WO2007141201A1

WO2007141201A1 - Adapter with an attachment for an atomizer

Info

Publication number: WO2007141201A1
Application number: PCT/EP2007/055381
Authority: WO
Inventors: Michael Markert; Michael Pieper; Hans Schmitt; Jürgen Schraivogel; Thomas Trautmann
Original assignee: Boehringer Ingelheim International Gmbh; Boehringer Ingelheim Pharma Gmbh & Co. Kg
Priority date: 2006-06-02
Filing date: 2007-06-01
Publication date: 2007-12-13
Also published as: EP2023990A1; CA2653183A1; DE102006025884A1; JP2009538655A

Abstract

An adapter comprises an attachment (20) for an atomizer (1) for a fluid (2), in particular one containing a pharamaceutical, as aerosol through an atomizer nozzle (12), wherein the attachment (20) is coupled via a bore (23) to an outlet (22) towards the patient, and an inlet (25) on which a respiratory air tube is to be secured and which is connected to the bore (23) in terms of flow technology in such a way that the main direction of atomization of the fluid (2) is oriented parallel to the direction of flow of a respiratory gas, wherein an opening (27) extending parallel to the bore (23) in the direction of the atomizer (1) is let into a passage (24) assigned to the inlet (25). The opening (27) extends into an area facing towards the atomizer (1) and behind the atomizer nozzle (12).

Description

Adapter with a connector for a nebulizer

description

The invention relates to an adapter with a connection for a nebulizer for, in particular a drug exhibiting fluid as aerosol through a nebulizer nozzle, wherein the port is gekopplet via a bore with a patient-side outlet, and connected to a fluidically connected to the bore Entrance for a breathing air hose to be fastened thereto, that the main atomizing direction of the fluid is aligned parallel to the flow direction of a breathing gas, wherein in an opening associated with the inlet opening parallel to the bore in the direction of the atomizer is inserted.

Ventilators are used to supply a patient with a breathing gas via at least one gas-carrying hose line. For example, in a ventilated patient with an inflammatory lung disease, such. As asthma or COPD ("chronic obstructive pulmonary disease"), there is a need to distribute a drug over the inhalative route. In these patients, topical treatment in the lungs is often beneficial to reduce systemic side effects of the drugs. However, there may also be the need or a therapeutic option to bring a drug to the systemic effect via the inhalative route in a ventilated patient.

WO 02/089887 A1 discloses a T-shaped adapter for releasably securing a nebulizer in a breathing circuit, the adapter having a housing with an upper one

Section having a first passage therein and a lower portion having a second passage adjacent to the first passage. Between the first passage and an inner wall surface of the upper portion is a spring chamber with a spring, and a valve seat is formed at an upper edge of the upper portion. The reciprocable valve includes a valve actuator slidably received in the second passage and including a top surface for biasing the spring and a valve member secured to the valve actuator. Furthermore, WO 2004/098689 discloses a nebuliser connection device for connecting a nebuliser to a respiratory air hose of a ventilator, which device comprises a respiratory air supply device with a first connection device for connecting a respiratory air line leading to a respiratory air A second connection device 5 is for connection of a respiratory air line A closure device is provided on the distal connection device, through which a flow path for an aerosol generated by the nebulizer can be closed when connecting the nebulizer. A closure element is opened when the nebuliser is connected and at 0 Removal closed The nebulizer connection device is disadvantageous insofar as the aerosol generated by the nebulizer flows into the respiratory gas in a direction perpendicular to the flow direction of the respiratory gas leading hose line is introduced, wherein a significant impaction and thus a separation of the dissolved in the aerosol 5 active substance in the tubing, resulting in a deficiency of the patient with the active substance is given by the entry angle of the aerosol into the tube leading the breathing gas

Furthermore, the Journal of Pharmacological and Toxicological Methods 50 (2004) 109-119, ELSEVIER, shows an adapter with a connector for a nebuliser, which is opposite to a patient-side outlet, with an inlet for the breathing tube to be connected thereto common opening with the connection and the outlet and such a flow channel is formed, that the Hauptzerstaubungsπch- tion of a drug in parallel to Stromungsπchtung a breathing gas ausgeπchtet This publication, however, are no further details for the design of the shock duct 5 and the internal structure of the adapter refer to

Finally, EP 0 521 061 B1 discloses a dosing device for dispensing a measured amount of a liquid as a spray with droplets of a size suitable for inhalation into the lungs by dispensing the measured amount of liquid through a atomizing means having a chamber for receiving the measured Amount of the liquid, an energy store and means for delivering a predetermined amount of energy to the energy storage device In addition, means for releasing the predetermined amount of energy from the energy store are provided on the chamber, so as sensitive liquid to a predetermined pressure rise from a low pressure to a higher pressure and initiate a discharge of the liquid from the chamber. A nebulizer is used to nebulize the metered amount of the pressurized fluid.

The compounds mentioned below can be used alone or in combination for use in the device according to the invention. In the compounds listed below W is a pharmacologically active agent and (for example) selected from the group consisting of betamimetics, anticholinergics, corticosteroids, PDE4 inhibitors, LTD4 antagonists, EGFR inhibitors, dopamine agonists, HI antihistamines, PAF- Antagonists and PI3 kinase inhibitors. Furthermore, two- or three-fold combinations of W can be combined and used for application in the device according to the invention. Exemplary combinations of W would be:

W represents a betamimetics combined with an anticholinergic, corticosteroids, PDE4 inhibitors, EGFR inhibitors or LTD4 antagonists,

W represents an anticholinergic agent combined with a betamimetics, corticosteroids, PDE4 inhibitors, EGFR inhibitors or LTD4 antagonists, W represents a corticosteroid combined with a PDE4 inhibitor, EGFR inhibitors or LTD4 antagonists - W represents a PDE4 Inhibitors combined with an EGFR inhibitor or LTD4 antagonist W represents an EGFR inhibitor combined with a LTD4 antagonist.

