HK1123233A - Dispensing device, storage device and method for dispensing a formulation - Google Patents

Description

Dispensing device, storage device and method for dispensing a preparation

Technical Field

The present invention relates to a dispensing device for dispensing a preferred pharmaceutical preparation, in particular comprising or consisting of a drug or a drug mixture, according to the preamble of claim 1; to a storage device for preferably pharmaceutical preparations, in particular comprising or consisting of a drug or a drug mixture, according to the preamble of claim 30; and to a method for dispensing a preferred pharmaceutical preparation, in particular comprising or consisting of a drug or a drug mixture, according to the preamble of claim 50.

Background

The medicament delivered by the dispensing device, in particular the inhaler, is intended to optimally target a specific location in the respiratory system. Including the nasal passages, throat, and various locations within the lungs, such as the bronchi, bronchioles, and alveolar regions. The ability to deliver a drug to a target area depends inter alia on the aerodynamic size of the particles or droplets. As presently understood, particles having an aerodynamic diameter of less than 2 microns are believed to be suitable for deposition in the alveolar region of the lung. Particles having an aerodynamic diameter between 2 microns and about 5 microns may be more suitable for delivery to the bronchiole or bronchi regions. Particles having an aerodynamic particle size range greater than 6 microns and more preferably 10 microns are generally suitable for delivery to the throat, throat or nasal passage.

In most cases, it is desirable to achieve a high respirable fraction and high delivery efficiency, i.e. the fraction of the drug that can reach the desired region (in particular the lungs) in the initial dose. This depends on various factors, in particular on the characteristics of the spray plume produced, such as the propagation velocity of the plume, the particle size and its distribution, the fraction of small particles, the gas fraction or the like. In the present invention, desirable spray plume characteristics preferably include small particle size, high fraction of drug particles below 6 microns in diameter, low propagation velocity and/or long duration of spray generation and possible inhalation.

Disclosure of Invention

The present invention relates to the dispensing of a preferred pharmaceutical formulation. The term "formulation" relates specifically to powders, but may also include or relate to liquids. Thus, the fine "particles" may be solid or liquid. The term "liquid" is preferably to be understood in a broad sense, which covers inter alia solutions, suspensions (suspensions), mixtures thereof or the like. More particularly, the present invention relates to the dispensing of inhalation formulations (e.g., pharmaceutical formulations comprising or consisting of at least one drug).

In the following, the present description will focus on powder formulations. However, it is equally applicable to liquid formulations.

In particular, the present invention relates to dry powder inhalers for delivering drugs to the lungs. Many dry powder inhalers are on the market or have been proposed. There are two main types, passive and active. In passive inhalers, all of the energy required to deagglomerate the powder and deliver the powder to the lungs is provided by the user, i.e. the breathing of the respective patient. In active inhalers, there is an additional energy source to help de-agglomerate the powder.

Most powder inhalers are of the passive type, in which the powder is inhaled by the patient without the aid of an additional energy source. A problem with passive inhalers is that the respirable fraction, or indeed the proportion of powder that enters the lungs, is primarily dependent on the patient's breath. The deagglomeration and hence respirable fraction of the powder is a function of the flow rate of air inhaled through the device and therefore varies greatly from patient to patient.

Dry powder inhalers can be subdivided into single dose and multi-dose devices or inhalers. Multi-dose inhalers can be further subdivided into metered dose inhalers where the doses are stored separately in pre-metered forms and where each powder dose is metered in the device.

Multi-dose pre-metered inhalers have the advantage that the single doses are all metered under stringent factory conditions and the powder can be isolated from the atmosphere quite easily. In many applications, the active drug powder is mixed with a carrier that readily absorbs moisture from the atmosphere (e.g., lactose), which makes it coherent and difficult to deagglomerate.

The invention relates in particular to an active gas (preferably air) powered pre-metered multi-dose dispensing device, such as a dry powder inhaler, for dispensing a formulation comprising or consisting of a drug.

U.S. patent No. 4,627,432A discloses a device for administering a medicament to a patient, an inhaler. The inhaler comprises a disc-shaped blister pack having a plurality of blisters arranged in a circular pattern. Each blister contains a dose of powder. A plunger may open a blister pocket. When a blister is opened, the medicament may be removed by a patient inhaling through a mouthpiece.

It is difficult to completely empty each blister pocket during the dispensing operation. Incomplete emptying results in reduced delivery efficiency. Some powder may fall into the inhaler and not be dispensed because known solutions require a relatively long path for the powder until it reaches the nozzle and is actually dispensed. This can further reduce delivery efficiency. Furthermore, it is difficult to deagglomerate the powder and the powder can clog the outlet nozzle for successive dispensing of multiple doses.

It is an object of the present invention to provide an improved dispensing device, storage device and method of dispensing a preferred pharmaceutical formulation, in particular wherein high delivery efficiency, good sealing and/or desired spray plume characteristics can be achieved.

The above object is achieved by a dispensing device according to claim 1, by a storage device according to claim 30 or by a method according to claim 50. Preferred embodiments are the subject of the respective dependent claims.

One aspect of the invention is to provide a carrier having a plurality of inserts, wherein each insert contains one dose of a formulation to be dispensed. Thus, the carrier can be sealed in an optimal (i.e. extremely efficient) manner. Furthermore, the insert may store the formulation in an optimal manner such that a simple, effective and complete delivery of the respective dose of the formulation may be achieved.

According to a preferred embodiment, said inserts are usable respectively to open an associated seal, in particular by pushing the respective insert through the associated seal of the carrier or at least partially out of the cavity of the carrier containing the respective insert.

According to another embodiment, each insert comprises at least one conduit or nozzle to dispense a respective dose of the formulation and produce the desired spray with the particles.

Drawings

Other aspects, advantages and features of the present invention will become apparent from the claims and the detailed description of the preferred embodiments which follows. In the figure, it shows:

FIG. 1 is a schematic cross-sectional view of a dispensing device having a storage device during dispensing according to an embodiment of the present invention;

FIG. 2 is a top view of the storage device with multiple inserts;

FIG. 3 is a schematic cross-sectional view of an insert;

FIG. 4 is another schematic cross-sectional view of the insert;

FIG. 5 is a schematic longitudinal section of a conduit with a nozzle;

FIG. 6 is a schematic cross-sectional view similar to FIG. 4 with an inserted piercing element;

FIGS. 7a-7c are cross-sectional views of catheters with different cross-sections of the insert;

FIG. 8 is a schematic cross-sectional view of another insert;

FIG. 9 is a schematic cross-sectional view of yet another insert;

FIG. 10 is a schematic cross-sectional view of yet another insert;

FIG. 11 is a schematic cross-sectional view of a dispensing device having a storage device according to another embodiment of the present invention during dispensing; and

FIG. 12 is a schematic view of another storage device.

Detailed Description

In the drawings, the same reference numerals are used for the same or similar components, wherein the same or similar features, characteristics or advantages may be achieved or attained even though a repeated discussion is omitted. Furthermore, the features and aspects of the different embodiments may be combined in any desired manner and/or used in other dispensing devices or methods for dispensing in particular inhaled pharmaceutical preparations.

Fig. 1 shows a schematic cross-sectional view of a dispensing device 1 of the present invention, for illustrative purposes and drawn to scale. The dispensing device 1 is an active device, in particular a pneumatic device. Preferably, the dispensing device 1 is a preferably oral or nasal inhaler (in particular a dry powder inhaler) for a user, i.e. a respective patient (not shown).

The dispensing device 1 can be used to dispense any of the formulations 2 defined in the introductory part of the description. Specifically, pharmaceutical preparation 2 or inhalation preparation 2 may be used. Formulation 2 preferably comprises or consists of at least one drug. When formulation 2 is applied, a spray 3 as shown in fig. 1 is produced. The spray 3 comprises particles (solid and/or liquid) and preferably has the desired spray plume characteristics.

Formulation 2 may be a liquid, in particular a solution, suspension or any mixture thereof, so-called suspension solution (suspension). Preferably, a single suspension solution is used when different drugs are to be administered simultaneously. The principle of the suspension is based on the fact that different drugs can be combined in one formulation simultaneously as a solution and as a suspension. In this respect, reference is made to european patent No. 1087750 a1, which is incorporated herein as an additional disclosure in this respect.

