WO2008146025A2 - Procédé pour le traitement des composants d'un dispositif distributeur médical - Google Patents

Procédé pour le traitement des composants d'un dispositif distributeur médical Download PDF

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Publication number
WO2008146025A2
WO2008146025A2 PCT/GB2008/001875 GB2008001875W WO2008146025A2 WO 2008146025 A2 WO2008146025 A2 WO 2008146025A2 GB 2008001875 W GB2008001875 W GB 2008001875W WO 2008146025 A2 WO2008146025 A2 WO 2008146025A2
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WO
WIPO (PCT)
Prior art keywords
component
plasma
medicament
treatment step
previous
Prior art date
Application number
PCT/GB2008/001875
Other languages
English (en)
Other versions
WO2008146025A3 (fr
Inventor
Paul Stevenson
Darren Bromley-Davenport
Original Assignee
Innovatek Medical Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Innovatek Medical Limited filed Critical Innovatek Medical Limited
Publication of WO2008146025A2 publication Critical patent/WO2008146025A2/fr
Publication of WO2008146025A3 publication Critical patent/WO2008146025A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D5/00—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
    • B05D5/08—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures to obtain an anti-friction or anti-adhesive surface
    • B05D5/083—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures to obtain an anti-friction or anti-adhesive surface involving the use of fluoropolymers
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D1/00—Processes for applying liquids or other fluent materials
    • B05D1/62—Plasma-deposition of organic layers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D3/00—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials
    • B05D3/14—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials by electrical means
    • B05D3/141—Plasma treatment
    • B05D3/142—Pretreatment
    • 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/02—General characteristics of the apparatus characterised by a particular materials
    • A61M2205/0222—Materials for reducing friction

