EP1957042A2 - Formulation d'aerosol destinee a l'inhalation contenant un agent anticholinergique - Google Patents

Formulation d'aerosol destinee a l'inhalation contenant un agent anticholinergique

Info

Publication number
EP1957042A2
EP1957042A2 EP06819434A EP06819434A EP1957042A2 EP 1957042 A2 EP1957042 A2 EP 1957042A2 EP 06819434 A EP06819434 A EP 06819434A EP 06819434 A EP06819434 A EP 06819434A EP 1957042 A2 EP1957042 A2 EP 1957042A2
Authority
EP
European Patent Office
Prior art keywords
pharmaceutical preparation
acid
aqueous pharmaceutical
preparation according
formula
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.)
Withdrawn
Application number
EP06819434A
Other languages
German (de)
English (en)
Inventor
Friedrich Schmidt
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.)
Boehringer Ingelheim International GmbH
Boehringer Ingelheim Pharma GmbH and Co KG
Original Assignee
Boehringer Ingelheim International GmbH
Boehringer Ingelheim Pharma GmbH and Co KG
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 Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharma GmbH and Co KG filed Critical Boehringer Ingelheim International GmbH
Publication of EP1957042A2 publication Critical patent/EP1957042A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system

Definitions

  • the present invention relates to specific propellant-free, aqueous aerosol formulations comprising one or more anticholinergics of the formula I
  • At least one pharmacologically acceptable, organic acid and optionally further pharmacologically acceptable excipients and / or complexing agents at least one pharmacologically acceptable, organic acid and optionally further pharmacologically acceptable excipients and / or complexing agents
  • Medicament preparation is included.
  • the present invention is concerned with inhalable liquid drug formulations of these compounds, wherein the liquid formulations of the invention must meet high quality standards.
  • the formulations according to the invention can be inhaled orally or pernasally.
  • the application of a liquid, dispensing with propellant gases, formulation by means of suitable inhalers offers.
  • the inhalative administration of such a formulation can be carried out both orally and nasally.
  • Particularly suitable are those inhalers which can nebulise a small amount of a liquid formulation in the therapeutically necessary dosage within a few seconds in a therapeutically inhalable aerosol.
  • nebulizers in which an amount of less than 100 microliters, preferably less than 50 microliters, more preferably less than 20 microliters of active solution, preferably one stroke or two strokes, results in an aerosol with an average particle size of less than 20 microns, preferably less than 10 microns, can be so nebulised that the inhalable fraction of the aerosol already corresponds to the therapeutically effective amount.
  • Such a device for propellant-free administration of a metered quantity of a liquid medicament for inhalation use is described, for example, in International Patent Application WO 91/14468 "Atomizing Device and Methods" and also in WO 97/12687 (there FIGS. 6a and 6b and the associated description). described in detail.
  • a drug solution is transferred by means of high pressure of up to 500 bar in a respirable aerosol and sprayed.
  • the solution formulations are stored in a reservoir.
  • the active compound formulations used have sufficient storage stability and at the same time are such that they can be applied directly for medical purposes as possible without further manipulation. Furthermore, they must not contain components which may interact with the inhaler in such a way that the inhaler or the pharmaceutical quality of the solution or of the aerosol produced could be damaged.
  • a special nozzle is used, as described, for example, WO 94/07607 or WO 99/16530. Both are hereby incorporated by reference.
  • WO 04/022052 A1 likewise describes aqueous propellant-free aerosol formulations for the anticholinergic of the formula 1.
  • the anticholinergic of formula 1_ in combination with at least one organic or inorganic, pharmacologically acceptable acid and optionally with other pharmacologically acceptable excipients and / or complexing agents.
  • the active ingredient formulations according to the invention must also have a sufficient pharmaceutical grade, i. they should be pharmaceutically stable over a shelf life of a few years, preferably at least one year, more preferably two years.
  • propellant-free solution formulations must also be able to be atomized under pressure by means of an inhaler, wherein the mass discharged in the generated aerosol is reproducibly within a defined range.
  • the object of the invention is achieved by an aqueous
  • X ⁇ is an anion, a pharmacologically acceptable, organic acid and other pharmacologically acceptable excipients and / or complexing agents, wherein the cation of formula 1 1
  • anion X is selected from the group consisting of chloride, bromide, iodide, sulfate, phosphate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, Tartrate, oxalate, succinate, benzoate and p-toluenesulfonate.
  • X.sup.- is an anion selected from the group consisting of chloride, bromide, 4-toluenesulfonate and methanesulfonate.
  • Particularly preferred for the purposes of the present invention are those formulations which contain the compound of the formula I in which X.sup.- is bromide.
