale de produit fluide

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201121812D0 (en) * 2011-12-07 2012-02-01 Teva Branded Pharmaceutical Prod R & D Inc NAsal formulation
CN103550058B (zh) * 2013-11-21 2015-08-19 江门大诚医疗器械有限公司 一种加氧清创器
JP6785373B2 (ja) * 2016-11-06 2020-11-18 微邦科技股▲ふん▼有限公司Ｍｉｃｒｏｂａｓｅ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐ． 微細構造化通路モジュール
US10556072B2 (en) * 2017-01-31 2020-02-11 Dunan Microstaq, Inc. Metering device for a metered dose inhaler
KR102140739B1 (ko) 2018-04-23 2020-08-04 충남대학교산학협력단 상기도 분무 장치
JOP20210068A1 (ar) * 2018-10-08 2023-01-30 Troikaa Pharmaceuticals Ltd محاليل الزولبيديم أو أملاح مقبولة صيدلانيًا منه عبر الغشاء المخاطي الفموي
KR20200098188A (ko) 2019-02-12 2020-08-20 조민수 다기능 상기도 분무 장치
CN210123827U (zh) * 2019-05-31 2020-03-03 庆虹电子(苏州)有限公司 电连接器
WO2021247283A1 (fr) * 2020-06-04 2021-12-09 Amcyte Pharma, Inc. Administration de concentrations micromolaires de composition en aérosol
WO2024079676A1 (fr) * 2022-10-12 2024-04-18 Glenmark Specialty S.A. Nouveau procédé d'assemblage de dispositif de pulvérisation nasale
CN116688331B (zh) * 2023-05-29 2024-02-20 山东京卫制药有限公司 一种鼻气雾剂给药器及其方法

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5116311A (en) * 1987-11-30 1992-05-26 Loefstedt Sigmund J Method for drug administration
WO2001058508A2 (fr) * 2000-02-09 2001-08-16 Glaxo Group Limited Buse d'actionneur pour aerosol-doseur
US20050220717A1 (en) * 1999-06-18 2005-10-06 3M Innovative Properties Company Steroid solution aerosol products with enhanced chemical stability
US20060107949A1 (en) * 2002-11-07 2006-05-25 Davies Michael B Holder for a dispensing container system
US20070175469A1 (en) * 2005-12-02 2007-08-02 Boehringer Ingelheim International Gmbh, Dispensing device
US20080163874A1 (en) * 2001-09-06 2008-07-10 Optinose As Nasal delivery device
US20080203193A1 (en) * 2007-02-28 2008-08-28 Abbott Laboratories Nozzle-based atomization system
US20090050158A1 (en) * 2004-06-07 2009-02-26 Wilem Wassenaar Nasal adaptation of an oral inhaler device
US20090159081A1 (en) * 2007-12-20 2009-06-25 Peter Stadelhofer Discharge device for nasal application
US20100218760A1 (en) * 2006-08-22 2010-09-02 Anderson Gregor John Mclennan Actuator for an inhaler

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3361306A (en) * 1966-03-31 1968-01-02 Merck & Co Inc Aerosol unit dispensing uniform amounts of a medically active ingredient
JP2922935B2 (ja) * 1989-08-11 1999-07-26 東興薬品工業株式会社 粘稠液用鼻孔内噴霧容器の使捨てアダプタ
JP2769925B2 (ja) 1990-10-18 1998-06-25 ミネソタ マイニング アンド マニュファクチャリング カンパニー ベクロメタゾン１７，２１ジプロピオネートを含んで成るエアロゾル製剤
GB9705657D0 (en) * 1997-03-19 1997-05-07 Bacon Raymond J Dispenser
GB9805938D0 (en) 1998-03-19 1998-05-13 Glaxo Group Ltd Valve for aerosol container
JP4472105B2 (ja) * 2000-04-20 2010-06-02 株式会社ダイゾー 噴霧製品
GB2367011A (en) * 2000-08-26 2002-03-27 Glaxo Group Ltd Metered dose inhaler for salmeterol
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
US7055541B2 (en) 2004-09-07 2006-06-06 Ramot At Tel-Aviv University Ltd. Method and mechanism for producing suction and periodic excitation flow
FR2881119B1 (fr) * 2005-01-25 2010-07-30 Valois Sas Dispositif de distribution de produit fluide.
RU2009105638A (ru) * 2006-08-22 2010-09-27 Глакса Груп Лимитед (GB) Средство приведения в действие для ингалятора
EP2011534A1 (fr) 2007-07-03 2009-01-07 CHIESI FARMACEUTICI S.p.A. Actionneur d'inhalateur à dosage mesuré