Definitions

  • pressurised dispenser devices which dispense the medicament in a carrier fluid, commonly as an aerosol.
  • Such devices are often referred to as pressurised metered dose inhalers (pMDIs), and are very commonly used for treating asthma and chronic obstructive pulmonary disease (COPD).
  • pMDIs pressurised metered dose inhalers
  • COPD chronic obstructive pulmonary disease
  • One problem associated with dispenser devices of this kind is absorption of the active medicament on the internal surfaces of the device. This in turn can lead to a loss of potency and/or erratic dosing during the shelf-life of the device. In some instances clustering of drug particles can occur if the active medicament is present as a suspension of particles.
  • the present inventors have realised that the quality of many of the known prior art surface coatings is variable.
  • the present inventors have conducted extensive studies into the deficiencies in the prior art techniques, and have developed novel techniques which enable improved treatments for preventing absorption of the medicament onto the internal surfaces of the device.
  • the present invention relates to some of the investigations made by the present inventors and, in at least some of its embodiments, addresses the above- described problems, needs and desires.
  • a method of treating a component of a medicament dispenser device including the steps of: providing said component; subjecting the component to a plasma induced pre-treatment step in which at least one of said surface is cleaned and/or conditioned using a plasma; and subjecting the pre-treated surface or surfaces to a subsequent treatment step which inhibits surface deposition of the medicament.
  • the present inventors have found that the condition and chemical speciation of the surfaces is important if the treatment to inhibit surface deposition of the medicament is to be accomplished successfully.
  • the present invention provides a range of conditioning and cleaning pre-treatments which can, for example, remove surface contaminants such as oils and unreacted materials, and provide an improved substrate for the subsequent treatment to be performed upon.
  • the plasma induced pre-treatment may cause reactive etching of at least one of said surfaces.
  • at least one of said surfaces may be cleaned using a plasma formed using oxygen, a noble gas, preferably argon, a fluorocarbon, preferably CF 4 , or mixtures thereof.
  • a noble gas refers to a Group VIII gas.
  • the plasma is formed using a noble gas/oxygen or oxygen/fluorocarbon mixture.
  • the conditioning step preferably includes etching using a plasma formed using oxygen, a noble gas, preferably argon, a fluorocarbon, preferably CF 4 , a chlorinated etching gas, or mixtures thereof.
  • the oxide layer may be removed by etching, and the rebuilding of a layer can be performed by exposure of the surface to oxygen or a fluorine containing plasma.
  • the component may be a component of a pressurised dispenser that dispenses a medicament in a carrier fluid.
  • the dispenser device may be a pMDI device.
  • the component may be a can body for use in the pressurised dispenser, wherein at least a portion of an interior surface of the can body is subjected to the pre-treatment step and the subsequent treatment step.
  • the can body may be formed from a metal, such as aluminium. Aluminium can bodies are an example of a component having an oxide layer which may be conditioned by removing the oxide layer and rebuilding.
  • the component may be formed from a polymeric material, and the pre- treatment step may cause cross-linking of polymeric material at the surface and/or may cause polymerisation of unreacted monomeric material present at or near to the surface.
  • the term "near to the surface” generally refers to a depth of about 30 ⁇ m from the surface, although the invention is not limited in this regard.
  • Elastomeric seals, particularly nitrile rubber seals are example of components which may be pre-treated in this manner.
  • the pre-treatment step uses an ozone producing plasma, the ozone causing the cross linking and/or polymerisation. Cross-linking of unreacted monomeric material removes monomeric material which might instead react with or otherwise absorb the medicament.
  • the subsequent treatment step may comprise coating the pre-treated surface or surface with a polymer.
  • the subsequent treatment step may utilise a plasma.
  • the subsequent treatment step includes a plasma polymerisation step which coats the pre-treated surface or surfaces with a polymer which inhibits surface deposition of the medicament.
  • the subsequent treatment step may include surface modification of the pre-treated surface or surfaces. The surface modification may be followed by a step in which the modified surface is coated with a polymer. The surface modification may modify the chemistry of the surface so as to reduce the polar component of the surface energy.
  • a method of manufacturing a medicament dispenser device including the steps of: treating a component of the medicament dispenser device in a method according to the first aspect of the invention; providing other components of the device; and assembling the components to provide an assembled medicament dispenser device.
  • a medicament dispenser device treated by a method according to the first aspect of the invention.