Preferably, the formulation is a powder. The powder may be a pure drug or a mixture of at least two drugs. In addition, the powder may comprise at least one other material, in particular a pharmaceutical carrier (e.g. lactose). In the following, the description focuses on the powder as formulation 2. However, this can be applied in a similar manner if liquid formulation 2 is used.

Preferably, the powder particles have an average diameter of about 2 to 7 microns, in particular below 6 microns. This is particularly true if the powder does not contain any pharmaceutical carrier (e.g. lactose).

If the powder comprises a pharmaceutical carrier (e.g., lactose) and at least one drug, powder 2 may have a particle size of 20-300 microns, specifically about 30-60 microns. However, even in this case deagglomeration, which will be described in more detail later, a spray 3 having a particle size of, for example, about 10 microns or less can be obtained. In particular, when the dispensing device is used as an inhaler, the drug may be separated from the drug carrier during deagglomeration so that the drug is inhaled first due to its small particle size of about 2 to 6 microns and the larger drug carrier will be swallowed. Alternatively or additionally, the pharmaceutical carrier may be broken or opened during deagglomeration.

The diameters mentioned above and below are to be understood as mass median aerodynamic diameter and/or particle size or particle fraction applicable to the spray 3.

The dispensing device 1 is adapted to receive or comprise storage means 4 for storing preferably a plurality and pre-metered doses of the formulation 2. The storage means 4 may be integrated in the dispensing device 1 or form part of the dispensing device 1. Alternatively, the storage means 4 may be a separate part which can be inserted or connected to the dispensing device 1 and optionally replaced.

The storage device 4 comprises a carrier 5 with at least one insert 6, preferably a plurality of inserts 6. In particular, the carrier 5 may comprise 20 to 100, preferably 30 to 60 inserts 6. Each insert 6 preferably contains a pre-metered dose of formulation 2. However, each insert 6 may also contain a plurality of formulations 2, i.e. different formulations 2. Additionally or alternatively, different inserts 6 may contain different formulations. In the present invention, "different" specifically means that the formulation 2 differs in at least one of composition, drug, dose or amount, concentration and consistency of the formulation 2 (e.g., liquid or dry or powder 5).

The carrier 5 comprises a plurality of cavities 7 for receiving the inserts 6. In particular, each insert 6 is located in a separate cavity 7.

The cavities 7 are spaced apart from each other and in particular sealed against each other.

In the present embodiment, each cavity 7 comprises two preferably opposing openings 8. Before use, the openings 8 are covered by respective seals 9, said seals 9 preferably being formed by foils (in particular metal foils, plastic foils, multi-layer arrangements or the like) on opposite sides of the carrier 5.

Fig. 2 shows a storage device 4 with a carrier 5, wherein the top seal 9 and some inserts 6 are omitted. In this embodiment, the carrier 5 is ring-shaped and the cavity 7 extends at least substantially in the axial direction. The cavities 7 are distributed around the periphery of the carrier 5 or along the carrier 5, preferably with the same spacing as adjacent cavities 7.

The carrier 5 may be a molded element, a ring, a strip, a box, a blister or a container. Preferably, the carrier 5 is rigid or at least substantially rigid.

Preferably, the carrier 5 is made of foil, plastic, ceramic and/or composite material, in particular thermoplastic or thermoplastic elastomer and is used for elastomer or silicone sealing.

Each cavity 7 preferably forms a guide for the associated insert 6, in particular so that the insert 6 can be moved at least partially out of the cavity 7 in at least one direction.

Fig. 1 shows a situation in which the insert 6 on the left has been pushed at least partially out of its associated cavity 7 and/or past the respective seal 9 of its associated cavity 7 to open the seal 9. The insert 6 shown on the right side of fig. 1 is still in its closed and sealed cavity 7.

Each insert 6 is preferably manufactured separately from the carrier 5 and then inserted into its respective cavity 7.

Preferably, each insert 6 is made of foil, plastic, ceramic and/or composite material, in particular thermoplastic or thermoplastic elastomer and is used for elastomer or silicone sealing.

According to a preferred embodiment, the carrier 5 and/or the insert 6 are made of at least one of the following materials or any mixture or blend thereof:

ABS (acrylonitrile-butadiene-styrene copolymer); SAN (styrene-acrylonitrile-copolymer); PBT (polybutylene terephthalate); PC (polycarbonate); CA (cellulose acetate); EVA (ethylene vinyl acetate copolymer); PA (polyamide); PE (polyethylene); PP (polypropylene); PMMA (polymethyl methacrylate); POM (polyoxymethylene, polyacetal), PPS (polyphenylene sulfide); PS (polystyrene); PBTP (polybutylene terephthalate); TPU (thermoplastic polyurethane); a blend of PC and PBTP; blends of PC and ABS; LCP (liquid crystal polymers); PHCS (polypyrrole or polythiophene); PPA (polyphthalamide); PSU (polysulfone); PTFE (polytetrafluoroethylene); PUR (polyurethane); SB (styrene-butadiene copolymer); PIB (polyisobutylene); PAN (peroxyacyl nitrate); PET (polyethylene terephthalate); AMMA (acrylonitrile-methyl methacrylate copolymer); PAR (polyarylate); PEEK (polyetheretherketone).

Each insert 6 may form a preferably block-shaped unit and is rigid. Alternatively, the insert 6 may be flexible. In particular, each insert 6 may be an integral unit or be made up of a plurality of elements. Each insert 6 may be a molded element, a cartridge, a blister, a capsule, a container, or the like.

In the following, a preferred configuration of the insert 6 is explained. Preferably, all inserts 6 are identical. However, the (all or some) inserts 6 may also be different. For example, two or more different sets of inserts 6 may be provided. One group may have a different dose or a different formulation 2 than the other group. For example, different sets of inserts 6 may be arranged in alternating succession so that a patient or user may use one insert 6 of one set each morning and one insert 6 of another set each evening, for example.

Each insert 6 comprises a storage cavity 10 for a single dose of the preparation 2. The schematic cross-sectional view of fig. 3 and the schematic cross-sectional view of fig. 4 along the line IV-IV of fig. 3 show a preferred embodiment of the insert 6. The insert 6 comprises a reservoir 10 for the preparation 2. In an embodiment of the invention, the reservoir 10 is preferably formed in a molded base part 11 of the insert 6.

The insert 6/base part 11 further comprises a conduit 12 or the like for expelling the preparation 2 during a dispensing operation. During the dispensing operation the formulation 2 is dispensed through the conduit 12, in particular for deagglomerating the powder and/or forming the spray 3.

The conduit 12 may preferably comprise a nozzle (orifice) 13 at the outlet, as shown in the schematic longitudinal section of fig. 5. Alternatively, a nozzle 13 or any other suitable nozzle arrangement may be used instead of the conduit 12 or the nozzle 13 may be used in any other combination with the conduit 12.

Preferably, the conduit 12/nozzle 13 is formed by the base part 11, in particular by a recess, groove or the like in the base part 11 and by the associated cover part 14, as shown in fig. 4. In particular, the conduit 12 forms a passage from the reservoir 10 to the outlet 15 of the insert 6 to discharge the formulation 2 as a spray 3, as shown in fig. 1.

The insert 6 preferably comprises an inlet for supplying pressurised gas to the reservoir 10 to force the formulation 2 through the conduit 12/nozzle 13 and dispense the formulation 2 as a spray 3. In the present embodiment, the inlet is preferably designed as a tubular recess or blind hole 16 formed in the base part 11. Preferably, the recesses 16 are not directly connected to the reservoir 10, but are separated by an intermediate wall. This wall can be pierced, for example, by a piercing element 17 (for example a needle schematically illustrated in fig. 6) or by any other suitable opening and/or supply means, in particular when the respective insert 6 is connected to a gas source as described hereinafter. In the present invention, the expression "piercing element 17" preferably also covers all other suitable types of means for opening the carrier 5, the cavity 7 and/or the insert 6 and/or for directly or indirectly supplying gas to the insert 6 or its respective storage chamber 10.

The dispensing device 1 uses pressurized gas to force the formulation 2 through the conduit 12/nozzle 13 to deagglomerate the powder and/or produce a spray 3 with fine particles. Preferably, the dispensing device 1 comprises means for providing pressurized gas (in this embodiment an air pump 18), which preferably can be manually actuated or operated as shown by a handle or actuator 19. Specifically, the air pump 18 includes or is formed of a bellows (bellow). However, it may also be a piston-cylinder arrangement. In addition to the air pump 18, the means for providing pressurized gas may be, for example, a bladder, container, or the like, containing a pressurized or liquefied gas to energize the dispensing device 1 (i.e., dispense the formulation 2 as desired).