Preferred betamimetics for this purpose are compounds selected from the group consisting of albuterol, arformoterol, bambuterol, bitolertrol, broxaterol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, isoetharine, isoprenaline, levosalbutamol, mabuterol , Meluadrine, Metaproterenol, Orciprenaline, Pirbuterol, Procaterol, Reproterol, Rimiterol, Ritodrine, Salmefamol, Salmetrol, Soterenol, Sulphone terol, Terbutaline, Tiaramide, Tolubuterol, Zinterol, CHF-1035, HOKU-81, KUL-1248 and

3- (4- {6- [2-Hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethyl-amino] -hexyloxy} -butyl) -benzyl-sulfonamide - 5- [2- (5,6- diethyl-indan-2-ylamino) -l-hydroxy-ethyl] -8-hydroxy-lH-quinolin-2-one 4-Hydroxy-7- [2- {[2- {[3- (2-phenylethoxy) propyl] sulphonyl} ethyl] amino} ethyl] -2 (3H) -benzothiazolone 1- (2-fluoro-4-) hydroxyphenyl) -2- [4- (1-benzimidazolyl) -2-methyl-2-butylamino] ethanol 1- [3- (4-methoxybenzylamino) -4-hydroxyphenyl] -2- [4- (1-benzimidazolyl ) -2-methyl-2-butylamino] ethanol 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-N, N-dimethylaminophenyl ) - 2-methyl-2-propylamino] ethanol 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-methoxyphenyl) -2- Methyl 2-propylaminoethanol - 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-n-butyloxyphenyl) -2-methyl-2 propylamino] ethanol

- 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- {4- [3- (4-methoxyphenyl) -l, 2,4-triazole-3 -yl] -2-methyl-2-butylamino Jethanoi 5-Hydroxy-8- (1-hydroxy-2-isopropylaminobutyl) -2H-1,4-benzoxazine-3- (4H) -one - 1- (4-amino -3-chloro-5-trifluoromethylphenyl) -2-tert.-butylamino) ethanol

- 6-hydroxy-8- {1-hydroxy-2- [2- (4-methoxyphenyl) -1,1-dimethylethylamino] ethyl} -4H-benzo [1,4] oxazin-3-one

6-Hydroxy-8- {1-hydroxy-2- [2- (4-phenoxy-acetic acid ethyl ester) -1,1-dimethyl-ethylamino] -ethyl} -4 H -benzo [1,4] oxazin-3-one 6-hydroxy-8- {1-hydroxy-2- [2- (4-phenoxyacetic acid) -l, 1-dimethyl-ethylamino] ethyl} -4H-benzo [1,4] oxazin-3-one

- 8- {2- [l, l-dimethyl-2- (2,4,6-trimethylphenyl) ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazine-3 -one

6-Hydroxy-8- {1-hydroxy-2- [2- (4-hydroxyphenyl) -1,1-dimethylethylamino] ethyl} -4H-benzo [1,4] oxazin-3-one

6-Hydroxy-8- {1-hydroxy-2- [2- (4-isopropyl-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4-oxazin-3-one

- 8- {2- [2- (4-ethylphenyl) -1,1-dimethylethylamino] -1-hydroxyethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one - 8- {2- [2- (4-Ethoxy-phenyl) -l, l-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one

, 4- (4- {2- [2-Hydroxy-2- (6-hydroxy-3-oxo-3,4-dihydro-2H-benzo [l, 4] oxazin-8-yl) - ethyl 1 amino] 2-methyl-propyl} -phenoxy) -butyric acid 8- {2- [2- (3,4-difluoro-phenyl) -l, l-dimethyl-ethylammo] -l-hydroxy-ethyl} -6-hydroxy-

4H-benzo [1,4] oxazin-3-one 1- (4-ethoxycarbonylamino-3-cyano-5-fluorophenyl) -2- (tert -butylamino) ethanol

2-Hydroxy-5- (1-hydroxy-2- {2- [4- (2-hydroxy-2-phenyl-ethylamino) -phenyl] -ethylamino} -ethyl) -benzaldehyde

N- [2-Hydroxy-5- (1-hydroxy-2- {2- [4- (2-hydroxy-2-phenyl-ethylamino) -phenyl] -ethylamino} -ethyl) -phenyl] -formamide

8-Hydroxy-5- (1-hydroxy-2- {2- [4- (6-methoxy-biphenyl-3-ylamino) -phenyl] -ethylamino} -ethyl) -LH-quin-2-one - 8- hydroxy-5- [l-hydroxy-2- (6-phenethylamino-hexylamino) -ethyl] -lH-qumohn-2-one

5- [2- (2- {4- [4- (2-amino-2-methyl-propoxy) -phenyl-amino] -phenyl} -ethyl-amino) -l-hydroxy-ethyl] -8-hydroxy-1H-quinone 2-one

[3- (4- {6- [2-Hydroxy-2- (4-hydroxy-3-hydroxymethylphenyl) -ethylamino] -hexyloxy} -butyl) -5-methylphenyl] -urea 4- (2 - {6- [2- (2,6-dichloro-benzyloxy) -ethoxy] -hexylammo} -l-hydroxy-ethyl) -2-hydroxymethyl-phenol

3- (4- {6- [2-Hydroxy-2- (4-hydroxy-3-hydroxymethylphenyl) -ethylamino] -hexyloxy} -butyl) -benzylsulfonamide

3- (3- {7- [2-Hydroxy-2- (4-hydroxy-3-hydroxymethylphenyl) -ethylamino] -heptyloxy} -propyl) -benzylsulfonamide

4- (2- {6- [4- (3-Cyclopentanesulfonyl-phenyl) -butoxy] -hexylamino} -l-hydroxy-ethyl) -2-hydroxymethyl-phenol-N-adamantan-2-yl-2- (3 - {2- [2-hydroxy-2- (4-hydroxy-3-hydroxymethylphenyl) ethylamino] -propyl} -phenyl) -acetamide

optionally in the form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates. According to the invention, the acid addition salts of the betamimetics are preferably selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate,

Hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate Preferred anticholinergic compounds here are compounds which are selected from the group consisting of tiotropium salts, preferably the bromide salt, oxitropium salts, preferably the bromide salt, flutropium salts, preferably the bromide salt, ipratropium salts, preferably the bromide salt, glycopyrronium salts, preferably the bromide salt Trospium salts, preferably the chloride salt, tolterodine. In the salts mentioned above, the cations are the pharmacologically active ingredients. As anions, the abovementioned salts may preferably contain chloride, bromide, iodine, sulfate, phosphate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate , Succinate, benzoate or p-toluenesulfonate, with chloride, bromide, iodide, sulfate, methanesulfonate or p-toluenesulfonate being preferred as counterions. Of all the salts, the chlorides, bromides, iodides and methanesulfonates are particularly preferred.

Likewise preferred anticholinergics are selected from the salts of the formula AC-I

where X ^"is a singly negatively charged anion, preferably an anion selected from the group consisting of fluoride, chloride, bromide, iodide, sulfate, phosphate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-Toluenesulfonate, preferably a singly negatively charged anion, more preferably an anion selected from the group consisting of fluoride, chloride, bromide, methanesulfonate and p-toluenesulfonate, most preferably bromide, optionally in the form of their racemates, enantiomers or hydrates Significance are those drug combinations that the enantiomers of the formula AC-l-en

contain, wherein X ^{~ can have} the meanings given above. Further preferred anticholinergics are selected from the salts of the formula AC-2

wherein R is either methyl or ethyl and where X ^{~ may have} the meanings given above. In an alternative embodiment, the compound of the formula AC-2 may also be present in the form of the free base AC-2-base.

Other compounds mentioned are: 2,2-diphenylpropionic acid tropol ester methobromide 2,2-diphenylpropionic acid copoprene methobromide 2-fluoro-2,2-diphenylacetic acid copoprene methobromide 2-fluoro-2,2-diphenylacetic acid-tropol ester methobromide 3,3 ', 4,4 Tetrafluorobenzylic acid tropol ester methobromide - 3,3 ', 4,4'-tetrafluorobenzilatecopine ester methobromide 4,4'-Difluorobenzilsauretropenol ester methobromide 4,4'-Difluorobenzilic acid copopriester methobromide 3,3'-Difluorobenzylauretropenol ester methobromide 3,3'-Difluorobenzilate copoprene methobromide - 9-hydroxy-fluorene-9-carboxylic acid-tropol ester-methobromide 9-fluoro-fluorene 9-Carboxylic acid tropol ester methobromide 9-Hydroxy-fluorene-9-carboxylic acid copoprene methobromide

9-fluoro-fluorene-9-carboxylic acid copoprene methobromide

9-Methyl-fluorene-9-carboxylic acid-tropol ester-methobromide - 9-methyl-fluorene-9-carboxylic acid copoprene methobromide

Benzylacourcyclopropyltropine ester methobromide 2,2-Diphenylpropionic acid cyclopropyltropine ester methobromide 9-Hydroxy-xanthene-9-carboxylic acid cyclopropyltropine ester methobromide 9-Methyl-fluorene-9-carboxylic acid cyclopropyltropine ester methobromide - 9-methyl-xanthene-9-carboxylic acid cyclopropyltropine ester methobromide 9-hydroxyfluorene 9-carbonsaurecyclopropyltropinester methobromide

4,4'-Difluorobenzilate methylcyclopropyltropine ester methobromide 9-hydroxy-xanthene-9-carboxylic acid sterol ester-methobromide 9-hydroxy-xanthene-9-carboxylic acid copoproester-methobromide - 9-methyl-xanthene-9-carboxylic acid-tropol ester-methobromide

9-methyl-xanthene-9-carboxylic acid copoprene-methobromide 9-ethyl-xanthene-9-carboxylic acid-tropol ester-methobromide

9-Difluoromethyl-xanthene-9-carbonsauretropenol ester-methobromide 9-hydroxymethyl-xanthene-9-carboxylic acid-co-ester methobromide The abovementioned compounds can also be used in the context of the present invention as salts in which instead of the methobromide, the salts Metho-X Apply application, wherein X may have the meanings given above for X.

Preferred corticosteroids here are compounds selected from the group consisting of beclomethasone, betamethasone, budesonide, butixocort, ciclesonide, deflazacort, dexamethasone, etiprednol, flunisolide, fluticasone, loteprednol, mometasone, prednisolone, prednisone, rofleponide, triamcinolone , RPR-106541, NS-126, ST-26 and

6,9-Difluoro-17 - [(2-furanylcarbonyl) oxy] -1-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carbothionic acid (S) -fluoromethyl ester

6,9-Difluoro-1-hydroxy-16-methyl-3-oxo-17-propionyloxy-androsta-1,4-diene-17-carbothionic acid (S) - (2-oxo-tetrahydrofuran-3S-yl ) ester,

- 6α, 9α-difluoro-l lß-hydroxy-16α-methyl-3-oxo-17α- (2,2,3,3-tertamethylcyclopropylcarbony ^ oxy-androsta-l ^ -diene-πß-carboxylic acid cyanomethyl ester optionally in the form of their racemates, enantiomers or diastereomers and optionally in the form of their salts and derivatives, their solvates and / or hydrates Any reference to steroids includes reference to their optionally existing salts or derivatives, hydrates or solvates Examples of possible salts and derivatives The steroids may be: alkali metal salts, for example sodium or potassium salts, sulfobenzoates, phosphates, isonicotinates, acetates, dichloroacetates, propionates, dihydrogen phosphates, palmitates, pivalates or even furoates.

