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WO2009006137A1 - Cartouche d'aérosol employant un film polymère ayant des propriétés de barrière à l'humidité améliorées - Google Patents

Cartouche d'aérosol employant un film polymère ayant des propriétés de barrière à l'humidité améliorées Download PDF

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Publication number
WO2009006137A1
WO2009006137A1 PCT/US2008/068117 US2008068117W WO2009006137A1 WO 2009006137 A1 WO2009006137 A1 WO 2009006137A1 US 2008068117 W US2008068117 W US 2008068117W WO 2009006137 A1 WO2009006137 A1 WO 2009006137A1
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WO
WIPO (PCT)
Prior art keywords
canister
polymeric film
aerosol formulation
ferrule
inhaler
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.)
Ceased
Application number
PCT/US2008/068117
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English (en)
Inventor
Christopher William Kidd, Iii
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.)
Glaxo Group Ltd
Original Assignee
Glaxo Group Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd
Publication of WO2009006137A1 publication Critical patent/WO2009006137A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • 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 for dispensing liquid or semi-liquid contents by internal gaseous pressure, i.e. aerosol containers comprising propellant
    • B65D83/38—Details of the container body

Definitions

  • the present invention generally relates to aerosol canisters used in conjunction with metered dose inhalers for dispensing pharmaceutical aerosol formulations therefrom.
  • CFCs chlorofluorocarbons
  • hydrofluoroalkane propellants such as HFA-134a and HFA-227.
  • hydrofluoroalkane propellants such as HFA-134a and HFA-227.
  • Non-CFC propellants are believed to have a greater water solubility than the CFC propellants traditionally used in MDI's.
  • the maximum water solubility in HFC 134a is estimated to be about 2200 ppm whereas for CFC 11 , 12 and 114, the maximum water solubilities are about
  • Moisture ingress is particularly problematic in drug systems that are susceptible to agglomeration or other decrease in fine particle mass due to the presence of moisture. In such systems, moisture ingress may shorten the useful life of an MDI. It is believed that moisture transport is often influenced by the elastomeric nature of the valve gaskets as well as the type of HFA formulation and storage conditions employed. Having the capability to regulate the level of moisture ingress in an inhaler would be highly desirable.
  • the invention provides an aerosol inhaler.
  • the inhaler comprises a canister housing a pharmaceutical aerosol formulation therein; a ferrule attached to the canister, the ferrule comprising a valve body having at least one opening therein to allow a quantity of the pharmaceutical aerosol formulation to pass from the container into the valve; and a polymeric film positioned between the ferrule and the canister, the polymeric film being present so as to serve as a barrier to moisture entering the canister.
  • the invention provides a method for the treatment or prophylaxis of a respiratory disorder. The method comprises administering to a patient by oral inhalation a pharmaceutical aerosol formulation by using the aerosol inhaler.
  • the invention provides a method of making an aerosol inhaler.
  • the method comprises applying a polymeric film to an outside surface of a canister, attaching a ferrule to the canister, the ferrule comprising a valve body having at least one opening therein, and filling the canister with a pharmaceutical aerosol formulation through the opening of the valve body.
  • FIG. 1 illustrates a cross-sectional view of a Metered Dose Inhaler in accordance with the present invention.
  • FIG. 2 illustrates a cross-sectional view of the bottom portion of a Metered Dose Inhaler
  • FIGS. 3, 5, and 7 illustrate Cascade Impaction (Cl) fine particle mass data for various inhalers containing polymeric seals.
  • FIGS. 4, 6, and 8 illustrate moisture data for various inhalers containing polymeric seals
  • the invention provides an aerosol inhaler
  • the inhaler comprises a canister housing the pharmaceutical aerosol formulation therein, a ferrule attached to the canister, the ferrule comprising a valve body having at least one opening therein to allow a quantity of the pharmaceutical aerosol formulation to pass from the canister into the valve, and a polymeric film positioned between the ferrule and the canister, the polymeric film being present so as to serve as a barrier to moisture entering the canister
  • a number of polymeric films may be employed in accordance with the invention
  • the polymeric film may be formed from one or more polymers, the selection of which is known to one skilled in the art
  • the term "polymeric" should be broadly construed to include, without limitation, homopolymers, copolymers, terpolymers, and the like as well as interpolymers, and blends and combinations of all of the above.
  • polymers examples include, without limitation, thermoplastic polymers.
