HK1227333B - Inhaler - Google Patents

Description

inhaler

Technical Field

The present invention relates to an inhalation device for inhaling a powdered pharmaceutical composition contained in a capsule, said capsule being inserted into a drug reservoir of the inhalation device.

Background Art

The invention of inhalation devices paved a barrier-free path for the treatment and management of respiratory diseases. Today, dry powder inhalers play a vital role in targeted drug delivery to the affected lung airways. Dry powder inhalers (DPIs) have been available since 1967, with Aventis being the first to develop the SPINHALER DPI for the delivery of cromolyn sodium. Since then, numerous improvements have been observed in the design and use of inhalation devices.

Typically, a powder inhaler device is used to inhale single or multiple doses of a powdered medication from a capsule. The device is configured with a medication reservoir that holds a capsule containing the powdered medication. During inhalation, the device, which has a puncture mechanism, punctures the capsule, allowing the medication to be dispersed into the air inhaled by the user. The empty capsule remains in the device and is then discarded before the next use of the device.

US Pat. No. 3,807,400 discloses improvements in inhalation devices with a vortex chamber. The devices, which are considered to operate in a basic manner known per se, are intended to disperse the contents of a capsule filled with a powdered pharmaceutical composition. The device according to the invention comprises a mouthpiece in the form of a telescopic structure and two piercing means arranged in diametrically opposed positions in a rotatable member and driven by the member. The telescopic structure forms the vortex chamber when extended, and the mantel of the latter member is provided with a cam capable of providing a piercing operation to the two piercing means.

US 8,006,695 describes an inhaler device for inhaling a medicament from a pierceable capsule, the inhaler device comprising a housing for receiving the medicament capsule; a closure means for closing the housing, the closure means being movable relative to the housing; and a piercing means adapted to pierce the medicament capsule, wherein movement of the closure means relative to the housing causes movement of the piercing means. The present invention also provides a reservoir for medicament capsules, the reservoir comprising a chamber adapted to receive the medicament capsule; and means for generating turbulence in a flow of liquid through the chamber, wherein, in use, the turbulent flow of liquid causes vibration of the capsule received by the chamber to assist in releasing the medicament contained in the capsule.

US 7,694,676 describes an inhaler for inhaling a powdered pharmaceutical composition from a capsule, the inhaler comprising: a lower part; a plate that can be locked onto the lower part and with which the lower part can be closed; a capsule reservoir for accommodating capsules, the reservoir being adapted to be lowered into the lower part; a mouthpiece that can be locked to the plate; and a cover that covers and locks the mouthpiece in the closed position by a closure element, the lower part, the plate, the mouthpiece and the cover being hinged together by a single joint.

US 8,022,082 discloses an inhaler comprising: a housing with two windows, a flat surface with an air inlet and provided with a screen fixed by a screen housing, an inhalation chamber connected to the flat surface with a button, the inhalation chamber having two sharp needles movable opposite to a spring, an inhalation mouth connected to the housing, the flat surface and a cover which can be flipped open and closed by an axis, and three holes with a diameter of less than 1 mm in a central area surrounding the capsule chamber and below the screen housing and the screen.

US 7,252,087 discloses an inhaler utilizing a multifunctional actuating member. The multifunctional actuating member disclosed in US ' 087 allows the closure element to break away from the bottom of the housing in a first functional position and allows the mouthpiece to rotate away from the bottom of the housing in a second functional position.

US 7,284,553 discloses a powder inhaler operating according to the Bernoulli principle. It discloses an inhaler having a capsule chamber, which comprises raised elements on the inner surface of the capsule chamber or on the outer surface of the capsule.

Although the prior art discusses many different types of inhalers for delivering medications, there remains a need in the art for the design and development of improved inhalers for the delivery of powder inhalants based on factors that influence treatment compliance, such as the medication to be delivered, ease of operation, and patient preferences. The present invention is therefore intended to fully address these and other needs in the art by further improving known inhalers with respect to their operation.

The present invention therefore relates to an improved inhalation device having a two-hinge system intended to dispense the contents of a powdered pharmaceutical composition.