  • the arrangement 14 comprises a can body 16 on which is crimped a ferrule 18.
  • a metering valve system mounted on the ferrule 18 is a metering valve system, shown generally at 20.
  • the metering valve system 20 comprises a valve stem 22, a portion of which is disposed in a valve member 24.
  • the valve stem 22 and valve member 24 are both located in a valve housing 26, and the valve stem 22 is axially reciprocable therein against the action of a spring 28 which biases the valve stem 22 into a closed position as shown in Figure 1.
  • the valve stem 22 has two channels 44,46.
  • Each channel, 44,46 comprises a longitudinal passageway and a transverse passageway.
  • the transverse passageway of the valve stem channel 44 is disposed so that, when the pressurised medicament container arrangement 14 is in its closed position as shown in Figure 1 , the metering chamber 30 is in communication with the interior 36 of the valve housing 26 and thus is also in communication with the interior 40 of the can body 16.
  • the volume of the metering chamber 30 corresponds to the volume of medicament containing fluid administered in a single dose. In the closed position shown in Figure 1 , the dose is wholly contained in the metering chamber 30 and cannot escape to the outside of the pressurised medicament container arrangement 14 owing to the action of the outer seal 34.
  • valve stem 22 To release a dose of medicament containing fluid, the valve stem 22 is pushed against the biasing action of the spring 28 into the interior 36 of the valve housing 26 to an extent that the valve stem channel 44 no longer communicates with the metering chamber 30.
  • the valve stem 22 is designed so that, in this dispensing position, the valve stem channel 46 of the valve stem 22 communicates with the metering chamber 30, thereby allowing the dose of medicament containing fluid in the metering chamber 30 to be dispensed through the valve stem 22.
  • the dose then passes through the passageway 12e, opening 12f and open ended passage 12b to exit the device.
  • valve stem channel 46 assumes a position whereby the metering chamber 30 is sealed against the outside, and the valve stem channel 44 assumes a position whereby the interior 36 of the valve housing 26 is in communication with the metering chamber 30. Owing to the pressure differential between the relatively high pressure interior 40 of the can body 16 and the relatively low pressure of the metering chamber 30, the metering chamber 30 is refilled with another dose of the medicament containing fluid.
  • the pressurised dispenser device 10 shown in Figure 1 is one example of such a device, and many other metering arrangements are known which differ to a greater or lesser degree in their precise mode of action.
  • the present invention does not lay claim to the mode of action of the device shown in Figure 1 or of any other pressurised dispenser device. Rather, the present invention concerns methods for producing devices and components for same which inhibit losses of medicaments to internal surfaces of the device.
  • the device shown in Figure 1 is provided in order to assist the reader's appreciation of how the present invention might be applied. The skilled reader will appreciate that the present invention can be applied to other designs of pressurised dispenser device than the one shown in Figure 1 , and indeed can be applied to different types of medicament dispenser devices than pressurised dispenser devices.
  • the present invention provides a range of pre-treatment steps prior to one or more steps which inhibit losses of the medicament to the internal surfaces of the pressurised dispensing device.
  • it is the interior surfaces of the can body which are pre-treated and subsequently coated with a polymer.
  • many other components of a pressurised dispensing device may be pre-treated using the methodologies of the present invention, and this is explained in some more detail below.
  • Figure 2 shows an arrangement in which a can body 50 is cleaned and conditioned by plasma polymerisation.
  • the can body is maintained at earth, and the mouth of the can body is sealed with a suitable vacuum tight lid 52.
  • the lid 52 permits entry of a gas feed inlet 54, an outlet 56 for exhausting gases using a vacuum pump 58, and an RF electrode which protrudes into the interior of the can body 50 and is disposed substantially along the longitudinal axis of the can body 50.
  • the appropriate cleaning and conditioning gases are delivered into the can body 50 through the gas feed inlet 54 from an appropriate delivery source (not shown) which typically includes one or more mass flow controllers.
  • Cleaning and conditioning of the interior surfaces of the can body 50 is achieved by striking and maintaining a plasma whilst the gas or gases are flowed into the can body 50.
  • 13.56 MHz RF power is applied to the RF electrode 60, and the plasma is struck using techniques well known in the art.
  • Other RF frequencies might be used, and it is anticipated that frequencies within the range 4kHz to 20MHz might be utilised. It has been found that gas pressures in the range 5xe "2 mbar to 1xe '1 mbar give rise to particularly good results, although gas pressures in the range of 5xe "2 mbar to 9xe "1 mbar can be used. Power densities between 0.1 and 1.5 watts cm '2 of electrode are employed.