  • Exemplary polymers that may be employed include, without limitation, polyolefins (e.g., low density polyethylene (LDPE), linear low density polyethylene (LLDPE), medium density polyethylene (MDPE), high density polyethylene (HDPE), ultra high molecular weight polyethylene (UMWPE), and polypropylene (PP)), amorphous and crystalline polyamides, crystalline polyesters, poly(ethylene 2,6-naphthalene dicarboxylate), polycarbonates, methyl methacrylate-styrene copolymer grafted onto a diene elastomer, polyphenylene oxide, polystyrene, polyphenylene oxide/polystyrene blends, polyvinyl chloride)s, polyacrylates, polymethacrylates, polyalkyl methacrylates, polyethers, polysiloxanes, polysulfones, polyphenylene sulfide, polyether
  • polyvinylidene chloride resins can be used, e.g., SARAN WRAP® (F-310) made commercially available from S. C. Johnson of Racine, Wisconsin.
  • a fluorocarbon-based polymer may be used, e.g., polytetrafluoroethylene (PTFE), and in particular a blend of a fluorocarbon polymer and a non-fluorocarbon polymer.
  • PTFE polytetrafluoroethylene
  • An example of such an embodiment is a blend of polytetrafluoroethylene and polyethersulfone (PES) sold commercially as TEFLON® 3200-100 made commercially available from E.I. du Pont de Nemours Company of Wilmington, Delaware.
  • the polymeric film may include VAPORCOATTM120 made commercially available from Michelman Inc. of Cincinnati Ohio.
  • the polymeric film may include Valspar Latex (Sealant Lacquer LO7505 Grey) made commercially available from The Valspar (Vermicolor) Corporation AG of Gr ⁇ ningen, Switzerland.
  • the term "film” is to be widely interpreted and refers to a thin sheet of a substance that is in contact with the ferrule and container.
  • the polymeric film may be formed according to techniques known in the art. After applied and optionally cured, the film advantageously has a thickness from 0.05 mm to 0.75 mm, and more advantageously from 0.1 mm to 0.5 mm. Said thickness may vary across the applied area of the film.
  • the polymeric film may be applied to the canister by employing methods known to the skilled artisan.
  • the polymeric film may be sprayed to the outer surface of the container and then heated to assist drying the film.
  • the film may be applied by using a syringe or a brush.
  • the polymeric film is advantageously applied to the outer surface of the container prior to crimping the ferrule to the container.
  • the polymeric film may be applied to the internal surface of the ferrule prior to crimping the ferrule to the container.
  • the polymeric film may be applied after crimping of the ferrule to the container.
  • the polymeric film may require curing, typically with heat, or alternatively with ultraviolet light or in such other manner as known in the art. Curing advantageously takes place prior to crimping the container and the ferrule. According to an advantageous embodiment, the polymeric film is applied to the outer surface of the container and cured prior to crimping the ferrule with the container. According to an embodiment, the polymeric film is co-cured with one or more polymer coatings on the inside of an MDI canister (described in more detail below). Alternatively, the polymeric film is cured before or after the one or more coatings on the inside of the MDI canister.
  • the aerosol inhaler may be a pressurized inhaler, e.g., a Metered Dose Inhaler (MDI).
  • MDI Metered Dose Inhaler
  • a number of MDIs can be employed.
  • the pharmaceutical aerosol formulations delivered from such inhalers also are numerous.
  • the formulations may be employed in or as suspensions or as aerosols delivered from pressurised packs, with the use of a suitable propellant, e.g., a hydrofluoroalkane (HFA) (e.g., 1 ,1 ,1 ,2,3,3,3-heptafluoropropane, 1 ,1 ,1 ,2- tetrafluoroethane), carbon dioxide or other suitable gases.
  • HFA hydrofluoroalkane
  • Exemplary MDIs typically include canisters suitable for delivering the pharmaceutical aerosol formulations.
  • Canisters generally comprise a container capable of withstanding the vapor pressure of the propellant used such as a plastic or plastic-coated glass bottle or preferably a metal can, for example, an aluminum can which may optionally be anodised, lacquer-coated and/or plastic-coated, which container is closed with a metering valve.
  • Aluminum cans which have their inner surfaces coated with a fluorocarbon polymer are particularly preferred.
  • Such polymers can be made of multiples of the following monomeric units: tetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), perfluoroalkoxyalkane (PFA), ethylene tetrafluoroethylene (EFTE), vinyldienefluoride (PVDF), and chlorinated ethylene tetrafluoroethylene.
  • PTFE tetrafluoroethylene
  • FEP fluorinated ethylene propylene
  • PFA perfluoroalkoxyalkane
  • EFTE ethylene tetrafluoroethylene
  • PVDF vinyldienefluoride
  • chlorinated ethylene tetrafluoroethylene tetrafluoroethylene
  • cans having inner surfaces coated with blends of fluorocarbon polymers and non- fluorocarbon polymers may also be employed s. Embodiments of coatings used on all or part of the internal surfaces of an MDI are set forth in U.S.
  • MDIs may also include metering valves designed to deliver a metered amount of the formulation per actuation and incorporate a gasket to prevent leakage of propellant through the valve.
  • the gasket may comprise any suitable elastomeric material such as, for example, low density polyethylene, chlorobutyl, black and white butadiene-acrylonitrile rubbers, butyl rubber and neoprene.
  • Suitable valves are commercially available from manufacturers well known in the aerosol industry, for example, from Valois, France (e.g. DF10, DF30, DF60), Bespak pic, UK (e.g. BK300, BK356) and 3M-Neotechnic
  • Embodiments of metering valves are set forth in U.S. Patent Nos. 6,170,717; 6,315,173; and 6,318,603.