Preferred PDE4 inhibitors here are compounds selected from the group consisting of enprofylline, theophylline, roflumilast, A-riflo (cilomilast), tofimilast, pumafentrin, lirimilast, arofylline, atizoram, D-4418, bay 198004, BY343, CP-325,366, D-4396 (Sch-351591), AWD-12-281 (GW-842470), NCS-613, CDP-840, D-4418, PD-168787, T-440, T-2585, V-11294A, Cl-1018, CDC-801, CDC-3052, D-22888, YM-58997, Z-15370 and

N- (3,5-dichloro-1-oxo-pyridin-4-yl) -4-difluoromethoxy-3-cyclopropylmethoxybenzamide - (-) p - [(4αR *, 106S *) - 9-ethoxy-1, 2, 3,4,4a, 10b-hexahydro-8-methoxy-2-methylbenzo [s] [l, 6] naphthyridin-6-yl] -N, N-diisopropylbenzamide

(R) - (+) - l- (4-bromobenzyl) -4 - [(3-cyclopentyloxy) -4-methoxyphenyl] -2-pyrrolidone

3- (cyclopentyloxy-4-methoxyphenyl) -1- (4-N '- [N-2-cyano-S-methylisothioureido] benzyl) -2-pyrrolidone - cis [4-cyano-4- (3 cyclopentyloxy-4-methoxyphenyl) cyclohexane-1-carboxylic acid] 2-carbomethoxy-4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan-1-one

cis [4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan-1-ol] (R) - (+) - Ethyl [4- (3-cyclopentyloxy-4-methoxyphenyl) pyrrolidin-2-ylidene] acetate (S) - (-) - Ethyl [4- (3-cyclopentyloxy-4-methoxyphenyl) pyrrolidine -2-ylidene] acetate

9-cyclopentyl-5,6-dihydro-7-ethyl-3- (2-thienyl) -9H-pyrazolo [3,4-c] -1,4,4-triazolo [4,3-a] pyridine 9-Cyclopentyl-5,6-dihydro-7-ethyl-3- (tert-butyl) -9H-pyrazolo [3,4-c] -1,4,4-triazolo [4,3-a] pyridine optionally in Form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates. According to the invention, the acid addition salts of the PDE4 inhibitors are preferably selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.

Preferred LTD4 antagonists here are compounds selected from the group consisting of montelukast, pranlukast, zafirlukast, MCC-847 (ZD-3523), MN-001, MEN-91507 (LM-1507), VUF-5078 , VUF-K-8707, L-733321 and - l - (((R) - (3- (2- (6,7-Difluoro-2-quinolinyl) ethenyl) phenyl) -3- (2- (2- hydroxy-2-propyl) phenyl) thio) methylcyclopropane-acetic acid,

- l - (((l (R) -3 (3- (2- (2,3-dichlorothieno [3,2-b] pyridin-5-yl) - (E) -ethenyl) phenyl) -3- ( 2- (1-hydroxy-1-methylethyl) phenyl) propyl) thio) methyl) cyclopropaneacetic acid [2 - [[2- (4-tert-butyl-2-thiazolyl) -5-benzofuranyl] oxymethyl] phenyl] acetic acid optionally in Form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates. According to the invention, these acid addition salts are selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate. Examples of salts or derivatives which the LTD4 antagonists are able to form are understood as meaning: alkali metal salts, such as, for example, sodium or potassium salts, alkaline earth salts, sulfobenzoates, phosphates, isonicotinates, acetates, propionates. nate, dihydrogen phosphates, palmitates, pivalates or even furoates.

Preferred EGFR inhibitors are compounds selected from the group consisting of cetuximab, trastuzumab, ABX-EGF, Mab ICR-62 and

4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {[4- (4-chloro-4-yl) -l-oxo-2-buten-1-yl] -amino} -7-cyclopropyl-methoxy-quinazoline

4 - [(3-Chloro-4-fluorophenyl) amino] -6- {[4- (N, N-diethylamino) -l-oxo-2-buten-1-yl] -amino J-7-cyclopropylmethoxy-quinazoline

4- [(3-chloro-4-fluorophenyl) amino] -6- {[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7-cyclopropyl] methoxy -quinazoline

- 4 - [(R) - (1-Phenylethyl) amino] -6- {[4- (morpholin-4-yl) -1-oxo-2-buten-1-yl] amino} -7-cyclopentyloxy quinazoline - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {[4 - ((R) -6-methyl-2-oxo-4-methyl-4-yl) -oxo] 2-buten-l-yl] amino} -7-cyclopropylmethoxy-quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {[4 - ((R) -6-methyl-2-oxo-morpholin-4-yl) -l-oxo-2-ol] buten-l-yl] amino} -7 - [(S) - (tetrahydrofuran-3-yl) oxy] -quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {[4 - ((R) -2-methoxymethyl-6-oxo-4-fluoro-4-yl-1-oxo] -butene ly ^ ^ aminoJ -cyclopropylmethoxy-quinazoline

4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2 - ((S) -6-methyl-2-oxo-4-methyl-4-yl) -ethoxy] -7-methoxy-quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - ({4- [N- (2-methoxyethyl) -N-methyl-amino] -l-oxo-2-butene-1 - yl} amino) -7-cyclopropylmethoxyquinazoline - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {[4- (N, N-dimethylamino) -l-oxo-2-butene-1-one yl] amino} ^ -cyclopentyloxy-quinazoline

- 4 - [(R) - (1-phenyl-ethyl) -amino] -6- {[4- (N, N-bis (2-methoxy-ethyl) -amino] -l-oxo-2-butene l-yllaminoj ^ -cyclopropylmethoxy-quinazoline

- 4 - [(R) - (1-Phenyl-ethyl) -amino] -6 - ({4- [N- (2-methoxyethyl) -N-ethyl-amino] -l-oxo-2-butene 1 -y 1} amino) -7-cyclopropylmethoxy-quinazoline