The air pump 18 may provide a gas pressure of less than 300kPa, specifically about 50 to 200 kPa. This is preferably sufficient for operating the dispensing device 1. If a liquefied gas or a container with pressurized gas is used, the gas pressure may be between 100kPa to about 700 kPa. The pressure may then be reduced or throttled to the preferred pressure range before supplying the gas to the storage means 4, in particular the storage chamber 10 of the respective insert 6.

Preferably, all pressure values mentioned in this specification are gauge pressures, i.e. pressure differences. All pressure values relate to the pressure in the gas reservoir, for example with a pressurised or liquefied gas container, or the pressure provided by the air pump 18, or to the pressure acting in the chamber 10 and/or the conduit 12.

Fig. 1 shows that the dispensing device 1 comprises means 20 for individually connecting the inserts 6 to the gas source, in particular to the air pump 18. The mechanism 20 preferably comprises a piercing element 17 or any other suitable connecting element. In this embodiment, the mechanism 20 is coupled to a first (lower) housing part 21 of the dispensing device 1. The dispensing device 1 further comprises a second (upper) housing part 22 which can support the storage means 4/carrier 5.

According to an embodiment, the first and second housing parts 21, 22 are movable relative to each other, in particular in axial direction relative to the axis of rotation of the carrier 5 or parallel to the orientation of the cavity 7. This relative movement enables the mechanism 20, in particular the piercing element 17 thereof, to connect or pierce the respective insert 6 close to the mechanism 20.

In particular, this relative movement causes a first phase in which the piercing element 17 pierces the seal 9 and is then inserted into the recess 16 and through the end wall into the storage chamber 10 and thus connects the respective insert 6 to the gas source. In the next stage, i.e. during further movement, a shoulder or abutment 23, preferably schematically shown in fig. 6, abuts at the insert 6 so that the insert 6 protrudes at least partially out of its cavity 7 through the further opening 8 and through the respective seal 9. This final situation is shown in fig. 1.

The relative movement of the first and second housing members 21, 22 may also cause the air pump 18 to actuate or turn on any other gas reservoir. In an embodiment of the invention, the air pump 18 may be actuated solely by means of the actuator 19.

For dispensing, the gas is supplied under pressure to the storage chamber 10 via the piercing element 17 or any other suitable supply element.

The gas (air) creates a corresponding flow in the reservoir 10 to force the full dose through the conduit 12.

The powder will be discharged, in particular forced, through the conduit 12 at a relatively low gas pressure, preferably less than 300kPa, in particular about 50 to 200 kPa. This low gas pressure, which is significantly lower than the gas pressure in previous dispensing devices, enables a correspondingly low discharge velocity and thus a slow propagation velocity of the low spray 3.

Preferably, the storage chamber 10 forms a mixing chamber for mixing the gas with the powder. The chamber 10 is preferably designed so that the gas can create a vortex or vortex to better mix the powder with the gas. Preferably, the cross-section of the chamber 10 is substantially circular, in particular cylindrical. However, other shapes are possible.

Furthermore, the chamber 10 is formed without sharp edges, corners or the like, but with a smooth profile so that the gas can be blown across all chamber surfaces to prevent powder from collecting on the surfaces and to ensure or allow complete discharge of the powder. In particular, the gas inlet formed by the piercing element 17 or any other supply element is positioned opposite the outlet (i.e. the conduit 12 and/or the nozzle 13) with respect to the axial or outlet direction.

The storage device 14 may comprise only one insert 6 with one storage chamber 10 for a single dose or with a plurality of storage chambers 10 with different preparations 2, in which case the storage device 4 is used for only a single dose or use, but the storage device 4 preferably comprises a plurality of inserts 6 and thus contains a plurality of doses of preparations 2 that can be dispensed sequentially.

During this dispensing operation, the spray 3 is preferably generated directly by the respective insert 6 or its conduit 12/nozzle 13 and output to a mouthpiece 24 (as shown in fig. 1) of the dispensing device 1 for inhalation by a patient or user (not shown).

After dispensing of a dose or when dispensing the next dose, the piercing element 17 will be withdrawn through the connecting insert 6, in particular due to the opposite relative movement of the first and second housing parts 21 and 22. During this reverse movement or by separate actuation or during the movement connecting the next card 6 to the gas source, the carrier 5 is further indexed by one step or to the next card 6, in particular by means of a indexing or transport mechanism (not shown) rotating. This mechanism is preferably operated by relative transport of the first and second housing parts 21, 22 or by actuating another actuator, by opening a lid of the dispensing device 1 or the like.

In the present embodiment, the carrier 5 is preferably rotatable about the axis "a" shown in fig. 1 and is supported by a holder 25 preferably connected to the second case member 21. In particular, the dispensing device 1 can be opened and the storage device 4/carrier 5 can be inserted or replaced.

It should be noted that the first and second case units 21, 22 may alternatively or additionally rotate relative to each other in addition to the relative axial movement described above. Thus, the mechanism 20 may be adapted to provide the desired function, in particular the axial connection and replacement of the respective insert 6, respectively.

It should be noted that the insert 6 is preferably open, i.e. not sealed. Tests have shown that the carrier 5/cavity 7 seal is sufficient. The conduit 12/nozzle 13 is preferably so small that the preparation 2 cannot be discharged even if the seal 9 is opened and during vigorous shaking of the dispensing device 1/storage device 4.

Furthermore, the insert 6 and the cavity 7 are preferably adapted to each other such that the seal 9 contacts an end face of the insert 6 and thus covers the outlet 15. This may further prevent any formulation 2 from being expelled through the conduit 12/outlet 15 before it is desired to be dispensed.

It should be noted that the cross-section of the insert 6 and the cavity 7 is preferably polygonal, in particular rectangular, to avoid that the insert 6 rotates within the cavity 7. However, if the insert 6 is symmetrically rotatable with respect to the recess 16 or the connection/inlet of any other gas source and with respect to its outlet 15, the insert 6 may also be cylindrical and/or may rotate in the cavity 7. This may facilitate insertion of the insert 6 into the cavity 7 during manufacture.

According to a preferred aspect, the conduit 12 has a flattened (inner) cross-section. Figures 7a to 7c show possible cross-sections of the conduit 12. Fig. 7a shows a substantially rectangular cross-section. Figure 7b shows a flat cross-section with two opposing straight sides connected by two curved portions. Figure 7c shows an oval or elliptical cross-section.

A cross-section is considered flat when the ratio of the largest side d1 to the smallest side d2 of the cross-section is at least 2.0. Preferably, the ratio is between 3 and 50 and in particular about 5 to 70. It should be noted that the cross-sections shown in fig. 7 are not drawn to scale.

The maximum edge d1 is preferably between 0.5 mm and 5 mm, in particular between 1 mm and 3 mm. Most preferably, the ratio of the maximum side d1 to the (desired) particle size of the particles (mass median diameter of the powder particles or drug particles of the spray 3) is less than 500, preferably less than 300, in particular about 30 to 300.

The minimum edge d2 is preferably between 0.05 mm and 0.5 mm, specifically about 0.07 mm to 0.25 mm. Most preferably, the ratio of the minimum edge d2 to the mass median (desired) particle size of the particles (median diameter of powder particles/drug particles of spray 3) is less than 50, preferably less than 30, in particular about 3 to 20.

The length of the conduit 12 refers to the length having this flattened cross section. Thus, the conduit 12 may have a longer length, i.e. another cross-sectional shape and/or other parts having a larger cross-sectional area, so that the influence of said other parts on the mixture of gas and powder is lower than in the part of the conduit 12 with the flat cross-section. However, the cross-sectional area and/or shape of the flattened cross-section may vary over the length of the conduit 12 (the portion with the flattened cross-section). Thus, the cross-sectional area of the conduit 12 may decrease from the inlet to the outlet or vice versa.

Most preferably, the conduit 12 comprises at least a portion of a flat cross-section having a constant cross-sectional area (i.e., constant diameter and/or shape).