During normal use of a dry powder inhaler, the patient opens the cap, then the mouthpiece, and inserts a capsule containing a powdered pharmaceutical composition. The patient then depresses the actuator, which punctures the capsule containing the powdered pharmaceutical composition. A puncturing element connected to the actuator punctures the capsule from one side, allowing the powdered pharmaceutical composition contained in the capsule to escape when the patient inhales through the mouthpiece.

The "two-hinge" design of the inhaler of the present invention utilizes two separate hinges. One hinge serves the lid and mouthpiece, and the second hinge serves the base plate. The patient only needs to open the base plate when needed. The use of a second, distinct hinge prevents accidental opening of the base plate, thereby avoiding contamination of the medication. Furthermore, the non-protruding actuating components make the device very convenient to operate and store.

Furthermore, the shape of the inhaler is rounded over the top and one side, and the shape of the inhaler is configured at an angle in such a way that the patient can hold the device properly and find it convenient to actuate the device without losing control while holding the device.

Purpose of the Invention

The purpose of the present invention is to overcome the defects of the prior art.

Another object of the present invention is to provide an inhaler device having two hinge systems (6, 8).

Another object of the present invention is to provide an inhaler device having a two-hinge system, wherein the mouthpiece (3) and the lid (1) are connected to one hinge (8)

Another object of the present invention is to provide an inhaler device having a two-hinge system, wherein the base plate (4) is hinged to the hinge (6) separately from the mouthpiece and the lid.

Another object of the present invention is to provide an inhaler using a base plate (4) that does not have any holes.

Another object of the present invention is to provide an inhaler wherein the gripping aid (9) is provided at the distal end of the actuating member (5).

Summary of the Invention

According to one aspect of the present invention, an inhaler device is provided, comprising a housing (2), a base plate (4) covering the housing (2), a drug reservoir (10) integrated with the base plate (4), a mouthpiece (3) located above the base plate (4), a cover (1) covering the mouthpiece (3), at least one piercing element (11), an actuating member (5), and a spring (12), characterized in that the inhaler device is a two-hinge system (6, 8), wherein the base plate (4) is connected to the hinge (6); and the mouthpiece (3) and the cover (1) are connected to the hinge (8).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 illustrates the basic assembly of an inhaler according to the present invention, wherein the housing (2) accommodates a base plate (4) and is covered by the base plate (4), the mouthpiece (3) and a gripping aid (9). The base plate (4) is connected to a hinge (6), and the mouthpiece (3) and the lid (1) are hinged together to a hinge (8) different from the base plate. The gripping aid (9) is arranged at the distal end of the actuating member (5).

Figure 2 illustrates a top view of the drug reservoir (10) mounted below the base plate (4).

Figure 3 illustrates a close up view of the mouthpiece (3) positioned above a base plate (4) integral with the drug reservoir (10). The two hinges (6, 8) are labeled differently.

Figure 4 illustrates a radial partial cross-section of the inhaler depicting the cap (1), mouthpiece (3), piercing element (11), actuating member (5), spring (12), drug reservoir (10), viewing window (7), and the mouthpiece and cap connected to a hinge (8).

Figure 5 illustrates a side view of the inhaler in the fully closed state.

Figure 6 illustrates a top view of the inhaler base plate (4) without any holes.

FIG. 7 illustrates an inhaler with two different hinge systems ( 6 , 8 ).

FIG. 8 illustrates a graph of the square root of the pressure difference versus flow rate in the inhaler of the present invention, depicting the relatively high resistance to air flow.

DETAILED DESCRIPTION

A simplified summary of the present invention is provided below to provide a basic understanding of some aspects of the present invention. This summary is not an extensive overview of the present invention. It is not intended to identify key/critical elements of the present invention or to delineate the scope of the present invention. Its sole purpose is to provide some concepts of the present invention in a simplified form as a prelude to a more detailed description of the present invention that will be provided later.

According to the present invention, an inhaler is provided for inhaling a powdered pharmaceutical composition from a capsule, the capsule being inserted into a drug reservoir provided in the inhaler prior to use. According to the present invention, after inserting the capsule into the drug reservoir of the device, the patient can depress an actuating member, which can be moved from a rest position to interact with at least one piercing element that can access the drug reservoir. The capsule is pierced by a minimal portion of one of the piercing elements, releasing the pharmaceutical composition.