- 4 - [(R) - (1-Phenyl-ethyl) -amino] -6 - ({4- [N- (2-methoxyethyl) -N-methyl-amino] -l-oxo-2-butene 1 -y 1} amino) -7-cyclopropylmethoxy-quinazoline - 4 - [(R) - (1-phenylethyl) amino] -6 - ({4- [N- (tetrahydropyran-4-yl) -N-methylamino] -l-oxo-2-butene l-yl} amino) -7-cyclopropylmethoxy-quinazoline 4 - [(3-chloro-4-fluoro-1-yl) -amino] -6- {[4- (N, N-dimethylamino) -l-oxo-2-butene -l-yl] amino} -7 - ((R) -tetrahydrofuran-3-yloxy) quinazoline - 4 - [(3-chloro-4-fluorophenyl) amino] -6- {[4- (N, N- dimethylamino) -1-oxo-2-buten-1-yl] amino} -7 - ((S) -tetrahydrofuran-3-yloxy) quinazoline

- 4 - [(3-chloro-4-fluorophenyl) amino] -6 - ({4- [N- (2-methoxyethyl) -N-methyl-amino] -l-oxo-2-butene-1 - yl} amino) -7-cyclopentyloxy-quinazoline 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {[4- (N-cyclopropyl-N-methylamino) -l-oxo-2-butene -l ^ yljaminoj -cyclopentyloxy-quinazoline

- 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- {[4- (N, N-dimethylamino) -l-oxo-2-buten-1-yl] -amino} -7 - [(R ) - (tetrahydrofuran-2-yl) methoxy] quinazoline 4 - [(3-chloro-4-fluorophenyl) amino] -6- {[4- (N, N-dimethylamino) -l-oxo-2-butene] 1-yl] amino} -7 - [(S) - (tetrahydrofuran-2-yl) methoxy] quinazoline - 4 - [(3-ethynylphenyl) amino] -6,7-bis (2-methoxy) ethoxy) -quinazoline

- 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -7- [3- (methyl-4-yl) -propyloxy] -6 - [(vinylcarbonyl) -amino] -quinazoline

- 4 - [(R) - (1-Phenylethyl) amino] -6- (4-hydroxy-phenyl) -7H-pyrrolo [2,3-d] pyrimidine 3-cyano-4 - [(3-chloro -4-fluoro-phenyl) -amino] -6- {[4- (N, N-dimethylamino) -l-oxo-2-butlen-1-yl] -amino} -7-ethoxy-quinoline

- 4- {[3-Chloro-4- (3-fluoro-benzyloxy) -phenyl] -amino} -6- (5- {[(2-methanesulfonyl-ethyl) -amino] -methyl} -furan-2-yl) -quinazoline

- 4 - [(R) - (1-phenylethyl) amino] -6 - {[4 - ((R) -6-methyl-2-oxo-4-methyl-4-yl) -l-oxo-2-one butene-1-yl] amino} -7-methoxy-quinazoline - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {[4- (4-methyl-4-yl) -l-oxo-2-one] buten-1-yl] amino} - 7 - [(tetrahydrofuran-2-yl) methoxy] quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - ({4- [N, N-bis (2-methoxy-ethyl) -amino] -l-oxo-2-butene-1-one yl} amino) -7 - [(tetrahydrofuran-2-yl) methoxy] quinazoline

- 4 - [(3-ethynyl-phenyl) -amino] -6- {4- (5,5-dimethyl-2-oxo-4-methyl-4-yl) -l-oxo-2-butene-1-yl] amino} -quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2- (2,2-dimethyl-6-oxo-4-methyl-4-yl) -ethoxy] -7-methoxy-quinazoline - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2- (2,2-dimethyl-6-oxomorpholin-4-yl) -ethoxy] - 7 - [(R) - (tetrahydrofuran-2-yl) methoxy] -quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -7- [2- (2,2-dimethyl-6-oxomorpholin-4-yl) -ethoxy] - 6 - [(S) - (tetrahydrofuran-2-yl) methoxy] quinazoline - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {2- [4- (2-oxo-morpholin-4-yl) - piperidin-1-yl] ethoxy} -7-methoxy-quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [1- (tert-butyloxycarbonyl) -piperidin-4-yloxy] -7-methoxy-quinazoline 4 - [(3-chloro-4-yl) 4-fluoro-phenyl) amino] -6- (trans-4-amino-cyclohexan-1-yloxy) -7-methoxy-quinazoline

- 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (trans-4-methanesulfonylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-3-yloxy) -7-methoxyquinazoline 4 - [(3-chloro-4-fluoro-phenyl) -amino] - 6- (1-methyl-piperidin-4-yloxy) -7-methoxy-quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(4-methyl-4-yl) carbonyl] -piperidin-4-yl-oxy} -7-methoxy-quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(methoxymethyl) -carbonyl] -piperidin-4-yl-oxy} -7-methoxy-quinazolin-4 - [(3 chloro-4-fluoro-phenyl) amino] -6- (piperidin-3-yloxy) -7-methoxy-quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [1- (2-acetylamino-ethyl) -piperidin-4-yloxy] -7-methoxy-quinazoline

4-[(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-4-yloxy) -7-ethoxy-quinazoline 4 - [(3-chloro-4-fluoro-phenyl) -amino] - 6 - ((S) -tetrahydrofuran-3-yloxy) -7-hydroxyquinazoline

- 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-4-yloxy) -7- (2-methoxy-ethoxy) -quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {trans-4 - [(dimethylamino) sulfonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline-4 - [(3 -Chloro-4-fluoro-phenyl) amino] -6- {trans-4 - [(morpholin-4-yl) carbonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline

4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- {trans-4 - [(4-methyl-4-yl) -sulfonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline - 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-4-yloxy) -7- (2-acetylamino-ethoxy) -quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl)) amino] -6- (tetrahydropyran-4-yloxy) -7- (2-methanesulfonylamino-ethoxy) -quinazoline-4 - [(3-chloro-4 fluorophenyl) amino] -6- {1- (piperidin-1-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline

4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (1-aminocarbonylmethyl-piperidin-4-yloxy) -7-methoxy-quinazoline 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (cis-4- {N - [(tetrahydropyran-4-yl) carbonyl] -N-methyl-1-amino} -cyclohexan-1-ylxy) -7-methoxy-quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [(morpholin-4-yl) -carbonyl] -N-methyl-amino} -cyclohexan-1-one yloxy) -7-methoxy-quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [(morpholin-4-yl) -sulfonyl] -N-methyl-amino} -cyclohexane-1-one yloxy) -7-methoxy-quinazoline - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-ethanesulfonylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline

- 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7-ethoxy-quinazoline

- 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7- (2-methoxy-ethoxy) -quinazoline

- 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- [1- (2-methoxy-acetyl) -piperidin-4-yloxy] -7- (2-methoxyethoxy) -quinazoline

4-[(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4-acetylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline - 4 - [(3-ethynyl-phenyl) amino] -6- [1- (tert-butyloxycarbonyl) -piperidin-4-yloxy] -7-methoxy-quinazoline

- 4 - [(3-ethynylphenyl) amino] -6- (tetrahydropyran-4-yloxy) -7-methoxy-quinazoline

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [(piperidin-1-yl) -carbonyl] -N-methyl-amino} -cyclohexan-1-one yloxy) -7-methoxy-quinazoline - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [(4-methylpiperazin-1-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline

- 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- {cis-4 - [(morpholin-4-yl) carbonylamino] -cyclohexane-1-yloxy} -7-methoxy-quinazoline - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1- [2- (2-oxo-pyrrohdin-1-yl) -ethyl] -piperidin-4-yloxy} -7-methoxy-quinazone

4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- {1 - [(morphohn-4-yl) -carbonyl] -piperidin-4-yloxy} -7- (2-methoxy-ethoxy) - chmazoline - 4 - [(3-ethynyl-phenyl) -amino] -6- (1-acetyl-pipptin-4-yloxy) -7-methoxy-quinazone

- 4 - [(3-ethynylphenyl) amino] -6- (1-methyl-piperidin-4-yloxy) -7-methoxy-quinazone 4 - [(3-ethynylphenyl) amino] -6- (1 -methanesulfonyl-piperidine-4-yloxy) -7-methoxy-quinazoline 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methyl-piperidine-4-yloxy) -7 (2 methoxyethoxy) -quinazone

4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (1-isopropyloxycarbonyl-piperidine-4-yloxy) -7-methoxy-quinazone

4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (cis-4-methylamino-cyclohexan-1-yloxy) -7-methoxy-quinazone-4 - [(3-chloro-4-fluoro -phenyl) -amino] -6- {cis-4- [N- (2-methoxy-acetyl) -N-methyl-amino] -cyclohexan-1-yloxy-1-methoxy-quinazone

- 4 - [(3-Ethmyl-phenyl) -amino] -6- (piperidine-4-yloxy) -7-methoxy-quinazone

- 4 - [(3-ethynylphenyl) ammo] -6- [1- (2-methoxy-acetyl) -piphenyl-4-yloxy] -7-methoxy-quinazone - 4 - [(3-ethynyl-phenyl) amino] -6- {1- (morpholin-4-yl) carbonyl] -purpline-4-yloxy} -7-methoxy-quinazone

4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(cis-2,6-dimethyl-morphohn-4-yl) -carbonyl] -pipeπdm-4-yloxy} -7- methoxy-quinazoline 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(2-methyl-morphomo-4-yl) -carbonyl] -piphenyl-4-yloxy} -7-methoxy -chmazolin

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(S, S) - (2-oxa-5-azabicyclo [2,11] -hept-5-yl) carbonyl] -pipeπdin-4-yloxy} -7-methoxy-quinazone 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(N-methyl-N-2-methoxyethyl-amino ) carbonyl] -pipeπdin-4-yloxy} -7-methoxy-quinazone - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-ethyl-pipidin-4-yloxy) -7- methoxyquinazone

- 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- {1 - [(2-methoxyethyl) carbonyl] -piphenyl-4-yloxy} -7-methoxy-quinazone - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(3-methoxy-propyl-amino) -carbonyl] -piphenyl-4-yloxy} -7-methoxy-quinazone

4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [cis-4- (N-methanesulfonyl-N-methyl-amino) -cyclohexdn-1-yloxy] -7-methoxy-quinazone - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [cis-4- (N-acetyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-chymazoyl

4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (trans-4-methyl-aminocyclohexan-1-yloxy) -7-methoxy-quinazone

- 4 - [(3-chloro-4-fluoro-phenyl) -ammo] -6- [trans-4- (N-methanesulfonyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazone

4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-dimethylammo-cyclohexane-1-ylxy) -7-methoxy-quinazone

4 - [(3-chloro-4-fluoro-phenyl) -moomo] -6- (trans-4- {N - [(morphomo-4-yl) -carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy ) -7-methoxy-quinazolm - 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2- (2,2-dimethyl-6-oxo-momo-hohn-4-yl) -ethoxy] - 7 - [(S) - (tetrahydrofuran-2-yl) methoxy] quinazone

- 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidine-4-yloxy) -7-methoxy-quinazoline 4 - [(3-chloro-4-fluoro-phenyl ) amino] -6- (1-cyano-piperidin-4-yloxy) -7-methoxy-quinazone, optionally in the form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates. According to the invention, these acid addition salts are selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate

Compounds which are preferably used as dopamine agomsts are those which are selected from the group consisting of bromocriptine, cabergon, alpha-

Dihydroei gocryptin, Lisuπd, Pergohd, Pramipexole, Roxindol, Ropinirol, Talipexol, Tergu- πd and Viozan, optionally in the form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates. According to the invention, these acid addition salts are selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.