  • aqueous pharmaceutical preparation for inhalation containing one or more, preferably a compound of formula 1, in which X " bromide is a pharmacologically acceptable, organic acid and other pharmacologically acceptable excipients and / or complexing agents, wherein per 100 ml of pharmaceutical preparation 1010 to 1100 mg of Bromides of the formula 1 are included.
  • references to the compound of formula 1 in the context of the present invention always include all possible amorphous and crystalline Modifications of this connection with. References to the compound of formula 1 in the context of the present invention furthermore include all possible solvates and hydrates which can be formed by this compound.
  • compound 1 is dissolved in water. If necessary, co-solvents can be used. According to the invention, however, a further solvent is not used.
  • the concentration of the compound of the formula 1 based on the proportion of pharmacologically active cation V in the pharmaceutical preparation according to the invention is preferably about 838.44 to 887.76 mg per 100 ml. More preferably, 100 ml of the formulations according to the invention contain about 854.88 to 879.54 mg 1 ', in particular about 869.38 mg 1 ⁇
  • the proportion of .sigma._ of the invention is preferably about 1020 to 1080 mg of pharmaceutical preparation
  • the formulation preferably contains only a single salt of formula 1.
  • the formulation may also contain a mixture of different salts of formula 1.
  • the pH of the formulation according to the invention is preferably in a range from 2.5 to 6.5, preferably in a range from 3.0 to 5.0, more preferably in the range from 3.5 to 4.5, in particular in the range from 2.5 to 6.5 Range 3.6 to 4.4.
  • the pH is adjusted by adding organic, pharmacologically acceptable acids.
  • organic, pharmacologically acceptable acids are selected from the group consisting of ascorbic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid and propionic acid.
  • Preferred organic, pharmacologically acceptable acids are ascorbic acid, fumaric acid and citric acid, citric acid being particularly preferred according to the invention.
  • mixtures of said acids may also be employed, particularly in the case of acids which, in addition to their acidification properties, also possess other properties, e.g. as flavorants or antioxidants, such as citric acid or ascorbic acid.
  • pharmacologically acceptable bases can be used to accurately titrate out the pH.
  • Suitable bases are, for example, alkali metal hydroxides and alkali metal carbonates. Preferred alkali ion is sodium. If such bases are used, care should be taken that the resulting salts, which are then included in the finished drug formulation, are pharmacologically acceptable with the above acid.
  • the formulations according to the invention contain as organic, pharmacologically acceptable acid citric acid in a concentration of 2 to 5 mg per 100 ml solution, in particular in a concentration of 3 mg per 100 ml solution.
  • the formulations according to the invention may contain complexing agents as further constituents.
  • complexing agents are understood to mean molecules capable of complexing. Cations, more preferably metallic cations, are preferably to be complexed by these compounds.
  • the formulations according to the invention contain as complexing agents preferably editic acid (EDTA) or a known salt thereof, for example sodium EDTA or disodium EDTA. Preference is given to using sodium edetate, if appropriate in the form of its hydrates, particularly preferably in the form of its dihydrate.
  • complexing agents are used in the context of the formulations according to the invention, their content is preferably in a range from 5 to 20 mg per 100 ml, more preferably in a range of 7 to 15 mg per 100 ml of the formulation according to the invention.
  • the formulations according to the invention particularly preferably contain a complexing agent, preferably sodium edetate or one of its hydrates, in an amount of about 9 to 12 mg per 100 ml, in particular about 10 mg per 100 ml of the formulation according to the invention.
  • the formulation according to the invention may be added further pharmacologically acceptable excipients.
  • auxiliaries and additives are understood as meaning any pharmacologically acceptable and therapeutically useful substance which is not an active substance but which can be formulated together with the active substance in the pharmacologically suitable solvent in order to improve the qualitative properties of the active ingredient formulation. These substances preferably do not develop any appreciable or at least no undesirable pharmacological effect in the context of the intended therapy.
  • the auxiliaries and additives include e.g. Stabilizers, antioxidants and / or preservatives that extend the useful life of the finished drug formulation as well as flavorings, vitamins and / or other additives known in the art.
  • the additives also include pharmacologically acceptable salts such as sodium chloride.
  • Preferred excipients include antioxidants, such as ascorbic acid, if not already used for pH adjustment, vitamin A 1, vitamin E, tocopherols, and similar vitamins or provitamins found in the human organism.
  • antioxidants such as ascorbic acid, if not already used for pH adjustment, vitamin A 1, vitamin E, tocopherols, and similar vitamins or provitamins found in the human organism.