  • the MDIs may also be used in conjunction with other structures such as, without limitation, overwrap packages for storing and containing the MDIs, including those described in U.S. Patent No.
  • the pharmaceutical aerosol formulation according to the invention includes at least one medicament and at least one propellant, typically an HFA propellant.
  • Medicaments for the purposes of the invention, include a variety of pharmaceutically active ingredients, such as, for example, those which are useful in inhalation therapy.
  • the term "medicament” is to be broadly construed and include, without limitation, actives, drugs and bioactive agents, as well as biopharmaceuticals.
  • medicaments may thus be selected from, for example, analgesics, (e.g., codeine, dihydromorphine, ergotamine, fentanyl or morphine); anginal preparations,
  • anti-allergies e.g., cromoglicate, ketotifen or nedocromil
  • antiinfectives e.g., cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines and pentamidine
  • antihistamines e.g., methapyrilene
  • antiinflammatories e.g., anti-inflammatory steroids, beclomethasone (e.g. beclomethasone dipropionate), fluticasone (e.g.
  • salbutamol e.g. as the free base or the sulphate salt
  • salmeterol e.g. as xinafoate
  • ephedrine adrenaline
  • fenoterol e.g as hydrobromide
  • bitolterol formoterol (e.g., as fumarate)
  • isoprenaline metaproterenol
  • phenylephrine phenylpropanolamine
  • pirbuterol e.g., as acetate
  • reproterol e.g., as hydrochloride
  • rimiterol terbutaline (e.g., as sulphate)
  • isoetharine tulobuterol
  • diuretics e.g., amiloride
  • anticholinergics e.g., ipatropium (e.g., as bromide), ti
  • the medicaments may be used in the form of salts, (e.g., as alkali metal or amine salts or as acid addition salts) or as esters (e.g., lower alkyl esters) or as solvates (e.g., hydrates) to optimize the activity and/or stability of the medicament.
  • the medicaments may be used in the form of a pure isomer, for example, R-salbutamol or RR-formoterol.
  • Particular medicaments for administration using pharmaceutical formulations in accordance with the invention include anti-allergies, bronchodilators, beta agonists (e.g., long-acting beta agonists), and antiinflammatory steroids of use in the treatment of respiratory conditions, as defined herein, by inhalation therapy, for example, cromoglicate (e.g. as the sodium salt), salbutamol (e.g. as the free base or the sulphate salt), salmeterol (e.g. as the xinafoate salt), bitolterol, formoterol (e.g. as the fumarate salt), terbutaline (e.g. as the sulphate salt), 3-(4- ⁇ [6-( ⁇ (2R)-2- hydroxy-2-[4-hydroxy-3-
  • cromoglicate e.g. as the sodium salt
  • salbutamol e.g. as the free base or the sulphate salt
  • salmeterol e.g. as the xinafoate
  • hydrochloride salt a beclomethasone ester (e.g. the dipropionate), a fluticasone ester (e.g. the propionate), a mometasone ester (e.g., the furoate), budesonide, dexamethasone, flunisolide, triamcinolone, tripredane, (22R)-
  • a beclomethasone ester e.g. the dipropionate
  • fluticasone ester e.g. the propionate
  • mometasone ester e.g., the furoate
  • budesonide dexamethasone, flunisolide, triamcinolone, tripredane, (22R)-
  • Salmeterol especially salmeterol xinafoate, salbutamol, fluticasone propionate, beclomethasone dipropionate and physiologically acceptable salts and solvates thereof are especially preferred.
  • the formulations according to the invention may, if desired, contain a combination of two or more of any of the above medicaments.
  • formulations containing two active ingredients are known for the treatment and/or prophylaxis of respiratory disorders such as those described herein, for example, formoterol (e.g. as the fumarate) and budesonide, salmeterol (e.g. as the xinafoate salt) and fluticasone (e.g. as the propionate ester), salbutamol (e.g. as free base or sulphate salt) and beclomethasone (as the dipropionate ester) are preferred.
  • a particular combination that may be employed is a combination of a beta agonist (e.g., a long-acting beta agonist) and an antiinflammatory steroid.
  • a beta agonist e.g., a long-acting beta agonist
  • an antiinflammatory steroid e.g., a beta agonist
  • One embodiment encompasses a combination of salmeterol, or a salt thereof (particularly the xinafoate salt) and fluticasone propionate.
  • the ratio of salmeterol to fluticasone propionate in the formulations according to the present invention is preferably within the range 4:1 to 1 :20.
  • the two drugs may be administered in various manners, simultaneously, sequentially, or separately, in the same or different ratios.
  • each metered dose or actuation of the inhaler will typically contain from 25 ⁇ g to 100 ⁇ g of salmeterol and from 25 ⁇ g to 500 ⁇ g of fluticasone propionate.
  • the pharmaceutical formulation may be administered according to various occurrences per day. In one embodiment, the pharmaceutical formulation may be administered twice daily. In one embodiment, the pharmaceutical formulation may be administered once daily.
  • the present invention provides a method for the prophylaxis or treatment of a respiratory disorder in a patient.
  • the present invention provides such a method for the prophylaxis or treatment of disorders associated with reversible airways obstruction such as asthma, chronic obstructive pulmonary disease (COPD), respiratory tract infection or upper respiratory tract disease, and rhinitis (e.g., allergic and non-allergic).