The length of the conduit 12 (i.e. the portion having a flat cross-section) may be between 3 mm and 80 mm, in particular 5 mm to 15 mm. Preferably, the conduit length is adapted to the average hydraulic diameter of the conduit 12 such that the ratio of the length of the conduit 12 to the average hydraulic diameter, defined as the ratio of four cross-sectional areas over the circumference of the conduit, is at least 5, in particular about 10, preferably 20 to 60, or more.

The diameter of the preferably circular or cylindrical or conical chamber 10 depends on the volume or mass of the respective dose of formulation 2. A single dose may have, for example, 1 mg to 2 mg (pure drug, without carrier) or 2 mg to 10 mg (blend of drug and carrier, in particular lactose). In this first case, the diameter preferably ranges between 1.5 mm and 2.5 mm. In this second case, the diameter preferably ranges between 2 mm and 5 mm. Preferably, the cross-section of the conduit 12 varies in a similar manner. For example, the minimum side d2 is about 0.07 to 0.1 millimeters in the first case and about 0.15 to 0.25 millimeters in the second case. The larger (inner) side d1 is not strongly dependent on the powder or spray particle size. Preferably, it ranges from about 1 to 2 mm in the first case and from 1 to 3 mm in the second case.

The conduit 12 preferably has an average hydraulic diameter of less than 1 mm, specifically 0.1 mm to 0.6 mm.

Preferably, the conduit 12 is molded and/or formed by a flat groove with a cover.

According to another embodiment, the dispensing device 1 may comprise a common conduit 12/nozzle 13 to sequentially dispense doses of the formulation 2 from the insert 6. In this case, the insert 6 can press with its outlet 15 this common conduit 12/nozzle 13 (not shown), which can be arranged, for example, above the raised insert 6 shown in fig. 1, i.e. in or below the blowing nozzle 24.

Each insert may comprise a plurality of conduits 12 for simultaneously dispensing a dose, in particular for increasing the total mass flow or output, so that a desired dose may be expelled or dispensed in a sufficiently short time as desired and/or required.

Fig. 8 shows a further embodiment of the insert 6 in a sectional view similar to fig. 3. Here, the insert 6 comprises two conduits 12 associated or connected to the same reservoir 10.

Fig. 9 shows in a schematic sectional view a further insert 6 with a means of slowing down the velocity, which forms a multiple jet impingement device 18. The device 18 forms a plurality of-at least two-jets P that impinge upon each other (i.e., collide with each other as shown in fig. 9). In this embodiment, the conduit 12 is divided into two portions 12a and 12b, which are designed so that the openings or outlets 15 are inclined to each other so that the jets P emitted from the portions 12a and 12b are inclined to each other and impinge. For example, a flow splitter 27 or any directing device may be positioned in the flow path to form at least two sections 12a and 12b of the conduit 12, as shown in fig. 9.

It should be noted that the cross-section of the conduit portions 12a and 12b is preferably not flat, but may have any suitable cross-sectional shape.

The angle of impingement α between the jets P is between 30 ° and 180 °, preferably at least 90 °, in particular about 90 ° to 150 ° for powders. The impact of the jet P leads to a reduction in the velocity of the spray 3 and/or to deagglomeration or droplet formation of the powder and/or to separation of the medicament particles from a carrier and/or to preferential concentration of the spray 3. The effect depends on the impact angle alpha. A larger impact angle alpha tends to result in a better effect. In contrast to liquid jets, an impingement angle α of 90 ° and above is possible and preferred for powders. The angles also apply to the following embodiments.

In the embodiment shown in fig. 9, the conduit 12 is preferably at least tangentially connected to the reservoir 10. Preferably, the conduit 12 is connected at one axial end of the preferably cylindrical chamber 10 and the gas inlet is connected to the other axial end of the chamber 10. In particular, the gas inlet is also tangentially connected to the reservoir 10 so as to generate a vortex when the gas enters in a vortex direction to support the exit of the mixture of gas and agent 2 through a conduit 12 tangentially connected to the direction of rotation of the vortex.

It should be noted that the present invention, in particular the dispensing device 1 and/or the storage device 4, may be used for dispensing one drug, a blend of drugs or at least two or three separate drugs. In the latter case, the individual medicaments are stored in individual storage chambers 10 and during the dispensing operation the medicaments are mixed with the gas in a common mixing chamber or in their respective storage chambers 10. Furthermore, the individual drugs may be discharged through the common conduit 12 nozzle 13 or through the individual conduit 12 nozzles 13. In the latter case, the individual medicaments will be mixed after leaving the individual conduits 12/nozzles 13 or in the mouthpiece 24 or in any other suitable (additional) mixing chamber. The individual drugs may also be mixed by impinging jets of the individual drugs. To dispense the individual drugs, a common gas source or means for pressurizing the gas (e.g., air pump 18) is preferably used.

Fig. 10 shows a further embodiment of the insert 6 in a schematic sectional view. Two different formulations 2 'and 2 "are contained in separate reservoirs 10' and 10", respectively. Gas may be supplied to chambers 10' and 10 ", respectively, via common inlet/recess 16. The formulations 2 'and 2 "may be dispensed and deagglomerated by means of separate conduits 12' and 12" or (not shown) separate nozzles or the like. The jets P of separate and distinct formulations 2 ' and 2 "ejected from separate conduits 12 ' and 12" preferably impinge to mix the separate formulations 2 ' and 2 "at the very time the spray 3 (not shown) is formed. The jet impingement device 26 mixes the individual formulations 2 'and 2 ", but may also be used to slow the propagation velocity of the spray 3 and/or to support deagglomeration of the powder formulations 2' and 2" or separation of the individual drugs from the carrier.

The embodiments of fig. 9 to 10 are also suitable for impingement of more than two jets P. For example, there may be a similar arrangement in a cross-sectional plane perpendicular to the plane of the figure to obtain four outlet directions and a jet P arranged on a conical surface. However, a number of other arrangements with similar effect are possible.

According to another (not shown) embodiment, the conduit 5 may also serve as a reservoir (reservoir 10) for the formulation 2. In this case, the separate storage chamber 10 is not required. The conduit 12 is then designed to enable sufficient mixing of the gas with the formulation 2 and sufficient deagglomeration of the powder formulation 2.

Preferably, the spray 3 has an average velocity (taken at 20 cm from the outlet 15 or the mouthpiece 24) of less than 2 m/s, in particular less than 1 m/s. Preferably, the average duration of the spray 3 should be at least 0.2 or 0.3 seconds, in particular about 0.5 to 25.

Fig. 11 shows another embodiment of the dispensing device 1. In the following, only the differences will be emphasized. The previous description, particularly with respect to the fig. 1 embodiment, may additionally or similarly apply.

In the embodiment of fig. 11, the cavities 7 are oriented in a tangential or radial direction of the carrier 5. Thus, the insert 6 can be moved individually in a tangential or radial direction, in particular outwards, to open the respective outer seal 9 for dispensing the respective dose of the formulation 2, as shown in fig. 11. Thus, the mechanism 20 operates in a radial direction to connect the inserts 6 individually to a source of gas and to push the inserts 6 individually at least partially out of the respective cavities 7 and/or through the respective seals 9. This radial movement allows an extremely compact design of the dispensing device 1, in particular in the axial direction.

Preferably, the mouthpiece 24 and the dispensing direction extend in a radial or tangential direction, as shown in fig. 11.

Preferably, the dispensing device 1 comprises a lever or handle (not shown) for manual actuation to further index the carrier 5 by one step (i.e. to the next insert 6), and/or an operating mechanism 20, preferably connecting the respective insert 6 to the gas source or moving/pushing the respective insert 6 and opening the respective seal to dispense the respective dose of the formulation 2.

It should be noted that all the dispensing devices 1 described above preferably operate only mechanically.

Fig. 12 shows another embodiment of the storage device 4/carrier 5. Here, the carrier 5 is like a strip or a bar, i.e. preferably substantially linear or rectilinear. This facilitates the manufacture of the carrier 5, since the lamination of the seal 9 on the opposite straight side of the carrier 5 is simple. In particular, the seal 9 (e.g. a foil) is laminated to the carrier 5 by e.g. heat sealing or the like.

In the above embodiment, the carrier 5 is preferably rigid. In the present embodiment, the carrier 5 is preferably flexible and bendable into a preferably circular arrangement and attached to its ends, e.g. by gluing, into a closed band or loop.