Other aspects, advantages, and salient features of the invention will become apparent to those skilled in the art from the following detailed description, which, taken in conjunction with the accompanying drawings, discloses exemplary embodiments of the invention.

As shown in Figures 1, 2, 3 and 4, the inhaler according to the present invention basically consists of a housing (2) that accommodates and is covered by a base plate (4), and a mouthpiece (3) with a gripping aid (9); the base plate (4) is connected to a hinge (6), and the mouthpiece (3) and the cover (1) are hinged to a hinge (8) separately from the base plate; the gripping aid (9) is arranged at the distal end of the actuating member (5). An observation window (7) also allows observation of the internal components of the device. A drug reservoir (10) is mounted below the base plate (4). One or more piercing elements (11) for piercing the capsule are connected from the inside of the actuating member (5), and a spring (12) is also configured to be connected to the actuating member; the characteristic is that when the actuator is pressed from the outside, the spring element (12) is compressed and enables the piercing element (11) to move linearly and pierce the capsule to release the drug inside the capsule, and then the spring element retracts.

The terms and words used in the following description and claims are not limited to the bibliographical meanings, but, are merely used by the inventor to enable a clear and consistent understanding of the invention.

The cover (1) provides protection to the device components by preventing the ingress of dust or any other foreign particles.

The mouthpiece (3) is a component through which the patient inhales the powdered pharmaceutical composition.

The base plate (4) ensures that the drug reservoir (10) is securely held and that the drug reservoir (10) always remains aligned with the mouthpiece (3) for a smooth flow of the drug.

The actuating member (5) is responsible for locking and unlocking the lid (1) and keeping the piercing element (11) in place. When the actuating member (5) is moved upwards, it ensures that the capsule is properly pierced, in this way the powdered pharmaceutical composition can be inhaled by the patient.

The hinge (6) is responsible for keeping the base plate in place in such a way that the drug reservoir (10) is always aligned with the mouthpiece (3).

The viewing window (7) provides for viewing of the drug reservoir (10), allowing the patient to confirm that the capsule is present in the drug reservoir (10).

The hinge (8) is responsible for the proper movement of the lid (1) and the mouthpiece (3).

A gripping aid (9) on the mouthpiece provides the patient with a handle to open the mouthpiece (3) so that a capsule containing the powdered pharmaceutical composition may be placed into the drug reservoir (10).

In one embodiment of the invention, the inhaler operates in the following manner.

a) Open the cover (1) by pressing the actuating member (5)

b) The cover (1) is pulled upwards and away from the base to expose the suction port (3)

c) Open the suction opening (3) by pulling the gripping aids (9) located on both sides of the suction opening (3)

d) placing the capsule into the drug reservoir (10) of the inhaler of the present invention

e) Close the suction port (3). Keep the cover (1) open.

f) The inhaler of the present invention is held in a position where the mouthpiece (3) points upwards

g) Press the actuating member (5) to move the piercing element (11) to pierce the capsule

h) inhaling the powdered pharmaceutical composition from the capsule.

The device can be made of any suitable material. Preferably the device is made of plastic, such as ABS (Acrylic Butadiene Styrene), PC (Polycarbonate), PA (Polyacetal) or PS (Polystyrene) or a mixture thereof, or made of antistatic material (Dellin or stainless steel).

The inhaler according to the invention allows for a more reliable delivery of the pharmaceutical composition compared to devices known from the prior art.

The advantages of the inhaler of the present invention are as follows:

1. The patient only needs to open the bottom plate when needed. A second, different hinge prevents accidental opening of the bottom plate, thereby avoiding contamination of the medication.

2. Furthermore, the non-protruding actuating member makes the operation of the device and the storage of the device very convenient.

3. Furthermore, the shape of the inhaler is rounded over the top and one side, and the shape of the inhaler is configured at an angle in such a way that the patient can hold the device properly and find it convenient to actuate the device without losing control while holding the device.