  • COPD chronic obstructive pulmonary disease
  • the method comprises administering an effective amount of a pharmaceutical aerosol formulation from a metered dose inhaler described herein.
  • FIG. 1 illustrates a cross-sectional view of a portion of an aerosol inhaler 10 in accordance with the present invention.
  • the inhaler 10 includes a ferrule 20 attached to a canister 30.
  • the ferrule 20 is crimped to the canister 30 such that the outer surface of the canister and the inner surface of the ferrule are in flush contact with one another at contact area 90.
  • polymeric film 40 is present between ferrule 20 and canister 30 intended to serve as a moisture barrier, and extends throughout the circumference of the canister 30 where indicated.
  • the canister 30 (alternatively referred to as a can or container) may be selected from those that are conventionally used in metered dose inhaler applications.
  • the canister 30 may be fabricated from a number of materials.
  • materials include, without limitation, aluminium, an alloy of aluminium, stainless steel, tin plate, an alloy of copper, glass, or plastic, as well as combinations of the above.
  • Embodiments of containers are described in U.S. Patent No. 6,253,762.
  • Ferrule 20 may contain a valve stem 50 suitable for delivering a pharmaceutical aerosol formulation to a patient.
  • the valve body may be structured to deliver a metered quantity of pharmaceutical aerosol formulation to the patient. Examples of valve bodies are set forth in U.S. Patent Nos. 6,170,717; 6,315,173; and 6,318,603. industry, for example, from
  • the canister 30 contains a polymer coating 70 on the inside walls of the canister.
  • a polymer coating 70 is set forth in U.S. Patent Nos. 6,131 ,566; 6,143,277; 6,149,892; 6,253,762; 6,511 ,652; 6,511 ,653;
  • FIG. 2 illustrates a cross-sectional view of the bottom portion of the inhaler.
  • the present invention is highly advantageous.
  • the invention is capable of allowing an aerosol inhaler to exhibit improved moisture and cascade impaction (Cl) performance.
  • the polymeric seal is used in a fashion such that it does not come into direct contact with the aerosol formulation.
  • the polymer film is advantageously postitioned adjacent the crimped contact area 90 near the lip of the ferrule 20 (as opposed to the body of the ferrule in open communication with the inside of the container). Accordingly, such a feature may be clearly distinguished from a conventional gasket 25 used in an MDI which often contacts the formulation.
  • E Syringe Valspar Latex - Assembled
  • F Syringe - Liquid ethylene propylene diene monomer rubber (EPDM) - Assembled
  • the term “assembled can” refers to the polymeric material which forms the film being applied to the canister after the valve was crimped to the canister to attempt to block the gap between the valve and canister.
  • the term “open can” refers to polymeric material which forms the film being applied to the canister prior to crimping the valve.
  • Control samples refer to commercially available canisters employed in Ventolin® HFA made commercially available by GlaxoSmithkline. Polymer spraying was carried out by Sprimag in Germany. Polymer application by syringe was carried out by Sprimag in Germany. Polymer application by brush was carried out by GlaxoSmithkline in Research Triangle Park, North Carolina. Polymer application via heat shrinking tube was carried out by GlaxoSmithkline in Research Triangle Park, North Carolina. Example 1 Cascade Impaction Results
  • Samples A, B, E, F, I, J, K, C, D, G and H were manufactured and stored for 14 days under dry conditions. The samples were then stored under wet conditions of 25°C and 75% relative humidity until they were tested. These samples were tested for Cascade Impaction performance, as an indication of moisture ingress, in accordance with U.S. Pharmacopeia Monograph 601 , using an 8-stage impactor with induction port similar to that specified as Apparatus #1. The samples were measured at 0, 4 weeks, 8 weeks and 12 weeks. The results are set forth in FIG. 3. As shown, samples F and H exhibited very good performance.
  • Example 2 Moisture Results Samples were manufactured and stored (dry and wet) as in Example
  • Example 3 Cascade Impaction Results Samples shown in Table 1 were prepared, stored, and tested as in
  • Example 1 The samples were measured at 0, 4 weeks, 8 weeks and 12 weeks. Where indicated, a "control" indicates that no polymer film was applied. The results are set forth in FIG. 5. Table 1
  • Example 3 The samples from Example 3 were tested for moisture according to the method of Example 2. The samples were measured at 0, 4 weeks, 8 weeks and 12 weeks. The results are set forth in FIG. 6.
  • Example 2 Samples shown in Table 2 were prepared, stored, and tested as in Example 1 , with some of the polymers applied to the ferrule rather than the canister, as indicated. The samples were measured at 0, 4 weeks, 8 weeks and 12 weeks. The results are set forth in FIG. 7. Where indicated, "Mk12" or “Mk98” indicates the model number of the type valve used in the MDI. As shown, samples of Vaporcoat, EPDM, and Trilene exhibited very good performance.
  • Example 5 The samples from Example 5 were tested for moisture according to the method of Example 2. The samples were measured at 0, 4 weeks, 8 weeks and 12 weeks. The results are set forth in FIG. 8. As shown, samples of Vaporcoat, EPDM, and Trilene exhibited very good performance.