The insert 6 is preferably rigid, in particular if formed by a moulded element or the like. However, the insert 6 may alternatively be flexible, in particular if formed by a bubble or the like.

The arrow P indicates the possible movement of one of the inserts 6 in order to open the respective seal 9.

According to another embodiment (not shown), the insert 6 may be formed as a balloon or the like without any conduits 12, nozzles 13 or the like. Instead, each insert 6 is individually connected to a gas source and to a common outlet arrangement (e.g. conduit 12, nozzle 13 or the like) to administer a respective dose of formulation 2.

According to another embodiment, a secondary packaging may be used for packaging and protecting the storage means 4/carrier 5, in particular for the purpose of storage before the storage means 4/carrier 5 is inserted into the dispensing device 1. Furthermore, the entire device 1 including the storage means 4/carrier 5 can be stored in a secondary moisture-proof package.

According to another embodiment, the dispensing device 1 may be breath activated, in particular wherein the formulation 2 is released only after the patient or user inhalation rate reaches a predetermined level, preferably by using a pressure sensitive device (e.g. a bursting element, membrane or valve) or any other mechanism.

In the following, two examples are set forth showing the function of the preferred insert 6 with the conduit 12.

Example 1: a blend of 90.0 wt% lactose 200, 9.7 wt% fine lactose, and 0.3 wt% tiotropium was used. Lactose 200 has an average particle diameter of about 45 microns, fine lactose of about 4 microns and tiotropium of about 4 microns. About 5.5 mg of the blend was placed as a powder in a reservoir 10 having a substantially cylindrical shape with a diameter of 3 mm and an axial length of 3 mm. 5 ml of compressed air was supplied to the chamber 10 at a gauge pressure of about 100 kPa. The powder is dispensed through a conduit 12 of substantially rectangular cross-section having a minimum dimension of about 0.18 mm and a maximum dimension of about 1.5 mm. The conduit 12 is divided into two conduit portions 12a and 12b (specifically as shown in fig. 9), wherein each portion has a substantially rectangular cross-section with a minimum side of about 0.18 millimeters and a maximum side of about 0.75 millimeters. The total length of the conduit 12 (including the sections 12a, 12b) is about 8 mm. The result is that 100% of the metered mass (i.e., all of the powder in chamber 10) is dispensed. About 50% tiotropium was measured as a fine fraction on an Anderson Cascade Impactor at 30 and 60 litres/min.

Example 2: about 1.5 mg of fenoterol having an average particle diameter of 4 μm was placed as a powder in a reservoir 10, the reservoir 10 having a substantially cylindrical shape with a diameter of 2 mm and an axial length of 2 mm. 5 ml of compressed air was supplied to chamber 10 via a gas inlet having a 0.5 mm inlet orifice at a gauge pressure of about 150 kPa. The powder is dispensed through a conduit 12 of substantially rectangular cross-section having a minimum side of 0.075 mm and a maximum side of 1.5 mm. The conduit 12 is divided into two conduit portions 12a and 12b (specifically as shown in fig. 9), wherein each portion has a substantially rectangular cross-section with a minimum side of about 0.075 mm and a maximum side of about 0.75 mm. The total length of the channel (including the portions 12a, 12b) is about 8 mm. The result is that 100% of the metered mass (i.e., all of the powder in chamber 10) is dispensed. About 45% of fenoterol was measured as a fine fraction on an Anderson Cascade Impactor at 30 and 60 liters/min.

The formulation may comprise or consist of a further pharmacologically active substance or substance mixture preferably selected from the group consisting of:

the compounds mentioned below can be used alone or in combination with other active substances for use in the device according to the invention. These compounds include, inter alia, betamimetics, anticholinergics, corticosteroids, PDE 4-inhibitors, LTD 4-antagonists, EGFR-inhibitors, dopamine agonists, antiallergic agents, PAF-antagonists and PI 3-enzyme inhibitors, as well as combinations of two or three active substances, namely:

- β mimetics with corticosteroids, PDE 4-inhibitors, EGFR-inhibitors or LTD 4-antagonists;

-anticholinergics with beta mimetics, corticosteroids, PDE 4-inhibitors, EGFR-inhibitors or LTD 4-antagonists;

-corticosteroids with PDE 4-inhibitors, EGFR-inhibitors or LTD 4-antagonists;

-PDE 4-inhibitors with EGFR-inhibitors or LTD 4-antagonists;

EGFR-inhibitors and LTD 4-antagonists.

Examples of preferred betamimetics that may be mentioned include: salbutamol, arformoterol (arformoterol), bambuterol, bitolterol, bromsalterol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, ethylisoproterenol, isoproterenol, levalbuterol, mabuterol, meluadrine, metaproterenol, pirbuterol, procaterol, reproterol, rimiterol, ritodrine, salmeterol, soterel (soterenot), sulphoterol, terbutaline, tiaramide, terlubuterol (tolbuterol), clenbuterol (zinterole), CHF-1035, HOKU-81, KUL-1248, and

3- (4- {6- [ 2-hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino ] -hexyloxy } -butyl) -benzyl-sulphonamide

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-benzimidazolyl) -2-methyl-2-butylamino ] ethanol

1- [3- (4-methoxybenzyl-amino) -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-propylamino ] ethanol

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) -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

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

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

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

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

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

8- {2- [2- (4-ethoxy-phenyl) -1, 1-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 [1, 4] oxazin-8-yl) -ethylamino ] -2-methyl-propyl } -phenoxy) -butyric acid

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

1- (4-ethoxy-carbonylamino-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 ] -carboxamide

8-hydroxy-5- (1-hydroxy-2- {2- [4- (6-methoxy-biphenyl-3-ylamino) -phenyl ] -ethylamino } -ethyl) -1H-quinolin-2-one

8-hydroxy-5- [ 1-hydroxy-2- (6-phenethylamino-hexylamino) -ethyl ] -1H-quinolin-2-one

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

[3- (4- {6- [ 2-hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino ] -hexyloxy } -butyl) -5-methyl-phenyl ] -urea

4- (2- {6- [2- (2, 6-dichloro-benzyloxy) -ethoxy ] -hexylamino } -1-hydroxy-ethyl) -2-hydroxymethyl-phenol

3- (4- {6- [ 2-hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino ] -hexyloxy } -butyl) -benzenesulfonamide

3- (3- {7- [ 2-hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino ] -heptyloxy } -propyl) -benzenesulfonamide

4- (2- {6- [4- (3-cyclopentanesulfonyl-phenyl) -butoxy ] -hexylamino } -1-hydroxy-ethyl) -2-hydroxymethyl-phenol

N-adamantan-2-yl-2- (3- {2- [ 2-hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino ] -propyl } -phenyl) -acetamide,

optionally in the form of its racemate, enantiomers or diastereomers, or optionally in the form of a pharmacologically acceptable acid addition salt, solvate or hydrate thereof. Preferably selected from the following salts: hydrochloride, hydrobromide, hydroiodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate.

Examples of preferred anticholinergic agents that may be mentioned include: tiotropium (Tiotropium) salts, preferably bromide salts; an Oxitropium (Oxitropium) salt, preferably a bromide salt; a fluorotropium (flutropimum) salt, preferably a bromide salt; ipratropium (Ipratropium) salts, preferably bromide salts; glycopyrronium (Glycopyrronium) salts, preferably bromide salts; trospium (Trospium) salt, preferably the chloride salt, tolterodine (Tolterodin). In the above mentioned salts the pharmacologically active moiety is a cation and possible anions are chloride, bromide, iodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate or p-toluenesulphonate. In addition to this, the present invention is,