The flow resistance of an inhaler device with two hinge systems using a base plate without any holes was measured to be about 0.07/L min" ¹ , resulting in a flow rate of about 40 L min" ¹ and a pressure difference from one side of the inhaler to the other of about 4 kPa.

The flow resistance can be calculated using the following formula: R = P ^0.5 /Q

Where Q is the flow rate (L/min), P is the pressure difference from one side of the inhaler to the other (kPa) and R is the resistance to flow [kPa ^0.5 /(L/min)].

In this system, a suction pressure differential between 2 kPa and 6 kPa produces a resultant flow rate between approximately 25 and 55 liters per minute.

The present invention relates to the use of an inhaler device as described above for administering by inhalation a powdered pharmaceutical composition suitable for the treatment of asthma or chronic obstructive pulmonary disease.

The pressure difference versus flow rate curve depends on the design of the inhaler.

The inhaler according to the present invention was tested to measure its flow resistance, which is an important property of an inhaler.

According to Bernoulli's principle, when mapping flow velocity with the square root of pressure differential, the resistance of inhaler is the slope of the linear portion of curve.In Figure 8, can find out for the example diagram according to inhaler device of the present invention.Figure shown in Figure 8 has shown relatively high airflow resistance, and curve increases fast with flow velocity.

Inhaler according to the present invention can comprise the design feature that this understanding provides according to different powder medicines has different characteristics.Therefore, in order to improve delivery efficiency, the flow parameter of inhaler should be advantageously regulated at the concrete medicine to be delivered.These adjustments can be carried out by regulating airflow.Airflow can be controlled by drilling extra air supply hole or by increasing or reducing the opening size of air supply hole.

Preferably, the powdered pharmaceutical composition contained in the capsule is a dry powdered drug. The term capsule is intended to be understood in a broad sense and includes any suitable container for the powdered pharmaceutical composition. The capsule can be formed from any suitable material, including gelatin, HPMC or plastic.

In one embodiment, the present invention provides a pharmaceutical composition comprising a powdered drug that can be administered by inhalation. Particularly preferred in this regard are pharmaceutical compositions selected from the group consisting of anticholinergics, beta-2 agonists, steroids, PDE IV inhibitors, LTD4 antagonists, and EGFR kinase inhibitors.

The anticholinergic drug for use is preferably selected from the group consisting of tiotropium bromide, oxitropium bromide, flutropium bromide, ipratropium bromide, glycopyrronium salts, trospium chloride, tolterodine, tropine 2,2-diphenylpropionate methylbromide, scopolol 2,2-diphenylpropionate methylbromide, scopolol 2-fluoro-2,2-diphenylacetate methylbromide, tropine 2-fluoro-2,2-diphenylacetate methylbromide, tropenol 3,3',4,4'-tetrafluorobenzilate methobromide, scopolol 3,3',4,4'-tetrafluorobenzilate methobromide, tropine ...2,2-diphenylpropionate methylbromide, tropine 2,2-diphenylpropionate methylbromide, tropine 2,2-diphenylacetate methylbromide, tropine 3,3',4,4'-tetrafluorobenzilate methobromide, tropine 2,2-diphenylacetate methylbromide, tropine 2,2-diphenylacetate methylbromide, tropine 3,3',4,4'-tetrafluorobenzilate methobromide, tropine 2,2-diphenylpropionate methylbromide, tropine 2,2-diphenylpropionate methylbromide, tropine 2,2-diphenylacetate methylbromide, tropine 3,3',4,4'-tetrafluorobenzilate methobromide, tropine 2,2-diphenylacetate methylbromide, 3,3',4,4'-tetrafluorobenzilate methobromide), tropenol 4,4'-difluorobenzilate methobromide, scopine 4,4'-difluorobenzilate methobromide, tropenol3,3'-difluorobenzilate methobromide, scopine3,3'-difluorobenzilate methobromide methobromide), tropine 9-hydroxy-fluorene-9-carboxylate methyl bromide, tropine 9-fluoro-fluorene-9-carboxylate methyl bromide, scopolol 9-hydroxy-fluorene-9-carboxylate methyl bromide, scopolol 9-fluoro-fluorene-9-carboxylate methyl bromide, tropine 9-methyl-fluorene-9-carboxylate methyl bromide, scopolol 9-methyl-fluorene-9-carboxylate methyl bromide, cyclopropyltropine benzilate methyl bromide methobromide), 2,2-diphenylpropionate cyclopropyl tropine methyl bromide, cyclopropyl tropine 9-hydroxy-xanthene-9-carboxylate methyl bromide, cyclopropyl tropine 9-methyl-fluorene-9-carboxylate methyl bromide, cyclopropyl tropine-9-methyl-xanthene-9-carboxylate methyl bromide, cyclopropyl tropine 9-hydroxy-fluorene-9-carboxylate methyl bromide, methyl 4,4'-difluorotrityl ester cyclopropyl tropine methyl bromide, tropine 9 -hydroxy-xanthene-9-carboxylate methyl bromide, scopolol 9-hydroxy-xanthene-9-carboxylate methyl bromide, tropine 9methyl-xanthene-9-carboxylate methyl bromide, scopolol 9-methyl-xanthene-9-carboxylate methyl bromide, tropine 9-ethyl-xanthene-9-carboxylate methyl bromide, tropine 9-difluoromethyl-xanthene-9-carboxylate methyl bromide and scopolol 9-hydroxymethyl-xanthene-9-carboxylate methyl bromide.