As Hl -Antihistaminika here are preferably compounds used, which are selected from the group consisting of epinastine, cetirizine, azelastine, fexofenadine, levocabastine, loratadine, mizolastine, ketotifen, emedastine, dimetindene, clemastine, bamipine, Cexchlorpheniramin, pheniramine, doxylamine , Chlorphenoxamine, dimenhydrinate, diphenhydramine, promethazine, ebastine, desloratidine and meclocine, optionally in the form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates. According to the invention, these acid addition salts are selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate.

As pharmaceutically active substances, substance formulations or mixtures of substances all inhalable compounds are used, such. also inhalable macromolecules, as disclosed in EP 1 003 478. Preferably, substances, substance formulations or substance mixtures are used for the treatment of respiratory diseases, which are used in the inhalation area.

Furthermore, the compound may be derived from the group of derivatives of ergot alkaloids, the triptans, the CGRP inhibitors, the phosphodiesterase V inhibitors, optionally in the form of their racemates, enantiomers or diastereomers, optionally in the form of their pharmacologically acceptable acid addition salts, their solvates and / or hydrates.

As derivatives of ergot alkaloids: dihydroergotamine, ergotamine.

It is an object of the invention to provide an adapter of the type mentioned, the optimal introduction of a generated aerosol in a simple structure Guaranteed hose for the ventilation of a particular human patient.

According to the invention, the object is achieved in that the opening extends into a region facing the atomizer behind the atomizer nozzle.

The inhaler-shaped atomizer is connected to the adapter for a respiratory system in such a way that a flow channel for the respiratory gas is provided, which ensures that the complete dose of the atomized fluid, ie the complete amount of the aerosol generated by the atomizer, from the respiratory gas is promoted to the patient by the breathing gas is passed behind the atomizer nozzle in the corresponding flow channel and thus entrains the spray cloud. The aerosol generated by the atomizer is taken up directly at the place of its generation by the respiratory gas flowing through the adapter and supplied to the ventilated patient with a slight impaction in the tube, since the main atomizing direction of the fluid is parallel to the flow direction of the respiratory gas. Accordingly, the ventilated patient is supplied with aerosolized active substances and a continuous inhaled medication already carried out with the atomizer can be continued after the patient has been connected to the respiratory system or a medication or active ingredient administration of the patient connected to the respiratory system can take place. As is known from the prior art, a respiratory mask or a tracheal tube or the like can be connected to the patient-side outlet.

In its embodiment, the connection for the atomizer is adapted in its geometry in regions to a mouthpiece of the atomizer into which the atomizer nozzle protrudes and which has at least one recess in an area facing away from the inhalation opening in its wall which communicates with the opening for the respiratory gas Flow connection is. Accordingly, in a further treatment of a patient with a respiratory system of the atomizer can be used, which is also used without the respiratory system. Preferably, the mouthpiece is provided with two opposing recesses through which the breathing gas or air sucked in by the patient flows, for example to inhale respirable particles of the drug.

Preferably, the connection for the atomizer is supported on a shoulder of the atomizer The connection can be sealed to the cylindrical shoulder of the atomizer, for example

Preferably, the opening is formed in the region of the mouthpiece as a groove. The groove is relatively easy to manufacture and after insertion of the mouthpiece into the connection, the groove forms a circumferentially closed flow channel with a corresponding wall of the mouthpiece

Expediently, the breakthrough associated with the inlet for the respiratory gas is perpendicular to the bore. The respiratory gas thus passes into the breakthrough, is diverted at its end into the flow channel formed by the groove and the corresponding wall of the mouthpiece, flows through the recesses into the mouthpiece, into which makes a further directional diversion, and carries the aerosol generated by the nebulizer nozzle into the mouthpiece through the bore to supply the patient with both AT gas and the drug

According to a further development, at least one valve is provided, which separates the atomizer from the respiratory gas in terms of flow and directs the respiratory gas from the inlet directly to the patient-side outlet. Sonach can then be used to ventilate the patient either via the atomizer or directly

The atomizer for the above-described adapter for dispensing a certain amount of the fluid, in particular having a medicament, is formed as an aerosol from the pressure accumulator through the atomizer nozzle arranged inside the mouthpiece, wherein a mechanical pressure generator applies the measured fluid to the pressure accumulator, which is to be released abruptly for atomization, and the mouthpiece has at least one opening which, seen in Zerstaubungsπchtung, formed behind the nozzle Preferably, the pressure generator comprises a holder for a fluid receiving replaceable Vorratsbehalter, an associated Antπebsfeder with a Losetaste and a A conveyor tube, wherein an axial clamping of the Antπebsfeder shifts the holder with the Vorratsbehalter and the Forderrohr in a direction opposite to the Mundstuck direction and sucks fluid from the Vorratsbehalter in a pressure chamber and an actuation of the release button En tspannung the strained Antπebsfeder causes the conveyor tube in the direction of the Mundstucks and thereby pressurizes the fluid for discharge through the nebulizer nozzle Advantageously, the nebulizer nozzle comprises a filter system for generating two juxtaposed spray jets to produce a spray cloud

It is understood that the features mentioned above and those yet to be explained can be used not only in the combination given, but also in other combinations. The scope of the invention is defined only by the claims

The invention will be explained in more detail below with reference to an exemplary embodiment with reference to the accompanying drawings It shows

1 shows a partial view of a longitudinal section through an inventive adapter A and

FIG. 2 is a sectional view of an atomizer for use with the adapter of FIG. 1

The nebulizer 1 is used for nebulizing a fluid 2, in particular a highly effective drug or the like, and is designed as a portable inhaler which operates without propellant gas in the atomization of the fluid 2, preferably a liquid, an aerosol is formed, which is not a represented user can be inhaled