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dispersion Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Anesthesiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur un aérosol-doseur pour administrer une formulation aérosol pharmaceutique, lequel aérosol-doseur comprend une cartouche contenant la formulation aérosol pharmaceutique dans celle-ci ; une virole fixée à ladite cartouche, la virole comprenant un corps de soupape ayant au moins une ouverture dans celui-ci pour permettre à une quantité de la formulation aérosol pharmaceutique de passer de la cartouche à la soupape ; et un film polymère positionné entre la virole et la cartouche, le film polymère étant présent de façon à servir de barrière contre l'humidité par rapport à ladite cartouche.
PCT/US2008/068117 2007-07-03 2008-06-25 Cartouche d'aérosol employant un film polymère ayant des propriétés de barrière à l'humidité améliorées Ceased WO2009006137A1 (fr)

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US94775607P 2007-07-03 2007-07-03
US60/947,756 2007-07-03

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WO2009006137A1 true WO2009006137A1 (fr) 2009-01-08

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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
US9545487B2 (en) 2012-04-13 2017-01-17 Boehringer Ingelheim International Gmbh Dispenser with encoding means
WO2017021038A1 (fr) * 2015-08-04 2017-02-09 Coster Tecnologie Speciali S.P.A. Coupelles de valve et récipients à utiliser dans des systèmes de distribution de milieu fluide
US9682202B2 (en) 2009-05-18 2017-06-20 Boehringer Ingelheim International Gmbh Adapter, inhalation device, and atomizer
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
KR20180037207A (ko) * 2015-08-04 2018-04-11 코스터 테크날러지 스페셜리 에스.피.에이. 유체 매체 분사 시스템에서 사용하기 위한 밸브 컵 및 용기
US9943654B2 (en) 2010-06-24 2018-04-17 Boehringer Ingelheim International Gmbh Nebulizer
CN108025857A (zh) * 2015-08-04 2018-05-11 科斯特专业技术股份公司 用于组装用于分配流体介质的分配系统的方法
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
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
US10195374B2 (en) 2014-05-07 2019-02-05 Boehringer Ingelheim International Gmbh Container, nebulizer and use

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Cited By (25)

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Publication number Priority date Publication date Assignee Title
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
US8495901B2 (en) 2009-03-30 2013-07-30 Boehringer Ingelheim International Gmbh Shaping tool having a rotatable base member
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