  • the embodiment shown in Figure 2 is a single can treatment process in which the can acts as an earth electrode.
  • the can may act as the RF electrode.
  • An earth electrode may be inserted into the centre of the can body through the vacuum tight lid thereby preventing excessive heating through the so-called "hollow cathode effect".
  • the RF power may be pulsed.
  • the RF and earth electrodes may be discrete from the can.
  • a plurality of cans may be coated at the same time using these configurations.
  • the RF plasma electrodes may be parallel plate or barrel configuration with the cans being placed either on the RF or the earth electrode or at a floating potential between the two electrodes.
  • the plasma cleaning step ensures that the condition and chemical speciation at the substrate surface is adequate for a subsequent polymerisation process to proceed.
  • oils and other contaminants can be removed by the cleaning process.
  • the plasma can be formed using a noble gas such as argon, oxygen, a fluorocarbon (especially CF4) or a mixture of these gasses. Preferred mixtures include argon/oxygen, and oxygen/fluorocarbon.
  • Cleaning can be achieved by etching or reactive etching. Additionally, with components such as aluminium can bodies, it can be advantageous to condition the surface by removing or partially removing and then rebuilding the oxide top surface layer.
  • Etching of the aluminium to remove the existing oxide layer can be achieved using a noble gas such as argon, oxygen, fluorocarbon (especially CF4), chlorinated gases as used in the semiconductor industry, or mixtures of these gases.
  • a noble gas such as argon, oxygen, fluorocarbon (especially CF4), chlorinated gases as used in the semiconductor industry, or mixtures of these gases.
  • the rebuilding of the oxide top layer is performed using oxygen only.
  • the apparatus shown in Figure 2 can be used to perform a subsequent plasma polymerisation step, and similar pressure and power densities to those employed during the pre-treatment process can be utilised. It is preferred that a pure monomer plasma is used, by which is meant that the gaseous atmosphere in which the plasma is struck and maintained consists entirely of the monomer or monomers. However, it is in principle possible to form a plasma in a gaseous atmosphere which includes one or more diluent gases. In the context of the plasma generation, the term 'gases' is understood to include volatile species which are evaporated from a solid or liquid source in a heat vaporisation system prior to introduction into the plasma.
  • the present invention can also be used to pre-treat other components of a pressurised dispenser device.
  • various interior surfaces of the metering valve system and the housing for the pressurised medicament container arrangement might be pre-treated.
  • the housing 12, valve member 24, valve housing 26, spring 28, valve stem 22, and the seals 42,44,46 can be usefully pre-treated using the present invention.
  • It can be desirable to stabilise the surfaces of seals using one or more pre-treatment steps prior to one or more further steps.
  • Such pre-treatment steps are important with seals formed from elastomeric material, particularly nitrile materials, since the outer layer of the rubber is semi-porous, and typically contains material such as fillers, plasticisers, and unreacted monomers.
  • elastomeric seals can also be usefully pre-treated prior to surface modification.
  • the pre-treatment can comprise a heat treatment, a plasma treatment, or a combination of the two.
  • the heat treatment drives off some of the lower molecular weight volatile contaminants andZor promote additional cross-linking.
  • a further advantage of the heating step is that the seals are relatively hot at the commencement of a further step, which results in better efficiency and fluorination during the surface modification step.
  • the heat treatment is advantageously performed at greater than 9O 0 C, most preferably in the range 90-120 0 C.
  • a plasma pre-treatment can sputter away any residual surface contaminants and can cause cross-linking of monomers present on the surface.
  • the plasma cleaning/cross-linking step can be performed using similar gas pressures and power densities to those used in the polymerisation process described above.
  • the plasma pre-treatment step may be performed using an argon, oxygen, or argon/oxygen plasma. Oxygen can containing plasmas have the advantage of producing ozone which enables the cross-linking of unreacted material to take place.
  • seals which have been surface modified in accordance with the invention can be highly resistant to deposition of the medicament, and thus may be used directly in a pressurised dispenser device.
  • CF 4 and to bleed a second gas into the CF 4 gas flow to produce a gas blend which is used to perform the plasma polymerisation.
  • Suitable monomeric gases include C 4 F 8, C 2 H 6 , and CF 3 CHFCF 3 but other species described earlier might be used instead. These gases can also be used to form a blend with the CF 4 for polymerisation purposes. Similar pressures and power densities to those used during the surface modification step can be used during the polymerisation step.
  • the present invention is not limited to pressurised dispenser devices, and can be used in conjunction with delivery systems for dry powder drugs and active liquids.