2, 2-diphenyl-propionic acid tropine ester methyl bromide,

2, 2-diphenyl-propionic acid tropyl ester methyl bromide,

2-fluoro-2, 2-diphenyl acetic acid tropyl ester methyl bromide,

2-fluoro-2, 2-diphenylacetic acid tropine ester methyl bromide,

3, 3 ', 4, 4' -tetrafluoro-benzilic acid tropine ester methyl bromide,

3, 3 ', 4, 4' -tetrafluorobenzilic acid tropine ester bromide,

4, 4' -difluoro-diphenyl glycol tropine ester methyl bromide,

4, 4' -difluorobenzilic acid tropine ester methyl bromide,

3, 3' -difluoro-diphenyl glycol tropine ester methyl bromide,

3, 3' -difluorobenzilic acid tropine ester methyl bromide,

9-hydroxy-fluorene-9-carboxylic acid tropine ester methyl bromide,

9-fluoro-fluorene-9-carboxylic acid tropine ester methyl bromide,

9-hydroxy-fluorene-9-carboxylic acid tropyl ester methyl bromide,

9-fluoro-fluorene-9-carboxylic acid tropyl ester methyl bromide,

9-methyl-fluorene-9-carboxylic acid tropine ester methyl bromide,

9-methyl-fluorene-9-carboxylic acid tropyl ester methyl bromide,

Benzhydryl glycollic acid cyclopropyl hyoscyamine ester bromide,

Cyclopropyl scopolamine ester methyl bromide of 2, 2-diphenyl propionic acid,

9-hydroxy-xanthene-9-carboxylic acid cyclopropyl hyoscyamine ester methyl bromide,

9-methyl-fluorene-9-carboxylic acid cyclopropyl scopolamine ester methyl bromide,

9-methyl-xanthene-9-carboxylic acid cyclopropyl hyoscyamine ester methyl bromide,

9-hydroxy-fluorene-9-carboxylic acid cyclopropyl hyoscyamine ester methyl bromide,

4, 4' -difluorobenzilic acid cyclopropyl scopolamine methyl ester methyl bromide,

9-hydroxy-xanthene-9-carboxylic acid tropine ester methyl bromide,

9-hydroxy-xanthene-9-carboxylic acid tropyl ester methyl bromide,

9-methyl-xanthene-9-carboxylic acid tropine ester methyl bromide,

9-methyl-xanthene-9-carboxylic acid tropyl ester methyl bromide,

9-ethyl-xanthene-9-carboxylic acid tropine ester methyl bromide,

9-difluoromethyl-xanthene-9-carboxylic acid tropine ester methyl bromide,

9-hydroxymethyl-xanthene-9-carboxylic acid tropyl ester methobromide.

Examples of preferred corticosteroids that may be mentioned include: beclomethasone, betamethasone, budesonide, buticorte (Butixocorte), ciclesonide, Deflazacorte (Deflazacorte), dexamethasone, eprinonol (etipredinole), flunisolide, fluticasone, loteprednol (Loteprednole), mometasone, prednisolone, prednisone, rofleponide, triamcinolone, RPR-106541, NS-126, ST-26, and

6, 9-difluoro-17- [ (2-furylcarbonyl) oxy ] -11-hydroxy-16-methyl-3-oxo-androsta-1, 4-diene-17-thiocarbonic acid (S) -fluoromethyl ester

6, 9-difluoro-11-hydroxy-16-methyl-3-oxo-17-propionyloxy-androsta-1, 4-diene-17-carbothioic acid (S) - (2-oxo-tetrahydro-furan-3S-yl) ester

6 α, 9 α -difluoro-11 β -hydroxy-16 α -methyl-3-oxo-17 α - (2, 2, 3, 3-tetramethylcyclopropylcarbonyl) oxy-androsta-1, 4-diene-17 β -carboxylic acid cyanomethyl ester

Optionally in racemic form, as enantiomers, diastereomers, or as pharmacologically acceptable salts, solvates or hydrates. Examples of preferred salts and derivatives are alkali metal salts (i.e. sodium or potassium salts), sulphobenzoates, phosphates, isonicotinates, acetates, dichloroacetates, propionates, dihydrogen phosphates, palmitates, pivaloates or furoates.

Examples of preferred PDE 4-inhibitors which may be mentioned include: enprophylline, theophylline, roflumilast, Elefurt (cilomilast), tolofurate (Tofimilate), Premafenprox, Lirimalate (Lirimalate), arotheophylline, Altiroma, D4418, 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, C1-1018, 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- [ (4 aR)^*，10bS^*) -9-ethoxy-1, 2, 3, 4, 4a, 10 b-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-pyrrolidinone

Cis [ 4-cyano-4- (3-cyclopentyloxy-4-methoxyphenyl) cyclohexane-1-carboxylic acid ]

2-carbomethoxy-4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohex-1-one

Cis [ 4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohex-1-ol ]

(R) - (+) -ethyl [4- (3-cyclopentyloxy-4-methoxyphenyl) pyrrolidin-2-ylidene ] acetate

(S) - (-) -ethyl [4- (3-cyclopentyloxy-4-methoxyphenyl) pyrrolidin-2-ylidene ] acetate

9-cyclopentyl-5, 6-dihydro-7-ethyl-3- (2-thienyl) -9H-pyrazolo [3, 4-c ] -1, 2, 4-triazolo [4, 3-a ] pyridine

9-cyclopentyl-5, 6-dihydro-7-ethyl-3- (tert-butyl) -9H-pyrazolo [3, 4-c ] -1, 2, 4-triazolo [4, 3-a ] pyridine,

optionally in the form of its racemate, enantiomers or diastereomers, or optionally in the form of a pharmacologically acceptable acid addition salt, solvate or hydrate thereof. Preferably selected from the following salts: hydrochloride, hydrobromide, hydroiodide, sulphate, phosphate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate salts.

Examples of preferred LTD 4-antagonists which may be mentioned include: montelukast, pranlukast, zafirlukast, MCC-847(ZD-3523), MN-001, MEN-91507(LM-1507), VUF-5078, VUF-K-8707, L-733321 and

1- (((R) - (3- (2- (6, 7-difluoro-2-quinolinyl) ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl) phenyl) -sulfanyl) -methyl-cyclopropane-acetic acid

1- (((1(R) -3(3- (2- (2, 3-dichlorothieno [3, 2-b ] pyridin-5-yl) - (E) -vinyl) phenyl) -3- (2- (1-hydroxy-1-methyl-ethyl) phenyl) propyl) thio) methyl) cyclopropane-acetic acid

[2- [ [2- (4-tert-butyl-2-thiazolyl) -5-benzofuranyl ] oxymethyl ] phenyl ] -acetic acid

Optionally in the form of its racemate, enantiomers or diastereomers, or optionally in the form of a pharmacologically acceptable acid addition salt, solvate or hydrate thereof. Preferably selected from the respective salts: hydrochloride, hydrobromide, hydroiodide, sulphate, phosphate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate salts. Other examples of optionally preferred salts and derivatives are alkali metal salts (i.e. sodium or potassium salts), sulphobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates, palmitates, pivaloates or furoates.

Examples of preferred EGFR-inhibitors which may be mentioned include: cetuximab, trastuzumab, ABX-EGF, Mab ICR-62 and

4- [ (3-chloro-4-fluorophenyl) amino ] -6- { [4- (morpholin-4-yl) -1-oxo-2-buten-1-yl ] amino } -7-cyclopropylmethoxy-quinazoline

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

4- [ (3-chloro-4-fluorophenyl) amino ] -6- { [4- (N, N-dimethylamino) -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-cyclopropylmethoxy-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- { [4- ((R) -2-methoxymethyl-6-oxo-morpholin-4-yl) -1-oxo-2-buten-1-yl ] amino } -7-cyclopropylmethoxy-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- [ (3-chloro-4-fluorophenyl) amino ] -6- { [4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl ] amino } -7-cyclopentyloxy-quinazoline

4- [ (R) - (1-phenyl-ethyl) amino ] -6- { [4- (N, N-bis- (2-methoxy-ethyl) -amino) -1-oxo-2-buten-1-yl ] amino } -7-cyclopropylmethoxy-quinazoline

4- [ (R) - (1-phenyl-ethyl) amino ] -6- ({4- [ N- (2-methoxy-ethyl) -N-ethyl-amino ] -1-oxo-2-buten-1-yl } amino) -7-cyclopropylmethoxy-quinazoline

4- [ (R) - (1-phenyl-ethyl) 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, N-dimethylamino) -1-oxo-2-buten-1-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-methoxy-ethyl) -N-methyl-amino ] -1-oxo-2-buten-1-yl } amino) -7-cyclopentyloxy-quinazoline

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

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

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

4- [ (3-ethynyl-phenyl) amino ] -6, 7-bis- (2-methoxy-ethoxy) -quinazoline

4- [ (3-chloro-4-fluorophenyl) amino ] -7- [3- (morpholin-4-yl) -propyloxy ] -6- [ (vinyl-carbonyl) amino ] -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-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-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-chloro-4-fluorophenyl) amino ] -6- ({4- [ N, N-bis- (2-methoxy-ethyl) -amino ] -1-oxo-2-buten-1-yl } amino) -7- [ (tetrahydrofuran-2-yl) methoxy ] -quinazoline