The beta-2 agonist employed is preferably selected from the group consisting of salbutamol, bambuterol, bitolterol, bromosatrol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, neoproterenol, isoproterenol, levalbuterol, mabuterol, meluadrine, metaproterenol, metaproterenol, pirbuterol, procaterol, reproterol, rimiterol, ritodrine, salmeterol, salmethamine, soterenot, salfonteinol, optionally in the form of their racemates, enantiomers or diastereoisomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates and/or hydrates. honterol), thiamide, terbutaline, toluenterol, CHF-1035, HOKU-81, KUL-1248, 3-(4-{6-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-hexyl-oxy}-butyl)-benzenesulfonamide, 5-[2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one, 4-hydroxy-7-[2-{[2-{[3-(2-phenylethoxy)propyl]sulfonyl}ethyl]-amino}ethyl]-2(3H)-benzothiazolone, 1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-phenyl)- 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-propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-methoxyphenyl)-2-methyl-2-propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-[3-(4-methoxyphenyl)-2-methyl-2-propylamino]ethanol, oxazin-8-yl]-2-[3-(4-n-butoxyphenyl)-2-methyl-2-propylamino]ethanol, 1-[2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl]-2-{4-[3-(4-methoxyphenyl)-1,2,4-triazol-3-yl]-2-methyl-2-butylamino}ethanol, 5-hydroxy-8-(1-hydroxy-2-isopropylaminobutyl)-2H-1,4-benzoxazin-3-(4H)-one, 1-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-tert-butylamino)ethanol and 1-(4-ethoxycarbonylamino-3-cyano-5-fluorophenyl)-2-(tert-butylamino)-ethanol.

The steroids employed are preferably selected from prednisolone, prednisone, butixocortpropionate, RPR-106541, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, roflenide, ST-126, dexamethasone, (S)-fluoromethyl 6.ortho., 9.ortho.-difluoro-17.ortho.-[(2-furylcarbonyl)oxy]-11.ortho.-hydroxy-16.ortho. (S)-fluoromethyl-3-oxo-androsta-1,4-diene-17-quadrature-carbothionate ((S)-fluoromethyl-6-quadrature,9-quadrature-difluoro-17-quadrature-[(2-furanylcarbonyl)oxy]-11-quadrature-hydroxy-16-quadrature-methyl-3-oxo-androsta-1,4-diene-17-quadrature-carbothionate e), (S)-(2-oxo-tetrahydro-furan-3S-yl)6.orth.,9.orth.-difluoro-11.orth.-hydroxy-16.orth.-methyl-3-oxo-17.orth.-propionyloxy-androsta-1,4-diene-17.orth.-carbothionate and etiprednol-dichloroacetate (BNP-166).