  • Preservatives may be used to protect the formulation from contamination with pathogenic germs. Suitable preservatives are those known in the art, in particular benzalkonium chloride or benzoic acid or benzoates such as sodium benzoate in the concentration known from the prior art.
  • benzalkonium chloride is added.
  • the amount of benzalkonium chloride is between 1 mg and 50 mg per 100 ml formulation, preferably about 7 to 15 mg per 100 ml, more preferably about 9 to 12 mg per 100 ml of the formulation according to the invention, in particular 10 mg per 100 ml of the formulation according to the invention.
  • Preferred formulations contain, in addition to the solvent water and the compound of formula 1, only benzalkonium chloride, sodium edetate and the acid necessary for adjusting the pH.
  • WO 97/12687 a further developed embodiment of the preferred inhaler is disclosed in WO 97/12687 (see there in particular FIGS. 6a and 6b and the relevant parts of the description).
  • This nebuliser (Respimat ®) can advantageously be used to produce the inhalable aerosols according to the invention. Due to its cylindrical shape and a handy size of less than 9 to 15 cm in length and 2 to 4 cm in width, this device can always be carried by the patient.
  • the nebulizer sprays a defined volume of the drug formulation using high pressures through small nozzles to produce inhalable aerosols.
  • the preferred atomizer of an upper housing part, a pump housing, a nozzle, a locking mechanism, a spring housing, a spring and a reservoir characterized by
  • a pump housing which is fastened in the housing upper part and which carries at its one end a nozzle body with the nozzle or nozzle arrangement, a hollow piston with valve body,
  • a spring housing with the spring located therein, which is rotatably mounted on the upper housing part by means of a rotary bearing,
  • the hollow piston with valve body corresponds to a disclosed in WO 97/12687 devices. It partially protrudes into the cylinder of the pump housing and is arranged axially displaceably in the cylinder.
  • Valve body exerts on its high pressure side at the time of release of the spring a pressure of 5 to 60 MPa (about 50 to 600 bar), preferably 10 to 60 MPa (about 100 to 600 bar) on the fluid, the measured drug solution from.
  • Volumes of from 10 to 50 microliters are preferred, with volumes of from 10 to 20 microliters being particularly preferred, very particularly preferably a volume of from 10 to 15 microliters per actuation (stroke).
  • the valve body is preferably attached to the end of the hollow piston, which faces the nozzle body.
  • the nozzle in the nozzle body is preferably microstructured, i. produced by microtechnology.
  • Microstructured nozzle bodies are disclosed, for example, in WO-99/16530; This document is hereby incorporated by reference, in particular to the figure 1 and its description disclosed therein.
  • the nozzle body consists e.g. of two fixed plates of glass and / or silicon, at least one plate of which has one or more microstructured channels connecting the nozzle inlet side to the nozzle outlet side.
  • At the nozzle outlet side, at least one round or non-round aperture is 2 to 10 microns deep and 5 to 15 microns wide, with the depth preferably being 4.5 to 6.5 microns and the length being 7 to 9 microns.
  • the jet directions of the nozzles in the nozzle body can be parallel to one another or they are inclined towards one another in the direction of the nozzle opening.
  • the jet directions may be inclined at an angle of 20 degrees to 160 degrees to each other, preferably an angle of 60 to 150 degrees, particularly preferably 80 to 100 °.
  • the nozzle orifices are preferably located at a distance of 10 to 200 microns, more preferably at a distance of 10 to 100 microns, more preferably 30 to 70 microns. Most preferred are 50 microns.
  • the liquid pharmaceutical preparation meets as already mentioned with an inlet pressure of up to 600 bar, preferably 200 to 300 bar to the nozzle body and is atomized via the nozzle openings in an inhalable aerosol.
  • the preferred particle sizes of the aerosol are up to 20 microns, preferably 3 to 10 microns.
  • the locking mechanism includes a spring, preferably a cylindrical helical compression spring, as a memory for the mechanical energy.
  • the spring acts on the output flange as a jump piece whose movement is determined by the position of a locking member.
  • the path of the output flange is precisely limited by an upper and a lower stop.
  • the spring is preferably transmitted via a force translating gear, e.g. a fferschubgetriebe, stretched by an external torque that is generated when turning the upper housing part against the spring housing in the lower housing part.
  • the upper housing part and the output flange contain a single or multi-start wedge gear.
  • the locking member with engaging locking surfaces is arranged annularly around the output flange.
  • the ring is arranged in a plane perpendicular to the atomizer axis. After tensioning the spring, the push
  • the Sprerrglied is triggered by a button.
  • the release button is connected or coupled to the locking member.
  • the shutter button is parallel to the ring plane, and preferably in the atomizer, moved; while the deformable ring is deformed in the ring plane. Constructive details of the locking mechanism are described in WO 97/20590.