4- [ (3-ethynyl-phenyl) amino ] -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- (2, 2-dimethyl-6-oxo-morpholin-4-yl) -ethoxy ] -7-methoxy-quinazoline

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

4- [ (3-chloro-4-fluoro-phenyl) amino ] -7- [2- (2, 2-dimethyl-6-oxo-morpholin-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-fluoro-phenyl) amino ] -6- (trans-4-amino-cyclohex-1-yloxy) -7-methoxy-quinazoline

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- (trans-4-methanesulfonylamino-cyclohex-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-methyl-piperidin-4-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- {1- [ (methoxymethyl) carbonyl ] -piperidin-4-yloxy } -7-methoxy-quinazoline

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-hydroxy-quinazoline

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 ] -cyclohex-1-yloxy } -7-methoxy-quinazoline

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

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

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

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

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- (trans-4-ethanesulfonylamino-cyclohex-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-methoxy-ethoxy) -quinazoline

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- (cis-4-acetylamino-cyclohex-1-yloxy) -7-methoxy-quinazoline

4- [ (3-ethynyl-phenyl) amino ] -6- [1- (tert-butyloxycarbonyl) -piperidin-4-yloxy ] -7-methoxy-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 } -cyclohex-1-yloxy) -7-methoxy-quinazoline

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

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- { cis-4- [ (morpholin-4-yl) carbonylamino ] -cyclohex-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-chloro-4-fluoro-phenyl) amino ] -6- {1- [ (morpholin-4-yl) carbonyl ] -piperidin-4-yloxy } -7- (2-methoxy-ethoxy) -quinazoline

4- [ (3-ethynyl-phenyl) amino ] -6- (1-acetyl-piperidin-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-methanesulfonyl-piperidin-4-yloxy) -7-methoxy-quinazoline

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

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

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- (cis-4-methylamino-cyclohex-1-yloxy) -7-methoxy-quinazoline

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- { cis-4- [ N- (2-methoxy-acetyl) -N-methyl-amino ] -cyclohex-1-yloxy } -7-methoxy-quinazoline

4- [ (3-ethynyl-phenyl) amino ] -6- (piperidin-4-yloxy) -7-methoxy-quinazoline

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

4- [ (3-ethynyl-phenyl) amino ] -6- {1- [ (morpholin-4-yl) carbonyl ] -piperidin-4-yloxy } -7-methoxy-quinazoline

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- {1- [ (cis-2, 6-dimethyl-morpholin-4-yl) carbonyl ] -piperidin-4-yloxy ] -7-methoxy-quinazoline

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- {1- [ (2-methyl-morpholin-4-yl) carbonyl ] -piperidin-4-yloxy ] -7-methoxy-quinazoline

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- {1- [ (S, S) - (2-oxa-5-aza-bicyclo [2.2.1] hept-5-yl) carbonyl ] -piperidin-4-yloxy ] -7-methoxy-quinazoline

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- {1- [ (2-methoxyethyl) carbonyl ] -piperidin-4-yloxy } -7-methoxy-quinazoline

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

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- [ cis-4- (N-methanesulfonyl-N-methyl-amino) -cyclohex-1-yloxy ] -7-methoxy-quinazoline

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- [ cis-4- (N-acetyl-N-methyl-amino) -cyclohex-1-yloxy ] -7-methoxy-quinazoline

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- (trans-4-methylamino-cyclohex-1-yloxy) -7-methoxy-quinazoline

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

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- (trans-4-dimethylamino-cyclohex-1-yloxy) -7-methoxy-quinazoline

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

4- [ (3-chloro-4-fluoro-phenyl) amino ] -6- [2- (2, 2-dimethyl-6-oxo-morpholin-4-yl) -ethoxy ] -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,

optionally in the form of its racemate, enantiomers or diastereomers and optionally in the form of its pharmacologically acceptable acid addition salts, solvates or hydrates. Preferably selected from the following salts: hydrochloride, hydrobromide, hydroiodide, sulphate, phosphate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate salts.

Examples of preferred dopamine antagonists which may be mentioned include: bromocriptine, cabergoline, alpha-dihydroergocarine (alpha-Dihydroergocryptine), lisuride, pergolide, pramipexole, rocyline, ropinirole, talipexole, terguride and vozan (Viozane), optionally in racemic form, as enantiomers, diastereomers, or as a pharmacologically acceptable salt, solvate or hydrate. Preferably selected from the following salts: hydrochloride, hydrobromide, hydroiodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate.

Examples of preferred antiallergic agents that may be mentioned include: epinastine, cetirizine, azelastine, fexofenadine, levocabastine, loratadine, mizolastine, colestifen (ketofene), emedastine, dimetindidine, clemastine, pamirine, dexchlorpheniramine (cexchlorphenamine), pheniramine, doxylamine, chlorphenxamine, dimenhydrinate, diphenhydramine, promethazine, ebastine, desloratadine (Desloratidine), and meclizine, optionally in racemic form, as enantiomers, diastereomers, or as pharmacologically acceptable salts, solvates, or hydrates. Preferably selected from the following salts: hydrochloride, hydrobromide, hydroiodide, sulphate, phosphate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate salts.

Furthermore, as disclosed in EP 1003478 a1 or CA 2297174 a1, inhalable macromolecules can be used as pharmacologically active substances.

Furthermore, the compound may be selected from derivatives of: ergot alkaloid derivatives, triptan (triptane), CGRP-antagonists, phosphodiesterase-V-inhibitors, optionally in the form of racemates, enantiomers, diastereomers, and optionally pharmacologically acceptable acid addition salts and hydrates thereof.

Such as derivatives of alkaloids: dihydroergotamine, ergotamine.

Claims (60)

1. Dispensing device (1) for dispensing a preferably pharmaceutical preparation (2), in particular containing or consisting of a drug, as a spray (3) comprising microparticles, wherein the dispensing device (1) is adapted to receive or comprises a storage device (4) with a plurality of individual and pre-metered doses of the preferably pharmaceutical preparation (2),

it is characterized in that

The storage device (4) comprises a carrier (5) with preferably a plurality of inserts (6), each insert (6) containing a single dose of the formulation (2).

2. Dispensing device according to claim 1, characterized in that the formulation (2) is a liquid, in particular a solution, suspension or suspension solution.

3. Dispensing device according to claim 1, characterized in that the preparation (2) is a powder.

4. Dispensing device according to any one of the preceding claims, characterized in that the carrier (5) comprises a plurality of cavities (7), each cavity (7) comprising one of the inserts (6).

5. Dispensing device according to claim 4, characterized in that the cavities (7) are spaced apart from each other, in particular sealed against each other.

6. Dispensing device according to claim 4 or 5, characterized in that each cavity (7) is sealed, in particular preferably by a plastic and/or metal foil.

7. Dispensing device according to any one of claims 4 to 6, characterized in that each cavity (7) has two opposite openings (8).

8. Dispensing device according to claim 7, characterized in that each insert (6) can be connected through one opening (8) for supplying pressurized gas and the corresponding dose can be dispensed through the other opening (8) or can be pushed at least partially out of the cavity (7) through the other opening (8).

9. Dispensing device according to any one of claims 4 to 8, characterized in that each insert (6) can be moved or pushed out of its respective cavity (7) at least partially.

10. Dispensing device according to any one of claims 4 to 9, characterized in that each insert (6) is capable of opening the seal (9) by means of a respective seal (9) of the associated cavity (7).

11. Dispensing device according to any one of the preceding claims, characterized in that the carrier (5) is a moulded element, ring, strip, box, blister or container.

12. Dispensing device according to any one of the preceding claims, characterized in that the carrier (5) is rigid or flexible.

13. Dispensing device according to any one of the preceding claims, characterized in that the carrier (5) is flexible and forms a preferably endless belt.

14. Dispensing device according to any one of the preceding claims, characterized in that the carrier (5) forms a preferably rigid guide for the insert (6).

15. Dispensing device according to any one of the preceding claims, characterized in that each insert (6) is a moulded element, cartridge, blister, capsule or container.