The atomizer 1 has a replaceable storage container 3 with the fluid 2, which essentially has a cylindrical or cartridge-like structure and can be inserted from below into the opened atomizer 1. In the rigid storage container 3, there is a bag 4 receiving the fluid 2 Fluids 2 in a predetermined adjustable amount comprises the atomizer 1, a pressure generator 5 with a holder 6 for the container 3, a Antπebsfeder 7 with a manually releasable to relax the release button 8, a Forderrohr 9 with an inserted check valve 10, a pressure chamber 11 and a Atomizing nozzle 12, which is associated with a mouthpiece 13 During axial tensioning of the drive spring 7 by rotating a lower housing part 18 with an inner part 17 detachably fastened thereto relative to an upper housing part 16 formed on the mouthpiece 13, the support 6 is moved downwards with the storage container 3 and the delivery pipe 9 and fluid from the container 3 sucked via the check valve 10 into the pressure chamber 11 of the pressure generator 5. During the subsequent abrupt release of the drive spring 7 by the actuation of the release button 8, the fluid 2 is pressurized in the pressure chamber 11 of the conveying tube 9 upwardly displacing the drive spring 7 and output via the atomizer nozzle 12 under atomization. Atomization takes place, for example, in particles in the μm or nm range, preferably in respirable particles with a size of about 5 μm, which form a cloud or a jet of an aerosol. A user can inhale the aerosol, wherein supply air or breathing gas via openings 15 in the mouthpiece 13 is sucked.

In order to be able to administer the fluid 2 as an aerosol in connection with a respiratory system for a patient, in particular human, the adapter 19 is provided which has a connection 20 for the atomizer 1, wherein the connection 20 comprises a region 21 which in its Geometry is adapted to the mouthpiece 13 of the atomizer 1. Opposite the connection 20, the adapter 19 has a patient-side outlet 22, which is in flow communication with the connection 20 via a bore. For coupling with a breathing tube of the adapter 19 with a

Passage 24 having the inlet 25, wherein the cylindrical cross-section entrance 25 is aligned with the coaxially extending passage 24 at right angles to the bore 23. Trained as a blind hole passage 24 opens into a groove 26 designed as an opening 27 which extends parallel to the bore 23 and extends to the recesses 15 in the mouthpiece 13, which are located below the atomizer 12.

The respiratory gas passes from the breathing air hose into the opening 24 and is diverted at its end into the flow channel formed by the groove 26 and a corresponding wall of the mouthpiece 13, at the end of which the breathing gas passes through the recesses

15 passes into the mouthpiece 13. In the mouthpiece 13, the breathing gas is redirected below the atomizing nozzle 12 again in its flow direction and takes the aerosol generated by the atomizer nozzle 12 in the mouthpiece 13 through the bore 23 with to supply the patient with both breathing gas and with the drug, wherein within the mouthpiece 13, the Hauptzerstäubungsrichtung a drug is aligned parallel to the flow direction of the breathing gas.

Claims

claims

1. Adapter with a connection (20) for a nebulizer (1) for a, in particular a drug exhibiting, fluid (2) as an aerosol through a nebulizer nozzle (12), wherein the terminal (20) via a bore (23) with a Patient-side outlet (22) is coupled, and with a bore (23) fluidly connected to the inlet (25) for a hose to be fastened Atemluft- that the Hauptzerstäubungsrichtung of the fluid (2) is aligned parallel to the flow direction of a breathing gas, wherein in an opening (25) associated with the opening (24) a parallel to the bore (23) in the direction of the atomizer (1) extending opening (27) is embedded, characterized in that the opening (27) into a the atomizer ( 1) facing area 5 behind the atomizer nozzle (12).

2. Adapter according to claim 1, characterized in that the connection (20) for the atomizer (1) in its geometry is partially adapted to a mouthpiece (13) of the atomizer (1) into which the atomizer nozzle (12) protrudes and the In its wall facing away in a region remote from the inhalation opening at least one 0 recess (15) which is in flow communication with the opening (27) for the breathing gas.

3. Adapter according to claim 1 or 2, characterized in that the connection (20) for the atomizer (1) on a shoulder of the atomizer (1) is supported.

4. Adapter according to one of claims 1 to 3, characterized in that the 5 opening (27) in the region of the mouthpiece (13) as a groove (26) is formed.

5. Adapter according to one of claims 1 to 4, characterized in that the inlet (25) for the respiratory gas associated breakthrough (22) perpendicular to the bore (23).

6. An adapter according to claim 1, characterized in that at least one valve o is provided, which separates the atomizer (1) fluidly from the breathing gas and directs the breathing gas from the inlet (25) directly to the patient-side outlet (22).

7. Atomizer for an adapter according to one of claims 1 to 6, characterized in that the atomizer (1) for delivering a certain amount of, in particular a drug having, fluid (2) as an aerosol by the inside of the mouthpiece (13 ) is formed from a pressure accumulator, wherein a mechanical pressure generator (5) acts on the measured fluid (2) in the pressure accumulator, which is to release abruptly for spraying, and the mouthpiece (13) has at least one recess (15) which, viewed in the direction of atomization, is formed behind the atomizer nozzle (12).

8. An atomiser according to claim 7, characterized in that the pressure generator (5) has a holder (6) for a fluid (2) receiving replaceable reservoir (3), an associated drive spring (7) with a release button (8) and a conveyor tube (9), wherein an axial tensioning of the drive spring (7) displaces the holder (6) with the reservoir (3) and the conveyor tube (9) in a direction opposite to the mouthpiece (13) and fluid (2) the reservoir (3) sucks in a pressure chamber (11) and an actuation of the release button (8) causes a relaxation of the tensioned drive spring (7), which moves the delivery pipe (9) in the direction of the mouthpiece (13) and thereby the fluid (2 ) is pressurized to discharge through the atomizing nozzle (12).

9. An atomiser according to claim 7 or 8, characterized in that the atomizer nozzle comprises a filter system for generating two spray jets on each other to produce a spray cloud.