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Plasma & Fusion (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Filling Or Discharging Of Gas Storage Vessels (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne un procédé destiné au traitement d'un composant d'un dispositif distributeur de médicament. Ce composant présente une ou plusieurs surfaces en contact avec le médicament pendant le stockage ou l'utilisation du médicament. Ce procédé consiste à prendre ledit composant, à le soumettre à un prétraitement induit par plasma, prétraitement au cours duquel lesdites surfaces sont nettoyées et/ou conditionnées au moyen d'un plasma, puis à soumettre la ou les surfaces prétraitées à un traitement ultérieur qui empêche le dépôt du médicament sur les surfaces.
PCT/GB2008/001875 2007-06-01 2008-06-02 Procédé pour le traitement des composants d'un dispositif distributeur médical WO2008146025A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0710488A GB0710488D0 (en) 2007-06-01 2007-06-01 Methods of treating components of a medical dispenser device
GB0710488.8 2007-06-01

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WO2008146025A2 true WO2008146025A2 (fr) 2008-12-04
WO2008146025A3 WO2008146025A3 (fr) 2009-01-15

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Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011104539A1 (fr) * 2010-02-26 2011-09-01 Portal Medical Ltd Dispositif de distribution de médicament
WO2011104541A1 (fr) * 2010-02-26 2011-09-01 Portal Medical Ltd Procédé de fabrication d'un dispositif de distribution de médicament
EP2236227A3 (fr) * 2009-03-30 2011-10-19 Boehringer Ingelheim International GmbH Outil de formage doté d'un corps de base rotatif
EP2236224A3 (fr) * 2009-03-30 2011-10-19 Boehringer Ingelheim International GmbH Outil de déformage doté d'un corps de base rotatif pour le formage d'une cartouche d'un inhalateur
GB2476004B (en) * 2011-02-23 2011-12-28 Portal Medical Ltd Medicament Dispenser Device
FR2979214A1 (fr) * 2011-08-26 2013-03-01 Seb Sa Article comportant un revetement antiadhesif presentant des proprietes ameliorees d'adherence au support
US9545487B2 (en) 2012-04-13 2017-01-17 Boehringer Ingelheim International Gmbh Dispenser with encoding means
US9682202B2 (en) 2009-05-18 2017-06-20 Boehringer Ingelheim International Gmbh Adapter, inhalation device, and atomizer
US9724482B2 (en) 2009-11-25 2017-08-08 Boehringer Ingelheim International Gmbh Nebulizer
US9744313B2 (en) 2013-08-09 2017-08-29 Boehringer Ingelheim International Gmbh Nebulizer
US9757750B2 (en) 2011-04-01 2017-09-12 Boehringer Ingelheim International Gmbh Medicinal device with container
US9827384B2 (en) 2011-05-23 2017-11-28 Boehringer Ingelheim International Gmbh Nebulizer
US9943654B2 (en) 2010-06-24 2018-04-17 Boehringer Ingelheim International Gmbh Nebulizer
US10004857B2 (en) 2013-08-09 2018-06-26 Boehringer Ingelheim International Gmbh Nebulizer
US10011906B2 (en) 2009-03-31 2018-07-03 Beohringer Ingelheim International Gmbh Method for coating a surface of a component
US10016568B2 (en) 2009-11-25 2018-07-10 Boehringer Ingelheim International Gmbh Nebulizer
US10099022B2 (en) 2014-05-07 2018-10-16 Boehringer Ingelheim International Gmbh Nebulizer
US10124125B2 (en) 2009-11-25 2018-11-13 Boehringer Ingelheim International Gmbh Nebulizer
US10124129B2 (en) 2008-01-02 2018-11-13 Boehringer Ingelheim International Gmbh Dispensing device, storage device and method for dispensing a formulation
US10195374B2 (en) 2014-05-07 2019-02-05 Boehringer Ingelheim International Gmbh Container, nebulizer and use
US10410838B2 (en) 2009-05-06 2019-09-10 3M Innovative Properties Company Apparatus and method for plasma treatment of containers
US10722666B2 (en) 2014-05-07 2020-07-28 Boehringer Ingelheim International Gmbh Nebulizer with axially movable and lockable container and indicator
US11464922B2 (en) 2017-10-31 2022-10-11 Portal Medical Limited Medicament dispenser device

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003035154A1 (fr) * 2001-10-23 2003-05-01 Glaxo Group Limited Distributeur de medicaments

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003035154A1 (fr) * 2001-10-23 2003-05-01 Glaxo Group Limited Distributeur de medicaments

Cited By (42)