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5116311A (en) * 1987-11-30 1992-05-26 Loefstedt Sigmund J Method for drug administration
US20050220717A1 (en) * 1999-06-18 2005-10-06 3M Innovative Properties Company Steroid solution aerosol products with enhanced chemical stability
WO2001058508A2 (fr) * 2000-02-09 2001-08-16 Glaxo Group Limited Buse d'actionneur pour aerosol-doseur
US20080163874A1 (en) * 2001-09-06 2008-07-10 Optinose As Nasal delivery device
US20060107949A1 (en) * 2002-11-07 2006-05-25 Davies Michael B Holder for a dispensing container system
US20090050158A1 (en) * 2004-06-07 2009-02-26 Wilem Wassenaar Nasal adaptation of an oral inhaler device
US20070175469A1 (en) * 2005-12-02 2007-08-02 Boehringer Ingelheim International Gmbh, Dispensing device
US20100218760A1 (en) * 2006-08-22 2010-09-02 Anderson Gregor John Mclennan Actuator for an inhaler
US20080203193A1 (en) * 2007-02-28 2008-08-28 Abbott Laboratories Nozzle-based atomization system
US20090159081A1 (en) * 2007-12-20 2009-06-25 Peter Stadelhofer Discharge device for nasal application

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Changning, Guo et al, Evaluation of Impaction Force of Nasal Sprays and Metered-Dose Inhalers Using the TExture Analyser, 18 December, 2008, J of Pharmeceutrical Sciences, Vol. 98, No. 8, 2799-2806. *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9655969B2 (en) 2011-12-19 2017-05-23 Teva Branded Pharmaceutical Products R&D, Inc. Inhalable medicament comprising tiotropium
EP2890437B1 (fr) 2012-08-29 2019-12-18 Chiesi Farmaceutici S.p.A. Dispositif d'inhalation d'aérosol
EA033581B1 (ru) * 2012-08-29 2019-11-06 Chiesi Farm Spa Аэрозольное ингаляционное устройство
US20170080168A1 (en) * 2012-08-29 2017-03-23 Chiesi Farmaceutici S.P.A. Aerosol inhalation device
CN104582771A (zh) * 2012-08-29 2015-04-29 奇斯药制品公司 气溶胶吸入装置
US10737044B2 (en) 2012-08-29 2020-08-11 Chiesi Farmaceutici S.P.A. Aerosol inhalation device
WO2014033057A1 (fr) * 2012-08-29 2014-03-06 Chiesi Farmaceutici S.P.A. Dispositif d'inhalation d'aérosol
EP2996747A4 (fr) * 2013-05-14 2017-01-18 3M Innovative Properties Company Actionneur pour inhalateur
US20160121060A1 (en) * 2013-05-14 2016-05-05 3M Innovative Properties Company Actuator for an inhaler
CN105246534A (zh) * 2013-05-14 2016-01-13 3M创新有限公司 用于吸入器的致动器
US10335563B2 (en) * 2013-05-14 2019-07-02 3M Innovative Properties Company Actuator for an inhaler
EP2996747B1 (fr) 2013-05-14 2020-05-20 3M Innovative Properties Company Actionneur pour inhalateur
WO2015095341A1 (fr) * 2013-12-20 2015-06-25 3M Innovative Properties Company Actionneur d'inhalateur
WO2015169974A1 (fr) * 2014-05-09 2015-11-12 Norton (Waterford) Limited Dispositif d'aérosol
US10960154B2 (en) 2014-05-09 2021-03-30 Norton (Waterford) Limited Aerosol device
US20170189630A1 (en) * 2014-05-09 2017-07-06 Norton (Waterford) Limited Aerosol device
US10034866B2 (en) 2014-06-19 2018-07-31 Teva Branded Pharmaceutical Products R&D, Inc. Inhalable medicament comprising tiotropium
WO2017008127A1 (fr) * 2015-07-16 2017-01-19 Gd Pharma Pty Ltd Dispositif de pulvérisation et cartouche de dosage
CN106376976A (zh) * 2016-10-13 2017-02-08 深圳市新宜康科技有限公司 一种单侧气道油气分离电子烟雾化器
WO2022189742A1 (fr) * 2021-03-09 2022-09-15 Aptar France Sas Dispositif de distribution nasale de produit fluide
FR3120534A1 (fr) * 2021-03-09 2022-09-16 Aptar France Sas Tête de distribution nasale de produit fluide et dispositif comportant une telle tête