16. Dispensing device according to any one of the preceding claims, characterized in that each insert (6) is rigid or flexible.

17. Dispensing device according to any one of the preceding claims, characterized in that each insert (6) comprises a storage chamber (10) containing a respective dose.

18. Dispensing device according to any one of the preceding claims, characterized in that each insert (6) comprises at least one duct (12) or nozzle (13) to dispense each respective dose.

19. Dispensing device according to any one of claims 1 to 17, characterized in that the dispensing device (1) comprises a common conduit (12), nozzle (13) and/or mouthpiece (24).

20. Dispensing device according to any one of the preceding claims, characterized in that each insert (6) comprises jet impingement means (26) for impinging at least two jets (P) to deagglomerate the preparation (2), to produce small particles in the spray (3), to slow down the propagation speed of the spray (3) and/or to mix different preparations (2).

21. Dispensing device according to any one of the preceding claims, characterized in that the insert (6) contains at least two or three different formulations (2), wherein the formulations (2) are preferably mixed only during the dispensing operation.

22. Dispensing device according to any one of the preceding claims, characterized in that the dispensing device (1) comprises opening and/or supplying means, in particular piercing elements (17), such as needles or the like, to individually open or pierce said inserts (6) and/or to supply pressurized gas to the respective inserts (6) to dispense each respective dose.

23. Dispensing device according to claim 22, characterized in that the opening and/or supplying means comprise an abutment (23) to push the insert (6) at least partially out of the carrier (5) and/or through the associated seal (9).

24. Dispensing device according to any one of the preceding claims, characterized in that the dispensing device (1) comprises means for providing a pressurized gas, in particular air, for dispensing the preparation (2), preferably wherein the dispensing device (1) comprises a preferably manually operated air pump (18) as the means for providing a pressurized gas.

25. Dispensing device according to any one of the preceding claims, characterized in that the dispensing device (1) is designed such that the carrier (5) can be moved or indexed, in particular rotated, in a stepwise manner from one card (6) to the next card (6).

26. Dispensing device according to claim 25, characterized in that the insert (6) can be rotated or moved into or out of the carrier (5) in a direction which is radial, tangential, axial or transverse to the direction of movement or indexing of the carrier (5).

27. Dispensing device according to any one of the preceding claims, characterized in that the storage means (4) is replaceable.

28. Dispensing device according to any one of the preceding claims, characterized in that the dispensing device (1) is preferably an oral inhaler, in particular a dry powder inhaler.

29. Dispensing device according to any one of the preceding claims, characterized in that the dispensing device (1) or the storage device (4) comprises the preparation (2) comprising at least one of an anticholinergic agent, a β -mimetic, a steroid, a PDEIV-inhibitor, an LTD 4-antagonist, an EGFR-kinase-inhibitor and an antiallergic.

30. Storage device (4), preferably for a pharmaceutical preparation (2), in particular containing or consisting of a drug, preferably for a dispensing device (1) according to any one of the preceding claims, the storage device (4) comprising a plurality of individual and pre-metered doses of the preparation (2),

it is characterized in that

The storage device (4) comprises a carrier (5) having a plurality of inserts (6), each insert (6) containing one of said doses of the preparation (2).

31. Storage device according to claim 30, characterized in that the preparation (2) is a liquid, in particular a solution, suspension or suspension.

32. Storage device according to claim 30, characterized in that the preparation (2) is a powder.

33. Storage device according to one of claims 30 to 32, characterized in that the carrier (5) comprises a plurality of cavities (7), each cavity (7) containing one of the inserts (6).

34. Storage device according to claim 33, characterized in that the cavities (7) are spaced apart from each other, in particular sealed against each other.

35. Storage device according to claim 33 or 34, characterized in that each cavity (7) is sealed, in particular preferably by a metal or plastic foil.

36. Storage device according to any of claims 33 to 35, characterized in that each cavity (7) has two opposite openings (8).

37. Storage device according to claim 36, characterized in that each insert (6) is connectable through one opening (8) for supplying pressurized gas and the respective dose can be dispensed through the other opening (8) or can be pushed at least partially out of the cavity (7) through the other opening (8).

38. A store as claimed in any one of claims 33 to 37, wherein each insert (6) is able to be pushed through a respective seal (9) of the associated cavity (7) to open the seal (9).

39. Storage device according to one of claims 30 to 38, characterized in that each insert (6) can be moved or pushed out of the carrier (5) at least partially, in particular in a radial, tangential, axial or transverse direction to the longitudinal or annular extension of the carrier (5) or to the rows of the inserts (6).

40. Storage device according to one of claims 30 to 39, characterized in that the carrier (5) is a molded element, a ring, a strip, a box, a blister or a container.

41. Storage device according to one of claims 30 to 40, characterized in that the carrier (5) is rigid or flexible.

42. Storage device according to one of claims 30 to 41, characterized in that the carrier (5) is flexible and forms a preferably endless belt, and/or in that the carrier (5) forms a preferably rigid guide for the insert (6).

43. Storage device according to one of claims 30 to 42, characterized in that each insert (6) is a molded element, a box, a blister, a capsule or a container.

44. Dispensing device according to any one of claims 30 to 43, characterized in that each insert (6) is rigid or flexible.

45. Dispensing device according to any one of claims 30 to 44, characterized in that each insert (6) comprises a storage chamber (10) containing a respective dose.

46. Storage device according to any of claims 30 to 45, characterized in that each insert (6) comprises at least one conduit (12) or nozzle (13).

47. A storage device as claimed in any one of claims 30 to 46, characterized in that each insert (6) comprises jet impingement means (26) for impinging at least two jets (P) to deagglomerate the preparation (2), to produce small particles in the spray (3), to slow down the propagation speed of the spray (3) and/or to mix different preparations (2).

48. Storage device according to any one of claims 30 to 47, characterized in that the storage device (4) or at least one insert (6) comprises the preparation (2) comprising at least one of an anticholinergic agent, a β -mimetic agent, a steroid, a PDEIV-inhibitor, a LTD 4-antagonist, an EGFR-kinase-inhibitor and an antiallergic.

49. The storage device according to any of the claims 30 to 48, characterized in that the insert (6) comprises at least two or three different formulations (2), wherein the formulations (2) are preferably mixed only during the dispensing operation.

50. A method for dispensing a preferred pharmaceutical formulation (2), in particular containing or consisting of a drug, as a spray (3) comprising microparticles from a storage device (4) comprising a plurality of individual and pre-metered doses of the formulation (2),

it is characterized in that

Said doses being stored in a plurality of inserts (6) in a carrier (5), each insert (6) containing one of said doses of the preparation (2) and being located in a separate and sealed cavity (7) of the carrier (5), and in that said cavities (7) are individually opened to dispense each respective dose from the respective insert (6).

51. A method according to claim 50, characterized in that the cavity (7) is sealed by one or two common seals (9).

52. The method according to claim 50 or 51, characterized in that each cavity (7) is opened by pushing the respective insert (6) at least partially out of the cavity (7) and/or by the respective seal (9).

53. The method according to any one of claims 50 to 52, characterized in that the inserts (6) are individually connected to a source of pressurized gas, in particular by piercing the respective insert (6) by a piercing element (17).

54. Method according to claims 52 and 53, characterized in that the respective insert (6) is at least partially pushed out by the piercing element (17), in particular by means of an abutment (23) at the piercing element (17).

55. The method according to claim 53 or 54, characterized in that the piercing element (17) is pushed through the seal (9) and/or the insert (6) of the respective cavity (7) to connect the respective insert (6) to the source of pressurized gas.

56. The method of any one of claims 50 to 55, wherein said doses are individually subjected to air pressure for dispensing.

57. Method according to claim 56, characterized in that air is pressurized and used as gas, in particular wherein air is pressurized by manually operating an air pump (18).

58. The method according to any one of claims 50 to 57, characterized in that each dose is dispensed through a conduit (12) or nozzle (13) of the respective insert (6).

59. The method according to any one of claims 50 to 58, characterized in that the formulation (2) is a liquid, in particular a solution, a suspension or a suspension, or is a powder.

60. The method according to any one of claims 50 to 59, wherein the preparation (2) comprises at least one of an anticholinergic agent, a β -mimetic agent, a steroid, a PDEIV-inhibitor, a LTD 4-antagonist, an EGFR-kinase-inhibitor and an antiallergic.