* Cited by examiner, † Cited by third party
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US10124129B2 (en) 2008-01-02 2018-11-13 Boehringer Ingelheim International Gmbh Dispensing device, storage device and method for dispensing a formulation
US8495901B2 (en) 2009-03-30 2013-07-30 Boehringer Ingelheim International Gmbh Shaping tool having a rotatable base member
EP2236227A3 (fr) * 2009-03-30 2011-10-19 Boehringer Ingelheim International GmbH Outil de formage doté d'un corps de base rotatif
EP2236224A3 (fr) * 2009-03-30 2011-10-19 Boehringer Ingelheim International GmbH Outil de déformage doté d'un corps de base rotatif pour le formage d'une cartouche d'un inhalateur
US8677793B2 (en) 2009-03-30 2014-03-25 Boehringer Ingelheim International Gmbh Shaping tool having a rotatable base member
US10011906B2 (en) 2009-03-31 2018-07-03 Beohringer Ingelheim International Gmbh Method for coating a surface of a component
US10410838B2 (en) 2009-05-06 2019-09-10 3M Innovative Properties Company Apparatus and method for plasma treatment of containers
US9682202B2 (en) 2009-05-18 2017-06-20 Boehringer Ingelheim International Gmbh Adapter, inhalation device, and atomizer
US10124125B2 (en) 2009-11-25 2018-11-13 Boehringer Ingelheim International Gmbh Nebulizer
US10016568B2 (en) 2009-11-25 2018-07-10 Boehringer Ingelheim International Gmbh Nebulizer
US9724482B2 (en) 2009-11-25 2017-08-08 Boehringer Ingelheim International Gmbh Nebulizer
US8877336B2 (en) 2010-02-26 2014-11-04 Portal Medical Ltd. Medicament dispenser device
CN102883826B (zh) * 2010-02-26 2014-08-06 门户医疗有限公司 药剂分配器装置的制造方法
JP2013520267A (ja) * 2010-02-26 2013-06-06 ポータル メディカル リミテッド 薬剤ディスペンサー装置の製造方法
GB2490260B (en) * 2010-02-26 2013-08-07 Portal Medical Ltd Method of manufacturing a medicament dispenser device
WO2011104541A1 (fr) * 2010-02-26 2011-09-01 Portal Medical Ltd Procédé de fabrication d'un dispositif de distribution de médicament
AU2011219607B2 (en) * 2010-02-26 2014-05-22 Portal Medical Ltd Method of manufacturing a medicament dispenser device
CN102844122B (zh) * 2010-02-26 2014-07-16 门户医疗有限公司 药剂分配器装置
CN102883826A (zh) * 2010-02-26 2013-01-16 门户医疗有限公司 药剂分配器装置的制造方法
US8865248B2 (en) * 2010-02-26 2014-10-21 Portal Medical Ltd. Method of manufacturing a medicament dispenser device
WO2011104539A1 (fr) * 2010-02-26 2011-09-01 Portal Medical Ltd Dispositif de distribution de médicament
JP2013520266A (ja) * 2010-02-26 2013-06-06 ポータル メディカル リミテッド 薬剤ディスペンサー装置
GB2490260A (en) * 2010-02-26 2012-10-24 Portal Medical Ltd Plasma coating medicament dispenser component under DC bias control
US20130019863A1 (en) * 2010-02-26 2013-01-24 Portal Medical Ltd. Method of manufacturing a medicament dispenser device
CN102844122A (zh) * 2010-02-26 2012-12-26 门户医疗有限公司 药剂分配器装置
US9943654B2 (en) 2010-06-24 2018-04-17 Boehringer Ingelheim International Gmbh Nebulizer
GB2476004B (en) * 2011-02-23 2011-12-28 Portal Medical Ltd Medicament Dispenser Device
US9757750B2 (en) 2011-04-01 2017-09-12 Boehringer Ingelheim International Gmbh Medicinal device with container
US9827384B2 (en) 2011-05-23 2017-11-28 Boehringer Ingelheim International Gmbh Nebulizer
FR2979214A1 (fr) * 2011-08-26 2013-03-01 Seb Sa Article comportant un revetement antiadhesif presentant des proprietes ameliorees d'adherence au support
WO2013030503A2 (fr) 2011-08-26 2013-03-07 Seb Sa Article comportant un revêtement antiadhesif presentant des proprietes ameliorees d'adherence au support
US9545487B2 (en) 2012-04-13 2017-01-17 Boehringer Ingelheim International Gmbh Dispenser with encoding means
US10220163B2 (en) 2012-04-13 2019-03-05 Boehringer Ingelheim International Gmbh Nebuliser with coding means
US9744313B2 (en) 2013-08-09 2017-08-29 Boehringer Ingelheim International Gmbh Nebulizer
US10004857B2 (en) 2013-08-09 2018-06-26 Boehringer Ingelheim International Gmbh Nebulizer
US10894134B2 (en) 2013-08-09 2021-01-19 Boehringer Ingelheim International Gmbh Nebulizer
US11642476B2 (en) 2013-08-09 2023-05-09 Boehringer Ingelheim International Gmbh Nebulizer
US10716905B2 (en) 2014-02-23 2020-07-21 Boehringer Lngelheim International Gmbh Container, nebulizer and use
US10099022B2 (en) 2014-05-07 2018-10-16 Boehringer Ingelheim International Gmbh Nebulizer
US10195374B2 (en) 2014-05-07 2019-02-05 Boehringer Ingelheim International Gmbh Container, nebulizer and use
US10722666B2 (en) 2014-05-07 2020-07-28 Boehringer Ingelheim International Gmbh Nebulizer with axially movable and lockable container and indicator
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