Also Published As

Publication number Publication date
EP2926855B1 (fr) 2018-12-05
PT2627386E (pt) 2015-06-11
ES2536969T3 (es) 2015-06-01
EA201390490A1 (ru) 2013-07-30
HK1214990A1 (zh) 2016-08-12
CA2814212C (fr) 2015-06-02
ZA201301938B (en) 2014-05-28
CN106178205A (zh) 2016-12-07
PT2926855T (pt) 2019-02-27
PL2627386T3 (pl) 2015-08-31
US10188811B2 (en) 2019-01-29
CL2013000958A1 (es) 2014-05-30
RS58574B1 (sr) 2019-05-31
JP2015147061A (ja) 2015-08-20
JP2013541378A (ja) 2013-11-14
LT2926855T (lt) 2019-03-25
DK2627386T3 (en) 2015-05-26
JP6023247B2 (ja) 2016-11-09
IL225712A (en) 2017-07-31
US20160082204A1 (en) 2016-03-24
EP2627386B1 (fr) 2015-04-22
EA023795B1 (ru) 2016-07-29
MX336164B (es) 2016-01-11
NZ608218A (en) 2014-10-31
CN103282070A (zh) 2013-09-04
CY1121719T1 (el) 2020-07-31
EP2926855A1 (fr) 2015-10-07
ES2712996T3 (es) 2019-05-17
CN103282070B (zh) 2016-08-10
CN106178206A (zh) 2016-12-07
HRP20150452T1 (hr) 2015-08-14
TR201902415T4 (tr) 2019-03-21
RS54037B1 (en) 2015-10-30
EP2627386A1 (fr) 2013-08-21
KR20130100334A (ko) 2013-09-10
BR112013008824A2 (pt) 2016-06-28
PE20131492A1 (es) 2014-01-17
JP6050236B2 (ja) 2016-12-21
KR101559639B1 (ko) 2015-10-12
DK2926855T3 (en) 2019-03-25
AU2011316124B2 (en) 2014-12-11
MX2013003840A (es) 2013-08-15
SI2926855T1 (sl) 2019-05-31
SI2627386T1 (sl) 2015-10-30
HRP20190337T1 (hr) 2019-05-03
PL2926855T3 (pl) 2019-06-28
HUE043276T2 (hu) 2019-08-28
SG189892A1 (en) 2013-06-28
IL225712A0 (en) 2013-06-27
WO2012048867A1 (fr) 2012-04-19
AU2011316124A1 (en) 2013-04-04
SMT201500114B (it) 2015-09-07
CA2814212A1 (fr) 2012-04-19

Similar Documents

Publication Publication Date Title
US10188811B2 (en) Nasal spray device
AU2008271599B2 (en) Metered dose inhaler actuator
US10960154B2 (en) Aerosol device
TW201119644A (en) Pharmaceutical aerosol formulations of formoterol and beclometasone dipropionate
AU2015201102B2 (en) Nasal spray device
CA2856043C (fr) Formulation nasale
US20110182830A1 (en) Inhalation drug products, systems and uses
KR20220108047A (ko) 가압 정량 흡입기를 위한 스테인리스 스틸 캔

Legal Events

Date Code Title Description
AS Assignment

Owner name: TEVA BRANDED PHARMACEUTICAL PRODUCTS R&D, INC., PE

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:ZENG, XIAN-MING;LY, JADE;MORALES, ARMANDO;SIGNING DATES FROM 20130709 TO 20130710;REEL/FRAME:030922/0181

Owner name: IVAX PHARMACEUTICALS IRELAND (A TRADING NAME OF NO

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:WALSH, DECLAN;REEL/FRAME:030922/0211

Effective date: 20130725

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO PAY ISSUE FEE