  • the lower housing part is pushed in the axial direction over the spring housing and covers the storage, the drive of the spindle and the reservoir for the fluid.
  • the upper housing part When actuating the atomizer, the upper housing part is rotated against the lower housing part, wherein the lower housing part entrains the spring housing.
  • the spring is compressed and tensioned via the screw slide, and the lock engages automatically.
  • the angle of rotation is preferably an integer fraction of 360 degrees, for example 180 degrees.
  • the driven part Simultaneously with the tensioning of the spring, the driven part is displaced in the upper housing part by a predetermined distance, the hollow piston is within the cylinder in the pump housing withdrawn, whereby a subset of the fluid from the reservoir is sucked into the high-pressure chamber in front of the nozzle.
  • the storage container contains the aqueous aerosol preparation according to the invention.
  • the sputtering process is initiated by lightly pressing the shutter button.
  • the blocking mechanism clears the way for the stripping section.
  • the tensioned spring pushes the piston into the cylinder of the pump housing.
  • the fluid exits the nozzle of the atomizer in atomized form.
  • the components of the atomizer are made of a functionally suitable material.
  • the housing of the atomizer and, as far as the function permits, other parts are preferably made of plastic, e.g. by injection molding. Physiologically harmless materials are used for medical purposes.
  • FIGS. 6 a / b of WO 97/12687 describe the nebuliser (Respimat®) with which the aqueous aerosol preparations according to the invention can advantageously be inhaled.
  • FIG. 6 a shows a longitudinal section through the atomizer with the spring tensioned
  • FIG. 6 b shows a longitudinal section through the atomizer with the spring relaxed.
  • the upper housing part (51) contains the pump housing (52), at the end of which the holder (53) for the atomizer nozzle is mounted. In the holder is the nozzle body (54) and a filter (55).
  • the hollow piston (57) fastened in the output flange (56) of the locking mechanism projects partially into the cylinder of the pump housing. At its end, the hollow piston carries the valve body (58).
  • the hollow piston is sealed by means of the seal (59).
  • the stop (60) on which the output flange rests with a relaxed spring.
  • the stop (61) On which the output flange rests when the spring is tensioned.
  • the locking member (62) slides between the stop (61) and a support (63) in the upper housing part.
  • the release button (64) is connected to the locking member in connection.
  • the G ⁇ phase top ends in the mouthpiece (65) and is closed with the attachable cap (66).
  • the spring housing (67) with compression spring (68) is rotatably supported by means of the snap lugs (69) and pivot bearing on the upper housing part.
  • the lower housing part (70) is pushed.
  • the replaceable reservoir (71) for the fluid (72) to be atomized Within the spring housing is the replaceable reservoir (71) for the fluid (72) to be atomized.
  • the reservoir is closed with the stopper (73) through which the hollow piston protrudes into the reservoir and with its end immersed in the fluid (stock of drug solution).
  • the spindle (74) for the mechanical counter is mounted in the lateral surface of the spring housing.
  • the Antriebs ⁇ tzel (75) At the end of the spindle, which faces the upper housing part, is the Antriebs ⁇ tzel (75). The rider (76) sits on the spindle.
  • the nebulizer described above is suitable for nebulizing the aerosol preparations according to the invention to form an aerosol suitable for inhalation.
  • the mass expelled in at least 97%, preferably at least 98% of all actuations of the inhaler (puffs) a defined quantity with a tolerance of not more than 25%, preferably from 20 % of this amount.
  • a defined quantity with a tolerance of not more than 25%, preferably from 20 % of this amount.
  • between 5 and 30 mg of formulation per stroke are applied as a defined mass, more preferably between 5 and 20 mg.
  • the formulation according to the invention can also be nebulized by means of inhalers other than those described above, for example jet stream inhalers.
  • the present invention further relates to an inhalation kit consisting of one of the above-described pharmaceutical preparations according to the invention and an inhaler suitable for fogging this pharmaceutical preparation.
  • the present invention preferably relates to an inhalation kit consisting of one of the pharmaceutical preparations according to the invention the inhaler described above and the Respimat ® described above.
  • 100 ml of a particularly preferred pharmaceutical preparation contains in purified water or in water for injections with a density of 1, 00 g / cm 3 at a temperature of 15 ° C to 31 0 C the following ingredients:
  • a dose to be administered comprises two actuations of the inhaler, i. two strokes. Consequently, in the case of the abovementioned particularly preferred pharmaceutical preparations, a total of about 192.88 to 204.23 ⁇ g, in particular 200 ⁇ g, of the compound of formula 1 are administered per patient dose.
  • the solutions are preferably in 4.5 ml cartridges in Respimat