The PDE IV inhibitor employed is preferably selected from the group consisting of enprophylline, theophylline, roflumilast, cilomilast, CP-325,366, BY343, D-4396 (Sch-351591), AWD-12-281 (GW-842470), N-(3,5-dichloro-1-oxo-pyridin-4-yl)-4-difluoromethoxy-3-cyclopropylmethoxybenzamide, NCS-613, pumafent, optionally in the form of their racemates, enantiomers or diastereoisomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates and/or hydrates. ine), (-)-[(4aR*,10bS*)-9-ethoxy-1,2,3,4,4a,10b-hexahydro-8-methoxy-2-methylbenzo[s][1,6]naphthyridin-6-yl]-N,N-diisopropylbenzamide, (R)-(+)-1-(4-bromobenzyl)-4-[(3-cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone, 3-(cyclopentyloxy-4-methoxyphenyl)-1-(4-N'-[N-2-cyano-S-methyl-isothioureido]benzyl)-2-pyrrolidone, cis-[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane -1-carboxylic acid], 2-methoxy-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)pyrrolidin-2-ylidene]acetate, CDP840, Bay-198004, D-4418, PD-168787, T-440, T-25 85. arophylline, atizoram, V-11294A, CI-1018, CDC-801, CDC-3052, D-22888, YM-58997, Z-15370, 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-thienyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine, and 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(tert-butyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine.

The LTD4 antagonist employed is preferably selected from montelukast, optionally in the form of its racemates, enantiomers or diastereomers, optionally in the form of its pharmacologically acceptable acid addition salts and optionally in the form of its salts and derivatives, solvates and/or hydrates, 1-(((R)-(3-(2-(6,7-difluoro-2-quinolyl)vinyl)phenyl)-3-(2-(2-hydroxy-2-propyl)phenyl)thio)methylcyclopropaneacetic acid, 1-(((1(R)-3(3-(2-(2,3-dichlorothieno[3 ,2-b]pyridin-5-yl)-(E)-vinyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropylacetic acid, pranlukast, zafirlukast, [2-[[2-(4-tert-butyl-2-thiazolyl)-5-benzofuranyl]oxymethyl]phenyl]acetic acid, MCC-847 (ZD-3523), MN-001, MEN-91507 (LM-1507), VUF-5078, VUF-K-8707 and L-733321.

The EGFR-kinase inhibitor employed is preferably selected from the group consisting of cetuximab, trastuzumab, ABX-EGF, Mab ICR-62, 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-cyclopropylmethoxy-quinazoline, 4-[(R)-(1-phenyl-ethyl)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-morpholin-4-yl)- 1-oxo-2-buten-1-yl]amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[2-((S)-6-methyl-2-oxo-morpholin-4-yl)-ethoxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline, 4 -[(R)-(1-phenyl-ethyl)amino]-6-({4-[N-(tetrahydropyran-4-yl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopropylmethoxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-({4-[N-(2-methoxy-ethyl)-N-methyl-amino]-1-oxo-2-buten-1-yl}amino)-7-cyclopentyloxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N- quinazoline, 4-[(3-ethynyl-phenyl)amino]-6,7-bis-(2-methoxy-ethoxy)-quinazoline, 4-[(R)-(1-phenyl-ethyl)amino]-6-(4-hydroxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidine, 3-cyano-4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-[(R)-(tetrahydrofuran-2-yl)methoxy]quinazoline, -buten-1-yl]amino}-7-ethoxy-quinoline, 4-[(R)-(1-phenyl-ethyl)amino]-6-{[4-((R)-6-methyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-[(tetrahydrofuran-2-yl)methoxy]quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-{[4-((R)-6-methyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-7-methoxy-quinazoline yl]-6-{[4-(5,5-dimethyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-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-(trans-4-amino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{[4-(5,5-dimethyl-2-oxo-morpholin-4-yl)-1-oxo-2-buten-1-yl]amino}-quinazoline ]-6-(trans-4-methanesulfonylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-3-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(piperidin-3-yloxy)-7-methoxy-quinazoline, -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-{trans-4-[(morpholin-4-yl)carbonylamino]-cyclohexan-1-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(piperidin-4-yloxy)-7-ethoxy-quinazoline -1-yl)carbonyl]-piperidin-4-yloxy}-7-methoxyquinazoline, 4-[(3-chloro-4-fluorophenyl)amino]-6-(cis-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-ethanesulfonamido-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methylsulfonyl-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-methoxy-ethoxy)-quinazoline, 4-[(3-ethynyl-phenyl)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}-cyclohexane quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{cis-4-[(morpholin-4-yl)carbonylamino]-cyclohexan-1-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[2-(2-oxopyrrolidin-1-yl)ethyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(1-acetylpiperidin-4-yloxy)-7-methoxy Quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(1-methyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-(1-methylsulfonyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-ethynyl-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]- 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(N-methyl-N-2-methoxyethyl-amino)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-ethyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-methylsulfonyl-N-methyl-amino)-cyclohexane]- -1-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-acetyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-methylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[trans-4-(N-methylsulfonyl-N-methyl-amino)-cyclohexan-1-yloxy quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-dimethylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[2-(2,2-dimethyl-6-oxo-morpholin-4-yl)-ethyl]- oxy]-7-[(S)-(tetrahydrofuran-2-yl)methoxy]-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulfonyl-piperidin-4-yloxy)-7-methoxy-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-cyano-piperidin-4-yloxy)-7-methoxy-quinazoline and 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(2-methoxyethyl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline.