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Dispersion Chemistry (AREA)
  • Otolaryngology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des formulations d'aérosol aqueuses spécifiques, exemptes de gaz propulseur, contenant un ou plusieurs agents anticholinergiques, représentées par la formule (1) dans laquelle X- est un anion, au moins un acide organique pharmaceutiquement compatible, et éventuellement d'autres agents auxiliaires et/ou complexants pharmaceutiquement compatibles, le cation de la formule (1') étant présent dans la préparation à une concentration de 830,22 à 904,2 mg pour 100 ml de préparation pharmaceutique.
EP06819434A 2005-11-24 2006-11-13 Formulation d'aerosol destinee a l'inhalation contenant un agent anticholinergique Withdrawn EP1957042A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102005055957A DE102005055957A1 (de) 2005-11-24 2005-11-24 Aerosolformulierung für die Inhalation enthaltend ein Anticholinergikum
PCT/EP2006/068395 WO2007060104A2 (fr) 2005-11-24 2006-11-13 Formulation d'aerosol destinee a l'inhalation contenant un agent anticholinergique

Publications (1)

Publication Number Publication Date
EP1957042A2 true EP1957042A2 (fr) 2008-08-20

Family

ID=37888061

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06819434A Withdrawn EP1957042A2 (fr) 2005-11-24 2006-11-13 Formulation d'aerosol destinee a l'inhalation contenant un agent anticholinergique

Country Status (6)

Country Link
US (1) US20090170839A1 (fr)
EP (1) EP1957042A2 (fr)
JP (1) JP2010509182A (fr)
CA (1) CA2629070A1 (fr)
DE (1) DE102005055957A1 (fr)
WO (1) WO2007060104A2 (fr)

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DE102005055961A1 (de) * 2005-11-24 2007-05-31 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosolformulierung für die Inhalation enthaltend ein Anticholinergikum
DE102005055963A1 (de) * 2005-11-24 2007-07-19 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosolformulierung für die Inhalation enthaltend ein Anticholinergikum
EP2077132A1 (fr) 2008-01-02 2009-07-08 Boehringer Ingelheim Pharma GmbH & Co. KG Dispositif distributeur, dispositif de stockage et procédé pour la distribution d'une formulation
US10011906B2 (en) 2009-03-31 2018-07-03 Beohringer Ingelheim International Gmbh Method for coating a surface of a component
EP3508239B1 (fr) 2009-05-18 2020-12-23 Boehringer Ingelheim International GmbH Adaptateur, dispositif d'inhalation et pulvérisateur
WO2011064163A1 (fr) 2009-11-25 2011-06-03 Boehringer Ingelheim International Gmbh Nébuliseur
UA107097C2 (en) 2009-11-25 2014-11-25 Бьорінгер Інгельхайм Інтернаціональ Гмбх Dispenser
US10016568B2 (en) 2009-11-25 2018-07-10 Boehringer Ingelheim International Gmbh Nebulizer
JP5874724B2 (ja) 2010-06-24 2016-03-02 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ネブライザ
EP2694220B1 (fr) 2011-04-01 2020-05-06 Boehringer Ingelheim International GmbH Appareil médical pourvu d'un récipient
US9827384B2 (en) 2011-05-23 2017-11-28 Boehringer Ingelheim International Gmbh Nebulizer
WO2013152894A1 (fr) 2012-04-13 2013-10-17 Boehringer Ingelheim International Gmbh Pulvérisateur comprenant des moyens de détrompage
EP3030298B1 (fr) 2013-08-09 2017-10-11 Boehringer Ingelheim International GmbH Nébuliseur
ES2836977T3 (es) 2013-08-09 2021-06-28 Boehringer Ingelheim Int Nebulizador
UA121114C2 (uk) 2014-05-07 2020-04-10 Бьорінгер Інгельхайм Інтернаціональ Гмбх Небулайзер, індикаторний пристрій і контейнер
ES2874029T3 (es) 2014-05-07 2021-11-04 Boehringer Ingelheim Int Nebulizador
ES2954961T3 (es) 2014-05-07 2023-11-27 Boehringer Ingelheim Int Unidad, nebulizador y método

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DE10050994A1 (de) * 2000-10-14 2002-04-18 Boehringer Ingelheim Pharma Neue als Arneimittel einsetzbare Anticholinergika sowie Verfahren zu deren Herstellung
NZ536337A (en) * 2002-04-12 2007-05-31 Boehringer Ingelheim Pharma Medicaments containing betamimetic drugs and a novel anticholinesterase drug
US20040166065A1 (en) * 2002-08-14 2004-08-26 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosol formulation for inhalation comprising an anticholinergic
CN1674887A (zh) * 2002-08-14 2005-09-28 贝林格尔英格海姆法玛两合公司 含抗胆碱能剂的吸入用的气雾剂制剂
DE10345065A1 (de) * 2003-09-26 2005-04-14 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosolformulierung für die Inhalation enthaltend ein Anticholinergikum
DE102005055960A1 (de) * 2005-11-24 2007-07-19 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosolformulierung für die Inhalation enthaltend ein Anticholinergikum
DE102005055961A1 (de) * 2005-11-24 2007-05-31 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosolformulierung für die Inhalation enthaltend ein Anticholinergikum
DE102005055963A1 (de) * 2005-11-24 2007-07-19 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosolformulierung für die Inhalation enthaltend ein Anticholinergikum

Non-Patent Citations (1)

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Also Published As

Publication number Publication date
JP2010509182A (ja) 2010-03-25
US20090170839A1 (en) 2009-07-02
CA2629070A1 (fr) 2007-05-31
WO2007060104A2 (fr) 2007-05-31
DE102005055957A1 (de) 2007-07-12
WO2007060104A3 (fr) 2007-08-16

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