Examples of acid addition salts (compounds that can be formed using pharmacologically acceptable acids) include salts selected from hydrochloride, hydrobromide, hydroiodide, hydrogen sulfate, hydrogen phosphate, hydrogen methanesulfonate, hydrogen nitrate, hydrogen maleate, hydrogen acetate, hydrogen benzoate, hydrogen citrate, hydrogen fumarate, hydrogen tartrate, hydrogen oxalate, hydrogen succinate, hydrogen benzoate and hydrogen p-toluenesulfonate, preferably salts selected from hydrochloride, hydrobromide, hydrogen sulfate, hydrogen phosphate, hydrogen fumarate and hydrogen methanesulfonate.

The powdered pharmaceutical composition may contain the above-mentioned active substances and their salts, esters, or a combination of these active substances, salts, and esters.

Although the invention has been described herein with reference to specific embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the invention. Therefore, it is to be understood that many modifications may be made to the illustrative embodiments and other arrangements may be devised without departing from the spirit and scope of the invention.

Claims (8)

1. An inhaler device, comprising: -Outer shell (2) -The base plate (4) covering the outer shell (2), - Drug storage container (10) integrated with the base plate (4) - Suction port (3) located above the base plate (4) - Cover (1) covering the suction port (3), -At least one puncture element (11) -Actuation component (5) -Spring(12), The device is characterized by connecting the puncture element (11) from the inside of the actuating component (5), the spring (12) being configured to connect the actuating component (5) to the drug reservoir (10), and the inhaler device being a two-hinge system (6, 8), the hinges (6, 8) being housed in the housing (2), wherein... -The base plate (4) is connected to the hinge (6), - The suction port (3) and the cover (1) are connected to another hinge (8), wherein - The base plate (4) is hinged separately from the suction port (3) and the cover (1). 2. The inhaler device according to claim 1, wherein, in order to assist puncture, when the actuating member (5) is pressed, the actuating member (5) causes the spring (12) to be compressed, so that the puncture element (11) can move linearly. 3. The inhaler device according to claim 1, wherein the device further comprises a gripping aid (9) on the inhalation port (3), the gripping aid (9) providing a grip for opening the inhalation port (3). 4. The inhaler device according to claim 1, wherein the device further comprises an observation window (7) for viewing the opposite side of the inhaler device. 5. The inhaler device according to claim 1, wherein the drug reservoir (10) is mounted below the base plate (4). 6. The inhaler device according to claim 1, wherein the drug reservoir (10) is designed to contain a capsule having a powdered drug composition. 7. The inhaler device of claim 6, wherein the powdered pharmaceutical composition is suitable for treating asthma or chronic obstructive pulmonary disease by inhalation. 8. The inhaler device according to claim 6, wherein the powdered pharmaceutical composition contained in the capsule is a dried powdered pharmaceutical product.